Datasets:

allenai

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cochrane_sparse_oracle

like 0

[ "14984373", "14666762", "2697693", "15383254", "12138321", "9820260" ]

[ "Treatment of irritable bowel syndrome with herbal preparations: results of a double-blind, randomized, placebo-controlled, multi-centre trial.", "[Randomized controlled clinical study on effect of Chinese compound changjitai in treating diarrheic irritable bowel syndrome].", "Irritable bowel syndrome: therapeutic evaluation of indigenous drugs.", "[Observation on intestinal flora in patients of irritable bowel syndrome after treatment of Chinese integrative medicine].", "A novel treatment for constipation-predominant irritable bowel syndrome using Padma Lax, a Tibetan herbal formula.", "Treatment of irritable bowel syndrome with Chinese herbal medicine: a randomized controlled trial." ]

[ "Herbal medications have been used in many countries for the treatment of patients with irritable bowel syndrome. Controlled data supporting the efficacy of these treatments in patients with irritable bowel syndrome are lacking.\n To assess the efficacy and safety of a commercially available herbal preparation (STW 5) (nine plant extracts), the research herbal preparation STW 5-II (six plant extracts) and the bitter candytuft mono-extract in patients with irritable bowel syndrome.\n Two hundred and eight patients with irritable bowel syndrome were recruited after standardized diagnostic work-up into a double-blind, placebo-controlled, multi-centre trial and were randomly assigned to receive one of four treatments: commercially available herbal preparation STW 5 (n = 51), research herbal preparation STW 5-II (n = 52), bitter candytuft mono-extract (n = 53) or placebo (n = 52). The main outcome variables were the changes in total abdominal pain and irritable bowel syndrome symptom scores.\n Two hundred and three patients completed the trial. STW 5 and STW 5-II were significantly better than placebo in reducing the total abdominal pain score (intention-to-treat: STW 5, P = 0.0009; STW 5-II, P = 0.0005) and the irritable bowel syndrome symptom score (intention-to-treat: STW 5, P = 0.001; STW 5-II, P = 0.0003) at 4 weeks. There were no statistically significant differences between the bitter candytuft mono-extract group and the placebo group (P = 0.1473, P = 0.1207).\n The commercially available herbal preparation STW 5 and its research preparation STW 5-II are both effective in alleviating irritable bowel syndrome symptoms.", "To verify the clinical efficacy and safety of the proven Chinese Compound Changjitai (CJT), in treating the diarrheic irritable bowel syndrome (DIBS).\n Randomized controlled open clinical trial design was adopted, 45 patients were randomly divided into two groups, CJT and pinaverium bromide (PVB) were given as treated and control agent respectively. IBS scoring system (BSS), defecation state questionnaire (DSQ) were used to record the changes of the patients' main symptoms before and after treatment.\n The total effective rate of CJT group was 83.3%, while that of PVB was 73.3%. CJT was superior in efficacy to that of PVB in improving stool quality, reducing defecation episodes of diarrheic patients, alleviating tenesmus symptoms, decreasing bellyache days and ameliorating abdominal distention. Any drug-related adverse reaction was not seen.\n The efficacy of CJT in treating DIBS is definite and without any toxic and adverse effects.", "Among 169 patients with irritable bowel syndrome (IBS), standard therapy (with clidinium bromide, chlordiazepoxide and isaphaghulla), a compound Ayurvedic preparation (with Aegle marmelos correa plus Bacopa monniere Linn) along with a matching placebo were given in a double blind randomised trial for 6 wk. The Ayurvedic preparation in 57 patients was found effective in 64.9 per cent, while standard therapy (60 patients) was useful in 78.3 per cent. Patients on placebo (52 patients) showed improvement in 32.7 per cent only. Ayurvedic therapy was particularly beneficial in diarrhoea predominant form as compared to placebo. The standard therapy was more useful in the painful form of IBS as compared to placebo and Ayurvedic preparation. In gas predominant form the effect of standard as well as Ayurvedic therapy, was similar to placebo. Long-term follow-up (greater than 6 months) showed that both forms of therapy were no better than placebo in limiting the relapse.", "To observe the clinical efficacy of the combination of traditional Chinese medicine and western medicine in treating irritable bowel syndrome (IBS) and the result of intestinal flora regulation. Methods: Sixty IBS patients, 36 males and 24 females, were divided into two groups, with 30 patients in each group. Herbal formula of TongxieYaofang and clostridium butyricum (Cb) were used in the first group for four weeks, while only Cb was used for four weeks in the second group. We observed the changes of coliform group, enterococcus, lactobacillus, bifidobacterium after treatment.\n The effective rate of the Tongxie Yaofang and Cb treated group was significantly higher than that of the Cb treated group (P < 0.05). The numbers of bifidobacterium and lactobacillus increased, while the numbers of coliform group and enterococcus decreased after the treatment, and the changes of intestinal flora in the integrative medicine treated group were significantly greater than those in the Cb treated group.\n After treatment with the combination of traditional Chinese medicine and western medicine, the intestinal flora can be regulated to equilibrium state.", "Padma Lax, a complex Tibetan herbal formula for constipation was evaluated for safety and effectiveness in treating constipation-predominant irritable bowel syndrome in a 3-month double-blind randomised pilot study.\n Patients were recruited from Hadassah Hospital's Gastroenterology clinic, using the Rome I Criteria for irritable bowel syndrome, and the international consensus criteria for constipation. Symptom severity was evaluated monthly by patients and gastroenterologist, using categorical and numerical rating scales. A patient diary recorded daily stool habit and trial medication.\n In 61 patients, (34 Padma Lax, 27 placebo), significant improvement was demonstrated after 3 months in the Padma Lax group compared to placebo in constipation, severity of abdominal pain, and its effect on daily activities, incomplete evacuation, abdominal distension and flatus/flatulence. A global assessment indicated that significantly more Padma Lax patients, compared to placebo, rated the current treatment superior to previous therapies tried for irritable bowel. Laboratory parameters displayed no clinically significant changes. Side effects, primarily loose stools in 7 Padma Lax patients responded well to lowering treatment dosage from 2 to 1 capsule/day.\n Padma Lax is a safe and effective treatment for constipation-predominant irritable bowel syndrome and may offer an alternative to the current multi drug approach.\n Copyright 2002 S. Karger AG, Basel", "Irritable bowel syndrome (IBS) is a common functional bowel disorder for which there is no reliable medical treatment.\n To determine whether Chinese herbal medicine (CHM) is of any benefit in the treatment of IBS.\n Randomized, double-blind, placebo-controlled trial conducted during 1996 through 1997.\n Patients were recruited through 2 teaching hospitals and 5 private practices of gastroenterologists, and received CHM in 3 Chinese herbal clinics.\n A total of 116 patients who fulfilled the Rome criteria, an established standard for diagnosis of IBS.\n Patients were randomly allocated to 1 of 3 treatment groups: individualized Chinese herbal formulations (n = 38), a standard Chinese herbal formulation (n = 43), or placebo (n = 35). Patients received 5 capsules 3 times daily for 16 weeks and were evaluated regularly by a traditional Chinese herbalist and by a gastroenterologist. Patients, gastroenterologists, and herbalists were all blinded to treatment group.\n Change in total bowel symptom scale scores and global improvement assessed by patients and gastroenterologists and change in the degree of interference in life caused by IBS symptoms assessed by patients.\n Compared with patients in the placebo group, patients in the active treatment groups (standard and individualized CHM) had significant improvement in bowel symptom scores as rated by patients (P=.03) and by gastroenterologists (P=.001), and significant global improvement as rated by patients (P=.007) and by gastroenterologists (P=.002). Patients reported that treatment significantly reduced the degree of interference with life caused by IBS symptoms (P=.03). Chinese herbal formulations individually tailored to the patient proved no more effective than standard CHM treatment. On follow-up 14 weeks after completion of treatment, only the individualized CHM treatment group maintained improvement.\n Chinese herbal formulations appear to offer improvement in symptoms for some patients with IBS." ]

[ "5652710", "16510640", "9258175", "19864673", "18490378", "12429323", "11865276", "6981165", "11713435", "20478580", "18977988", "18082208", "18020019", "11343739" ]

[ "Treatment of vesico-ureteric reflux in children.", "Clinical significance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after acute pyelonephritis: a multicenter, randomized, controlled study.", "GAX 65: new injectable cross-linked collagen for the endoscopic treatment of vesicoureteral reflux--a double-blind study evaluating its efficiency in children.", "Antibiotic prophylaxis and recurrent urinary tract infection in children.", "Is antibiotic prophylaxis in children with vesicoureteral reflux effective in preventing pyelonephritis and renal scars? A randomized, controlled trial.", "Prospective comparison and 1-year follow-up of a single endoscopic subureteral polydimethylsiloxane versus dextranomer/hyaluronic acid copolymer injection for treatment of vesicoureteral reflux in children.", "Dextranomer/hyaluronic acid copolymer implantation for vesico-ureteral reflux: a randomized comparison with antibiotic prophylaxis.", "Antimicrobial prophylaxis in children with urinary tract infection and vesicoureteral reflux.", "Vesicoureteral reflux and evidence-based management.", "The Swedish reflux trial in children: I. Study design and study population characteristics.", "Prophylaxis after first febrile urinary tract infection in children? A multicenter, randomized, controlled, noninferiority trial.", "Antibiotic prophylaxis for the prevention of recurrent urinary tract infection in children with low grade vesicoureteral reflux: results from a prospective randomized study.", "[Endoscopic and conservative treatment of vesicoureteric reflux].", "Medical versus surgical treatment in children with severe bilateral vesicoureteric reflux and bilateral nephropathy: a randomised trial." ]

[ "nan", "To evaluate the role of primary vesicoureteral reflux (VUR) in increasing the frequency and severity of urinary tract infections (UTIs) and renal parenchymal damage among patients with acute pyelonephritis and to determine whether urinary antibiotic prophylaxis reduces the frequency and/or severity of UTIs and/or prevents renal parenchymal damage among patients with mild/moderate VUR.\n Patients 3 months to 18 years of age with acute pyelonephritis, with or without VUR, were assigned randomly to receive urinary antibiotic prophylaxis or not. Patients were monitored every 3 months for 1 year. Dimercaptosuccinic acid renal scans were repeated at 6 months or if there was a recurrence of febrile UTI. Urinalysis and urine culture were performed at each clinic visit. Renal ultrasound scans and voiding cystourethrograms were repeated at the end of 1 year of follow-up monitoring.\n Of the 236 patients enrolled in the study, 218 completed the 1-year follow-up monitoring. Groups were similar with respect to age, gender, and reflux grade distribution for those with VUR. No statistically significant differences were found among the groups with respect to rate of recurrent UTI, type of recurrence, rate of subsequent pyelonephritis, and development of renal parenchymal scars.\n After 1 year of follow-up monitoring, mild/moderate VUR does not increase the incidence of UTI, pyelonephritis, or renal scarring after acute pyelonephritis. Moreover, a role for urinary antibiotic prophylaxis in preventing the recurrence of infection and the development of renal scars is not supported by this study.", "In the experimental model glutaraldehyde cross-linked collagen GAX 65 with a collagen concentration of 65 mg./ml. has proved to have more persistent implant volume and, therefore, a better antireflux effect than GAX 35, which is injected more commonly. The aim of this study was to evaluate the potential clinical application of GAX 65.\n Ten boys and 8 girls an average of 4.6 years old presented with unilateral or bilateral primary reflux and were randomly divided into 2 groups. All refluxing ureters received 1 endoscopic subureteral injection of an average of approximately 2.9 ml. collagen. In group 1, 16 refluxing ureters were treated with GAX 65 and in group 2, 12 were treated with GAX 35. In all patients voiding cystourethrography was performed immediately after injection and 3 months postoperatively, and ultrasound was done on day 1, and at 1 and 3 months. Implant volume was calculated at the day of injection and at 3 months. The distribution of reflux grades was comparable in the 2 groups.\n Both materials had excellent injection properties. Immediately after injection all ureters were reflux-free. Of the 16 ureters treated with GAX 65 14 (87.5%) were reflux-free at the 3-month followup. Three months postoperatively ultrasound revealed an average implant volume increase of one-third. However, of the 12 ureters treated with GAX 35 reflux had resolved in 59.3% and the average implant volume had decreased by half 3 months after injection.\n Three months after endoscopic subureteral injection of GAX 65 vesicoureteral reflux was absent in 87.5% of patients. Therefore, GAX 65 has greater potential for treating reflux in the short term than GAX 35. To define the final efficacy of GAX 65 for treating vesicoureteral reflux, long-term evaluation of this series is necessary. In addition, further studies are mandatory to prove the long-term advantage of this new injectable substance.", "Antibiotics are widely administered to children with the intention of preventing urinary tract infection, but adequately powered, placebo-controlled trials regarding efficacy are lacking. This study from four Australian centers examined whether low-dose, continuous oral antibiotic therapy prevents urinary tract infection in predisposed children.\n We randomly assigned children under the age of 18 years who had had one or more microbiologically proven urinary tract infections to receive either daily trimethoprim-sulfamethoxazole suspension (as 2 mg of trimethoprim plus 10 mg of sulfamethoxazole per kilogram of body weight) or placebo for 12 months. The primary outcome was microbiologically confirmed symptomatic urinary tract infection. Intention-to-treat analyses were performed with the use of time-to-event data.\n From December 1998 to March 2007, a total of 576 children (of 780 planned) underwent randomization. The median age at entry was 14 months; 64% of the patients were girls, 42% had known vesicoureteral reflux (at least grade III in 53% of these patients), and 71% were enrolled after the first diagnosis of urinary tract infection. During the study, urinary tract infection developed in 36 of 288 patients (13%) in the group receiving trimethoprim-sulfamethoxazole (antibiotic group) and in 55 of 288 patients (19%) in the placebo group (hazard ratio in the antibiotic group, 0.61; 95% confidence interval, 0.40 to 0.93; P = 0.02 by the log-rank test). In the antibiotic group, the reduction in the absolute risk of urinary tract infection (6 percentage points) appeared to be consistent across all subgroups of patients (P > or = 0.20 for all interactions).\n Long-term, low-dose trimethoprim-sulfamethoxazole was associated with a decreased number of urinary tract infections in predisposed children. The treatment effect appeared to be consistent but modest across subgroups. (Australian New Zealand Clinical Trials Registry number, ACTRN12608000470392.)\n 2009 Massachusetts Medical Society", "There has been intense discussion on the effectiveness of continuous antibiotic prophylaxis for children with vesicoureteral reflux, and randomized, controlled trials are still needed to determine the effectiveness of long-term antibiotics for the prevention of acute pyelonephritis. In this multicenter, open-label, randomized, controlled trial, we tested the effectiveness of antibiotic prophylaxis in preventing recurrence of pyelonephritis and avoiding new scars in a sample of children who were younger than 30 months and vesicoureteral reflux.\n One hundred patients with vesicoureteral reflux (grade II, III, or IV) diagnosed with cystourethrography after a first episode of acute pyelonephritis were randomly assigned to receive antibiotic prophylaxis with sulfamethoxazole/trimethoprim or not for 2 years. The main outcome of the study was the recurrence of pyelonephritis during a follow-up period of 4 years. During follow-up, the patients were evaluated through repeated cystourethrographies, renal ultrasounds, and dimercaptosuccinic acid scans.\n The baseline characteristics in the 2 study groups were similar. There were no differences in the risk for having at least 1 pyelonephritis episode between the intervention and control groups. At the end of follow-up, the presence of renal scars was the same in children with and without antibiotic prophylaxis.\n Continuous antibiotic prophylaxis was ineffective in reducing the rate of pyelonephritis recurrence and the incidence of renal damage in children who were younger than 30 months and had vesicoureteral reflux grades II through IV.", "To compare, in a prospective study, the efficacy of a single injection of polydimethylsiloxane (Macroplastique) or dextranomer/hyaluronic acid copolymer (Deflux), a new biodegradable substance, and to assess the short-term and 1-year clinical effects concerning reflux resolution and the safety of these two bulking agents. Subureteral injection of bulking agents has recently demonstrated good success rates for endoscopic treatment of vesicoureteral reflux. Macroplastique has been one of the most popular bulking agents during the past years. Nevertheless, considering the synthetic property, new biodegradable substances have become more relevant.\n From January 2000 to June 2001, 16 boys and 56 girls (total of 114 ureters) with a mean age of 34.5 months were treated endoscopically for vesicoureteral reflux. A single subureteral Macroplastique or Deflux injection was performed in 34 children (58 ureters) and 38 children (56 ureters), respectively. Both groups were comparable in terms of baseline parameters. Vesicoureteral reflux was grade II in 52, grade III in 57, and grade IV in 5 ureterorenal units. The procedure was performed on an outpatient basis, with the children under general anesthesia. In addition to the routine parameters, the follow-up evaluation consisted of renal ultrasonography and voiding cystourethrography at 3 and 12 months postoperatively.\n Endoscopic treatment was performed without any complications in all cases. At the 3-month follow-up visit, reflux was corrected in 50 (86.2%) of 58 refluxing ureters in the Macroplastique group and in 40 (71.4%) of 56 refluxing ureters in the Deflux group. At 1 year of follow-up, reflux correction was maintained in 80.9% of ureters in the Macroplastique group and in 67.6% of ureters in the Deflux group. No postoperative complications were observed in either group.\n A single subureteral injection of either polydimethylsiloxane (Macroplastique) or dextranomer/hyaluronic acid copolymer (Deflux) is an effective treatment modality for children with vesicoureteral reflux. The procedure was well tolerated, safe, and associated with low morbidity. Deflux, a new biocompatible, biodegradable substance, seems to be an alternative modality to other bulking agents for treating vesicoureteral reflux in children, with acceptable short-term and 1-year results.", "Dextranomer/hyaluronic acid (Dx/HA) copolymer has favorable properties for endoscopic treatment of vesico-ureteral reflux (VUR). This open, randomized study was performed to compare the efficacy and safety of Dx/HA copolymer with antibiotic prophylaxis in children with VUR.\n Children >1 year of age with VUR grade II to IV (confirmed by voiding cysto-urethrogram) received endoscopic treatment with Dx/HA copolymer (n = 40) or 12 months of antibiotic prophylaxis (n = 21). Patients in the latter group with reflux grade >or=II at month 3 received a second implantation. All patients were reassessed by voiding cysto-urethrogram at month 12. Scintigraphy and ultrasound were performed to investigate renal status.\n At month 12, 69% of patients in the Dx/HA copolymer group had reflux grade <or=I bilaterally, compared with 38% in the antibiotic group (P =.029). Of patients with reflux grade <or=I at month 3, 89% showed a sustained response at month 12. One serious adverse event was reported in the antibiotic prophylaxis group, but this was not attributed to study treatment. No other adverse events occurred.\n Endoscopic treatment with Dx/HA copolymer was more effective than antibiotic prophylaxis in alleviating childhood VUR, and there were no safety concerns with either treatment.", "Thirty children with urinary tract infection and nonobstructive vesicoureteral reflux have been followed prospectively for a mean of 17 months. After classification according to age and grade of reflux, 10 patients were assigned at random to treatment with antimicrobial prophylaxis alone or antimicrobial prophylaxis plus corrective surgery. Twenty other patients were also treated with antimicrobial prophylaxis alone. All were assigned at random to treatment with a single daily dose of trimethoprim-sulfamethoxazole or nitrofurantoin. Cultures of urine, complete blood cell counts, and determination of levels of aspartate aminotransferase in serum were performed regularly during follow-up. Both drugs proved effective in prevention of recurrent infection, and no significant hematologic or hepatic abnormalities were noted. Current results suggest that either prophylaxis or surgery may effectively prevent chronic pyelonephritis or reflux nephropathy, but only continuing evaluation of this group of patients will confirm these results.", "nan", "We compared the rates of febrile urinary tract infection, kidney damage and reflux resolution in children with vesicoureteral reflux treated in 3 ways, including antibiotic prophylaxis, endoscopic therapy and surveillance with antibiotics only for symptomatic urinary tract infection.\n Children 1 to younger than 2 years with grade III-IV reflux were recruited into this prospective, open, randomized, controlled, multicenter study and followed for 2 years after randomization. The main study end points were recurrent febrile urinary tract infection, renal status on dimercapto-succinic acid scintigraphy and reflux status. Outcomes were analyzed by the intent to treat principle.\n During a 6-year period 128 girls and 75 boys entered the study. In 96% of cases reflux was detected after urinary tract infection. The randomization procedure was successful and resulted in 3 groups matched for relevant factors. Recruitment was slower than anticipated but after patients were entered adherence to the protocol was good. Of the children 93% were followed for the intended 2 years without a treatment arm change. All except 2 patients completed 2-year followup scintigraphy.\n Recruitment was difficult but a substantial number of children were entered and randomly assigned to 3 groups with similar basic characteristics. Good adherence to the protocol made it possible to address the central study questions.\n Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.", "Febrile urinary tract infections are common in children and associated with the risk for renal scarring and long-term complications. Antimicrobial prophylaxis has been used to reduce the risk for recurrence. We performed a study to determine whether no prophylaxis is similar to antimicrobial prophylaxis for 12 months in reducing the recurrence of febrile urinary tract infections in children after a first febrile urinary tract infection.\n The study was a controlled, randomized, open-label, 2-armed, noninferiority trial comparing no prophylaxis with prophylaxis (co-trimoxazole 15 mg/kg per day or co-amoxiclav 15 mg/kg per day) for 12 months. A total of 338 children who were aged 2 months to <7 years and had a first episode of febrile urinary tract infection were enrolled: 309 with a confirmed pyelonephritis on a technetium 99m dimercaptosuccinic acid scan with or without reflux and 27 with a clinical pyelonephritis and reflux. The primary end point was recurrence rate of febrile urinary tract infections during 12 months. Secondary end point was the rate of renal scarring produced by recurrent urinary tract infections on technetium 99m dimercaptosuccinic acid scan after 12 months.\n Intention-to-treat analysis showed no significant differences in the primary outcome between no prophylaxis and prophylaxis: 12 (9.45%) of 127 vs 15 (7.11%) of 211. In the subgroup of children with reflux, the recurrence of febrile urinary tract infections was 9 (19.6%) of 46 on no prophylaxis and 10 (12.1%) of 82 on prophylaxis. No significant difference was found in the secondary outcome: 2 (1.9%) of 108 on no prophylaxis versus 2 (1.1%) of 187 on prophylaxis. Bivariate analysis and Cox proportional hazard model showed that grade III reflux was a risk factor for recurrent febrile urinary tract infections. Whereas increasing age was protective, use of no prophylaxis was not a risk factor.\n For children with or without primary nonsevere reflux, prophylaxis does not reduce the rate of recurrent febrile urinary tract infections after the first episode.", "Antibiotic prophylaxis is given to children at risk for urinary tract infection. However, evidence concerning its effectiveness in grade I to III vesicoureteral reflux is lacking. The objective of this study was to determine whether antibiotic prophylaxis reduces the incidence of urinary tract infection in young children with low grade vesicoureteral reflux.\n Children 1 month to 3 years old with grade I to III vesicoureteral reflux were assigned randomly to receive daily cotrimoxazole or no treatment, and followed for 18 months. A urinary tract infection constituted an exit criterion. Infection-free survival rates were calculated using the Kaplan-Meier method and compared using the log rank test.\n A total of 225 children were enrolled in the study. Distribution of gender, age at inclusion and reflux grade were similar between the 2 groups. There was no significant difference in the occurrence of urinary tract infection between the 2 groups (17% vs 26%, p = 0.2). However, a significant association was found between treatment and patient gender (p = 0.017). Prophylaxis significantly reduced urinary tract infection in boys (p = 0.013), most notably in boys with grade III vesicoureteral reflux (p = 0.042).\n These data suggest that antibiotic prophylaxis does not reduce the overall incidence of urinary tract infection in children with low grade vesicoureteral reflux. However, such a strategy may prevent further urinary tract infection in boys with grade III reflux.", "The aim of study is to evaluate the results of endoscopic treatment of vesicoureteric reflux (VUR) comparing with conservative mode.\n In the years 2003-2006 there were forty for children in prospective randomised study enrolled and divided into two groups. Twenty two children 1-40 months old (22.9 months) were operated. Dx/Ha (Deflux) was instilled for VUR grade 3-5. The results of treatment were compared with outcome of twenty two conservatively treated randomly assigned children aged 1-32 months (mean age 13.5 months) Postoperative videourodynamic study was used to evaluate for the presence of VUR and function of the bladder and ultrasound investigation was performed too (exclusion of obstructive megaureter in operated group). There were 22 children controled after instillation. The children were followed 11-24 months. VUR was cured in 12 cases (54.5%) and improved (grade 1-2) in 5 children (66.7%). All children absolved treatment without any complications, excluding one case with obstructive megaureter after pyelonephritis diagnosed. There were 22 children evaluated in conservative group. Five children were cured (22.7%) and VUR was improved (grade 1-2) in four (18.2%)\n Endoscopic miniinvasive instillation of dextranomer is safe and effective treatment of VUR in all age groups with good therapeutical outcome and minimum of adverse effects.", "Nephropathy associated with vesicoureteric reflux (VUR) and urinary tract infection can result in end-stage renal failure, hypertension, or both. Whether long-term VUR contributes to these outcomes is unknown. We compared, in a randomised trial, medical with surgical management of children with bilateral severe VUR and bilateral nephropathy.\n We stratified by age and glomerular filtration rate (GFR) 25 boys and 27 girls aged 1-12 years and randomly assigned them to medical or surgical management. At enrolment and 4 years' follow-up we estimated GFR from the plasma clearance of 51Cr-labelled edetic acid (EDTA), and did intravenous urography. We also did a metastable 99mTc-labelled dimercaptosuccinic acid (DMSA) assay and contrast cystography. The change in GFR at 4 years, expressed as a percentage change between enrolment and 4 years, was available for 26 of 27 patients in the medical and 24 of 25 in the surgical group. We assessed GFR in 48 patients 10 years after enrolment.\n Mean GFR at enrolment was 72.4 mL/min per 1.73 m(2) (SD 24.1) in the medical and 71.7 mL/min per 1.73 m(2) (22.6) in the surgical group. The mean percentage change in GFR at 4 years was 2.4% (SE 4.5) versus 4.7% (5.0) in the medical and surgical groups, respectively. The difference in change in GFR at 4 years between the two groups was not significant (7.1%, 95% CI 6.4% to 20.6%).\n Our data do not lend support to the view that the outcome for renal function is improved by surgical correction of VUR in children with bilateral disease." ]

[ "9585747", "10198656", "11996616", "8546549", "19858174", "10724056", "11165450", "11382368", "14974750", "12196616", "9626609" ]

[ "Tuberculosis screening and compliance with return for skin test reading among active drug users.", "Monetary versus nonmonetary incentives for TB skin test reading among drug users.", "Randomized controlled trial of interventions to improve follow-up for latent tuberculosis infection after release from jail.", "Tuberculosis prophylaxis in the homeless. A trial to improve adherence to referral.", "Food incentives to improve completion of tuberculosis treatment: randomised controlled trial in Dili, Timor-Leste.", "Adherence to isoniazid prophylaxis in the homeless: a randomized controlled trial.", "Incentives vs outreach workers for latent tuberculosis treatment in drug users.", "A randomized, controlled trial of interventions to improve adherence to isoniazid therapy to prevent tuberculosis in injection drug users.", "Can the poor adhere? Incentives for adherence to TB prevention in homeless adults.", "Behavioral interventions for the control of tuberculosis among adolescents.", "A clinical trial of a financial incentive to go to the tuberculosis clinic for isoniazid after release from jail." ]

[ "This study assessed the independent and combined effects of different levels of monetary incentives and a theory-based educational intervention on return for tuberculosis (TB) skin test reading in a sample of active injection drug and crack cocaine users. Prevalence of TB infection in this sample was also determined.\n Active or recent drug users (n = 1004), recruited via street outreach techniques, were skin tested for TB. They were randomly assigned to 1 of 2 levels of monetary incentive ($5 and $10) provided at return for skin test reading, alone or in combination with a brief motivational education session.\n More than 90% of those who received $10 returned for skin test reading, in comparison with 85% of those who received $5 and 33% of those who received no monetary incentive. The education session had no impact on return for skin test reading. The prevalence of a positive tuberculin test was 18.3%.\n Monetary incentives dramatically increase the return rate for TB skin test reading among drug users who are at high risk of TB infection.", "In a prior study, we reported that monetary incentives were effective in increasing return for tuberculosis (TB) skin test reading. The purpose of this study was to compare the effects of monetary versus nonmonetary incentives and a theory-based educational intervention on return for TB skin test reading in a sample of newly recruited active injection and crack cocaine users, and to determine the prevalence of TB infection in this sample.\n Active injection drug and/or crack cocaine users (n = 1,078), recruited using street outreach techniques, were skin tested for TB. They were randomly assigned to 1 of 5 experimental treatment conditions: $10 cash, grocery store coupons, bus tokens/fast-food coupons, motivational education, or usual encouragement to return. Nonmonetary incentives had a $10 value, and all incentives were provided at return for skin test reading.\n Ninety-five percent of those who received $10 returned for skin test reading compared to 86% of those who received grocery store coupons and 83% of those who received either bus tokens or fast-food coupons. In contrast, only 47% of those who received the educational session and only 49% of those who received usual encouragement returned for skin test reading. The prevalence of a positive tuberculin test was 21%, and was similar for crack cocaine and injection drug users.\n Nonmonetary and monetary incentives dramatically increased the return rate for TB skin test reading among drug users who are at high risk of TB infection. Nonmonetary incentives were somewhat less effective than monetary incentives.", "Adherence to treatment of persons with latent tuberculosis infection after release from jail has been poor.\n A randomized controlled trial was conducted at the San Francisco City and County Jail, San Francisco, Calif. Subjects undergoing therapy for latent tuberculosis infection who spoke either English or Spanish were randomly allocated to receive education every 2 weeks while in jail; an incentive if they went to the San Francisco County Tuberculosis Clinic within 1 month of release; or usual care. The main outcome measures were completion of a visit to the tuberculosis clinic within 1 month of release and completion of therapy.\n Of 558 inmates enrolled, 325 were released before completion of therapy. Subjects in either intervention group were significantly more likely to complete a first visit than were control subjects (education group, 37%; incentive group, 37%; and controls, 24%) (adjusted odds ratio based on pooled results for the education and incentive groups, 1.85; 95% confidence interval, 1.04-3.28; P =.02). Those in the education group were twice as likely to complete therapy compared with controls (adjusted odds ratio, 2.2; 95% confidence interval, 1.04-4.72; P =.04). Of those who went to the tuberculosis clinic after release, subjects in the education group were more likely to complete therapy (education group, 65% [24/37]; incentive group, 33% [14/42]; and control group, 48% [12/25]; P =.02).\n Education or the promise of an incentive improved initial follow-up. Education was superior to an incentive for the completion of therapy. Fairly modest strategies provided in jail can improve adherence. Further links between jail health services and community care should be explored.", "Adherence to tuberculosis evaluation is poor in a high-risk population such as the homeless.\n To test two interventions aimed at improving adherence to tuberculosis evaluation and to identify predictors of adherence.\n We conducted a randomized clinical trial in shelters and food lines in the inner city of San Francisco, Calif. We randomized 244 eligible subjects infected with tuberculosis to (1) peer health adviser (assistance by a peer [n = 83]), (2) monetary incentive ($5 payment [n = 82]), or (3) usual care (referral slips and bus tokens only [n = 79]). The primary outcome of the study was adherence to a first follow-up appointment at the tuberculosis clinic, where subjects were evaluated for active tuberculosis and the need for isoniazid prophylaxis.\n Of the subjects assigned to a monetary incentive, 69 (84%) completed their first follow-up appointment, compared with 62 subjects (75%) assigned to a peer health adviser and 42 subjects (53%) assigned to usual care. Adherence was higher in the monetary incentive and peer health adviser groups than in the usual care group (P < .001 and P = .004, respectively). Patients not using intravenous drugs and patients 50 years of age or older were more likely to adhere to a first follow-up appointment (odds ratios [95% confidence intervals], 2.5 [1.3 to 5.0] and 3.3 [1.2 to 8.8], respectively). Among the 173 tuberculosis-infected subjects who completed their appointment, isoniazid therapy was started for 72 individuals, and three cases of active tuberculosis were identified.\n A monetary incentive or a peer health adviser is effective in improving adherence to a first follow-up appointment in homeless individuals infected with tuberculosis. A monetary incentive appears to be superior. Intravenous drug users and young individuals are at high risk for poor adherence to referral.", "To determine the effectiveness of the provision of whole food to enhance completion of treatment for tuberculosis.\n Parallel group randomised controlled trial.\n Three primary care clinics in Dili, Timor-Leste.\n 270 adults aged >or=18 with previously untreated newly diagnosed pulmonary tuberculosis.\n Completion of treatment (including cure). Secondary outcomes included adherence to treatment, weight gain, and clearance of sputum smears. Outcomes were assessed remotely, blinded to allocation status. Interventions Participants started standard tuberculosis treatment and were randomly assigned to intervention (nutritious, culturally appropriate daily meal (weeks 1-8) and food package (weeks 9-32) (n=137) or control (nutritional advice, n=133) groups. Randomisation sequence was computer generated with allocation concealment by sequentially numbered, opaque, sealed envelopes.\n Most patients with tuberculosis were poor, malnourished men living close to the clinics; 265/270 (98%) contributed to the analysis. The intervention had no significant beneficial or harmful impact on the outcome of treatment (76% v 78% completion, P=0.7) or adherence (93% for both groups, P=0.7) but did lead to improved weight gain at the end of treatment (10.1% v 7.5% improvement, P=0.04). Itch was more common in the intervention group (21% v 9%, P<0.01). In a subgroup analysis of patients with positive results on sputum smears, there were clinically important improvements in one month sputum clearance (85% v 67%, P=0.13) and completion of treatment (78% v 68%, P=0.3).\n Provision of food did not improve outcomes with tuberculosis treatment in these patients in Timor-Leste. Further studies in different settings and measuring different outcomes are required.\n Clinical Trials NCT0019256.", "To test 2 interventions to improve adherence to isoniazid preventive therapy for tuberculosis in homeless adults. We compared (1) biweekly directly observed preventive therapy using a $5 monetary incentive and (2) biweekly directly observed preventive therapy using a peer health adviser, with (3) usual care at the tuberculosis clinic.\n Randomized controlled trial in tuberculosis-infected homeless adults. Outcomes were completion of 6 months of isoniazid treatment and number of months of isoniazid dispensed.\n A total of 118 subjects were randomized to the 3 arms of the study. Completion in the monetary incentive arm was significantly better than in the peer health adviser arm (P = .01) and the usual care arm (P = .04), by log-rank test. Overall, 19 subjects (44%) in the monetary incentive arm completed preventive therapy compared with 7 (19%) in the peer health adviser arm (P = .02) and 10 (26%) in the usual care arm (P = .11). The median number of months of isoniazid dispensed was 5 in the monetary incentive arm vs 2 months in the peer health adviser arm (P = .005) and 2 months in the usual care arm (P = .04). In multivariate analysis, independent predictors of completion were being in the monetary incentive arm (odds ratio, 2.57; 95% CI, 1.11-5.94) and residence in a hotel or other stable housing at entry into the study vs residence on the street or in a shelter at entry (odds ratio, 2.33; 95% CI, 1.00-5.47).\n A $5 biweekly cash incentive improved adherence to tuberculosis preventive therapy compared with a peer intervention or usual care. Living in a hotel or apartment at the start of treatment also predicted the completion of therapy.", "Drug users are at increased risk for latent tuberculosis infection (LTBI) and also at increased risk for noncompletion of medication regimens for treatment of LTBI or tuberculosis disease. Directly observed therapy (DOT) provided by outreach workers, the use of incentives, or both have been suggested as a means to increase adherence.\n To compare the independent and combined effects of monetary incentives and outreach worker provision of DOT for LTBI treatment in a sample of active drug users.\n The research design was a randomized controlled trial in a community outreach program setting. Participants consisted of a volunteer sample of 163 active injection drug and crack cocaine users placed on twice weekly DOT. Condition 1 of the interventions consisted of provision of DOT by an outreach worker at a location chosen by the participant (active outreach) and a $5 per visit incentive. Condition 2 was comprised of active outreach with no monetary incentive, and Condition 3, provision of DOT at the study community site and a $5 per visit incentive. The main outcome measures were percentage of medication taken as prescribed and completion of medication regimen.\n The percentage of prescribed medication taken was higher for those who received incentives, either with (71%) or without (68%) active outreach, compared to those who received active outreach alone (13%). Only 4% of participants assigned to Condition 2 completed treatment, compared to 53% of Condition 1 participants, and 60% of Condition 3 participants.\n Monetary incentives were clearly superior to active outreach. Active outreach in combination with monetary incentives did not increase adherence over incentives alone.", "To determine the effect of several interventions on adherence to tuberculosis preventive therapy.\n We conducted a randomized trial with a factorial design comparing strategies for improving adherence to isoniazid preventive therapy in 300 injection drug users with reactive tuberculin tests and no evidence of active tuberculosis. Patients were assigned to receive directly observed isoniazid preventive therapy twice weekly (Supervised group, n = 99), daily self-administered isoniazid with peer counseling and education (Peer group, n = 101), or routine care (Routine group, n = 100). Patients within each arm were also randomly assigned to receive an immediate or deferred monthly $10 stipend for maintaining adherence. The endpoints of the trial were completing 6 months of treatment, pill-taking as measured by self-report or observation, isoniazid metabolites present in urine, and bottle opening as determined by electronic monitors in a subset of patients.\n Completion of therapy was 80% for patients in the Supervised group, 78% in the Peer group, and 79% in the Routine group (P = 0.70). Completion was 83% (125 of 150) among patients receiving immediate incentives versus 75% (112 of 150) among patients with deferred incentives (P = 0.09). The proportion of patients who were observed or reported taking at least 80% of their doses was 82% for the Supervised arm of the study, compared with 71% for the Peer arm and 90% for the Routine arm. The proportion of patients who took 100% of doses was 77% for the Supervised arm (by observation), 6% for the Peer arm (by report), and 10% for the Routine arm (by report; P <0.001). Direct observation showed the median proportion of doses taken by the Supervised group was 100%, while electronic monitoring in a subset of patients showed the Peer group (n = 27) took 57% of prescribed doses and the Routine group (n = 32) took 49% (P <0.001). Patients in the Routine arm overreported adherence by twofold when data from electronic monitoring were used as a gold standard. There were no significant differences in electronically monitored adherence by type of incentive.\n Adherence to isoniazid preventive therapy by injection drug users is best with supervised care. Peer counseling improves adherence over routine care, as measured by electronic monitoring of pill caps, and patients receiving peer counseling more accurately reported their adherence. More widespread use of supervised care could contribute to reductions in tuberculosis rates among drug users and possibly other high-risk groups.", "Community-based population of homeless adults living in San Francisco, California.\n To compare the effect of cash and non-cash incentives on 1) adherence to treatment for latent tuberculosis infection, and 2) length of time needed to look for participants who missed their dose of medications.\n Prospective, randomized clinical trial comparing a 5 dollar cash or a 5 dollar non-cash incentive. All participants received directly observed preventive therapy and standardized follow-up per a predetermined protocol. Completion rates and amount of time needed to follow up participants was measured.\n Of the 119 participants, 102 (86%) completed therapy. There was no difference between the cash and non-cash arms. Completion was significantly higher among males (OR 5.65, 95%CI 1.36-23.40, P = 0.02) and persons in stable housing at study entry (OR 4.86, 95%CI 1.32-17.94, P = 0.02). No substance use or mental health measures were associated with completion. Participants in the cash arm needed significantly less follow-up to complete therapy compared to the non-cash arm (P = 0.03). In multivariate analysis, non-cash incentive, use of crack cocaine, and no prior preventive therapy were associated with more follow-up time.\n Simple, low cost incentives can be used to improve adherence to TB preventive therapy in indigent adults.", "Activation of latent tuberculosis infection into tuberculosis disease (TB), the primary killer among infectious diseases worldwide, can be prevented with six months of anti-TB medication. A large percentage of adolescents started on medication, however, fail to complete their treatment. The authors developed and tested the effects of innovative educational strategies on infected adolescents at two health centers serving ethnically diverse populations.\n The authors used a randomized experimental four-group design to assess the independent and combined effects of peer counseling and a participant-parent contingency contract intervention.\n A total of 794 adolescents were recruited into the study, for a 79% participation rate. The overall rate of treatment completion was 79.8%. Self-efficacy for medication-taking behavior at post-test correlated strongly with completion of care (R = 0.367, p = 0.002). Participants randomized to the peer counseling groups demonstrated significantly greater improvements in self-efficacy and mastery than the usual care control group. Based on the study results, continuing education seminars and workshops were implemented for TB control staff at the two health clinics and for all TB Control Division staff at the Los Angeles County Health Department. Educational materials and a training manual for enhancing completion of treatment of latent TB infection through tailored educational approaches were developed and disseminated to the clinics.\n Health education and incentives are helpful adjuncts to the completion of treatment for latent tuberculosis infection in adolescents.", "Screening for active tuberculosis (TB) and providing isoniazid (INH) preventive therapy in jails are important control measures. In San Francisco, however, historical data showed that 62% of inmates were released before completing preventive therapy, and of those only 3% attended the TB Clinic for follow-up.\n A randomized clinical trial to compare a $5 cash incentive plus standardized TB education with standardized TB education alone in encouraging released inmates to make a first visit to the clinic.\n Of 79 persons enrolled in the trial, 77.2% were released before INH completion. Rates of first visit were not significantly different for those receiving +5 plus standardized education (25.8%) versus standardized education alone (23.3%), but were higher than rates seen in historical data for inmates not receiving standardized education. Age was an important predictor of completion of a first visit (odds ratio 1.09, 95% confidence interval 1.02-1.16, P = 0.017). Other variables predicting adherence included intent to adhere, more previous time in jail, stable housing, and being partnered versus alone, although these were not statistically significant.\n Standardized education may be important in improving follow-up after release. Further work on the role of a financial incentive in this population is needed." ]

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[ "Efficacy and safety of sibutramine in obese white and African American patients with hypertension: a 1-year, double-blind, placebo-controlled, multicenter trial.", "Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study.", "Sibutramine is safe and effective for weight loss in obese patients whose hypertension is well controlled with angiotensin-converting enzyme inhibitors.", "Effect of orlistat on cardiovascular disease risk in obese adults.", "Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia.", "Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. European Orlistat Obesity Study Group.", "A randomized trial of sibutramine in the management of obese type 2 diabetic patients treated with metformin.", "Randomized, double-blind, placebo-controlled comparison of the action of orlistat, fluvastatin, or both an anthropometric measurements, blood pressure, and lipid profile in obese patients with hypercholesterolemia prescribed a standardized diet.", "Role of orlistat in the treatment of obese patients with type 2 diabetes. A 1-year randomized double-blind study.", "Orlistat in the long-term treatment of obesity in primary care settings.", "Use of sibutramine in overweight adult hispanic patients with type 2 diabetes mellitus: a 12-month, randomized, double-blind, placebo-controlled clinical trial.", "Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. European Multicentre Orlistat Study Group.", "Randomized placebo-controlled trial of long-term treatment with sibutramine in mild to moderate obesity.", "Effect of orlistat in overweight and obese patients with type 2 diabetes treated with metformin.", "Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study.", "Weight reduction and long-term maintenance after 18 months treatment with orlistat for obesity.", "The effect of orlistat on body weight and coronary heart disease risk profile in obese patients: the Swedish Multimorbidity Study.", "Health-related quality of life in a randomised placebo-controlled trial of sibutramine in obese patients with type II diabetes.", "Orlistat improves blood pressure control in obese subjects with treated but inadequately controlled hypertension.", "Long-term maintenance of weight loss after a very-low-calorie diet: a randomized blinded trial of the efficacy and tolerability of sibutramine.", "Effect of sibutramine on weight maintenance after weight loss: a randomised trial. STORM Study Group. Sibutramine Trial of Obesity Reduction and Maintenance.", "XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients.", "Randomised trial of the effect of orlistat on body weight and cardiovascular disease risk profile in obese patients: UK Multimorbidity Study.", "Weight reduction by sibutramine in obese subjects in primary care medicine: the SAT Study.", "Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial.", "Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial.", "Clinical efficacy of orlistat therapy in overweight and obese patients with insulin-treated type 2 diabetes: A 1-year randomized controlled trial.", "One-year treatment of obesity: a randomized, double-blind, placebo-controlled, multicentre study of orlistat, a gastrointestinal lipase inhibitor.", "A randomized study of orlistat in combination with a weight management programme in obese patients with Type 2 diabetes treated with metformin." ]

[ "Obesity is a highly prevalent medical condition and is commonly accompanied by hypertension. This study assessed the efficacy and safety of treatment with sibutramine hydrochloride for promoting and maintaining weight loss in obese patients with controlled hypertension, including a subset analysis of African American patients.\n Obese patients with a body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) between 27 and 40 and a history of hypertension controlled with a calcium channel blocker (with or without concomitant thiazide diuretic treatment) were randomized to receive sibutramine (n = 150) or placebo (n = 74) with minimal behavioral intervention for 52 weeks. African Americans constituted 36% of enrolled patients. Efficacy assessments were body weight and related parameters (BMI and waist and hip circumferences), metabolic parameters (serum levels of triglycerides, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], total cholesterol, glucose, and uric acid), and quality-of-life measures. Safety assessments included recording of blood pressure, pulse rate, adverse events, and reasons for discontinuation.\n For patients receiving sibutramine, weight loss occurred during the first 6 months of the trial and was maintained to the end of the 12-month treatment period. Among patients receiving sibutramine, 40.1% lost 5% or more of body weight (5% responders) and 13.4% lost 10% or more of body weight (10% responders) compared with 8.7% and 4.3% of patients in the placebo group, respectively (P<.05). Changes in body weight were similar among African Americans and whites. Sibutramine-induced weight loss was associated with significant improvements in serum levels of triglycerides, HDL-C, glucose, and uric acid. Waist circumference and quality-of-life measures also improved significantly in patients receiving sibutramine. Sibutramine-treated patients had small but statistically significant mean increases in diastolic blood pressure (2.0 mm Hg) and pulse rate (4.9 beats/min) compared with placebo-treated patients (-1.3 mm Hg and 0.0 beats/min; P<.05); these changes were similar among African Americans and whites. Most adverse events were mild to moderate in severity and transient. The most common adverse event resulting in discontinuation among patients receiving sibutramine was hypertension (5.3% of patients receiving sibutramine vs 1.4% of patients receiving placebo).\n In obese patients with controlled hypertension, sibutramine was an effective and well-tolerated treatment for weight loss and maintenance. Sibutramine-induced weight loss resulted in improvements in serum levels of triglycerides, HDL-C, uric acid, and glucose, and in waist circumference and quality-of-life measures. Blood pressure and heart rate increased by a small amount. Efficacy and safety profiles for sibutramine among African American and white obese patients with controlled hypertension were similar.", "Rimonabant, a selective cannabinoid type 1 receptor blocker, reduces bodyweight and improves cardiovascular and metabolic risk factors in non-diabetic overweight or obese patients. The aim of the RIO-Diabetes trial was to assess the efficacy and safety of rimonabant in overweight or obese patients with type 2 diabetes that was inadequately controlled by metformin or sulphonylureas.\n 1047 overweight or obese type 2 diabetes patients (body-mass index 27-40 kg/m2) with a haemoglobin A1c (HbA1c) concentration of 6.5-10.0% (mean 7.3% [SD 0.9] at baseline) already on metformin or sulphonylurea monotherapy were given a mild hypocaloric diet and advice for increased physical activity, and randomly assigned placebo (n=348), 5 mg/day rimonabant (360) or 20 mg/day rimonabant (339) for 1 year. Two individuals in the 5 mg/day group did not receive double-blind treatment and were thus not included in the final analysis. The primary endpoint was weight change from baseline after 1 year of treatment. Analyses were done on an intention-to-treat basis. This trial is registered at ClinicalTrials.gov, number NCT00029848.\n 692 patients completed the 1 year follow-up; numbers in each group after 1 year were much the same. Weight loss was significantly greater after 1 year in both rimonabant groups than in the placebo group (placebo: -1.4 kg [SD 3.6]; 5 mg/day: -2.3 kg [4.2], p=0.01 vs placebo; 20 mg/day: -5.3 kg [5.2], p<0.0001 vs placebo). Rimonabant was generally well tolerated. The incidence of adverse events that led to discontinuation was slightly greater in the 20 mg/day rimonabant group, mainly due to depressed mood disorders, nausea, and dizziness.\n These data indicate that 20 mg/day rimonabant, in combination with diet and exercise, can produce a clinically meaningful reduction in bodyweight and improve HbA1c and a number of cardiovascular and metabolic risk factors in overweight or obese patients with type 2 diabetes inadequately controlled by metformin or sulphonylureas.", "Sibutramine treatment in obesity results in significantly greater weight reduction compared with placebo, although weight loss with sibutramine may be accompanied by small but statistically significant mean increases in blood pressure (BP). This 52-week, placebo-controlled, double-blind, randomised study investigated the effects of sibutramine 20 mg once daily or placebo on body weight in 220 obese (body mass index (BMI) 27-40 kg/m2), hypertensive patients. At randomisation, hypertension was well controlled (< or = 95 mm Hg diastolic blood pressure (DBP)) with an angiotensin-converting enzyme (ACE) inhibitor, with or without concomitant thiazide diuretic therapy. Therapy for hypertension continued for the 52 weeks of the study. Sibutramine 20 mg produced significantly greater weight loss compared with placebo: 4.5 kg with sibutramine compared with 0.4 kg with placebo (last observation carried forward (LOCF); P < or = 0.05). A total of 62 patients (42.8%) treated with sibutramine lost < or = 5% of their body weight compared with six patients (8.3%) treated with placebo; 19 patients (13.1%) treated with sibutramine lost > or = 10% of their body weight compared with two patients (2.8%) treated with placebo (LOCF; P < or = 0.05 for both comparisons). Hypertension remained well controlled for the 52 weeks of the study with both sibutramine and placebo treatment. After 52 weeks, the differences between placebo treatment and sibutramine treatment for both mean supine systolic blood pressure (SBP) and DBP were approximately 3 mm Hg: mean DBP was 82.8 mm Hg with placebo treatment compared with 85.5 mm Hg with sibutramine treatment (LOCF; P = 0.004) and mean SBP was 130.4 mm Hg with placebo compared with 133.1 mm Hg with sibutramine (LOCF; P = 0.0497; both comparisons, sibutramine vs placebo). The mean increases in SBP and DBP did not appear to change the overall risk category for coronary heart disease end points. Changes in pulse rate at week 52 were a decrease of 0.3 beats per minute (bpm) for placebo treatment compared with an increase of 5.7 bpm for sibutramine treatment (P < 0.001). Mandated withdrawals from the study due to protocol-defined changes in BP were not statistically different between the two treatment groups. Greater favourable changes in lipid profile, serum glucose, and uric acid could be accounted for by greater weight losses occurring in the sibutramine treatment group. Sibutramine was well tolerated. This study indicates that in obese patients whose hypertension is well controlled at the outset with an ACE inhibitor, with or without concomitant thiazide diuretic therapy, sibutramine safely and effectively achieves weight loss without compromising good BP control.", "The aim of this study is to compare the effect of orlistat vs. placebo on the predicted 10-year cardiovascular disease (CVD) risk in obese people with one or more cardiovascular risk factors treated for 12 months, in conjunction with a fat-reduced, but otherwise ad libitum, diet.\n A double-blind, randomized, placebo-controlled, parallel study was performed in conjunction with a fat-reduced diet and physical activity advice for 1 year. Participants (n = 339) from eight centres in Australia and New Zealand were randomized to either orlistat (120 mg) three times daily (n = 104 women, 66 men; mean +/- s.d. age = 52.0 +/- 7.5 years, body mass index (BMI) = 37.6 +/- 5.1 kg/m(2)) or placebo three times daily (n = 89 women, 80 men; age = 52.5 +/- 7.4 years, BMI = 38.0 +/- 4.9 kg/m(2)). The primary efficacy criterion was the 10-year risk of developing CVD calculated from the Framingham equation. Secondary efficacy criteria were body weight, waist circumference, blood pressure and serum concentrations of triglycerides, cholesterol (total, LDL and HDL), glucose, insulin and glycated haemoglobin and quality of life.\n There was no difference in the change in 10-year CVD risk between orlistat and placebo groups over 1 year. The orlistat group, however, had significant favourable changes in many of the individual CVD risk factors (total cholesterol, LDL-cholesterol, glucose, glycated haemoglobin, insulin, body weight and waist circumference) and one of the domains of quality of life measured by means of the SF-36 questionnaire (vitality), compared to the placebo group. Significant reductions in medication use for hypertension and diabetes were observed in the orlistat group, compared to those in placebo, but there were no significant differences in medication use for blood lipids.\n Orlistat may have reduced CVD risk, as judged by the favourable changes in individual risk factors and reductions in medication use, but the method used in order to measure absolute CVD risk in this study (Framingham CVD equation) was not sensitive enough to detect the changes in this relatively low-risk group (approximately 10% of risk of a CVD event over 10 years).", "Rimonabant, a selective cannabinoid-1 receptor (CB1) blocker, has been shown to reduce body weight and improve cardiovascular risk factors in obese patients. The Rimonabant in Obesity-Lipids (RIO-Lipids) study examined the effects of rimonabant on metabolic risk factors, including adiponectin levels, in high-risk patients who are overweight or obese and have dyslipidemia.\n We randomly assigned 1036 overweight or obese patients (body-mass index [the weight in kilograms divided by the square of the height in meters], 27 to 40) with untreated dyslipidemia (triglyceride levels >1.69 to 7.90 mmol per liter, or a ratio of cholesterol to high-density lipoprotein [HDL] cholesterol of >4.5 among women and >5 among men) to double-blinded therapy with either placebo or rimonabant at a dose of 5 mg or 20 mg daily for 12 months in addition to a hypocaloric diet.\n The rates of completion of the study were 62.6 percent, 60.3 percent, and 63.9 percent in the placebo group, the group receiving 5 mg of rimonabant, and the group receiving 20 mg of rimonabant, respectively. The most frequent adverse events resulting in discontinuation of the drug were depression, anxiety, and nausea. As compared with placebo, rimonabant at a dose of 20 mg was associated with a significant (P<0.001) mean weight loss (repeated-measures method, -6.7+/-0.5 kg, and last-observation-carried-forward analyses, -5.4+/-0.4 kg), reduction in waist circumference (repeated-measures method, -5.8+/-0.5 cm, and last-observation-carried-forward analyses, -4.7+/-0.5 cm), increase in HDL cholesterol (repeated-measures method, +10.0+/-1.6 percent, and last-observation-carried-forward analyses, +8.1+/-1.5 percent), and reduction in triglycerides (repeated-measures method, -13.0+/-3.5 percent, and last-observation-carried-forward analyses, -12.4+/-3.2 percent). Rimonabant at a dose of 20 mg also resulted in an increase in plasma adiponectin levels (repeated-measures method, 57.7 percent, and last-observation-carried-forward analyses, 46.2 percent; P<0.001), for a change that was partly independent of weight loss alone.\n Selective CB1-receptor blockade with rimonabant significantly reduces body weight and waist circumference and improves the profile of several metabolic risk factors in high-risk patients who are overweight or obese and have an atherogenic dyslipidemia.\n Copyright 2005 Massachusetts Medical Society.", "To determine the effect of orlistat, a new lipase inhibitor, on long-term weight loss, to determine the extent to which orlistat treatment minimizes weight regain in a second year of treatment, and to assess the effects of orlistat on obesity-related risk factors.\n This was a 2-year, multicenter, randomized, double-blind, placebo-controlled study. Obese patients (body mass index 28 to 43 kg/m2) were randomized to placebo or orlistat (60 or 120 mg) three times a day, combined with a hypocaloric diet during the first year and a weight maintenance diet in the second year of treatment to prevent weight regain. Changes in body weight, lipid profile, glycemic control, blood pressure, quality of life, safety, and tolerability were measured.\n Orlistat-treated patients lost significantly more weight (p<0.001) than placebo-treated patients after Year 1 (6.6%, 8.6%, and 9.7% for the placebo, and orlistat 60 mg and 120 mg groups, respectively). During the second year, orlistat therapy produced less weight regain than placebo (p = 0.005 for orlistat 60 mg; p<0.001 for orlistat 120 mg). Several obesity-related risk factors improved significantly more with orlistat treatment than with placebo. Orlistat was generally well tolerated and only 6% of orlistat-treated patients withdrew because of adverse events. Orlistat leads to predictable gastrointestinal effects related to its mode of action, which were generally mild, transient, and self-limiting and usually occurred early during treatment.\n Orlistat administered for 2 years promotes weight loss and minimizes weight regain. Additionally, orlistat therapy improves lipid profile, blood pressure, and quality of life.", "To evaluate the effects of sibutramine (15 and 20 mg/day) on weight, metabolic control, and blood pressure in metformin-treated obese subjects with type 2 diabetes.\n A 12-month randomized prospective placebo-controlled double-blind study was performed. It included 21 primary and secondary care centers in England, Canada, France, and Belgium. A total of 195 subjects (44% male) with type 2 diabetes and a BMI >27 kg/m(2) were studied. Changes were assessed in weight, blood pressure and resting heart rate, HbA(1c), fasting glucose, and lipids.\n Sibutramine induced significant weight loss (P < 0.001) with both 15 mg/day (5.5 +/- 0.6 kg at 12 months) and 20 mg/day (8.0 +/- 0.9 kg), whereas placebo did not (0.2 +/- 0.5 kg). Weight loss > or = 10% was achieved by 14 and 27% of subjects receiving 15 and 20 mg, respectively, but by none given placebo. Glycemic control improved in parallel with weight loss, and subjects who lost > or = 10% weight showed significant decreases in both HbA(1c) (1.2 +/- 0.4%, P < 0.0001) and fasting plasma glucose (1.8 mmol/l, P < 0.001). HDL cholesterol increased slightly with the higher dose, whereas plasma triglycerides fell with both doses, especially in subjects with weight loss of > or = 10% (a 29% decrease, P < 0.01). Treatment was generally well tolerated. Sibutramine treatment raised sitting diastolic blood pressure by > or = 5 mmHg in a higher proportion of patients than did placebo (43% with 15 mg/day vs. 25% with placebo, P < 0.05), but this effect was less evident in subjects who had a weight loss of > or = 10% weight. Pulse rate increased significantly more with sibutramine, being > or = 10 bpm higher in 42% of treated patients versus 17% with placebo (P < 0.01).\n Sibutramine can be an effective adjunct to metformin treatment in selected obese type 2 diabetic subjects and improves metabolic control in individuals who lose weight.", "The aim of this study was to assess obese patients with hypercholesterolemia whom were prescribed a standardized diet, comparing the action of orlistat, fluvastatin, orlistat with fluvastatin, and placebo on anthropometric measurements, blood pressure (BP), and lipid profile.\n This was a 1-year, randomized, double-blind, placebo-controlled trial. The patients were prescribed a controlled-energy diet and were randomly allocated to receive placebo, orlistat 120 mg TID (O group), fluvastatin 80 mg/d (F group), or olistat 120 mg TID with fluvastatin 80 mg/d (OF group). Clinical measurements (body weight, body mass index [BMI], waist circumference, and BP) and lipid profile assessment (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides [TGs]) were performed at baseline and after 6 months and 1 year of treatment.\n The study included 99 obese patients with hypercholesterolemia (48 men and 51 women; mean [SD] age, 51 [9] years). There were no significant differences between groups in baseline demographic, BP, or plasma lipid values. Three patients dropped out (2 women in the O group and 1 man in the OF group) due to adverse events related to orlistat treatment, including gastrointestinal events (oily spotting and fecal urgency). Ninety-six patients completed the study. There were significant differences from baseline (mean [SD]) in BMI, waist circumference reduction (WCR), and body weight loss (BWL) at 6 months in the OF group (29.9 [1.1] kg/m(2), 2.7 [0.8] cm, and 7.4 [0.9] kg, respectively; all P < 0.05), and BMI, WCR, and BWL at 1 year in the O group (29.0 [1.0] kg/m(2), 3.0 [1.0] cm, and 8.6 [1.0] kg, respectively; all P < 0.02), the F group (29.3 [1.6] kg/m(2), 2.4 [1.0] cm, and 8/0 [1.0] kg, respectively; all P < 0.05), and the OF group (28.4 [0.6] kg/m(2), 4.0 [0.6] cm, and 11.4 [1.0] kg, respectively; all P < 0.01). Significant reductions from baseline in systolic and diastolic BP were observed at 1 year in the O and F groups (all P < 0.05) and the OF group (both P < 0.01). At 6 months, there were significant reductions from baseline in TC and LDL-C in the F group (both P < 0.05) and in TC, LDL-C, and TGs in the OF group (P < 0.02, P < 0.02, and P < 0.05, respectively), as well as a significant increase in HDL-C in the OF group (P < 0.02). At 1 year, there were significant reduction from baseline in TC in the O, F, and OF groups (P < 0.05 and P < 0.01, respectively), LDL-C (P < 0.05, P < 0.02, and P < 0.01, respectively), and TGs (P < 0.02, P < 0.05, and P < 0.02, respectively). Also at 1 year, HDL-C was significantly higher than baseline in the F and OF groups (P < 0.02 and P < 0.01, respectively).\n Improvements in clinical and lipid-profile parameters were found at 1 year with all 3 treatments.", "Obesity is an important risk factor for type 2 diabetes. Weight loss in patients with type 2 diabetes is associated with improved glycemic control and reduced cardiovascular disease risk factors, but weight loss is notably difficult to achieve and sustain with caloric restriction and exercise. The purpose of this study was to assess the impact of treatment with orlistat, a pancreatic lipase inhibitor, on weight loss, glycemic control, and serum lipid levels in obese patients with type 2 diabetes on sulfonylurea medications.\n In a multicenter 57-week randomized double-blind placebo-controlled study, 120 mg orlistat or placebo was administered orally three times a day with a mildly hypocaloric diet to 391 obese men and women with type 2 diabetes who were aged > 18 years, had a BMI of 28-40 kg/m2, and were clinically stable on oral sulfonylureas. Changes in body weight, glycemic control, lipid levels, and drug tolerability were measured.\n After 1 year of treatment, the orlistat group lost 6.2 +/- 0.45% (mean +/- SEM) of initial body weight vs. 4.3 +/- 0.49% in the placebo group (P < 0.001). Twice as many patients receiving orlistat (49 vs. 23%) lost > or = 5% of initial body weight (P < 0.001). Orlistat treatment plus diet compared with placebo plus diet was associated with significant improvement in glycemic control, as reflected in decreases in HbA1c (P < 0.001) and fasting plasma glucose (P < 0.001) and in dosage reductions of oral sulfonylurea medication (P < 0.01). Orlistat therapy also resulted in significantly greater improvements than placebo in several lipid parameters, namely, greater reductions in total cholesterol, (P < 0.001), LDL cholesterol (P < 0.001), triglycerides (P < 0.05), apolipoprotein B (P < 0.001), and the LDL-to-HDL cholesterol ratio (P < 0.001). Mild to moderate and transient gastrointestinal events were reported with orlistat therapy, although their association with study withdrawal was low. Fat-soluble vitamin levels generally remained within the reference range, and vitamin supplementation was required in only a few patients.\n Orlistat is an effective treatment modality in obese patients with type 2 diabetes with respect to clinically meaningful weight loss and maintenance of weight loss, improved glycemic control, and improved lipid profile.", "To evaluate the long-term efficacy and tolerability within primary care settings of orlistat, a gastrointestinal lipase inhibitor, for the treatment of obesity.\n Randomized, double-blind, placebo-controlled, multicenter study.\n A group of 796 obese patients (body mass index, 30-44 kg/m2), treated with placebo 3 times a day (TID), 60 mg of orlistat TID, or 120 mg of orlistat TID, in conjunction with a reduced-energy diet for the first year and a weight-maintenance diet during the second year.\n Seventeen primary care centers in the United States.\n Changes in body weight and obesity-related disease risk factors.\n Patients treated with orlistat lost significantly more weight (7.08 +/- 0.54 and 7.94 +/- 0.57 kg for the 60-mg and 120-mg orlistat groups, respectively) than those treated with placebo (4.14 +/- 0.56 kg) in year 1 (P<.001) and sustained more of this weight loss during year 2 (P<.001). More patients treated with orlistat lost 5% or more of their initial weight in year 1 (48.8% and 50.5% of patients in the 60-mg and 120-mg groups, respectively) compared with placebo (30.7%; P<.001), and approximately 34% of patients in the orlistat groups sustained weight loss of 5% or greater over 2 years compared with 24% in the placebo group (P<.001). Orlistat produced greater improvements than placebo in serum lipid levels and blood pressure and was well tolerated, although treatment resulted in a higher incidence of gastrointestinal events.\n This long-term study indicates that orlistat is an effective adjunct to dietary intervention in the treatment of obesity in primary care settings.", "The management of type 2 diabetes mellitus is complicated by the presence of risk factors related to overweight and obesity, particularly visceral adiposity. However, weight loss and weight maintenance are difficult for patients with diabetes, and the benefits of dietary modifications are typically modest. Sibutramine is a serotonin- and norepinephrine-reuptake inhibitor that reduces food intake by inducing early satiety and attenuates the decrease in basal energy expenditure associated with weight loss. Previous trials of sibutramine in overweight and obese patients with type 2 diabetes have shown significant weight loss accompanied by better glycemic control.\n The goal of this study was to assess the effect on body weight and glycemic control of sibutramine in combination with glibenclamide in obese Hispanic patients with type 2 diabetes.\n This was a 12-month, randomized, double-blind, placebo-controlled clinical trial conducted at the Endocrinology Service, General Hospital of Mexico, Mexico City. Included were overweight or obese (body mass index [BMI] >27 kg/M2) patients with type 2 diabetes between the ages of 24 and 65 years who had been receiving glibenclamide monotherapy for at least 2 weeks and whose glucose concentrations were stable. Patients were randomized to receive sibutramine 10 mg or placebo once daily. The primary efficacy measures were change in body weight, waist circumference, and glycosylated hemoglobin (HbA1c). Anthropometrics and fasting glucose concentrations were measured monthly. HbA1c was determined at baseline and at 6 and 12 months. Laboratory parameters were measured at baseline and at the end of the study.\n Forty-four patients were randomized to receive sibutramine (28 women, 16 men; mean [SD] age, 47.6 [9.0] years), and 42 were randomized to receive placebo (31 women, 11 men; mean age, 45.8 [8.1] years). Twenty-four patients in the sibutramine group and 23 in the placebo group completed the trial. In the sibutramine group, body weight was reduced from a mean (SD) of 73.9 (10.3) kg at baseline to 69.8 (10.6) kg at month 12; BMI decreased from 29.9 (2.6) to 28.2 (2.9) kg/M2; waist circumference was reduced from 94.9 (8.4) to 90.8 (8.4) cm; the plasma fasting glucose concentration decreased from 140.4 (29.4) to 114.2 (32.0) mg/dL; and the HbA1c value was reduced from 8.9% (1.2) to 8.3% (1.2) (all, P < 0.001). In the placebo group, the corresponding changes were from 74.5 (10.3) kg at baseline to 73.1 (11.2) kg at month 12; from 30.1 (2.5) to 29.5 (2.9) kg/M2; from 94.4 (7.3) to 93.1 (8.3) cm (P < 0.05); from 140.7 (25.2) to 123.9 (38.3) mg/dL (P < 0.05); and from 9.0% (1.2) to 9.1% (1.3). In the sibutramine group, weight loss continued for up to 12 months.\n In this population of obese Hispanic patients with type 2 diabetes, sibutramine combined with glibenclamide therapy achieved weight loss for up to 12 months and was associated with better glycemic control than placebo.", "We undertook a randomised controlled trial to assess the efficacy and tolerability of orlistat, a gastrointestinal lipase inhibitor, in promoting weight loss and preventing weight regain in obese patients over a 2-year period.\n 743 patients (body-mass index 28-47 kg/m2), recruited at 15 European centres, entered a 4-week, single-blind, placebo lead-in period on a slightly hypocaloric diet (600 kcal/day deficit). 688 patients who completed the lead-in were assigned double-blind treatment with orlistat 120 mg (three times a day) or placebo for 1 year in conjunction with the hypocaloric diet. In a second 52-week double-blind period patients were reassigned orlistat or placebo with a weight maintenance (eucaloric) diet.\n From the start of lead-in to the end of year 1, the orlistat group lost, on average, more bodyweight than the placebo group (10.2% [10.3 kg] vs 6.1% [6.1 kg]; LSM difference 3.9 kg [p<0.001] from randomisation to the end of year 1). During year 2, patients who continued with orlistat regained, on average, half as much weight as those patients switched to placebo (p<0.001). Patients switched from placebo to orlistat lost an additional 0.9 kg during year 2, compared with a mean regain of 2.5 kg in patients who continued on placebo (p<0.001). Total cholesterol, low-density lipoprotein (LDL) cholesterol, LDL/high-density lipoprotein ratio, and concentrations of glucose and insulin decreased more in the orlistat group than in the placebo group. Gastrointestinal adverse events were more common in the orlistat group. Other adverse symptoms occurred at a similar frequency during both treatments.\n Orlistat taken with an appropriate diet promotes clinically significant weight loss and reduces weight regain in obese patients over a 2-year period. The use of orlistat beyond 2 years needs careful monitoring with respect to efficacy and adverse events.", "The researchers assessed the long-term weight reduction efficacy, tolerability, and safety of sibutramine used once daily in conjunction with behavior modification to treat mild to moderate obesity.\n This was a double-blind randomized placebo-controlled parallel-group comparative study of sibutramine 10 mg or 15 mg (or placebo) once daily for 1 year, given with dietary advice.\n A total of 485 obese men and women with uncomplicated obesity were included (mean age=42 years, mean body mass index=32.7 kg/m2).\n The outcomes were mean weight loss, percentage losing more than 5% or 10% of their body weight, and adverse drug effects.\n Among patients completing the study, those taking sibutramine 10 mg or 15 mg had greater mean weight loss compared with placebo at 12-month assessment (P < or = .001). Changes in body weight from baseline to end point were -1.6 kg for those taking placebo, -4.4 kg for those taking sibutramine 10 mg (P < or =.01, last observation carried forward [LOCF]), and -6.4 kg for those taking sibutramine 15 mg (P < or =.001, LOCF). For placebo patients, 20% lost 5% or more of their body weight compared with 39% of patients taking sibutramine 10 mg and 57% taking sibutramine 15 mg. Only 7% of the patients taking placebo lost 10% or more of their body weight, compared with 19% taking sibutramine 10 mg and 34% taking sibutramine 15 mg (P <.001 for both 10 mg and 15 mg vs placebo, and for both > or =5% and > or =10%).\n Sibutramine 10 mg or 15 mg once daily given with dietary advice produces and maintains statistically and clinically significantly greater weight loss than dietary advice alone (placebo) throughout a 12-month treatment period, and is safe and well tolerated.", "The purpose of this study was to assess the effect of orlistat, a gastrointestinal lipase inhibitor, on body weight, glycemic control, and cardiovascular risk factors in metformin-treated type 2 diabetic patients.\n A 1-year multicenter, randomized, double-blind, placebo-controlled trial of 120 mg orlistat t.i.d. (n = 249) or placebo (n = 254) combined with a reduced-calorie diet was conducted in overweight and obese patients with suboptimal control of type 2 diabetes.\n After 1 year of treatment, mean (+/-SE) weight loss was greater in the orlistat than in the placebo group (-4.6 +/- 0.3% vs. -1.7 +/- 0.3% of baseline wt, P < 0.001). Orlistat treatment caused a greater improvement in glycemic control than placebo, as evidenced by a greater reduction in serum HbA(1c), adjusted for changes in metformin and sulfonylurea therapy (-0.90 +/- 0.08 vs. -0.61 +/- 0.08, P = 0.014); a greater proportion of patients achieving decreases in HbA(1c) of > or = 0.5 and > or = 1.0% (both P < 0.01); and a greater reduction in fasting serum glucose (-2.0 +/- 0.2 vs. -0.7 +/- 0.2 mmol/l, P = 0.001). Compared with the placebo group, patients treated with orlistat also had greater decreases in total cholesterol, LDL cholesterol, and systolic blood pressure (all P < 0.05). Although more subjects treated with orlistat experienced gastrointestinal side effects than placebo (83 vs. 62%, P < 0.05), more subjects in the placebo group withdrew prematurely from the study than in the orlistat group (44 vs. 35%, P < 0.05).\n Orlistat is a useful adjunctive treatment for producing weight loss and improving glycemic control, serum lipid levels, and blood pressure in obese patients with type 2 diabetes who are being treated with metformin.", "In animal models, cannabinoid-1 receptor (CB1) blockade produces a lean phenotype, with resistance to diet-induced obesity and associated dyslipidaemia. We assessed the effect of rimonabant, a selective CB1 blocker, on bodyweight and cardiovascular risk factors in overweight or obese patients.\n patients with body-mass index 30 kg/m2 or greater, or body-mass index greater than 27 kg/m2 with treated or untreated dyslipidaemia, hypertension, or both, were randomised to receive double-blind treatment with placebo, 5 mg rimonabant, or 20 mg rimonabant once daily in addition to a mild hypocaloric diet (600 kcal/day deficit). The primary efficacy endpoint was weight change from baseline after 1 year of treatment in the intention-to-treat population.\n Weight loss at 1 year was significantly greater in patients treated with rimonabant 5 mg (mean -3.4 kg [SD 5.7]; p=0.002 vs placebo) and 20 mg (-6.6 kg [7.2]; p<0.001 vs placebo) compared with placebo (-1.8 kg [6.4]). Significantly more patients treated with rimonabant 20 mg than placebo achieved weight loss of 5% or greater (p<0.001) and 10% or greater (p<0.001). Rimonabant 20 mg produced significantly greater improvements than placebo in waist circumference, HDL-cholesterol, triglycerides, and insulin resistance, and prevalence of the metabolic syndrome. The effects of rimonabant 5 mg were of less clinical significance. Rimonabant was generally well tolerated with mild and transient side effects.\n CB1 blockade with rimonabant 20 mg, combined with a hypocaloric diet over 1 year, promoted significant decrease of bodyweight and waist circumference, and improvement in cardiovascular risk factors.", "To determine the effect of orlistat on weight reduction and the long-term maintenance of this weight loss when associated with a continuous mildly reduced energy diet.\n A multicenter, 18-month, double-blind study conducted in 81 hospital centers. Patients were randomized to orlistat 120 mg or placebo three times daily in conjunction with a mildly reduced-energy diet maintained throughout the study.\n In total, 696 otherwise healthy, overweight patients aged 18-65 y (BMI >or=28 kg/m(2)) were randomized to treatment with orlistat (n=346) or placebo (n=350).\n Body weight, anthropometry, lipid and glycemic control parameters and blood pressure.\n After 18 months, patients treated with orlistat lost significantly more body weight compared with placebo (-6.5+/-0.8 vs -3.0+/-0.8%; P=0.0005). After 12 months, 32.9% of orlistat vs 24.5% of placebo patients lost >or=10% of their initial weight (P=0.04). A significantly greater number of patients receiving orlistat treatment maintained this >or=10% weight loss compared to those receiving placebo (28.1 vs 13.8%; P<0.0001). Compared with placebo, orlistat was associated with a greater decrease in fasting blood glucose (-0.86+/-0.12 vs -0.29+/-0.18 mmol/l; P<0.05) and LDL-cholesterol (-13.0+/-1.3 vs -7.0+/-1.3%; P<0.001).\n A clinically meaningful reduction in body weight and the maintenance of this weight loss is achievable with orlistat treatment and dietary restriction over a period of 18 months. This weight loss resulted in an improvement in risk factors for coronary heart disease.", "To assess the effect of orlistat on body weight and cardiovascular risk amongst obese patients at high coronary risk.\n After screening, patients entered a two-week single-blind placebo lead-in period, during which they followed a mildly hypocaloric diet, before being randomized to double-blind treatment with either orlistat 120 mg or placebo three times daily, in conjunction with dietary intervention for 1 years.\n The study was conducted at 33 primary care centres in Sweden.\n A total of 382 obese adults (body mass index 28-38 kg m-2) with type 2 diabetes, hypercholesterolaemia and/or hypertension were recruited, of whom 376 were randomized to orlistat (n = 190) or placebo (n = 186).\n Change in body weight, waist and hip circumferences, blood pressure, serum lipid profile, fasting glucose and HbA1c.\n After 1 years, mean weight loss was significantly greater with orlistat compared with placebo (5.9% vs. 4.6%; P < 0.05). Moreover, significantly more orlistat-treated patients than placebo recipients maintained weight loss of > or = 5% (54.2% vs. 40.9%; P < 0.001). Orlistat was also associated with significantly greater improvements than placebo in total serum cholesterol (- 3.3% vs. -0.5%; P < 0.05), LDL-cholesterol (- 7.0% vs. -1.1%; P < 0.05), fasting glucose (5.1% vs. -0.1%; P < 0.01) and HbA1c (- 2.7% vs. -0.5%; P < 0.05). Similar results were reported for the subgroup of patients with type 2 diabetes. Orlistat was well tolerated.\n Treatment with orlistat in conjunction with diet promotes significantly greater weight loss and cardiovascular risk factor reduction than diet alone amongst obese patients at high risk of future coronary events.", "We evaluated the effects of 12-month treatment with sibutramine 15 mg daily compared with placebo on health-related quality of life (HRQL) in obese type II diabetes patients. We examined the associations between the changes in HRQL and in weight, glycaemic control, and haemodynamic variables. We also explored the predictive value of HRQL and its changes early during treatment.\n A randomised clinical trial. The subjects were enrolled in a 2-week single-blind run-in period with a modestly hypocaloric diet (700 kcal daily deficit) and then randomised to receive either sibutramine 15 mg (n=114, 60% female) or placebo (n=122, 58% female) once daily with the hypocaloric diet for 12 months.\n Obese (mean BMI 36 kg/m(2) and age 54 y) type II diabetes patients untreated with antidiabetic medications.\n The main outcome measures included body weight and HRQL (the RAND 36-Item Health Survey 1.0).\n The mean weight loss was greater in the sibutramine group (-7.1 kg) than in the placebo group (-2.6 kg, P<0.001). The baseline HRQL was relatively high. There were no significant differences between the treatment groups in glycaemic control or in any of the RAND-36 scales during the study. The scores on physical functioning (PF) and health change (HC) since last year improved in both groups and this improvement was related to weight loss. When HRQL changes were examined in categories of weight loss, the scores on PF and HC increased with >/=5% weight loss, but the scores on vitality (V) and general health (GH) increased only after >/=15% weight loss. Decrease in HbA1c was associated with increases in the scores of PF, GH, V, mental health, and HC. In the sibutramine group, the increase in diastolic blood pressure was associated with the decrease in the scores of PF, physical role functioning, emotional role functioning (ERF), social functioning (SF), and bodily pain. High baseline scores on ERF and SF, and low scores on V predicted weight loss at 12 months. Also, increasing scores on PF and V during the first 3 months predicted weight loss at 12 months. The sum of four dichotomised HRQL variables (baseline ERF >/=75=1 and <75=0; baseline SF>/=80=1 and <80=0; 3-month change in PF>0=1 and </=0=0; 3-month change in V>0=1 and </=0=0) predicted weight loss: In the group with sum 0, the mean(s.d.) weight change at 12 months was 0.0(2.6)% and with sum 4 it was -9.0(8.1)% of baseline weight.\n Despite the superior weight loss, sibutramine 15 mg daily did not produce HRQL benefits over placebo when measured with the generic RAND-36 in obese type II diabetes patients. PF and HC since last year improved with >/=5% weight loss, but >/=15% weight loss was needed to achieve a cluster of HRQL improvements. The decrease in HbA1c was associated with many HRQL benefits. Poor baseline HRQL and the improvement observed in the first months of treatment may prove to be useful in predicting success in long-term weight loss.", "To investigate the hypothesis that weight reduction with orlistat plus mild caloric restriction leads to better blood pressure control than diet alone in obese individuals with inadequately controlled hypertension. DESIGN This was a 1-year, prospective, randomized, double-blind, placebo-controlled, multicenter trial of orlistat plus diet versus placebo plus diet in obese hypertensives.\n Participants were randomized to receive either orlistat or placebo; all received a 600 kcal deficient diet with no more than 30% of calories from fat. Weight and blood pressure, lipid levels and fasting glucose and insulin levels were followed.\n Patients on orlistat experienced greater weight loss (-5.4 +/- 6.4 versus -2.7 +/- 6.4 kg, P< 0.001) and greater reduction in body mass index (-1.9 +/- 2.3 versus -0.9 +/- 2.2 kg/m2, P<0.001). Target weight loss, defined as > or= 5% body weight (BW), was obtained in more orlistat-treated patients than in the placebo group (46 versus 23%, P<0.001). Diastolic BP decreased more in orlistat-treated patients than in the placebo group (-11.4 +/- 8.3 versus -9.2 +/- 8.4 mmHg, P = 0.002). A greater percentage of orlistat-treated patients reached goal diastolic blood pressure (BP), defined as final diastolic BP< 90 mmHg or a reduction of at least 10 mmHg (67 versus 53%, P< 0.001). The orlistat-treated group had significantly greater reductions in total cholesterol ( P<0.001), low-density lipoprotein cholesterol (P = 0.001) and non-high-density lipoprotein cholesterol (P< 0.005) and target 30% cardiovascular risk reduction was obtained in more orlistat-treated patients (36.1 versus 24.0%, P< 0.04).\n A weight-loss program with orlistat is more effective than diet alone to lower blood pressure and results in greater cardiovascular risk reduction.", "Very-low-calorie diets are a well established method to achieve substantial short-term weight loss in obese patients, but long-term maintenance of the weight loss is very disappointing. A combined very-low-calorie diet and pharmacologic approach could be an effective means of prolonging its benefits.\n Eligible patients had a body-mass index greater than 30 kg/m2; those who lost 6 kg or more during a 4-week treatment with a very-low-calorie diet were randomly assigned to 1 year of treatment with sibutramine (10 mg) or identical placebo.\n In an intention-to-treat analysis, mean (+/-SD) absolute weight change at 1 year (or study endpoint) was -5.2 (+/-7.5) kg in the 81 patients in the sibutramine group and +0.5 (+/-5.7) kg in the 78 patients in the placebo group (P = 0.004). When compared with their weight at study entry (before the very-low-calorie diet), 86% of patients in the sibutramine group had lost at least 5% of their weight, compared with only 55% of those in the placebo group (P <0.001) at the study endpoint. Similarly, at month 12, 75% of subjects in the sibutramine group maintained at least 100% of the weight loss achieved with a very-low-calorie diet, compared with 42% in the placebo group (P <0.01).\n Following a very-low-calorie diet, sibutramine is effective in maintaining and improving weight loss for up to 1 year.", "Sibutramine is a tertiary amine that has been shown to induce dose-dependent weight loss and to enhance the effects of a low-calorie diet for up to a year. We did a randomised, double-blind trial to assess the usefulness of sibutramine in maintaining substantial weight loss over 2 years.\n Eight European centres recruited 605 obese patients (body-mass index 30-45 kg/m2) for a 6-month period of weight loss with sibutramine (10 mg/day) and an individualised 600 kcal/day deficit programme based on measured resting metabolic rates. 467 (77%) patients with more than 5% weight loss were then randomly assigned 10 mg/day sibutramine (n=352) or placebo (n=115) for a further 18 months. Sibutramine was increased up to 20 mg/day if weight regain occurred. The primary outcome measure was the number of patients at year 2 maintaining at least 80% of the weight lost between baseline and month 6. Secondary outcomes included changes in uric acid concentrations and glycaemic and lipid variables. Analysis was by intention to treat.\n 148 (42%) individuals in the sibutramine group and 58 (50%) in the placebo group dropped out. Of the 204 sibutramine-treated individuals who completed the trial, 89 (43%) maintained 80% or more of their original weight loss, compared with nine (16%) of the 57 individuals in the placebo group (odds ratio 4.64, p<0.001). Patients had substantial decreases over the first 6 months with respect to triglycerides, VLDL cholesterol, insulin, C peptide, and uric acid; these changes were sustained in the sibutramine group but not the placebo group. HDL cholesterol concentrations rose substantially in the second year: overall increases were 20.7% (sibutramine) and 11.7% (placebo, p<0.001). 20 (3%) patients were withdrawn because of increases in blood pressure; in the sibutramine group, systolic blood pressure rose from baseline to 2 years by 0.1 mm Hg (SD 12.9), diastolic blood pressure by 2.3 mm Hg (9.4), and pulse rate by 4.1 beats/min (11.9).\n This individualised management programme achieved weight loss in 77% of obese patients and sustained weight loss in most patients continuing therapy for 2 years. Changes in concentrations of HDL cholesterol, VLDL cholesterol, and triglyceride, but not LDL cholesterol, exceed those expected either from weight loss alone or when induced by other selective therapies for low concentrations of HDL cholesterol relating to coronary heart disease.", "It is well established that the risk of developing type 2 diabetes is closely linked to the presence and duration of overweight and obesity. A reduction in the incidence of type 2 diabetes with lifestyle changes has previously been demonstrated. We hypothesized that adding a weight-reducing agent to lifestyle changes may lead to an even greater decrease in body weight, and thus the incidence of type 2 diabetes, in obese patients.\n In a 4-year, double-blind, prospective study, we randomized 3,305 patients to lifestyle changes plus either orlistat 120 mg or placebo, three times daily. Participants had a BMI >/=30 kg/m2 and normal (79%) or impaired (21%) glucose tolerance (IGT). Primary endpoints were time to onset of type 2 diabetes and change in body weight. Analyses were by intention to treat.\n Of orlistat-treated patients, 52% completed treatment compared with 34% of placebo recipients (P < 0.0001). After 4 years' treatment, the cumulative incidence of diabetes was 9.0% with placebo and 6.2% with orlistat, corresponding to a risk reduction of 37.3% (P = 0.0032). Exploratory analyses indicated that the preventive effect was explained by the difference in subjects with IGT. Mean weight loss after 4 years was significantly greater with orlistat (5.8 vs. 3.0 kg with placebo; P < 0.001) and similar between orlistat recipients with impaired (5.7 kg) or normal glucose tolerance (NGT) (5.8 kg) at baseline. A second analysis in which the baseline weights of subjects who dropped out of the study was carried forward also demonstrated greater weight loss in the orlistat group (3.6 vs. 1.4 kg; P < 0.001).\n Compared with lifestyle changes alone, orlistat plus lifestyle changes resulted in a greater reduction in the incidence of type 2 diabetes over 4 years and produced greater weight loss in a clinically representative obese population. Difference in diabetes incidence was detectable only in the IGT subgroup; weight loss was similar in subjects with IGT or NGT [correction].", "The potential effect of orlistat on cardiovascular co-morbidities may have been previously underestimated. This study assesses the efficacy of orlistat therapy for weight loss and cardiovascular risk factor reduction in obese patients with cardiovascular risk. This was a 54-week, double-blind, randomised, placebo-controlled, parallel group study with 531 patients being randomised. Mean weight loss was significantly greater with orlistat than with placebo (5.8% vs 2.3%; p<0.0001). Orlistat was also associated with significantly greater improvements than placebo in diastolic BP (-5.5 vs -3.1 mmHg; p<0.01), systolic blood pressure (-6.0 vs -2.3 mmHg; p<0.01), oral glucose tolerance test (-0.37 vs +0.09 mmol/l; p<0.05), fasting glucose (-0.19 vs +0.06 mmol/l; p<0.05), total cholesterol (-1.31% vs +3.78%; p<0.0001), LDL-cholesterol (-7.09% vs -0.55%; p<0.0001) and waist circumference (-5.99 vs -2.60 cm; p<0.0001). Orlistat was well tolerated. Orlistat weight loss is associated with improvements in cardiovascular co-morbidities, and hence cardiovascular risk.", "Sibutramine is a selective serotonin and noradrenaline reuptake inhibitor that is known to reduce body weight. The efficacy of this drug in primary care medicine is currently unknown.\n To study, in a primary healthcare setting, the effect of a standardized non-pharmacological treatment program and 15 mg sibutramine or placebo on long-term weight reduction in obese subjects with a body mass index >or= 30 and < 40 kg/m(2).\n A multicentre, double-blind, placebo-controlled, randomized, parallel group comparison over 54 weeks of continuous therapy.\n 33 general practitioners in Germany.\n 389 obese patients were recruited of whom 362 were randomized.\n Primary measure was weight reduction at week 54; others included reduction in BMI, waist circumference, waist-hip ratio, blood pressure and blood lipids.\n 348 obese subjects were analyzed using an intention-to-treat analysis. Mean weight loss in the sibutramine (S) group was 8.1 +/- 8.2 kg vs. 5.1 +/- 6.5 kg in the placebo (P) group (p < 0.001; Intent-to-treat analysis). More subjects lost more than 5 % and 10 % of initial weight with sibutramine than with placebo (5 %, S: 62.6 %, P: 41.4 %, p < 0.001; 10 %, S: 40.8, P: 19.0 %, p < 0.001). Weight loss was accompanied by an improvement in the lipid profile, in particular, an increase in HDL-cholesterol and a decrease in fasting triglycerides. In both groups, systolic and diastolic blood pressure decreased in those with moderate hypertension and remained unchanged in those with normal blood pressure at baseline. There was a modest increase in heart rate in S (1.9 beats/min) vs. P (- 0.9 beats/min) (p < 0.05).\n Under primary care conditions, sibutramine 15 mg daily proved to be a safe and effective drug for additional weight loss in obese subjects undergoing a comprehensive weight reduction program.", "Orlistat, a gastrointestinal lipase inhibitor that reduces dietary fat absorption by approximately 30%, may promote weight loss and reduce cardiovascular risk factors.\n To test the hypothesis that orlistat combined with dietary intervention is more effective than placebo plus diet for weight loss and maintenance over 2 years.\n Randomized, double-blind, placebo-controlled study conducted from October 1992 to October 1995.\n Obese adults (body mass index [weight in kilograms divided by the square of height in meters], 30-43 kg/m2) evaluated at 18 US research centers.\n Subjects received placebo plus a controlled-energy diet during a 4-week lead-in. On study day 1, the diet was continued and subjects were randomized to receive placebo 3 times a day or orlistat, 120 mg 3 times a day, for 52 weeks. After 52 weeks, subjects began a weight-maintenance diet, and the placebo group (n = 133) continued to receive placebo and orlistat-treated subjects were rerandomized to receive placebo 3 times a day (n = 138), orlistat, 60 mg (n = 152) or 120 mg (n = 153) 3 times a day, for an additional 52 weeks.\n Body weight change and changes in blood pressure and serum lipid, glucose, and insulin levels.\n A total of 1187 subjects entered the protocol, and 892 were randomly assigned on day 1 to double-blind treatment. For intent-to-treat analysis, 223 placebo-treated subjects and 657 orlistat-treated subjects were evaluated. During the first year orlistat-treated subjects lost more weight (mean +/- SEM, 8.76+/-0.37 kg) than placebo-treated subjects (5.81+/-0.67 kg) (P<.001). Subjects treated with orlistat, 120 mg 3 times a day, during year 1 and year 2 regained less weight during year 2 (3.2+/-0.45 kg; 35.2% regain) than those who received orlistat, 60 mg (4.26+/-0.57 kg; 51.3% regain), or placebo (5.63+/-0.42 kg; 63.4% regain) in year 2 (P<.001). Treatment with orlistat, 120 mg 3 times a day, was associated with improvements in fasting low-density lipoprotein cholesterol and insulin levels.\n Two-year treatment with orlistat plus diet significantly promotes weight loss, lessens weight regain, and improves some obesity-related disease risk factors.", "Rimonabant, a selective cannabinoid-1 receptor blocker, may reduce body weight and improve cardiometabolic risk factors in patients who are overweight or obese.\n To compare the efficacy and safety of rimonabant with placebo each in conjunction with diet and exercise for sustained changes in weight and cardiometabolic risk factors over 2 years.\n Randomized, double-blind, placebo-controlled trial of 3045 obese (body mass index > or =30) or overweight (body mass index >27 and treated or untreated hypertension or dyslipidemia) adult patients at 64 US and 8 Canadian clinical research centers from August 2001 to April 2004.\n After a 4-week single-blind placebo plus diet (600 kcal/d deficit) run-in period, patients were randomized to receive placebo, 5 mg/d of rimonabant, or 20 mg/d of rimonabant for 1 year. Rimonabant-treated patients were rerandomized to receive placebo or continued to receive the same rimonabant dose while the placebo group continued to receive placebo during year 2.\n Body weight change over year 1 and prevention of weight regain during year 2. Additional efficacy measures included changes in waist circumference, plasma lipid levels, and other cardiometabolic risk factors.\n At year 1, the completion rate was 309 (51%) patients in the placebo group, 620 (51%) patients in the 5 mg of rimonabant group, and 673 (55%) patients in the 20 mg of rimonabant group. Compared with the placebo group, the 20 mg of rimonabant group produced greater mean (SEM) reductions in weight (-6.3 [0.2] kg vs -1.6 [0.2] kg; P<.001), waist circumference (-6.1 [0.2] cm vs -2.5 [0.3] cm; P<.001), and level of triglycerides (percentage change, -5.3 [1.2] vs 7.9 [2.0]; P<.001) and a greater increase in level of high-density lipoprotein cholesterol (percentage change, 12.6 [0.5] vs 5.4 [0.7]; P<.001). Patients who were switched from the 20 mg of rimonabant group to the placebo group during year 2 experienced weight regain while those who continued to receive 20 mg of rimonabant maintained their weight loss and favorable changes in cardiometabolic risk factors. Use of different imputation methods to account for the high rate of dropouts in all 3 groups yielded similar results. Rimonabant was generally well tolerated; the most common drug-related adverse event was nausea (11.2% for the 20 mg of rimonabant group vs 5.8% for the placebo group).\n In this multicenter trial, treatment with 20 mg/d of rimonabant plus diet for 2 years promoted modest but sustained reductions in weight and waist circumference and favorable changes in cardiometabolic risk factors. However, the trial was limited by a high drop-out rate and longer-term effects of the drug require further study. Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00029861.", "OBJECTIVE; Weight loss improves glycemic control, lipid profiles, and blood pressure in patients with type 2 diabetes. However, successful long-term weight loss is difficult for these patients, particularly those treated with insulin. The aim of this study was to assess the effect of orlistat, a gastrointestinal lipase inhibitor, on weight loss, glycemic control, and cardiovascular risk factors in overweight or obese insulin-treated type 2 diabetic patients.\n This study was a 1-year multicenter, randomized, double-blind, placebo-controlled trial of orlistat (120 mg three times a day) or placebo combined with a reduced-calorie diet in overweight or obese adults (BMI 28-40 kg/m(2)) with type 2 diabetes treated with insulin alone or combined with oral agents, but with suboptimal metabolic control (HbA(1c) 7.5-12.0%). Outcome measurements included changes in body weight, glycemic control, blood pressure, and serum lipids. RESULTS; After 1 year, the orlistat group lost significantly more weight (-3.89 +/- 0.3% of baseline body weight, means +/- SE) than the placebo group (-1.27 +/- 0.3%, P < 0.001). Orlistat treatment, compared with placebo, produced greater decreases in HbA(1c) (-0.62 +/- 0.08 vs. -0.27 +/- 0.08%, P = 0.002), fasting serum glucose (-1.63 +/- 0.3 vs. -1.08 +/- 0.3 mmol/l, P = 0.02), and the required doses of insulin and other diabetic medications. Orlistat also produced greater improvements than placebo in serum total cholesterol (P = 0.0002) and LDL cholesterol concentrations (P = 0.001) and LDL/HDL ratio (P = 0.01). CONCLUSIONS; Orlistat therapy produces clinically significant weight loss, with improvements in glycemic control and cardiovascular disease risk factors, in overweight or obese patients with type 2 diabetes who have suboptimal metabolic control with insulin therapy.", "To assess the efficacy and tolerability of orlistat (Xenical) in producing and maintaining weight loss over a 12-month period.\n Patients were randomized to double-blind treatment with either orlistat 120 mg or placebo three times daily, in conjunction with a low-energy diet, for 12 months.\n Five centres in the UK.\n 228 obese adult patients with body mass index between 30 and 43 kg/m2 and mean weight 97 kg (range 74-144 kg).\n All patients were prescribed a low-energy diet, providing 30% of energy from fat, designed to produce an individually tailored energy deficit of approximately 600 kcal/day, for a run-in period of 4 weeks and then 12 months, plus orlistat 120 mg or placebo three times daily.\n Change in body weight (the primary efficacy parameter), waist circumference and adverse events were reviewed regularly, together with serum lipids, insulin, glucose and plasma levels of fat-soluble vitamins and beta carotene.\n Based on an intent-to-treat analysis, after 1 y of treatment patients receiving orlistat had lost an average of 8.5% of their initial body weight compared with 5.4% for placebo-treated patients; 35% of the orlistat group lost at least 5% of body weight compared with 21% of the placebo group (P < 0.05), and 28% and 17%, respectively (P = 0.04) lost at least 10% of body weight. Orlistat-treated patients showed significant decreases (P < 0.05) in serum levels of total cholesterol, low density lipoprotein cholesterol, and in the low density lipoprotein: high density lipoprotein ratio in comparison with placebo. Both groups had similar adverse-event profiles, except for gastrointestinal events, which were 26% more frequent in the orlistat group but were mostly mild and transient. To maintain normal plasma levels of fat-soluble vitamins, supplements of vitamins A, D and E were given to 1.8%, 8.0% and 3.6%, respectively, of orlistat-treated patients, compared with 0.9% of placebo-treated patients for each vitamin type. After 1 y, the decrease in vitamin E and beta carotene was significantly greater in orlistat-treated patients compared with those receiving placebo (P < 0.001). No significant change was found in the mean vitamin E:total cholesterol ratio in either group after 52 weeks.\n Orlistat, in conjunction with a low-energy diet, produced greater and more frequent significant weight loss than placebo during 1 y of treatment. One-third of orlistat-treated patients achieved clinically relevant weight loss (> or = 5% initial body weight). There was also an improvement in relevant serum lipid parameters. Fat-soluble vitamin supplements may be required during chronic therapy. Orlistat was well tolerated and offers a promising new approach to the long-term management of obesity.", "To assess the effects of orlistat vs. placebo, in combination with a weight management programme, on weight loss and metabolic control in obese patients with Type 2 diabetes.\n Patients treated with either metformin alone or metformin in combination with sulphonylurea were randomized to double-blind treatment with orlistat or placebo (120 mg) three times daily, combined with a mildly reduced calorie diet and a weight management programme for 52 weeks. Changes in body weight, anthropometry, glycaemic control and lipid profile were assessed.\n After 52 weeks, orlistat-treated patients achieved an almost threefold greater reduction in weight compared with placebo recipients (-5.0% vs. -1.8%; P<0.0001). The decrease in waist circumference was significantly greater with orlistat than placebo (-4.8 cm vs. -2.8 cm; P=0.0022). Orlistat treatment was also associated with significantly greater reductions in haemoglobin A(1c) (-1.1% vs. -0.2%; P<0.0001), fasting plasma glucose (-1.9 mmol/l vs. -0.3 mmol/l; P<0.0001), total cholesterol (-0.2 mmol/l vs. 0.1 mmol/l; P=0.03) and apolipoprotein B (-0.08 g/l vs. 0.01 g/l; P=0.0085) and greater improvements in beta-cell function (P=0.031) and insulin resistance (P=0.001) assessed using the homeostasis model assessment (HOMA). Similar results were obtained for subgroups of patients treated with metformin alone or metformin in combination with sulphonylurea. Orlistat treatment reduced the requirement for anti-diabetic medication more than placebo.\n Orlistat, in combination with a reduced calorie diet and a weight management programme, promotes weight loss and clinically relevant improvements in glycaemic control and other cardiovascular risk factors in obese patients with Type 2 diabetes." ]

[ "12504397", "9050955", "9048709" ]

[ "Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial.", "Randomized placebo-controlled trial of mitoxantrone in relapsing-remitting multiple sclerosis: 24-month clinical and MRI outcome.", "Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: a randomised multicentre study of active disease using MRI and clinical criteria." ]

[ "Treatment options for patients with secondary progressive multiple sclerosis are few. Encouraging results in open-label studies prompted this randomised trial of mitoxantrone in such patients.\n 194 patients with worsening relapsing-remitting or secondary progressive multiple sclerosis were assigned placebo or mitoxantrone (5 mg/m(2) [exploratory group] or 12 mg/m(2) intravenously) every 3 months for 24 months. Clinical assessments were made every 3 months for 24 months. The primary endpoint was a multivariate analysis of five clinical measures. Analyses of mitoxantrone 12 mg/m(2) versus placebo were based on patients who received at least one dose and returned for at least one assessment of efficacy.\n Of 194 patients enrolled, 188 were able to be assessed at 24 months. There were no drug-related serious adverse events or evidence of clinically significant cardiac dysfunction. At 24 months, the mitoxantrone group experienced benefits compared with the placebo group for the primary outcome (difference 0.30 [95% CI 0.17-0.44]; p<0.0001) and the preplanned univariate analyses of those measures: change in expanded disability status scale (0.24 [0.04-0.44]; p=0.0194), change in ambulation index (0.21 [0.02-0.40]; p=0.0306), adjusted total number of treated relapses (0.38 [0.18-0.59]; p=0.0002), time to first treated relapse (0.44 [0.20-0.69]; p=0.0004), and change in standardised neurological status (0.23 [0.03-0.43]; p=0.0268).\n Mitoxantrone 12 mg/m(2) was generally well tolerated and reduced progression of disability and clinical exacerbations. Further studies are needed to identify the patients with these forms of multiple sclerosis who are most likely to respond to therapy, the best treatment protocols, and the frequency of long-term drug-related side-effects.", "We designed a randomized, placebo-controlled, multicentre trial involving 51 relapsing-remitting multiple sclerosis patients to determine the clinical efficacy of mitoxantrone treatment over 2 years. Patients were allocated either to the mitoxantrone group (27 patients receiving I.V. infusion of mitoxantrone every month for 1 year at the dosage of 8 mg/m2) or to the placebo group (24 patients, receiving I.V. infusion of saline every month for 1 year) using a centralized randomization system. Disability at entry and at 12-24 months was evaluated by four blinded neurologists trained in the application of the Kurtzke Expanded Disability Scale (EDSS). In addition, the number and clinical characteristics of the exacerbations over the 24 months were recorded by the local investigators. MRI, at 0, 12 and 24 months, was performed with a 0.2 T permanent unit. MRI data were analysed by two blinded neuroradiologists. All patients underwent a clinical evaluation. A statistically significant difference in the mean number of exacerbations was observed between the mitoxantrone group and placebo group both during the 1st and the 2nd year. Although there was no statistically significant benefit in terms of mean EDSS progression over 2 years, the proportion of patients with confirmed progression of the disease, as measured by a one point increase on the EDSS scale, was significantly reduced at the 2nd year evaluation in the mitoxantrone group. Forty-two (23 mitoxantrone, 19 placebo) patients underwent all MRI examinations during the 24-month period. We observed a trend towards a reduction in the number of new lesions on T2-weighted images in the mitoxantrone group. Our study suggests that mitoxantrone might be effective in reducing disease activity, both by decreasing the mean number of exacerbations and by slowing the clinical progression sustained by most patients after 1 year from the end of treatment.", "To evaluate the efficiency of mitoxantrone in multiple sclerosis.\n Forty two patients with confirmed multiple sclerosis, selected as having a very active disease on clinical and MRI criteria were randomised to receive either mitoxantrone (20 mg intravenously (IV) monthly) and methylprednisolone (1 g iv monthly) or methylprednisolone alone over six months. In the steroid alone group five patients dropped out due to severe exacerbation.\n Blinded analysis of MRI data showed significantly more patients with no new enhancing lesions in the mitoxantrone group compared with the steroid alone group, (90% v 31%, P < 0.001). In the mitoxantrone group there was a month by month decrease almost to zero in the number of new enhancing lesions, and in the total number of enhancing lesions, whereas both remained high in the steroid alone group. The differences were significant for both indices at all months from 1-6. Unblinded clinical assessments showed a significant improvement in change in EDSS at months 2-6 in the mitoxantrone group, with a final mean improvement of more than one point (-1.1 v + 0.3; P < 0.001). There was a significant reduction in the number of relapses (7 v 31; P < 0.01), and an increase in the number of patients free of exacerbation (14 v 7; P < 0.05).\n In this selected group of patients with multiple sclerosis with very active disease, mitoxantrone combined with methylprednisolone was effective in improving both clinical and MRI indices of disease activity over a period of six months whereas methylprednisolone alone was not. Further double blinded long term studies are needed to properly evaluate the effect of mitoxantrone on progression in disability." ]

[ "9652613", "14656755", "17006278", "9893767", "8356846", "11791098", "6780837", "11794219", "340157", "19084453", "2194380", "8346005", "3709244", "7966893", "18097856", "10227267" ]

[ "Randomised placebo-controlled crossover trial on effect of inactivated influenza vaccine on pulmonary function in asthma.", "Influenza vaccination in children with asthma: randomized double-blind placebo-controlled trial.", "Comparison of the efficacy and safety of live attenuated cold-adapted influenza vaccine, trivalent, with trivalent inactivated influenza virus vaccine in children and adolescents with asthma.", "A double-blind placebo-controlled study of the effect of influenza vaccination on airway responsiveness in asthma.", "Immunization of institutionalized asthmatic children and patients with psychomotor retardation using live attenuated cold-adapted reassortment influenza A H1N1, H3N2 and B vaccines.", "Safety and tolerability of cold-adapted influenza virus vaccine in children and adolescents with asthma.", "[Influenza vaccination of risk patients with trivalent split virus vaccine and subunit vaccine].", "The safety of inactivated influenza vaccine in adults and children with asthma.", "Immunization with killed influenza virus in children with chronic asthma.", "The safety and immunogenicity of influenza vaccine in children with asthma in Mexico.", "Effect of live attenuated, cold recombinant (CR) influenza virus vaccines on pulmonary function in healthy and asthmatic adults.", "Trivalent cold recombinant influenza live vaccine in institutionalized children with bronchial asthma and patients with psychomotor retardation.", "Lack of clinical exacerbations in adults with chronic asthma after immunization with killed influenza virus.", "The efficacy of influenza vaccination in elderly individuals. A randomized double-blind placebo-controlled trial.", "Influenza vaccination in adults with asthma: safety of an inactivated trivalent influenza vaccine.", "Effects of inactivated influenza virus vaccination on bronchial reactivity symptom scores and peak expiratory flow variability in patients with asthma." ]

[ "Despite current recommendations, many people with asthma do not receive annual vaccination against influenza, partly because of concern that vaccine may trigger exacerbations. Colds can trigger exacerbations, which may be mistaken for vaccine-related adverse events. We undertook a double-blind placebo-controlled multicentre crossover study to assess the safety of influenza vaccine in patients with asthma, with allowance for the occurrence of colds.\n We studied 262 patients, aged 18-75 years, who recorded daily peak expiratory flow (PEF), respiratory symptoms, medication, medical consultations, and hospital admissions for 2 weeks before the first injection and until 2 weeks after the second injection. Order of injection (vaccine and placebo) was assigned randomly. There was an interval of 2 weeks between injections. The main outcome measure was an exacerbation of asthma within 72 h of injection (defined as a fall in PEF of >20%).\n Among 255 participants with paired data, 11 recorded a fall in PEF of more than 20% after vaccine compared with three after placebo (McNemar's test p=0.06); a fall of more than 30% was recorded by eight after vaccine compared with none after placebo (binomial test p=0.008). However, when participants with colds were excluded, there was no significant difference in the numbers with falls of more than 20% between vaccine and placebo (six vs three; binomial test p=0.51), although the difference for PEF decreases of more than 30% approached significance (five vs none; binomial test, p=0.06). This association was confined to first-time vaccinees.\n Our findings indicate that pulmonary-function abnormalities may occur as a complication of influenza vaccination. However, the risk of pulmonary complications is very small and outweighed by the benefits of vaccination.", "There is little evidence that influenza vaccination reduces asthma exacerbations. We determined whether influenza vaccination is more effective than placebo in 6-18-year-old children with asthma. We performed a randomized, double-blind, placebo-controlled trial. Parenteral vaccination with inactivated influenza vaccine or placebo took place approximately November 1, and children were followed until April 1 of the next year. Airway symptoms were reported in a diary. When symptom scores reached a predefined level, a pharyngeal swab was taken. Primary outcome was the number of asthma exacerbations associated with virologically proven influenza infection. Three hundred forty-nine children were assigned placebo, and 347 were assigned vaccine. Pharyngeal swabs positive for influenza were related to 42 asthma exacerbations, 24 in the vaccine group and 18 in the placebo group, a difference of 33% favoring placebo (31% after adjustment for confounders; 95% confidence interval, -34% to 161%). Influenza-related asthma exacerbations were of similar severity in both groups; they lasted 3.1 days shorter in the vaccine group (95% confidence interval, -6.2 to 0.002 days, p = 0.06). We conclude that influenza vaccination did not result in a significant reduction of the number, severity, or duration of asthma exacerbations caused by influenza. Additional studies are warranted to justify routine influenza vaccination of children with asthma.", "Despite their potential for increased morbidity, 75% to 90% of asthmatic children do not receive influenza vaccination. Live attenuated influenza vaccine (LAIV), a cold-adapted, temperature-sensitive, trivalent influenza vaccine, is approved for prevention of influenza in healthy children 5 to 19 years of age. LAIV has been studied in only a small number of children with asthma.\n Children 6 to 17 years of age, with a clinical diagnosis of asthma, received a single dose of either intranasal CAIV-T (an investigational refrigerator-stable formulation of LAIV; n = 1114) or injectable trivalent inactivated influenza vaccine (TIV; n = 1115) in this randomized, open-label study during the 2002-2003 influenza season. Participants were followed up for culture-confirmed influenza illness, respiratory outcome, and safety.\n The incidence of community-acquired culture-confirmed influenza illness was 4.1% (CAIV-T) versus 6.2% (TIV), demonstrating a significantly greater relative efficacy of CAIV-T versus TIV of 34.7% (90% confidence interval [CI] 9.4%-53.2%; 95% CI = 3.9%-56.0%). There were no significant differences between treatment groups in the incidence of asthma exacerbations, mean peak expiratory flow rate findings, asthma symptom scores, or nighttime awakening scores. The incidence of runny nose/nasal congestion was higher for CAIV-T (66.2%) than TIV (52.5%) recipients. Approximately 70% of TIV recipients reported injection site reactions.\n CAIV-T was well tolerated in children and adolescents with asthma. There was no evidence of a significant increase in adverse pulmonary outcomes for CAIV-T compared with TIV. CAIV-T had a significantly greater relative efficacy of 35% compared with TIV in this high-risk population.", "nan", "Live attenuated cold-adapted reassortant (CR) influenza virus vaccines were evaluated in institutionalized asthmatic children and severe psychomotor-retarded (SPR) patients. Almost all the vaccinees were seropositive to the vaccine strains before immunization. Trivalent CR vaccine (containing A H1N1 (CR-125), A H3N2 (CR-149) and B (CRB-117)), bivalent CR vaccine (CR-125 and CR-149) and monovalent CRB-117 were inoculated to 19 asthmatic children and 36 and 16 SPR patients, respectively. Overall 49, 22, and 11% of vaccinees were infected by A H1N1, A H3N2 or B vaccine viruses, respectively, as indicated by significant haemagglutination-inhibition (HI) antibody titre rises 4 weeks after inoculation. No severe adverse reactions associated with CR vaccination were observed in the handicapped patients. A nosocomial outbreak of influenza A H1N1 occurred in the ward with asthmatic children, but none of the 19 CR-trivalent vaccinees became infected. However, five of 20 non-vaccinees in the same ward, and ten of 30 vaccinees in another ward that received inactivated split vaccine became infected. The CR vaccines demonstrated significant protective effects against natural exposure to the A H1N1 virus, and were well tolerated and safe when given to patients with bronchial asthma and severe psychomotor retardation.", "Influenza infections can cause severe respiratory disease in high risk persons such as those with asthma, but immunization rates for high risk groups remain suboptimal. An investigational influenza virus vaccine, trivalent, types A and B, live, cold-adapted (CAIV-T) administered by intranasal spray was shown previously to be effective in healthy adults and healthy children.\n To assess the safety and tolerability of CAIV-T in subjects 9 years of age and older with moderate to severe asthma.\n In this randomized, double blind, placebo-controlled study, spirometry was performed twice before vaccination to establish a baseline forced expiratory volume at 1 s (FEV1) and once 2 to 5 days thereafter. The primary outcome index was the percent change in percent predicted FEV1 before and after vaccination. Peak flows, clinical asthma symptom scores and nighttime awakening scores were measured daily from 7 days pre- to 28 days postvaccination.\n The primary outcome index (percentage change in percent predicted FEV1) was not different between the two groups (0.2% vs. 0.4% for the treatment and placebo groups, respectively; P = 0.78). Secondary outcomes did not differ between the two groups; these included the number of subjects with a decrease in FEV1 > or =15% from baseline, reductions in peak flows > or =15%, > or =30% or > or =2 sd below baseline, use of beta-adrenergic rescue medications, asthma exacerbations and clinical asthma symptom scores before and after vaccination. The same proportion of subjects in each group experienced postvaccination symptoms within 10 days (92% and 91%, respectively; P = 1.0). No serious adverse event occurred.\n CAIV-T was generally safe and well-tolerated in children and adolescents with moderate to severe asthma.", "nan", "Influenza causes substantial morbidity in adults and children with asthma, and vaccination can prevent influenza and its complications. However, there is concern that vaccination may cause exacerbations of asthma.\n To investigate the safety of the inactivated trivalent split-virus influenza vaccine in adults and children with asthma, we conducted a multicenter, randomized, double-blind, placebo-controlled, cross-over trial in 2032 patients with asthma (age range, 3 to 64 years). The order of injection of vaccine and placebo was assigned randomly, with a mean of 22 days between the injections. Each day during the two weeks after each injection, the patients recorded peak expiratory flow rates, symptoms thought to be related to the injection, use of asthma medications, unscheduled health care visits for asthma, and asthma-related absences from school or work. The primary outcome measure was an exacerbation of asthma in the two weeks after the injections.\n The frequency of exacerbations of asthma was similar in the two weeks after the influenza vaccination and after placebo injection (28.8 percent and 27.7 percent, respectively; absolute difference, 1.1 percent; 95 percent confidence interval, -1.4 percent to 3.6 percent). The exacerbation rates were similar in subgroups defined according to age, severity of asthma, and other factors. Among symptoms thought to be associated with the injection, only body aches were more frequent after the vaccine injection than after placebo injection (25.1 percent vs. 20.8 percent, P<0.001).\n The inactivated influenza vaccine is safe to administer to adults and children with asthma, including those with severe asthma. Given the morbidity of influenza, all those with asthma should receive the vaccine annually.", "nan", "The morbidity and mortality associated with influenza is substantial in children with asthma. There are no available data on the safety and immunogenicity of influenza vaccine in children with asthma in Latin America. Furthermore, it is unclear if influenza vaccination may cause asthma exacerbations.\n We conducted a placebo-controlled trial to investigate the safety and immunogenicity of an inactivated trivalent split virus influenza vaccine in children with asthma in Mexico. We also measured the impact of influenza vaccination on pulmonary function tests in this population.\n The inactivated influenza vaccine was immunogenic and safe in terms of local and systemic side effects compared to placebo. We observed no significant impact on pulmonary function tests among vaccine recipients.\n Given the significant morbidity associated with influenza in children, strategies to promote increased influenza vaccination coverage in this high-risk group in Latin America and elsewhere are urgently needed.", "The effects of intranasal inoculation with live attenuated, CR influenza virus vaccines on pulmonary function in healthy and asthmatic adults were evaluated in placebo-controlled, double-blind studies. In 46 healthy adult volunteers, there were no statistically significant alterations in pulmonary function as measured by spirometry and histamine bronchoprovocation tests in the first week following monovalent CR influenza virus vaccine [type A (H3N2, H1N1) and type B]. Among healthy adults with pre-inoculation PC20s less than 10 mg ml-1, 8/12 were infected following vaccination but no significant alterations occurred in histamine bronchoprovocation. In 11 asthmatic adults, no statistically significant alterations in pulmonary function, as measured by spirometry, were noted during the first 7 days postinoculation with bivalent CR influenza virus vaccine type A (H3N2 and H1N1). Postinoculation respiratory illnesses were more common in CR influenza virus vaccine recipients than placebo recipients, but they were mild, consisting of afebrile pharyngitis and transient rhinorrhea. Attenuated CR influenza virus vaccines do not appear to impair pulmonary function during the first week following immunization of healthy and asthmatic adults.", "Twenty asthmatic children and 48 patients with severe psychomotor retardation were inoculated intranasally with trivalent cold-adapted recombinant (CR) influenza vaccine containing CR-125 (H1N1), CR-159 (H3N2) and CRB-117 (B). The vaccinees were mostly seropositive. Severe adverse reactions or asthmatic attacks were not observed, but 7 (15%) of 48 vaccinees with severe psychomotor retardation developed mild to moderate fever. Significant antibody responses in hemagglutination-inhibition tests were demonstrated in 33 (49%) vaccinees to CR-125, 20 (29%) to CR-159 and 8 (12%) to CRB-117. Two nosocomial outbreaks of influenza were observed in the subsequent winter. During an outbreak with H3N2 in one ward of severe psychomotor retardation patients, 2 (11%) of 18 vaccinees became infected compared with 10 (48%) of 21 placebo controls in the same ward (P < 0.05). In the other outbreak, with influenza B virus, 2 (14%) of 14 vaccinees and 13 (52%) of 25 controls in the ward for asthmatic children were infected (P < 0.05). The results indicate that trivalent CR vaccine is safe and effective against nosocomial outbreaks of influenza.", "The effects of immunization with killed influenza virus vaccine were assessed by comparison with placebo in a double-blind study of 318 adult patients with chronic asthma. The patients were randomly allocated to active vaccine and placebo. No difference was observed in peak expiratory flow rate or in clinical symptoms of bronchial obstruction between the groups receiving active vaccine and placebo during the first week after immunization. The data were analyzed separately for age, sex, duration of the disease, hypersensitivity to aspirin (acetylsalicylic acid), atopic status, patients with a history of attacks of asthma induced by viral infections, patients with a diurnal variation of baseline peak expiratory flow of 20 percent or more, and patients receiving continuous oral steroid medication, but none of these factors seemed to predict any short-term adverse effects of vaccination. Follow-up for eight months after the vaccination revealed no differences in asthmatic symptoms between the patients treated with active vaccine and those receiving placebo. The antiviral antibody response to vaccination was normal. The possible protection provided by the vaccination against exacerbation of asthma induced by influenza could not be evaluated, since the influenza epidemic expected during the season failed to occur in Finland. It is concluded that immunization with killed influenza vaccine is safe and is not associated with any significant side effects in adult patients with chronic asthma.", "To determine the efficacy of influenza vaccination in elderly people.\n Randomized double-blind placebo-controlled trial.\n Fifteen family practices in the Netherlands during influenza season 1991-1992.\n A total of 1838 subjects aged 60 years or older, not known as belonging to those high-risk groups in which vaccination was previously given.\n Purified split-virion vaccine containing A/Singapore/6/86(H1N1), A/Beijing/353/89(H3N2), B/Beijing/1/87, and B/Panama/45/90 (n = 927) or intramuscular placebo containing physiological saline solution (n = 911).\n Patients presenting with influenzalike illness up to 5 months after vaccination; self-reported influenza in postal questionnaires 10 weeks and 5 months after vaccination; serological influenza (fourfold increase of antibody titer between 3 weeks and 5 months after vaccination).\n The incidence of serological influenza was 4% in the vaccine group and 9% in the placebo group (relative risk [RR], 0.50; 95% confidence interval [CI], 0.35 to 0.61). The incidences of clinical influenza were 2% and 3%, respectively (RR, 0.53; 95% CI, 0.39 to 0.73). The effect was strongest for the combination of serological and clinical influenza (RR, 0.42; 95% CI, 0.23 to 0.74). The effect was less pronounced for self-reported influenza.\n In the elderly, influenza vaccination may halve the incidence of serological and clinical influenza (in periods of antigenic drift).", "Despite recommendations in most countries for giving inactivated influenza vaccine to people with asthma, only a minority currently receive it. One reason for low vaccine coverage has been concern that vaccination may induce exacerbations of asthma. In this randomized trial, 291 patients between 18 and 65 years of age received either an inactivated influenza vaccine followed 14 days later by a saline placebo or placebo followed by the vaccine. Each patient received 1 dose of vaccine and 1 dose of placebo. The percentage of patients reporting at least one asthma exacerbation within 14 days after injection was similar following vaccine or placebo (28.3% and 25.5%, respectively). The combined exacerbation rate during the first 14-day interval was higher (31.5%) than that during the second 14-day interval (22.4%, P = 0.0135), indicating that the occurrence of exacerbations was not likely to be related to the sequence of injections. The percentages of individuals with solicited systemic symptoms were 56.6% and 44.8% after vaccine or placebo injection, respectively. We conclude that influenza vaccination did not increase the incidence of asthma exacerbations compared to placebo in this study and the vaccine was well tolerated. The results thus support annual influenza vaccination in patients with asthma.", "Even though annual influenza vaccinations are recommended by many authorities, some doctors may be reluctant to vaccinate asthmatic patients because of the risk of inducing bronchial reactivity and exacerbating the asthma. In this study we investigated the effect of inactivated trivalent influenza vaccine on airway reactivity symptom scores and peak expiratory flow (PEF) variability in 24 patients with mild stable asthma. Baseline spirometry and methacholine challenge tests were performed on all patients. Patients were then asked to record their peak expiratory flow every morning and evening, complete daily symptom score charts (morning tightness, daytime asthma, cough, and night asthma), and note bronchodilator usage for 1 week. After baseline measurements, the patients were allocated to inactivated vaccine and placebo in a random and single-blind manner. The lung function measurements and methacholine challenge tests were repeated 1 week after vaccination and placebo administration at the same time of day. PD20 (mg/mL) methacholine doses were 3.06+/-3.0 mg/mL before vaccination, 2.96+/-3.2 mg/mL after vaccination, and 2.76+/-2.91 mg/mL after placebo administration. There were no significant changes in PD20 methacholine after influenza vaccination (p>0.05). There were also no significant changes in symptom scores, bronchodilator usage, and PEFR after vaccination (p>0.05). None of the patients experienced significant local or systemic side effects after vaccination. Immunization with inactivated influenza vaccine does not induce clinical exacerbations of asthma or airway hyperreactivity in patients with mild asthma." ]

[ "16393498" ]

[ "The use of ozone in dentistry and medicine. Part 2. Ozone and root caries." ]

[ "A previous paper, recently published in Primary Dental Care, gave an overview of the medical uses of ozone and outlined some of its uses in dentistry. The current paper focuses on a description of use of ozone in the management of root caries and considers recent studies in this area. There has been relatively limited research into the non-invasive (pharmaceutical) management of root caries. The best management strategy still remains to be developed. Initial studies have indicated that an application of ozone for a period of either 10 or 20 seconds is capable of clinically reversing leathery root carious lesions. It is suggested that, subject to confirmation from extensive trials, this simple and non-invasive technique may benefit many patients with root caries throughout the world since this approach to treat root caries can easily be employed in primary care clinics and in the domiciliary treatment of home-bound elderly people and immobile patients in hospices and hospitals." ]

[ "19692689", "16919749", "9651260", "6996635", "17602126", "17002810" ]

[ "Diacetylmorphine versus methadone for the treatment of opioid addiction.", "Controlled trial of prescribed heroin in the treatment of opioid addiction.", "Randomised trial of heroin maintenance programme for addicts who fail in conventional drug treatments.", "Evaluation of heroin maintenance in controlled trial.", "Heroin-assisted treatment for opioid dependence: randomised controlled trial.", "Methodology for the Randomised Injecting Opioid Treatment Trial (RIOTT): evaluating injectable methadone and injectable heroin treatment versus optimised oral methadone treatment in the UK." ]

[ "Studies in Europe have suggested that injectable diacetylmorphine, the active ingredient in heroin, can be an effective adjunctive treatment for chronic, relapsing opioid dependence.\n In an open-label, phase 3, randomized, controlled trial in Canada, we compared injectable diacetylmorphine with oral methadone maintenance therapy in patients with opioid dependence that was refractory to treatment. Long-term users of injectable heroin who had not benefited from at least two previous attempts at treatment for addiction (including at least one methadone treatment) were randomly assigned to receive methadone (111 patients) or diacetylmorphine (115 patients). The primary outcomes, assessed at 12 months, were retention in addiction treatment or drug-free status and a reduction in illicit-drug use or other illegal activity according to the European Addiction Severity Index.\n The primary outcomes were determined in 95.2% of the participants. On the basis of an intention-to-treat analysis, the rate of retention in addiction treatment in the diacetylmorphine group was 87.8%, as compared with 54.1% in the methadone group (rate ratio for retention, 1.62; 95% confidence interval [CI], 1.35 to 1.95; P<0.001). The reduction in rates of illicit-drug use or other illegal activity was 67.0% in the diacetylmorphine group and 47.7% in the methadone group (rate ratio, 1.40; 95% CI, 1.11 to 1.77; P=0.004). The most common serious adverse events associated with diacetylmorphine injections were overdoses (in 10 patients) and seizures (in 6 patients).\n Injectable diacetylmorphine was more effective than oral methadone. Because of a risk of overdoses and seizures, diacetylmorphine maintenance therapy should be delivered in settings where prompt medical intervention is available. (ClinicalTrials.gov number, NCT00175357.)\n 2009 Massachusetts Medical Society", "This study aimed to assess the efficacy of the prescription of intravenous diacetylmorphine (DAM) versus oral methadone with medical and psychosocial support, with a view of improving physical and mental health as well as social integration among socially excluded, opioid-dependent individuals for whom standard treatments have failed.\n This study used an open, randomized controlled trial.\n This study took place in Granada, Spain.\n Sixty-two opioid-dependent participants were randomized, 31 in each treatment group, and 50 of them were analyzed. The participants were recruited directly from the streets, through peer outreach, in well-known meeting places for drug-addicted individuals.\n Participants in the experimental group received injected DAM, twice a day, plus oral methadone, once a day, for 9 months. The control group received only oral methadone, once a day. The two groups received an equivalent opioid dosage. The average DAM dosage was 274.5 mg/day (range: 15-600 mg), and an average methadone dosage was 42.6 mg/day (range: 18-124 mg). The daily methadone dosage in the control group was 105 mg/day (range: 40-180 mg). Comprehensive clinical, psychological, social, and legal support was given to both groups.\n The following were measured in this study: general health, quality of life, drug-addiction-related problems, nonmedical use of heroin, risk behavior for HIV and HCV, and psychological, family, and social status.\n Both groups improved with respect to the total domain assessed. Those in the experimental group showed greater improvement in terms of physical health (the improvement was 2.5 times higher; p = .034) and risk behavior for HIV infection (the improvement was 1.6 times higher; p = .012). In addition, this group decreased its street heroin use from 25 days/month to 8 days/month as seen on the Addiction Severity Index (p = .020), as well as the number of days free from drug-related problems (the improvement was 2.1 times higher; p = .004) or involvement in crime (from 11 days/month to <1 day/month; p = .096 between groups).\n These findings support the hypothesis that, under the same conditions, DAM could be safely delivered, in our context. Also, in physical health, HIV risk behavior, street heroin use, and days involved in crime, DAM plus methadone was more efficacious than methadone alone. This implies that this treatment could provide an effective alternative for the treatment of socially excluded, opioid-dependent patients with severe physical and mental health problems because of drug addiction, when all available previous treatments have failed.", "To evaluate an experimental heroin maintenance programme. Design: Randomised trial.\n Outpatient clinic in Geneva, Switzerland.\n Heroin addicts recruited from the community who were socially marginalised and in poor health and had failed in at least two previous drug treatments.\n Patients in the experimental programme (n=27) received intravenous heroin and other health and psychosocial services. Control patients (n=24) received any other conventional drug treatment (usually methadone maintenance). Main outcome measures: Self reported drug use, health status (SF-36), and social functioning.\n 25 experimental patients completed 6 months in the programme, receiving a median of 480 mg of heroin daily. One experimental subject and 10 control subjects still used street heroin daily at follow up (difference 44%; 95% confidence interval 16% to 71%). Health status scores that improved significantly more in experimental subjects were mental health (0.58 SD; 0.07 to 1.10), role limitations due to emotional problems (0.95 SD; 0.11 to 1.79), and social functioning (0.65 SD; 0.03 to 1.26). Experimental subjects also significantly reduced their illegal income and drug expenses and committed fewer drug and property related offences. There were no benefits in terms of work, housing situation, somatic health status, and use of other drugs. Unexpectedly, only nine (38%) control subjects entered the heroin maintenance programme at follow up.\n A heroin maintenance programme is a feasible and clinically effective treatment for heroin users who fail in conventional drug treatment programmes. Even in this population, however, another attempt at methadone maintenance may be successful and help the patient to stop using injectable opioids.", "Ninety-six confirmed heroin addicts requesting a heroin maintenance prescription were randomly allocated to treatment with injectable heroin or oral methadone. Progress was monitored throughout the next 12 months by research workers operating independently of the clinic. Heroin can be seen as maintaining the status quo, with the majority continuing to inject heroin regularly and to supplement their maintenance prescription from other sources; it was associated with a continuing intermediate level of involvement with the drug subculture and criminal activity. Refusal to prescribe heroin while offering oral methadone constituted a more confrontational response and resulted in a higher abstinence rate, but also a greater dependence on illegal sources of drugs for these who continued to inject. Those offered oral methadone tended to polarize toward high or low categories of illegal drug use and involvement with the drug subculture, and were more likely to be arrested during the 12-month follow-up. There was no difference between the two groups in terms of employment, health, or consumption of nonopiate drugs. Refusal to prescribe heroin resulted in a significantly greater drop out from regular treatment.", "Heroin-assisted treatment has been found to be effective for people with severe opioid dependence who are not interested in or do poorly on methadone maintenance.\n To study heroin-assisted treatment in people on methadone who continue intravenous heroin and in those who are heroin dependent but currently not in treatment.\n In an open-label multicentre randomised controlled trial, 1015 people with heroin dependence received a variable dose of injectable heroin (n=515) or oral methadone (n=500) for 12 months. Two response criteria, improvement of physical and/or mental health and decrease in illicit drug use, were evaluated in an intent-to-treat analysis.\n Retention was higher in the heroin (67.2%) than in the methadone group (40.0%) and the heroin group showed a significantly greater response on both primary outcome measures. More serious adverse events were found in the heroin group, and were mainly associated with intravenous use.\n Heroin-assisted treatment is more effective for people with opioid dependence who continue intravenous heroin while on methadone maintenance or who are not enrolled in treatment. Despite a higher risk, it should be considered for treatment resistance under medical supervision.", "Whilst unsupervised injectable methadone and diamorphine treatment has been part of the British treatment system for decades, the numbers receiving injectable opioid treatment (IOT) has been steadily diminishing in recent years. In contrast, there has been a recent expansion of supervised injectable diamorphine programs under trial conditions in a number of European and North American cities, although the evidence regarding the safety, efficacy and cost effectiveness of this treatment approach remains equivocal. Recent British clinical guidance indicates that IOT should be a second-line treatment for those patients in high-quality oral methadone treatment who continue to regularly inject heroin, and that treatment be initiated in newly-developed supervised injecting clinics. The Randomised Injectable Opioid Treatment Trial (RIOTT) is a multisite, prospective open-label randomised controlled trial (RCT) examining the role of treatment with injected opioids (methadone and heroin) for the management of heroin dependence in patients not responding to conventional substitution treatment. Specifically, the study examines whether efforts should be made to optimise methadone treatment for such patients (e.g. regular attendance, supervised dosing, high oral doses, access to psychosocial services), or whether such patients should be treated with injected methadone or heroin. Eligible patients (in oral substitution treatment and injecting illicit heroin on a regular basis) are randomised to one of three conditions: (1) optimized oral methadone treatment (Control group); (2) injected methadone treatment; or (3) injected heroin treatment (with access to oral methadone doses). Subjects are followed up for 6-months, with between-group comparisons on an intention-to-treat basis across a range of outcome measures. The primary outcome is the proportion of patients who discontinue regular illicit heroin use (operationalised as providing >50% urine drug screens negative for markers of illicit heroin in months 4 to 6). Secondary outcomes include measures of other drug use, injecting practices, health and psychosocial functioning, criminal activity, patient satisfaction and incremental cost effectiveness. The study aims to recruit 150 subjects, with 50 patients per group, and is to be conducted in supervised injecting clinics across England." ]

[ "12671780", "15294086", "14509861", "11115952", "12698766", "15659884", "14526208", "15811483", "14617500", "12781934", "12469544", "15751766", "10193067", "14746666", "15040540", "15690118", "14526206" ]

[ "Efficacy of an educational and counseling intervention on adherence to highly active antiretroviral therapy: French prospective controlled study.", "Adherence to antiretroviral therapy in HIV-infected pediatric patients improves with home-based intensive nursing intervention.", "Influencing medication adherence among women with AIDS.", "Prospective randomized two-Arm controlled study to determine the efficacy of a specific intervention to improve long-term adherence to highly active antiretroviral therapy.", "Using motivational interviewing to promote adherence to antiretroviral medications: a pilot study.", "Multidisciplinary HIV adherence intervention: a randomized study.", "Impact of a patient education program on adherence to HIV medication: a randomized clinical trial.", "Impact of an adherence clinic on behavioral outcomes and virologic response in treatment of HIV infection: a prospective, randomized, controlled pilot study.", "Use of an on-line pager system to increase adherence to antiretroviral medications.", "A medication self-management program to improve adherence to HIV therapy regimens.", "Results of a pilot intervention trial to improve antiretroviral adherence among HIV-positive patients.", "A randomized controlled trial to enhance antiretroviral therapy adherence in patients with a history of alcohol problems.", "[Adherence to very active antiretroviral treatment: impact of individualized assessment].", "Program to enhance health literacy and treatment adherence in low-income HIV-infected Latino men and women.", "Effect of individual cognitive behaviour intervention on adherence to antiretroviral therapy: prospective randomized trial.", "The efficacy of an integrated risk reduction intervention for HIV-positive women with child sexual abuse histories.", "Impact of an educational program on efficacy and adherence with a twice-daily lamivudine/zidovudine/abacavir regimen in underrepresented HIV-infected patients." ]

[ "The objective was to evaluate the impact of an intervention for improving adherence to antiretroviral therapies (HAART) in HIV-infected patients.\n We designed a prospective, controlled, randomized trial to assess the impact of an educational and counseling intervention in addition to standard of care. At M0, the study enrolled 244 HAART-treated patients who attended a medical consultation between September and December 1999 who were not included in another protocol. Patients in the intervention group (IG) were offered three individual sessions by trained nurses. The proportions of adherent patients at 6 months followup (M6) and the change in HIV RNA between M0 and M6 were measured.\n Between M0 and M6, HIV RNA significantly decreased in the 123 patients of the IG (mean difference = -0.22 log [+/-0.86], p =.013), while it increased (+0.12 log [+/-0.90], p =.14) in the 121 patients of the control group. However, the proportion of patients with HIV RNA <40 copies/mL remained similar in both groups. In an intent-to-treat analysis, the only significant predictor of 100% adherence at M6 was the intervention group (p =.05) after adjustment for baseline adherence (p =.001). Among the 202 patients with available data on adherence, the proportion of adherent patients was similar in both groups at M0 (58% vs. 63%, p =.59) but became higher in the IG at M6 (75% vs. 61%, p =.04).\n The educational and counseling intervention was efficient for increasing adherence to HAART and could be implemented in most clinical settings.", "Adherence to combination antiretroviral therapy (ART) has been shown to be a determining factor in controlling viral replication, maintaining immunologic function and long-term survival in HIV-positive individuals. Little information is available on strategies to improve adherence in pediatric HIV-infected patients. We conducted a randomized, nonblinded, pilot study to determine if a home-based nursing intervention would improve medication adherence. The study was offered to all eligible HIV-positive patients receiving care at Connecticut Children's Medical Center's (CCMC) Pediatric and Youth HIV Program. Sixty-seven percent (37/55) of the patients and their caretakers participated. We randomized participants to either standard of care or the intervention trial. The intervention was designed to improve knowledge and understanding of HIV infection and HIV medications and to resolve or modify barriers to adherence. Both groups completed pre- and post-intervention questionnaires, assessing their knowledge and understanding of HIV, ART, and adherence. Adherence was estimated objectively from medication refill history and subjectively from a self-report score. We also inferred adherence from pre- to post-test plasma viral load and CD4+ T-cell percentages. The knowledge score (p = 0.02) and medication refill history (p = 0.002) improved significantly in the intervention group. The adherence self-report score improved, although not significantly (p = 0.07). We did not observe statistical differences in CD4+ T-cell counts or viral load between groups. We conclude that our home-based nursing intervention helped HIV-positive children and their families in better adhering to prescribed medication regimens.", "This study examined the effects of a ten-session cognitive-behavioural stress management/expressive supportive therapy (CBSM+) intervention on adherence to antiretroviral medication. Although the intervention was not designed to influence adherence, it was theorized that improved coping and social support could enhance adherence. Women with AIDS (N = 174) in Miami, New York and New Jersey, USA, were randomized to a group CBSM+ intervention or individual control condition. Participants were African American (55%), Latina (18%) and Caribbean (18%) with drug (55%) and/or alcohol (32%) histories. Participants were assessed on self-reported medication adherence over seven days, HIV-related coping strategies and beliefs regarding HIV medication. Baseline overall self-reported adherence rates were moderate and related to coping strategies and HIV medication beliefs. Low adherent (80%) participants in the intervention condition increased their mean self-reported medication adherence (30.4% increase, t44 = 3.1, p < 0.01), whereas low adherent women in the control condition showed a non-significant trend (19.6% increase, t44 = 2.0, p > 0.05). The intervention did not improve adherence in this population; conditions did not differ significantly on self-reported adherence. Low adhering intervention participants significantly decreased levels of denial-based coping (F1,88 = 5.97, p < 0.05). Results suggest that future interventions should utilize group formats and address adherence using coping and medication-knowledge focused strategies.", "Nearly perfect compliance seems to be indispensable to obtain the maximum benefit from highly active antiretroviral therapy (HAART). Interventions to ensure a high level of adherence during a relatively long-term period of therapy are necessary.\n This is a prospective, randomized, two-arm controlled study including patients starting their first-or second-line HAART who were randomized to receive psychoeducative intervention to implement adherence (experimental group [EG]) or a usual medical follow-up (control group [CG]). We aimed to study the efficacy of a psychoeducative intervention to ensure long-term adherence to HAART, its relation with the virologic efficacy of treatment, and to determine the variables related to long-term adherence. Visits were made at weeks 0, 4, 24, and 48 for data collection. Self-reported adherence was registered at each visit and its veracity was tested by randomized blood analyses performed without previous warning to 40% of patients. Appropriate adherence was defined as the consumption of >/=95% of medication prescribed. Statistical analyses were performed both by the as treated (AT) and the intention to treat missing = failure (ITT) methods.\n In all, 116 patients were included. At week 48, 94% of patients in the EG versus 69% controls achieved adherence >/=95% (p =.008); 89% of patients in the EG versus 66% controls had HIV-1 RNA levels <400 copies/ml (p =.026). Overall, 85% of patients with adherence >/=95% but only 45% of those with adherence <95% had viral load (VL) <400 copies/ml (p =. 008). In multivariate analysis, variables significantly related to adherence were having received a psychoeducative intervention (odds ratio [OR], 6.58; p =.04), poor effort to take medication (OR, 5.38; p =.03), and high self-perceived capacity to follow the regimen (OR, 13.76; p =.04). Self-reported adherence and drug plasma levels coincided in 93% of cases. However, differences in adherence did not reach statistical significance in the ITT analysis although a clear tendency toward benefit was observed in EG.\n Specific and maintained psychoeducative interventions based on excellence on clinical practice are useful to keep high levels of adherence as well as high levels of viral suppression. There is a clear relation between high adherence levels and virologic success. Assessment of certain specific variables related to adherence may be helpful to monitor patient's compliance in the clinical setting.", "This report describes a pilot study of a nursing intervention to increase adherence to combination therapy. The intervention was based on motivational interviewing (MI). Participants completed a baseline assessment using the computer-administered self-interview with audio (ACASI) data collection method and then were randomly assigned to the MI intervention or control condition. Nurse counselors met with participants in the MI intervention group for three adherence sessions. Two months following baseline, participants completed a follow-up assessment. Mean scores on ratings of missed medications were lower for participants in the intervention group than those in the control group. Although there were no significant differences in the number of medications missed during the past 4 days, participants in the MI group reported being more likely to follow the medication regimen as prescribed by their health care provider. The pilot study provided useful information about the acceptability of ACASI and the adequacy of intervention procedures. The results of this pilot study show promise for the use of MI as an intervention to promote adherence to antiretroviral medications.", "Maintaining greater than 95% adherence to antiretroviral medication is necessary in order to have the greatest therapeutic impact on HIV infection. Furthermore, evidence suggests that adherence rates of between 70% and 89% are significantly associated with viral rebound and the development of drug resistance. Adherence rates at and above the 95% level are difficult for patients to achieve and maintain. Our aim was to determine if an adherence intervention could improve adherence among patients attending an ambulatory care clinic at a large public hospital. The intervention was delivered by a multidisciplinary team of health care professionals and consisted of education coupled with the provision of devices designed to assist patient memory and adherence. A crucial component of the intervention consisted of the identification of patient specific barriers to adherence and the development of strategies to circumvent these problems. Adherence was assessed using patient self-report over the past 4, 7, and 28 days and by calculation of the Morisky score. The study was conducted as a randomised controlled trial using the stepped wedge design with a total of 68 subjects randomised to receive the intervention over a 20-week period. Adherence before and after the intervention formed the analysis. There was a significant decrease in the number of missed doses over the past 4 (1.9 to 1.0, p < 0.001), 7 (3.0 to 1.8, p < 0.001) and 28 (7.4 to 4.2, p < 0.001) days and a decrease in the Morisky score, indicating an improvement in medication taking behaviour (1.3 to 0.5 p < 0.001).", "Patients' knowledge of their HIV condition and its treatment, which has been recognized as a factor that influences adherence to antiretroviral therapy, can be improved through educational programs. This prospective, randomized, controlled trial compared an experimental group that participated in an educational program and a control group with standard care. The study evaluated the impact of an educational intervention on adherence to antiretroviral therapy, patients' knowledge, quality of life, and therapeutic response in patients treated with highly active antiretroviral therapy. Three hundred twenty-six patients were analyzed at inclusion. A higher level of adherence was associated with patients who were older, had higher incomes, and did not smoke. CD4 cell count and plasma viral load were correlated with adherence at entry. The educational intervention had an impact on adherence and knowledge in the experimental group at 6 months, which was maintained at 12 and 18 months. A delayed increase in adherence was observed in the control group at 12 months. No significant impact on quality of life was observed over time. The patients' health status improved in 56% of the experimental group subjects and 50% of the control subjects. However, no significant impact was shown on CD4 cell count and plasma viral load. This study shows that an educational intervention improves adherence to antiretroviral regimens and health status and suggests that it should be initiated early in therapy.", "The aim of this randomized, controlled pilot study was to examine the impact of a pharmacist operated adherence clinic on adherence to highly active antiretroviral therapy (HAART) and viral suppression in patients with HIV over 28 weeks.\n Consecutive eligible patients initiating HAART at an indigent-care clinic were randomized to an adherence clinic or to standard care (information provided by physician or nurse practitioner) for education and monitoring. Group assignment was stratified before randomization according to regimen complexity and potential tolerability. Adherence (electronic monitoring and patient self-report) and viral load (reverse-transcription polymerase chain reaction) were assessed at weeks 4, 16, and 28.\n Thirty-three randomized patients (adherence clinic, n = 16; standard care, n = 17) comprised the intent-to-treat population. The groups were well-matched for demographics and antiretroviral regimen. The median age was 38.0 years in both groups. Most patients were male (85%), had previously used HAART (78%), and had an AIDS diagnosis (79%). Mean (SD) adherence at weeks 4, 16, and 28 was 86% (27%), 77% (28%), and 74% (31%) in the adherence clinic group versus 73% (32%), 56% (39%), and 51% (41%) in the standard care group (week-16 difference, 21% [90% CI, 1%-42%]; week-28 difference, 23% [90% CI, 1%-44%]). Sixty-nine percent of patients in the adherence clinic group took their medication on schedule versus 42% in the standard care group (P = 0.025); mean decline in adherence from weeks 4 to 28 was 12% in the adherence clinic group (P = 0.15) versus 22% in the standard care group (P = 0.002). HIV-1 RNA levels were <400 copies/mL at weeks 4, 16, and 28 in 63%, 100%, and 94% of the adherence clinic group and 29% (P = NS), 71% (P = 0.04), and 65% (P = NS) of the standard care group.\n In this preliminary trial, an adherence clinic model improved adherence to HAART and virologic response over 28 weeks in the patients studied.", "Adherence to antiretroviral therapy is critical for treatment success. Antiretroviral therapy typically requires multiple pills at multiple dosing times. To address this, we tested the feasibility, utility, and efficacy of a customizable reminder system using pagers, which were programmed using web-based technology, to increase and maintain proper adherence in patients with pre-existing adherence problems. After a two-week monitoring period with an electronic pill-cap, participants with less than 90% adherence were randomized to continue monitoring or to receive a pager. The group who received the pagers had greater improvements in adherence from baseline to Week 2 and Week 12 than those who monitored their medications only. However, adherence in both groups at the outcome assessments points was still poor. While the provision of a reminder system helped improve adherence, it is likely that more intensive interventions are required for patients with pre-existing problems.", "This study examined whether a self-management intervention based on feedback of adherence performance and principles of social cognitive theory improves adherence to antiretroviral dosing schedules. Forty-three individuals with HIV/AIDS who were starting or switching to a new protease inhibitor regimen were randomly assigned to be in a medication self-management program or usual care control group. The self-management program included skills development exercises, three monthly visits for medication consultations, and monthly feedback of adherence performance using electronic monitors on medication bottles. Participants also completed a 40-item questionnaire that measured self-efficacy to take medications, on schedule, in a variety of situations. Logistic regression analysis indicated that individuals in the self-management group were significantly more likely to take 80% or more of their doses each week than individuals in the control group (n=29, OR=7.8, 95% CI=2.2-28.1). Self-management training with feedback of adherence performance is a potentially useful model for improving adherence to complex regimens in HIV/AIDS care.", "A small pilot trial of a multicomponent (behavioral strategies, simplified patient information, and social support) and multidisciplinary (cognitive-behavioral therapy and nursing) medication adherence intervention was conducted for HIV-infected adults prescribed antiretrovirals. Patients (N = 33) were randomly assigned to the intervention condition or standard care. Compared to the control group, patients in the intervention condition had significantly higher self-efficacy to communicate with clinic staff (p = .04) and to continue treatment (p = .04), were significantly more likely to be using behavioral and cognitive strategies (p = .01 and p = .04), reported significantly higher life satisfaction (p = .03), reported significantly increased feelings of social support (p = .04), and showed a trend toward an increase in taking their medications on schedule (p = .06). The intervention, however, did not appear to affect health-related anxiety or to significantly improve adherence to dose. Implications for future intervention planning are discussed.", "To assess the effectiveness of an individualized multicomponent intervention to promote adherence to antiretroviral therapy (ART) in a cohort of HIV-infected individuals with a history of alcohol problems.\n We conducted a randomized controlled trial to compare the usual medical follow-up with an adherence intervention.\n The principal enrolment site was Boston Medical Center, a private, not-for-profit, academic medical institution.\n HIV-infected patients with a history of alcohol problems on ART. A total of 151 were enrolled and 141 (93%) were assessed at follow-up. Intervention: A nurse, trained in motivational interviewing, completed the following over 3 months in four encounters: addressed alcohol problems; provided a watch with a programmable timer to facilitate pill taking; enhanced perception of treatment efficacy; and delivered individually tailored assistance to facilitate medication use.\n Prior 30-day adherence > or =95%, prior 3-day adherence of 100%, CD4 cell count, HIV RNA and alcohol consumption, each at both short- and long-term follow-up.\n At follow-up, no significant differences in medication adherence, CD4 cell count, HIV RNA or alcohol consumption were found (all P values >0.25).\n A multicomponent intervention to enhance adherence among HIV-infected individuals with a history of alcohol problems was not associated with changes in medication adherence, alcohol consumption or markers of HIV disease progression. The failure to change adherence in a group at high risk for poor adherence, despite utilizing an intensive individual-focused patient intervention, supports the idea of addressing medication adherence with supervised medication delivery or markedly simplified dosing regimens.", "To determine if the intervention of individual advice improves adherence and effectiveness to highly active antiretroviral therapy.\n Randomized open trial. Patients treated with zidovudine + lamivudine + indinavir were assigned (2/1) to conventional care or individual advise. Individual advise consists in adaptation to treatment to patient style of live and detailed information of therapy. Adherence were estimated with structured interview and pillo counts and were considered correct when more than 90% of prescribed drugs were taken.\n Patients 170, conventional care: 110 and IA: 60. Follow-up: 24 weeks. Baseline characteristics were similar in both groups. Correct adherence were estimated in 52.7% of conventional care and in 76.7% of individual advise (p = 0.002, relative risk: 1.45; CI 95%: 1.16-1.82). Undetectable viral load (NASBA < 50 copies/ml) in 54.5% of conventional care and in 65% of individual advise (p = 0.18, relative risk: 1.19; CI 95%: 0.93-1.53). Reduction of viral load in the conventional care group 1.02 +/- 0.5 log10/ml, and in the individual advise group 1.98 +/- 0.7 log10/ml.\n The individual advice improve adherence with a tendency to improve effectiveness of highly active antiretroviral therapy.", "This paper reports the initial results of a pilot study to evaluate the acceptability and effectiveness of a program to enhance health literacy in low-income HIV-infected Latino men and women receiving antiretroviral therapy. Participants rated the program highly on measures of satisfaction, providing evidence of its acceptability. The effectiveness of the program was assessed in comparisons of the intervention (n = 41) and standard care only (n = 40) groups at baseline and 6-week intervals. Program participants showed significant improvement over comparison group participants on measures of HIV/AIDS and treatment-related knowledge and recognition and understanding of HIV terms. Although there were no significant changes in adherence mastery and behaviors during the 6-week follow up period, there were significant changes in program participants' knowledge about medication adherence. Future steps to examine the sustainability of the program in the medical management of patients are planned in addition to determining its long-range relative impact.", "A high level of adherence to antiretroviral therapy is required for complete suppression of HIV replication, immunological and clinical effectiveness. We investigated whether cognitive behaviour therapy can improve medication adherence.\n Prospective randomized 1-year trial.\n Collaboration of HIV university outpatient clinic and psychotherapists in private practice.\n 60 HIV-infected persons on stable antiretroviral combination therapy and viral load below 50 copies/ml.\n Cognitive behaviour intervention in individual patients, in addition to standard of care.\n Feasibility and acceptance of intervention; adherence to therapy assessed using medication event monitoring system (MEMS) and self-report questionnaire; virological failure; psychosocial measures.\n The median number of sessions for cognitive behaviour intervention per patient during the 1-year trial was 11 (range 2-25). At months 10-12, mean adherence to therapy as assessed using MEMS was 92.8% in the intervention and 88.9% in the control group (P=0.2); the proportion of patients with adherence > or = 95% was 70 and 50.0% (P=0.014), respectively. While there was no significant deterioration of adherence during the study in the intervention arm, adherence decreased by 8.7% per year (P=0.006) in the control arm. No differences between the intervention group and standard of care group were found regarding virological outcome. Compared with the control group, participants in the intervention group perceived a significant improvement of their mental health during the study period.\n Cognitive behavioural support in addition to standard of care of HIV-infected persons is feasible in routine practice, and can improve medication adherence and mental health.", "Child sexual abuse (CSA) is associated with HIV risk behaviors [Bensley, L., Van Eenwyk, J., and Simmons, K. W., 2003.] and more prevalent among women living with HIV than in the general population [Koenig, L. J., and Clark, H., 2004]. This randomized Phase~I clinical trial tested the impact of a culturally congruent psychoeducational intervention designed to reduce sexual risks and increase HIV medication adherence for HIV-positive women with CSA histories. An ethnically diverse sample of 147 women were randomized to two conditions: an 11-session Enhanced Sexual Health Intervention (ESHI) or an attention control. Results based on \"intent to treat'' analyses of pre-post changes are reported here. Additional analyses explored whether the observed effects might depend on \"intervention dose,'' i.e., number of sessions attended. Women in the ESHI condition reported greater sexual risk reduction than women in the control condition. Although there were no differences between women in the ESHI and control groups on medication adherence, women in the ESHI condition who attended 8 or more sessions reported greater medication adherence at posttest than control women. The findings provide initial support for this culturally and gender-congruent psychoeducational intervention for HIV-positive women with CSA, and highlight the importance of addressing the effects of CSA on sexual risk reduction and medication adherence in preventive interventions for women.", "A 24-week open-label clinical trial was conducted in 195 HIV-infected adults commonly underrepresented in research (35% female, 71% African American, 21% Hispanic, and 20% injection drug users [IDUs]) to evaluate the effect of an HIV educational program on efficacy and adherence with a simple, compact, twice-daily triple nucleoside regimen containing a lamivudine (150 mg)/zidovudine (300 mg) combination (COM) tablet plus abacavir (ABC), 300 mg. At baseline, the patients' median plasma HIV-1 RNA level was 4.18 log10 copies/mL and the median CD4+ cell count was 379 cells/mm3. Patients were randomized 1:1 to 4 modules of the Tools for Health and Empowerment HIV education intervention plus routine counseling (EI + RC; n = 96) or to routine counseling alone (RC; n = 99). No differences between the EI + RC and RC treatment arms were observed with respect to the proportion of patients achieving plasma HIV-1 RNA levels <40 copies/mL (60% [33/55] vs. 55% [38/69]; P = 0.529) or <400 copies/mL (80% [44/55] vs. 80% [55/69]; P = 0.689) at week 24 (intent-to-treat observed analysis), increase in median CD4 cell count above baseline at week 24 (78.3 vs. 104.8 cells/mm3; P = 0.498), or mean overall adherence rates as measured by the Medication Event Monitoring System (MEMS) (70% vs. 74%). COM + ABC was generally well tolerated, and no association was observed between interruptions in treatment and the development of ABC hypersensitivity (5 suspected cases). In conclusion, in underrepresented patients, the EI used in this study did not affect the efficacy and adherence results with ABC + COM to any greater degree than did RC." ]

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[ "Comparison of topical glyceryl trinitrate ointment and oral nifedipine in the treatment of chronic anal fissure.", "Clove oil cream: a new effective treatment for chronic anal fissure.", "Chronic anal fissures treated with botulinum toxin injections: a dose-finding study with Dysport(®).", "Lack of effficacy of botulinum toxin in chronic anal fissure.", "Topical nifedipine with lidocaine ointment vs. active control for treatment of chronic anal fissure: results of a prospective, randomized, double-blind study.", "The conservative treatment of fissure-in-ano.", "Randomised trial of topical 0.2% glyceryl trinitrate and lateral internal sphincterotomy for the treatment of patients with chronic anal fissure: long-term follow-up.", "Influence of botulinum toxin site of injections on healing rate in patients with chronic anal fissure.", "Randomized clinical trial of botulinum toxin plus glyceryl trinitrate vs. botulinum toxin alone for medically resistant chronic anal fissure: overall poor healing rates.", "A randomized trial of glyceryl trinitrate ointment and nitroglycerin patch in healing of anal fissures.", "Local nitroglycerin for treatment of anal fissures: an alternative to lateral sphincterotomy?", "Randomised controlled trial shows that glyceryl trinitrate heals anal fissures, higher doses are not more effective, and there is a high recurrence rate.", "Isosorbide dinitrate in the treatment of anal fissure: a randomised, prospective, double blind, placebo-controlled trial.", "Topical mononitrate treatment in patients with anal fissure.", "A double-blind randomized placebo-controlled trial of oral indoramin to treat chronic anal fissure.", "Efficacy and safety of botulinum toxin a injection compared with topical nitroglycerin ointment for the treatment of chronic anal fissure: a prospective randomized study.", "The use of glyceryl trinitrate (GTN) in the treatment of chronic anal fissure in children.", "A study to determine the nitroglycerin ointment dose and dosing interval that best promote the healing of chronic anal fissures.", "A comparison of botulinum toxin and saline for the treatment of chronic anal fissure.", "Glyceryl trinitrate ointment (0.25%) and anal cryothermal dilators in the treatment of chronic anal fissures.", "Topical nitroglycerin versus lateral internal sphincterotomy for chronic anal fissure: prospective, randomized trial.", "[Surgical or biologic sphincterotomy in the treatment of chronic anal fissure].", "Comparative study of lateral internal sphincterotomy versus local 0.2% glyceryl trinitrate ointment for the treatment of chronic anal fissure.", "Randomized clinical trial comparing botulinum toxin injections with 0.2 per cent nitroglycerin ointment for chronic anal fissure.", "Maintenance therapy with unprocessed bran in the prevention of acute anal fissure recurrence.", "Comparison of topical glyceryl trinitrate with lignocaine ointment for treatment of anal fissure: a randomised controlled trial.", "Randomized, prospective trial comparing 0.2 percent isosorbide dinitrate ointment with sphincterotomy in treatment of chronic anal fissure: a two-year follow-up.", "Botulinum toxin injection versus lateral internal sphincterotomy in the treatment of chronic anal fissure: a randomized controlled trial.", "Study of efficacy and safety of a new local cream ('healer') in the treatment of chronic anal fissure: a prospective, randomized, single-blind, comparative study.", "A dose finding study with 0.1%, 0.2%, and 0.4% glyceryl trinitrate ointment in patients with chronic anal fissures.", "Hydropneumatic anal dilation in conservative treatment of chronic anal fissure: clinical outcomes and randomized comparison with topical nitroglycerin.", "The anal dilator in the conservative management of acute anal fissures.", "[Efficacy of anal dilators in the treatment of acute anal fissure. A controlled clinical trial].", "A randomized trial of oral vs. topical diltiazem for chronic anal fissures.", "[A prospective, randomized double-blind study on the treatment of anal fissures with Nitroglycerin ointment].", "Randomized prospective controlled trial of lateral internal sphincterotomy versus injection of botulinum toxin for the treatment of idiopathic fissure in ano.", "Internal sphincterotomy is superior to topical nitroglycerin in the treatment of chronic anal fissure: results of a randomized, controlled trial by the Canadian Colorectal Surgical Trials Group.", "A comparison of the effects of diltiazem and glyceryl trinitrate ointment in the treatment of chronic anal fissure: a randomized clinical trial.", "Glyceryl trinitrate vs. sphincterotomy for treatment of chronic fissure-in-ano: a randomized, controlled trial.", "Randomized, controlled study comparing sitz-bath and no-sitz-bath treatments in patients with acute anal fissures.", "Double blind randomised controlled trial of topical glyceryl trinitrate in anal fissure.", "A prospective, randomized, double-blind, placebo-controlled trial of glyceryl-trinitrate ointment in the treatment of children with anal fissure.", "Glyceryl trinitrate ointment for the treatment of chronic anal fissure: results of a placebo-controlled trial and long-term follow-up.", "A randomised, prospective, double-blind, placebo-controlled trial of glyceryl trinitrate ointment in treatment of anal fissure.", "Surgical versus chemical (botulinum toxin) sphincterotomy for chronic anal fissure: long-term results of a prospective randomized clinical and manometric study.", "Safety and efficacy of new glyceryl trinitrate suppository formula: first double blind placebo-controlled clinical trial.", "A randomized trial of botulinum toxin vs lidocain pomade for chronic anal fissure.", "A comparison of injections of botulinum toxin and topical nitroglycerin ointment for the treatment of chronic anal fissure.", "A prospective randomized trial of diltiazem and glyceryltrinitrate ointment in the treatment of chronic anal fissure.", "Topical 0.5% nifedipine vs. lateral internal sphincterotomy for the treatment of chronic anal fissure: long-term follow-up.", "Effectiveness of higher doses of botulinum toxin to induce healing in patients with chronic anal fissures.", "Controlled dose delivery in topical treatment of anal fissure: pilot study of a new paradigm.", "Treatment of anal fissures using a combination of minoxidil and lignocaine: a randomized, double-blind trial.", "A randomised study comparing systemic transdermal treatment and local application of glyceryl trinitrate ointment in the management of chronic anal fissure.", "Randomized clinical trial comparing oral nifedipine with lateral anal sphincterotomy and tailored sphincterotomy in the treatment of chronic anal fissure.", "Topical anal fissure treatment: placebo-controlled study of mononitrate and trinitrate therapies.", "Randomized, double-blind trial comparing topical nitroglycerine with xylocaine and Proctosedyl in idiopathic chronic anal fissure.", "Comparison of botulinum toxin injection and lateral internal sphincterotomy for the treatment of chronic anal fissure." ]

[ "This study was designed to compare the effect of topical glyceryl trinitrate (GTN) and oral nifedipine treatments on maximal anal resting pressure (MARP) and subsequently to assess their effectiveness in healing of chronic anal fissure (CAF). Patients were allocated randomly to receive either oral nifedipine retard (10 patients) 20 mg twice daily or instructed to apply glyceryl trinitrate (0.2 percent) ointment (10 patients) into the lower half of the anal canal twice daily. They were reviewed and assessed at the first visit and every fortnight for measurement of MARP, pain scores, blood pressure, pulse rate, healing of the fissure and adverse effects. Treatment were continued until healing had occurred or for up to 8 weeks. MARP values before and after application of the GTN ointment was 113.2 cm H2O and 72.5 cm H2O respectively (P < 0.001). Nifedipine caused a reduction in mean MARP from 105.2 to 74.0 cm H2O (P < 0.001). Linear analogue pain scores were significantly reduced after 2 weeks treatment with GTN and nifedipine (P < 0.001) and continued throughout the treatment period. At the end of the study; 7 of the 10 patients in the GTN group were deemed to be healed (5) or improved (2), compared with 6 of the 10 patients in the nifedipine group (5 healed, 1 improved). Headaches occurred in 3 patients in the GTN group, compared with one patient in the nifedipine group. There was no significant difference between GTN and nifedipine in terms of reduction in MARP and pain score, healing of the fissure and incidence of early recurrence and side effects of treatments. We conclude that GTN ointment and oral nifedipine are equally effective in the treatment of chronic anal fissure.", "Anal fissure is a common painful condition affecting the anal canal and causes considerable morbidity and reduction in quality of life. Surgical treatment has been associated with a degree of incontinence in up to 30% of patients. This study discussed the results of clove oil 1% cream in healing of chronic anal fissure.\n A single-blind randomized comparative trial was setup to compare traditional treatment with stool softeners and lignocaine cream 5% against clove oil 1% cream for 6 weeks.\n 55 patients were included in this study, 30 patients in clove oil group and 25 patients in control group. Healing had occurred in 60% of patients in clove oil group and in 12% of patients in the control group after 3-month follow up (P < 0.001). Patients in clove oil group showed significant reduction in resting anal pressure and almost all other anorectal manometric pressures compared with patients in control group.\n Topical application of clove oil cream demonstrated a significant beneficial effect when applied to patients suffering from chronic anal fissure.", "Botox(®) injection of the anal sphincter muscle cures chronic uncomplicated anal fissures in up to 80% of patients. This study examines the therapeutic efficacy and side effect profile of the British botulinum product Dysport(®) . Fifty patients (29 women) were recruited to participate in this randomized dose-finding study, their mean age being 32.9 years. The low dose group A was treated with a total dose of 20 U injected in two sites each lateral to the fissure, the high dose group B was treated with 40 U. Eighty-two percent of patients were pain-free within a week following the injections. The fissure was healed in 78% of treated patients after 3 months. Three patients relapsed within 6 months. The most common adverse side effect was transient incontinence (n = 4). Clinical outcome was not significantly different between the two treatment groups. The low dose can therefore be regarded sufficient for the treatment of anal fissure. Therapeutic efficacy was equivalent to published data on Botox treatment. Both Dysport(®) and Botox(®) can therefore be used to treat chronic uncomplicated anal fissures. Both Dysport(®) and Botox(®) therapy are well tolerated, can be performed on an out-patient basis and avoid the risk of permanent faecal incontinence which complicates surgical treatment of anal fissures.", "Hypertonicity of internal anal sphincter plays a major role in the persistence of chronic anal fissure. Botulinum toxin could induce internal anal sphincter relaxation without the adverse effects of surgery (long-term faecal incontinence) or topical nitrates (anal burning, headaches, hypotension).\n We conducted a placebo-controlled, randomised, double-blind study to assess the efficacy of a single injection of botulinum toxin in the internal anal sphincter of patients with chronic anal fissure in six ambulatory care clinics. Eligibility criteria included a mean value of post-defecation anal pain >or= 30 mm on a 100 mm visual analogue scale over the week preceding inclusion. Main endpoint was the proportion of patients with symptomatic improvement during the fourth week after inclusion (post-defecation anal pain below 10 mm).\n Forty-four patients (22 in each group) were included. At inclusion, there was no significant difference between groups on age, sex ratio, pain duration, post-defecation anal pain, analgesic consumption and stool frequency. Ten (45%) and 11 (50%) patients reported symptomatic improvement on the main endpoint (P=0.76) in placebo and botulinum toxin groups, respectively. Ten patients (five in each group) had healed fissure at week 4 and ten patients (five in each group) required surgical treatment between weeks 4 and 12. Similarly, there was no significant difference between groups on other variables between weeks 4 and 12.\n The efficacy of a single injection of botulinum toxin in the internal anal sphincter does not differ from that of a placebo in patients with chronic anal fissure.", "Chronic anal fissure may be treated by chemical or surgical sphincterotomy. The aim of this study was to test the efficacy of local application of nifedipine and lidocaine ointment in healing chronic anal fissure.\n The study was performed according to a prospective, randomized, double-blind design. One hundred ten patients who gave informed consent were recruited. They received a clinical examination, a questionnaire to evaluate symptoms and pain, anorectal manometry, and anoscopy. Healing of anal fissure at Day 42 of therapy was defined as the primary efficacy variable of the study. Patients treated with nifedipine (n = 55) used topical 0.3 percent nifedipine and 1.5 percent lidocaine ointment every 12 hours for 6 weeks. The control group (n = 55) received topical 1.5 percent lidocaine and 1 percent hydrocortisone acetate ointment during therapy. Anal pressures were measured by recording resting and maximal voluntary contraction pressures at baseline and at Day 21. Long-term outcomes were determined after a median follow-up of 18 months.\n Healing of chronic anal fissure was achieved after 6 weeks of therapy in 94.5 percent of the nifedipine-treated patients (P < 0.001) as opposed to 16.4 percent of the controls. Mean anal resting pressure decreased from a mean value +/- standard deviation of 47.2 +/- 14.6 to 42 +/- 12.4 mmHg in the nifedipine group. This represents a mean reduction of 11 percent (P = 0.002). Changes of maximal voluntary contraction in nifedipine-treated patients were not significant. No changes in mean anal resting pressure and maximal voluntary contraction were observed in the control group. We did not observe any systemic side effect in patients treated with nifedipine. After the blinding was removed, recurrence of the fissure was observed in 3 of 52 patients in the nifedipine group within 1 year of treatment, and 2 of these patients healed with an additional course of topical nifedipine and lidocaine ointment.\n Our study clearly demonstrates that the therapeutic use of topical nifedipine and lidocaine ointment should be extended to the conservative treatment of chronic anal fissure.", "A randomized clinical trial assessed the value of regular anal dilatation in combination with a topical local anaesthetic in the treatment of 82 patients with a posterior fissure-in-ano. One month after treatment the fissure had healed in 43.6 per cent of patients using 2 per cent lignocaine gel alone and in 41.9 per cent of patients who also used a St Mark's Hospital anal dilator. Thus the regular use of such a dilator did not contribute to the success of conservative therapy in patients with a posterior anal fissure. A review of patients who presented with anterior or lateral anal fissures during the trial period revealed that healing was achieved in 73.3 per cent of patients without operation within 1 month of diagnosis.", "To compare outcomes 24 months after treatment of chronic anal fissure with 0.2% glyceryl trinitrate ointment (GTN) or lateral internal sphincterotomy.\n Prospective, randomised trial.\n One teaching, one private, and 3 district hospitals, U.K.\n Seventy patients were randomised into two groups of 35 each to use 0.2% GTN ointment or have a lateral internal sphincterotomy.\n Resolution of symptoms and healing of fissures assessed after 24 months.\n All those operated on were initially cured but one fissure recurred after 8 months. Nineteen of 35 fissures treated with GTN healed. The remaining 16 patients randomised to use GTN ointment whose fissures did not heal were then treated by sphincterotomy. Three patients whose fissures healed successfully with GTN developed recurrences within 6 months of completing treatment. The remaining 16 of 19 patients treated with GTN whose fissures healed were free of symptoms with no clinical evidence of recurrence after 24 months follow-up.\n Many anal fissures heal with topical treatment with GTN. Lateral internal sphincterotomy remains effective but should be reserved for patients who fail to respond to initial chemical sphincterotomy.", "Botulinum toxin induces healing in patients with idiopathic anal fissure.\n Fifty patients affected by posterior anal fissure were treated with 20 units of botulinum toxin, injection in the internal anal sphincter on each side of the posterior midline (group I) or on each side of the anterior midline (group II).\n At 2 months evaluation, a healing scar was observed in 15 patients of group I and in 22 patients of group II(P = 0.025). Resting anal pressure was significantly different from the baseline values at 1-month as well as at 2-month check-ups in both groups, but the values were significantly lower in patients of group II.\n The intersite comparison revealed that anterior injection of the internal anal sphincter resulted in improved lowering of resting anal pressure and produced an earlier healing scar.", "This study was designed to assess whether addition of glyceryl trinitrate to botulinum toxin improves the healing rate of glyceryl trinitrate-resistant fissures over that achieved with botulinum toxin alone.\n Patients were randomized between botulinum toxin plus glyceryl trinitrate (Group A) and botulinum toxin plus placebo paste (Group B). Patients were seen at baseline, four and eight weeks, and six months. The primary end point was fissure healing at eight weeks. Secondary end points were symptomatic relief, need for surgery, side effects, and reduction in maximum resting and squeeze pressures.\n Thirty patients were randomized. Two-thirds of patients had maximum anal resting pressures below or within the normal range at entry to the study. Healing rates in both treatment groups were disappointing. There was a nonsignificant trend to better outcomes in Group A compared with Group B in terms of fissure healing (47 vs. 27 percent), symptomatic improvement (87 vs. 67 percent), and resort to surgery (27 vs. 47 percent).\n There is some evidence to suggest that combining glyceryl trinitrate with botulinum toxin is superior to the use of botulinum toxin alone for glyceryl trinitrate-resistant anal fissure. The poor healing rate may reflect the fact that many of the patients did not have significant anal spasm at trial entry.", "Mean maximum anal resting pressure is directly related to the activity of the smooth muscles of the internal and external sphincters and has been found to be increased in the patients of anal fissure. It has been shown that blood flow at the posterior midline of anoderm is inversely related to the mean maximum anal resting pressure, and topical application of glyceryl trinitrate (GTN) ointments is a very successful treatment. This randomized study was designed to evaluate the relative value of a nitroglycerin patch applied at a distance from the fissure site in healing anal fissure compared to GTN ointment and compared to surgical treatment. Forty-two consecutive patients with chronic anal fissure of more than 4 months' duration were randomized into two equally sized groups: those in group A received 0.2% GTN ointment while those in group B received a 10-mg nitroglycerin patch for 8 weeks. Patients were also asked to rate their pain intensity on a scale of 0-10. Five patients were excluded for various reasons; results were analyzed for the remaining 37 patients (group A, n=18; group B, n=19). A control group C consisted of 12 patients who underwent surgical treatment. Fissures healed completely in 12 of 18 (66.7%) patients in group A, 12 of 19 (63.2%) in group B and 11/12 (91.7%) in group C. The healing rates in groups A and B did not differ significantly (P=0.7), nor was there a difference between these and surgical group C (P=0.13). The local application of GTN ointment and the nitroglycerin patch are both effective, economical, and alternative treatment options for most patients with anal fissures.", "Nitric oxide is an important neurotransmitter mediating internal anal sphincter relaxation. Patients suffering from fissure-in-ano were treated with topical nitroglycerine. The clinical evidence for therapeutic adequacy was examined in a prospective, randomized study.\n The study included 35 patients with acute and chronic anal fissures. In Group A, including 20 patients with the clinical diagnosis of acute (12 patients) and chronic (8 patients) anal fissures, treatment consisted of topical nitroglycerine. Group B, consisting of 15 patients (10 acute and 5 chronic fissures), received topical anesthetic gel during therapy. Manometry was performed before and on days 14 and 28 in the course of topical application of either 0.2 percent glyceryl trinitrate ointment or anesthetic gel (lignocaine). Anal pressures were documented by recording the maximum resting and squeeze pressures.\n In 60 percent of cases treated with topical nitroglycerine (Group A, 11 acute (91.6 percent) and 1 chronic (12.5 percent)), anal fissure healed within 14 days, in contrast to Group B in which no healing was observed. The healing rate after one month was 80 percent (11 acute (91.6 percent); 5 chronic (62.5 percent)) in Group A and was significantly superior to Group B (healing rate, 40 percent: 5 acute (50 percent); 1 chronic (20 percent)).\n Previously increased maximum resting pressures decreased from a mean value of 110 to 87 cm H2O. This represents a mean reduction of 20 percent (P = 0.0022). We also noted a significant decrease in squeeze pressures (from 177.8 to 157.9 cm H2O (11 percent)). However, anal pressures did not decrease significantly in the four chronic fissure patients from Group A, whose fissures only healed after 28 days. Similarly to these Group A chronic fissure patients, no significant anal pressure reduction was observed in any Group B patients. Except for mild headache (20 percent), no side effects of treatment were reported.\n Topical application of nitroglycerine represents a new, easily handled, and effective alternative in the treatment of anal fissures. All of our patients reported a dramatic reduction in acute anal pain. However, it should be noted that a lack of sphincter tone reduction is a likely reason for the great tendency of chronic anal fissures to recur.", "Topical application of glyceryl trinitrate (GTN) ointment heals chronic anal fissures, providing an alternative to the traditional first line treatment of surgical sphincterotomy.\n To determine the most effective dose of topical GTN for treatment of chronic anal fissures and to assess long term results.\n Seventy consecutive patients with chronic anal fissure, were randomly allocated to eight weeks treatment with placebo, 0.2% GTN three times daily, or GTN starting at 0.2% with weekly 0.1% increments to a maximum of 0.6%, in a double blind study.\n After eight weeks fissure had healed in 67% of patients treated with GTN compared with 32% with placebo (p=0.008). No significant difference was seen between the two active treatments. Headaches were reported by 72% of patients on GTN compared with 27% on placebo (p<0.001). Maximum anal sphincter pressure reduced significantly from baseline by GTN treatment (p=0.02), but not placebo (p=0.8). Mean pain scores were lower after treatment with GTN compared with placebo (NS). Of fissures healed with placebo 43% recurred, compared with 33% of those healed with 0.2% GTN and 25% healed with escalating dose GTN (p=0.7).\n GTN is a good first line treatment for two thirds of patients with anal fissure. An escalating dose of GTN does not result in earlier healing. Significant recurrence of symptomatic fissures and a high incidence of headaches are limitations of the treatment.", "To assess the efficacy of isosorbide dinitrate in healing anal fissures.\n Randomised, prospective, double blind, placebo controlled trial.\n Teaching hospital, The Netherlands.\n 37 consecutive subjects with anal fissure diagnosed in the surgical outpatient department.\n After randomisation, 20 patients were given isosorbide dinitrate, and 17 patients placebo.\n Healing of anal fissure, recurrence, and tolerance.\n Both groups were treated for a median (range) of 5 weeks (range 1-10). After this period, 17 in the isosorbide group had healed compared with 6 controls (p < 0.003). The fissure recurred in 2 patients who had had an initial good response to isosorbide, and in 2 in the control group. Side effects (particularly headache) were more common after isosorbide dinitrate, but not significantly so (9/20 compared with 3/17).\n Isosorbide dinitrate is an effective treatment for anal fissure, and is significantly better than placebo.", "To assess the efficacy and patient compliance of topical mononitrate hydrogel for the treatment of anal fissure.\n Nineteen patients with symptomatic chronic anal fissures were randomly allocated to receive either active (10 patients) or placebo (nine patients) gel treatment. Rectal administration of hydrogel containing 0.2% isosorbide-5-mononitrate was prescribed. Patients were instructed on its application to the anal canal twice daily for 3 weeks. A questionnaire was used to determine patient compliance with therapy. Anal manometry was performed before and after therapy.\n At the end of therapy, the fissures were healed in 80% of actively treated patients compared with 22% of the control group. There was a mean reduction of 28% in mean resting anal pressure. Two actively treated patients (20%) suffered from mild headache relieved with oral analgesics and menthol lozenges. Faecal incontinence was not observed. There were no recurrences during at least 3 months of follow-up.\n Topical mononitrate gel therapy of anal fissures is an effective and safe approach. In this study, the few cases of headache were rapidly relieved with oral analgesia and menthol lozenges.", "Indoramin is an alpha1-adrenoceptor antagonist and has been shown to reduce anal resting pressure. Its therapeutic potential has not been explored. The aim of this study was to determine the outcome of treatment with oral indoramin on patients with chronic anal fissure in the setting of a double-blind randomized placebo-controlled trial.\n Twenty-three patients with chronic anal fissure were computer randomized to receive a 6-week course of oral indoramin (20 mg) or placebo in identical capsules, twice daily and with bulk-forming laxatives. Pain was assessed by a visual analogue scale from 0 to 10. Anal resting pressure, heart rate and blood pressure were recorded. Patients were reviewed 1 h after taking the capsule and at 2, 6 and 12 weeks thereafter.\n Fourteen patients were randomized to indoramin and 9 to placebo. Maximum anal resting pressure was reduced from a mean of 96.4 cm H2O (+/- 32) to 67.6 cm H2O (+/- 26), 1 h after indoramin (P=0.02) and there was no significant change after placebo. There were no significant changes in heart rate or blood pressure. Pain was reduced in the placebo group from a score of 4.9 to 2.0 after 6 weeks (P < 0.01) but not in the indoramin group. After 6 weeks, healing had occurred in one (7%) patient in the indoramin group and in 2 (22%) in the placebo group (P > 0.1). After 3 months, the chronic anal fissure in the indoramin group had recurred. The trial was terminated early because of poor healing rates.\n An oral dose of indoramin (20 mg) administered twice daily reduced anal resting pressure by 30% compared with pretreatment levels but was ineffective in healing chronic anal fissures.", "To evaluate the efficacy and safety of botulinum toxin A injection compared with topical nitroglycerin ointment for the treatment of chronic anal fissure (CAF).\n Fifty outpatients with CAF were randomized to receive either a single botulinum toxin injection (30 IU Botox) or topical nitroglycerin ointment 0.2% b.i.d. for 2 wk. If the initial therapy failed, patients were assigned to the other treatment group for a further 2 wk. If CAF still showed no healing at wk 4, patients received combination therapy of botulinum toxin and nitroglycerin for 4 additional wk. Persisting CAF at wk 8 was treated according to the investigator's decision. Healing rates, symptoms, and side effects of the therapy were recorded at wk 2, 4, 8, 12, and 24 after randomization.\n The group initially treated with nitroglycerin showed a higher healing rate of CAF (13 of 25, 52%) as compared with the botulinum toxin group (6 of 25, 24%) after the first 2 wk of therapy (p < 0.05). At the end of wk 4, CAF healed in three additional patients, all receiving nitroglycerin after initial botulinum toxin injection. Mild side effects occurred in 13 of 50 (26%) patients, all except one were on nitroglycerin.\n Nitroglycerin ointment was superior to the more expensive and invasive botulinum toxin injection for initial healing of CAF, but was associated with more but mild side effects.", "0.2 per cent topical glyceryl trinitrate (GTN) ointment heals up to two-thirds of chronic anal fissures in adults although many patients experience troublesome headaches. This double blind randomised pilot study assessed the efficacy and side effects of 0.1 and 0.05 per cent GTN ointment in treatment of chronic anal fissures in children.\n 15 consecutive children with chronic anal fissures were randomised to receive either 0.05 or 0.1 per cent GTN ointment applied topically twice daily for eight weeks. Clinical review was undertaken at weeks 4 and 8 and questions relating to symptoms and the incidence of headache were asked.\n The median age of the 15 (8 male) patients was 6 years (range 3-13). There were 5 anterior and 10 posterior fissures. The median duration of symptoms was 9 (3-30) months. 13/15 (86.7%) patients were taking laxatives at the time of referral. Fissure healing was complete at 8 weeks in all seven patients who received 0.05% and in 5/8 (62.5%) patients using the 0.1% ointment (Fisher's exact test, not significant). One patient from each arm experienced headaches during the first week of the trial which resolved without treatment and did not affect compliance. There were no other side effects.\n Topical glyceryl trinitrate ointment is effective in healing chronic anal fissures in children. Healing rates and side effect profile are comparable when either 0.05 or 0.1 per cent ointment is used.", "The aim of this study was to determine the optimal dose and dosing interval of nitroglycerin ointment to heal chronic anal fissures.\n A randomized, double-blind study of intra-anally applied nitroglycerin ointment (Anogesic) was conducted in 17 centers in 304 patients with chronic anal fissures. The patients were randomly assigned to one of eight treatment regimens (0.0, 0.1, 0.2, 0.4 percent nitroglycerin ointment applied twice or three times per day), for up to eight weeks. A dose-measuring device standardized the delivery of 374 mg ointment. Healing of fissures (complete reepithelialization) was assessed by physical examination using an observer unaware of treatment allocation. The subjects assessed pain intensity daily by completing a diary containing a visual analog scale for average pain intensity for the day, the worst pain intensity for the day, and pain intensity at the last defecation.\n There were no significant differences in fissure healing among any of the treatment groups; all groups, including placebo had a healing rate of approximately 50 percent. This rate of placebo response was inexplicably higher than previously reported in the literature. Treatment with 0.4 percent (1.5 mg) nitroglycerin ointment was associated with a significant (P < 0.0002) decrease in average pain intensity compared with vehicle as assessed by patients with a visual analog scale. The decreases were observed by Day 4 of treatment. At 8 weeks the magnitude of the difference between 0.4 percent nitroglycerin and control was a 21 percent reduction in average pain. Treatment was well tolerated, with only 3.29 percent of patients discontinuing treatment because of headache. Headaches were the primary adverse event and were dose related.\n Nitroglycerin ointment did not alter healing but significantly and rapidly reduced the pain associated with chronic anal fissures.", "Chronic anal fissure is a tear in the lower half of the anal canal that is maintained by contraction of the internal anal sphincter. Sphincterotomy, the most widely used treatment, is a surgical procedure that permanently weakens the internal sphincter and may lead to anal deformity and incontinence.\n We conducted a double-blind, placebo-controlled study of botulinum toxin for the treatment of chronic anal fissure in 30 consecutive symptomatic adults. All the patients received two injections (total volume, 0.4 ml) into the internal anal sphincter; the treated group (15 patients) received 20 U of botulinum toxin A, and the control group (15 patients) received saline. Success was defined as healing of the fissure (formation of a scar), and symptomatic improvement was defined as the presence of a persistent fissure without symptoms.\n After two months, 11 patients in the treated group and 2 in the control group had healed fissures (P=0.003); 13 in the treated group and 4 in the control group had symptomatic relief (P=0.003). The maximal voluntary pressures were similar to those at base line in both groups, and the resting anal pressure was reduced by 25 percent in the treated group but not in the control group. Three patients in the control group later underwent sphincterotomy, and 10 received botulinum-toxin injections (20 U). Of the latter, seven had healed fissures after two months; the other three left the study and underwent surgery. Four patients in the treated group were later re-treated (with 25 U of botulinum toxin); all had healed fissures after two months. One patient in the control group had temporary flatus incontinence after treatment with botulinum toxin. No relapses occurred during an average of 16 months of follow-up.\n Local infiltration of botulinum toxin into the internal anal sphincter is an effective treatment of chronic anal fissure.", "Chronic anal fissure is a common benign disorder; for this condition, lateral internal sphincterotomy is the \"gold standard\" of treatment. Alternative medical treatments have not proven to be as effective as left lateral internal sphincterotomy.\n This randomized trial was designed to compare the use of 0.25% glyceryl trinitrate ointment and anal cryothermal dilators with the use of 0.4% glyceryl trinitrate ointment alone in the treatment of chronic anal fissures.\n Between 1 June 2006 and 31 December 2007, 60 consecutive patients who were suffering from chronic anal fissures were randomized into two groups. The patients in group A (n = 30) were treated with 0.25% glyceryl trinitrate ointment and anal cryothermal dilators twice daily, and those in group B (n = 30) were treated with 0.4% glyceryl trinitrate ointment alone twice daily. The treatment was administered to the patients in each group for 6 weeks, and all patients were examined 7 weeks after the start of the trial.\n Prior to treatment, the symptoms and the measurements of anal pressure were similar in both groups. At 7 weeks, the maximum resting pressure was significantly lower in group A (P < 0.05), in which 86.6% of the patients were asymptomatic in comparison with 73.3% of the patients in group B. After 1 year of follow-up, 25 patients (83.3%) in group A and 18 patients (60%) in group B presented no recurrence of symptoms (P < 0.05)\n Treatment of chronic anal fissures with 0.25% glyceryl trinitrate ointment and anal cryothermal dilators was more effective than the administration of 0.4% glyceryl trinitrate ointment alone.", "Topical nitroglycerin (GTN) is one of the medical treatments of choice in chronic anal fissure. The present prospective, randomized, clinical trial was conducted to study the symptomatic relief, healing, and changes in the maximum anal resting pressure (MARP) in patients with chronic anal fissure comparing topical GTN and lateral sphincterotomy.\n Forty consecutive patients with chronic anal fissure were randomized for treatment with either topical GTN or internal sphincterotomy (20 patients in each group). Anal manometry was done before treatment in all patients, and 1 h after application of GTN or sphincterotomy. Patients were followed at 2-weekly intervals for 6 weeks for symptomatic relief and healing.\n Both GTN and sphincterotomy brought about a highly significant, but comparable drop in the MARP after treatment (P < 0.0001 in both groups). Sphincterotomy relieved pain much earlier compared to GTN (70% vs 40% at 2 weeks, P = 0.0032); but after 4 weeks of treatment, pain relief in both groups was comparable. Healing in the sphincterotomy group was also earlier than with GTN (55% vs 0% at 2 weeks, P < 0.0001; and 85% vs 30% at 4 weeks, P < 0.0001); but after 6 weeks, healing in both groups was comparable. Sphincterotomy had a significant incidence of minor, short-term complications; it also required surgical expertise, theatre time, and day-care beds. Nitroglycerin is safe, with mild and tolerable side-effects of headache and local burning sensation.\n Topical GTN should be the initial treatment in chronic anal fissure. Lateral sphincterotomy should be reserved for patients with severe disabling pain (because pain relief is much faster), and for patients not responding to at least 4 weeks of GTN therapy.", "Chronic anal fissure is a lineal ulcer of the lower part of the anal canal. It is a painful condition characterized by postdefecational pain and bleeding. It is associated with internal anal sphincter spasm. The relief of internal anal sphincter spasm is the key for providing fissure healing. Gold standard in the treatment of chronic anal fissure is partial lateral internal anal sphincterotomy.\n Sixty patients with chronic anal fissure were randomly assigned into two groups treated either by surgical sphincterotomy or injections of botulinum toxin into internal anal sphincter. Manometric measurements were performed before and three months after treatment. Follow up period was six months. The aim of the study was to compare results between these two groups.\n Both methods efficiently reduced resting anal pressure and successfully healed chronic anal fissure.\n Surgical and biologic sphincterotomy are almost equally effective in the treatment of chronic anal fissure. Injecting botulinum toxin into internal anal sphincter is a safe, easy to apply and effective method in the management of anal fissure.", "The gold standard surgical treatment of chronic anal fissure is lateral internal sphincterotomy which lowers the resting anal pressure and effectively heals the majority of fissures. Local application of 0.2% glyceryl trinitrate ointment has been used as an agent for chemical sphincterotomy, causing temporary alleviation of sphincter spasm and allowing the fissure to heal without compromising the anal continence. The aim of the present study was to compare the results of surgical sphincterotomy with that of local 0.2% glyceryl trinitrate ointment in the treatment of chronic anal fissure. Seventy adult patients between the age of 18 and 50 years with chronic anal fissure were randomized in a prospective trial to receive either surgical sphincterotomy or 0.2% glyceryl trinitrate ointment locally. Patients were followed up at 2 weeks' interval for 10 weeks. Symptom relief, fissure healing and continence scores were the outcomes assessed. Six patients were excluded for protocol violations. Surgical sphincterotomy was significantly more effective in providing pain relief and was associated with significantly better fissure healing rates at 6 weeks and 10 weeks (both p < 0.001). There were substantial problems with compliance in ointment group related to slow healing and longer time needed for symptomatic relief. Minor incontinence was 6% in sphincterotomy group and none in ointment group (p > 0.05). Considering early symptomatic relief, rapid fissure healing and better patient compliance surgical sphincterotomy is the treatment of choice for chronic anal fissure.", "In recent years treatment of chronic anal fissure has shifted from surgical to medical. This study compared the ability of two non-surgical treatments-botulinum toxin injections and nitroglycerin ointment-to induce healing in patients with idiopathic anal fissure.\n One hundred adults were assigned randomly to receive treatment with either type A botulinum toxin (30 units Botox or 90 units Dysport) injected into the internal anal sphincter or 0.2 per cent nitroglycerin ointment applied three times daily for 8 weeks.\n After 2 months, the fissures were healed in 46 (92 per cent) of 50 patients in the botulinum toxin group and in 35 (70 per cent) of 50 in the nitroglycerin group (P=0.009). Three patients in the botulinum toxin group and 17 in the nitroglycerin group reported adverse effects (P<0.001). Those treated with botulinum toxin had mild incontinence to flatus that lasted 3 weeks after treatment but disappeared spontaneously, whereas nitroglycerin treatment was associated with transient, moderate-to-severe headaches. Nineteen patients who did not have a response to the assigned treatment crossed over to the other therapy.\n Although treatment with either topical nitroglycerin or botulinum toxin is effective as an alternative to surgery for patients with chronic anal fissure, botulinum toxin is the more effective option.\n Copyright (c) 2007 British Journal of Surgery Society Ltd.", "The effect of unprocessed bran in a dose of 5 g three times daily and a dose of 2.5 g three times daily for one year on the recurrence rate of anal fissures was studied in a double-blind, placebo-controlled trial in 90 patients with recently healed acute posterior anal fissures. Fifteen patients (16.6%) were withdrawn before the code was broken due to failure to follow the trial protocol for various reasons. Significantly fewer recurrences occurred in patients receiving bran 5 g three times daily (recurrence rate 16%, 95% confidence limits, 4.54 to 36.08) when compared with patients receiving bran 2.5 g three times daily (60%; 38.67 to 78.87) (P less than 0.01) and with patients receiving placebo three times daily (68%; 46.50 to 85.05) (P less than 0.01). No significant difference in recurrences was found between patients on bran 2.5 g and those on placebo.", "Topical glyceryl trinitrate (GTN) has gained popularity as a treatment for anal fissure in the West. In our country, lignocaine is still the current treatment for the entity. This study was done to compare the effect of GTN with lignocaine in terms of healing rate and recurrence in South Asian population.\n A prospective, double blinded, randomised controlled trial was conducted on 50 patients (both treatment arms included) of all ages and either gender with a clinical diagnosis of anal fissure. Group A was given 0.2% GTN ointment and Group B was given lignocaine ointment. Both subjective and objective signs of healing were assessed and adverse effects of the treatment were sought.\n Symptomatic relief was earlier with GTN as compared with lignocaine. Pain relief was steady and sustained in those treated with GTN but returned to pre-treatment status within 5 weeks in patients with lignocaine. After 8 weeks of treatment, 80% of patients in Group A showed clinical signs of healing compared to 32% in Group B (p=0.001). Headache was the main side effect of GTN. At 6-month follow-up, recurrence was seen in 3/8 patients in Group B compared to 8/20 in the GTN Group (p=1).\n Topical GTN has earlier and a higher rate of clinical healing of anal fissure with acceptable side effects. The recurrence rate is high and comparable to lignocaine ointment. It is a safe and an effective treatment of anal fissure in a South Asian population.", "The aim of this trial was to compare lateral internal sphincterotomy with local 0.2 percent isosorbide dinitrate in the treatment of chronic anal fissure to minimize surgical complications such as minor fecal incontinence.\n Fifty-four patients with chronic anal fissure were randomized in a prospective trial to either sphincterotomy or local 0.2 percent isosorbide dinitrate. All patients had anal function tests before and 5 weeks after treatment.\n In the ointment group, 18 patients (67 percent) healed at 5 weeks and 24 (89 percent) healed at 10 weeks of treatment. Maximum resting anal pressure was reduced 30 percent. Eight patients (30 percent) had minor side effects. In the surgical group, 26 patients (96 percent) healed at 5 weeks and 100 percent healed at 10 weeks after treatment, with 33 percent reduction in maximum resting anal pressure. Forty-four percent of patients had minor fecal incontinence, which remained in 15 percent after 24 months follow-up. No statistical difference in maximum resting anal pressure was found between groups ( P = 0.16), but the percentage of healing at 5 weeks was greater in the surgical group ( P < 0.001).\n Isosorbide dinitrate ointment must be considered as the first choice of treatment in patients with chronic anal fissure. Surgery should be indicated if chemical sphincterotomy fails.", "Although lateral internal sphincterotomy has been the gold standard of treatment for chronic anal fissure, the main concern remains its effects on anal continence. Intrasphincteric injection of botulinum toxin seems to be a reliable option providing temporary alleviation of sphincter spasm and allowing the fissure to heal. The aim of the present prospective controlled randomized study was to compare the outcome of lateral internal sphincterotomy and botulinum toxin injection treatments in patients with uncomplicated chronic anal fissure.\n Eighty consecutive patients with uncomplicated chronic anal fissure who had failed conservative treatment were randomized to receive either intrasphincteric injection of botulinum toxin (BT) or lateral internal sphincterotomy (LIS). Postoperative pain relief, healing of fissure, continence scores, and fissure relapse during 18 weeks of follow-up were the outcomes assessed.\n There was a statistically significantly higher healing in the LIS group than the BT group (p = 0.0086 and 95% CI = 7.38-45.69%). In addition, LIS was associated with a high rate of anal incontinence as compared to BT (p = 0.0338 and 95% CI = -1.64-27.53%). The recurrence rate in the BT group was significantly higher statistically than that in the LIS group (p = 0.0111 and 95% CI = 6.68-46.13%).\n Surgical internal sphincterotomy has a higher healing rate and a lower recurrence rate than intrasphincteric injection of botulinum toxin in the treatment of uncomplicated chronic anal fissure. Injection of botulinum toxin, however, is a simple noninvasive technique that avoids the greater risk of incontinence. It could be used as the first therapeutic approach in patients without clinical risk factors of recurrence.", "To determine the efficacy and safety of 'healer' cream as monotherapy in the treatment of acute and chronic anal fissure.\n A prospective, randomized, single blinded, comparative trial.\n Sixty patients suffering from anal fissure were included in the study. Patients were randomly divided into three groups: group A: treated with 'healer' local cream application 3 times daily; group B: treated with nitroglycerine 0.25% local cream 3 times daily; group C: treated with a lidocaine 2% cream applied locally 3 times daily. All the followings were followed up and compared between groups. (1) Visual pain analogue score after defecation; (2) severity of straining and discomfort during defecation; (3) frequency of ulcer healed at 30 days; (4) any side effects or complications.\n The pain scoring after defecation was significantly reduced in the three treatment groups. The group treated with 'healer' isosorbide-di-nitrate showed the greatest reduction of the visual pain analogue score median from 9 before treatment to 3 & 1 after 10 and 20 days respectively, while the median visual pain analogue score in group B treated with nitroglycerine cream was 9 reduced to 4 & 2 after 10 and 20 days respectively, and the median visual pain analogue score in lidocaine group only dropped from 9 to 6 and 4, respectively. The reduction of both pain scoring and defecation scoring with 'healer' was statistically significantly greater than the other two treatments by Kruskal-Wallis test, P<0.001. The number of patients experiencing complete relief and passing stools easily after 10 days was significantly higher in 'healer' group, by Pearson Chi square = 22.94, P<0.001. After 30 days, the fissures were healed in 18 (90%) of 20 patients in the 'healer' group and in 12 (60%) of 20 in the nitroglycerin group, while only 6 (30%) of patients treated with lidocaine cream had their fissures healed by the 30 days treatment. Chi square = 15 (P = 0.001).\n 'Healer' is a promising effective and safe line of treatment in acute and chronic anal fissure. The characteristic pharmacokinetics of isosorbide-di-nitrate leads to a better effect than nitroglycerin in healing (more prolonged action). Also the less fast absorption than nitroglycerin leading to a smoother dose concentration curve, may be the cause that headache is less frequent and less severe in 'healer' treatment versus nitroglycerin.", "Anal fissure is a common painful condition affecting the anal canal. The majority of acute fissures heal spontaneously. However, some of these acute fissures do not resolve but become chronic. Chronic anal fissures were traditionally treated by anal dilation or by lateral sphincterotomy. However, both of these surgical treatments may cause a degree of incontinence in up to 30% of patients. Several recent trials have shown that nitric oxide donors such as glyceryl trinitrate (GTN) can reduce sphincter pressure and heal up to 70% of chronic fissures.\n This study addressed the dose-response to three different concentrations of GTN ointment compared with placebo in a double blind randomised controlled trial.\n A double blind, multicentre, randomised controlled trial was set up to compare placebo ointment against three active treatment arms (0.1%, 0.2%, and 0.4% GTN ointment applied at a dose of 220 mg twice daily) in chronic anal fissures. The primary end point was complete healing of the fissure.\n Two hundred patients were recruited over an eight month period from 18 centres. After eight weeks of treatment the healing rate in the placebo group was 37.5% compared with 46.9% for 0.1%, 40.4% for 0.2%, and 54.1% for 0.4% GTN. None was significantly better than the placebo response. A secondary analysis excluded fissures without secondary criteria for chronicity. Healing rates were then found to be 24% in the placebo group compared with 50% in the 0.1% GTN group, 36% in the 0.2% group, and 57% in the 0.4% GTN group. These values were statistically significantly different for the placebo group compared with 0.1% GTN, 0.4% GTN, and for the GTN treated group as a whole.\n The results of this study have demonstrated the significant benefit of topical GTN when applied to patients suffering from chronic anal fissures but acute fissures showed a tendency to resolve spontaneously. The high proportion of fissures which healed in the placebo group suggests that the definition of \"chronicity\" needs to be reassessed. Further studies are required to confirm the optimal therapeutic strategy.", "The surgical approach in chronic anal fissures (CAF) may, occasionally result in anal incontinence. The aim of this investigation was to study feasibility, effectiveness, and safety of hydropneumatic anal dilation (HAD) in conservative treatment of CAF and to compare it with local nitroglycerin (GTN) treatment.\n Efficacy of HAD was evaluated in 109 patients (65 male, 44 female; mean age, 53.3 years), following anal dilation using Microvasive Rigiflex instrument (Otw 40 mm). Thereafter, 36 patients were randomly divided into two groups to undergo treatment with 0.25% GTN or HAD.\n Recovery rate with HAD was 79.8% after 10 days and 94.5% after 30 days. An immediate (within 24 hours) drop was observed in the level of pain; no significant complications or recurrence were reported within 2 years. Healing rate was 94.5% following HAD vs. 38.9% after GTN.\n HAD should be considered a new safe option in CAF treatment.", "Patients presenting with acute anal fissure were randomized into two treatment groups in a prospective clinical trial. Both groups received treatment for 3 weeks with a stool softener and lignocaine jelly. Those entered in group 1 (35 patients) were asked in addition to insert an anal dilator (no. 2) twice daily while those in group 2 (31 patients) applied the anaesthetic jelly without a dilator. At 6 weeks 11 (31.4 per cent) patients in group 1 and 12 (38.7 per cent) patients in group 2 had been referred for sphincterotomy owing to failure of the treatment. At 6 months this figure had risen to 14 (40 per cent) in group 1 and 15 (48.4 per cent) in group 2. This difference was not statistically significant, suggesting that the addition of a dilator to the conservative treatment regimen did not diminish the likelihood of surgery.", "Procedures involving the use of anal dilators or topical nitroderivatives for the treatment of anal fissure are efficacious, economic and safe. The aim of our study was to compare the efficacy of two conservative treatments - passive dilation with anal dilators or topical nitroderivatives - in reducing anal pressure and resolving anal fissures. A total of 40 patients with a clinical diagnosis of acute anal fissure in the absence of hypotonic anal sphincter, abscess or perianal fistula, haemorrhoidal thrombosis, chronic inflammatory bowel disease or lower gastrointestinal neoplasia were randomly assigned to treatment with dilators (20 patients) or topical nitroderivatives (20 patients). After 4 weeks of treatment, 90% of patients treated with dilators and only 45% treated with topical nitroderivatives showed complete resolution of their anal fissures and a reduction of sphincter hypertone. After 12 weeks, 2/18 patients successfully treated with dilators and 1/9 patients successfully treated with topical derivatives presented recurrence of the anal fissure. The use of anal dilators would appear to induce better resolution of acute anal fissures than topical nitroderivates, as confirmed by the low relapse rate at 12 weeks.", "Chemical sphincterotomy has proved effective in treating chronic anal fissure. Glyceryl trinitrate is the most widely used agent, and topical 0.2 percent glyceryl trinitrate ointment heals up to two thirds of chronic anal fissures. Unfortunately, however, many patients experience troublesome headaches as a side effect of this treatment. This study assessed the effectiveness of oral and topical diltiazem in healing chronic fissures.\n Fifty consecutive patients with chronic anal fissures were randomly assigned to receive oral (60 mg) or topical (2 percent gel) diltiazem twice daily for up to eight weeks. Anal manometry was performed before and after the first dose, and blood pressure was recorded at 15-minute intervals. Patients were reviewed fortnightly, pain was expressed with a visual linear analog scale, blood pressure was recorded, fissure healing was assessed, and side effects were noted.\n Twenty-four patients received oral diltiazem, and 26 received topical diltiazem. Mean (+/- standard error of the mean) maximum resting anal pressures fell by 15 and 23 percent from 95 +/- 4 to 81 +/- 4 and from 102 +/- 5 to 79 +/- 5 cm H2O in the two groups, respectively. There was no significant reduction in blood pressure during the study or at follow-up in either group. Fissure healing was complete in 9 patients (38 percent) receiving oral diltiazem and 15 (65 percent) on topical treatment by eight weeks. Oral diltiazem caused side effects in eight patients (rash, two; headaches, two; nausea or vomiting, three; reduced smell and taste, one), whereas no side effects were seen in those receiving topical therapy (P = 0.001).\n Oral and topical diltiazem heal chronic anal fissures. Topical diltiazem is more effective, achieving healing rates comparable to those reported with topical nitrates, with significantly fewer side effects.", "Anal fissure is a common disease. Treatment includes conservative measures or surgery. One of the treatment options is topical Nitroglycerin ointment.\n We present a prospective, randomized, double-blind study, encompassing 48 patients suffering from chronic anal fissure. The subjects were divided into three groups according to the dose of Nitroglycerin ointment received--group I--0% (placebo), group II--0.2% (0.75 mg) and group III--0.4% (1.5 mg). Demographic data, medical history and physical findings were recorded. Healing, pain relief and adverse events were evaluated during and after the treatment period.\n No significant difference (p<0.05) was found between the groups with respect to patient age, gender, past history, physical examination, amount of ointment used and adverse events. Thirty three of the 48 (69%) patients completed the study. No significant differences were found between the groups with respect to the reasons and rates of leaving the study (p=0.494). Fifteen patients failed to complete the study; eight patients (17%) due to headaches, one patient was operated upon and six patients left the study because of cooperation problems. No significant difference was found between the groups regarding healing (p=0.952) or pain relief (p=0.458-0.8 according to the type of pain checked).\n According to our study, there was no benefit regarding healing or pain relief, in treating patients suffering from an anal fissure with Nitroglycerin ointment in combination with stool softeners and sitz baths, compared to the same treatment without Nitroglycerin ointment.", "Chronic anal fissure is a significant cause of morbidity. Internal sphincterotomy has long been the operative treatment of choice. Concerns remain, however, on its effects on continence. Botulinum toxin has been used as an agent for chemical sphincterotomy, causing temporary alleviation of sphincter spasm and allowing the fissure to heal. The aim of the present study was to compare the results of sphincterotomy to botulinum toxin.\n The study was designed as a randomized controlled trial. All adult patients over the age of 18 with chronic idiopathic fissure in ano who had failed conservative treatment were included in the trial. Patients were randomized to receive either Botox or sphincterotomy. Pain, healing of fissure and continence scores were the outcomes assessed.\n A total of 38 patients were studied. Seventeen patients were randomized to receive Botox and 21, sphincterotomy. Patients in the Botox group were found to have significantly higher 2-week pain scores and reoperation rates, and poor healing. Continence scores were not significantly different in the two groups.\n Sphincterotomy gives better results than Botox in the treatment of fissure. Botox, however, is safe with no complications and no detriment to continence and could be used in certain situations.", "This was a multicenter, randomized, controlled trial to compare the effectiveness of topical nitroglycerin with internal sphincterotomy in the treatment of chronic anal fissure.\n Patients with symptomatic chronic anal fissures were randomly assigned to 0.25 percent nitroglycerin tid or internal sphincterotomy. Both groups received stool softeners and fiber supplements and were assessed at six weeks and six months.\n Ninety patients were accrued, but 8 were excluded from the analysis because they refused internal sphincterotomy after randomization (6), the fissure healed before surgery (1), or a fissure was not observed at surgery (1). There were 38 patients in the internal sphincterotomy group (22 males; mean age, 40.3 years) and 44 patients in the nitroglycerin group (15 males; mean age, 38.7 years). At six weeks 34 patients (89.5 percent) in the internal sphincterotomy group compared with 13 patients (29.5 percent) in the nitroglycerin group had complete healing of the fissure (P = 5x10(-8)). Five of the 13 patients in the nitroglycerin group relapsed, whereas none in the internal sphincterotomy group did. At six months fissures in 35 (92.1 percent) patients in the internal sphincterotomy group compared with 12 (27.2 percent) patients in the nitroglycerin group had healed (P = 3x10(-9)). One (2.6 percent) patient in the internal sphincterotomy group required further surgery for a superficial fistula compared with 20 (45.4 percent) patients in the nitroglycerin group who required an internal sphincterotomy (P = 9x10(-6)). Eleven (28.9 percent) patients in the internal sphincterotomy group developed side effects compared with 37 (84 percent) patients in the nitroglycerin group (P<0.0001). Nine (20.5 percent) patients discontinued the nitroglycerin because of headaches (8) or a severe syncopal attack (1).\n Internal sphincterotomy is superior to topical nitroglycerin 0.25 percent in the treatment of chronic anal fissure, with a high rate of healing, few side effects, and low risk of early incontinence. Thus, internal sphincterotomy remains the treatment of choice for chronic anal fissure.", "Anal fissure is a common problem affecting all age groups with an equal incidence in both sexes. Traditional surgical treatments, like manual anal dilatation or a sphincterotomy, effectively heal most fissures within a few weeks but such procedures may result in anal incontinence. In recent years, various medical therapies have been used for the treatment of chronic anal fissure without fear of incontinence.\n Ninety patients with a symptomatic anal fissure were randomly divided into three groups. Group I was treated with 2% diltiazem ointment, Group II was treated with 0.2% glyceryl trinitrate (GTN) ointment, and Group III was kept as the control group. The improvement in the signs and symptoms, the time taken for healing, and side effects were recorded in each group. The patients were followed up monthly and then every 3 months for any recurrence of fissure. Comparative evaluations of the three groups regarding an improvement in symptoms, progress in healing, appearance of side effects, and recurrence were made using the Tukey HSD test.\n Diltiazem ointment was found to be superior regarding pain relief, fewer side effects, and late recurrence as compared with GTN ointment.\n Diltiazem ointment (2%) and GTN ointment (0.2%) are both effective treatment modalities for chronic anal fissure, with diltiazem giving better patient outcome.", "This study was undertaken to compare local application of a glyceryl trinitrate ointment with lateral internal sphincterotomy for the treatment of chronic fissure-in-ano.\n A sample of 24 consecutive patients with chronic anal fissure was randomly allocated to treatment with sphincterotomy or local glyceryl trinitrate. Patients were followed-up for a median of 22 months.\n All 12 patients healed following sphincterotomy; 10 of 12 healed with local glyceryl trinitrate (P = 0.239). There were no recurrences or side-effects in either group.\n Local application of glyceryl trinitrate can avoid surgery in more than 80 percent of patients with chronic anal fissure.", "To determine the efficacy and safety of sitz baths in the management of acute anal fissures.\n Individual patients were randomized to either receive sitz baths or no sitz baths for 4 weeks in addition to oral psyllium husk. Patients were asked to soak their hips and buttocks in a tub containing plain lukewarm water for 10 min, once after defecation in the morning and again at bedtime. Each week, the patients were called to assess pain scores and healing of fissures, whereas the level of satisfaction was recorded at the end of 4 weeks. Main outcome measures were validated pain scores and levels of satisfaction.\n Fifty-eight subjects were recruited for this study. In all, 52 of them completed the trial (27 in the sitz bath group and 25 in the control group). Although the pain score was lesser in the sitz bath group than in the control group, it failed to reach statistical significance. There were no significant differences in fissure healing between the two groups over the 4-week study period. However, patients in the sitz bath group reported better satisfaction levels than the control group (P < 0.01). Although no serious adverse effects were observed, two patients from sitz bath group developed perianal skin rash.\n This study suggests that sitz baths improve patient satisfaction in acute anal fissures. However, the healing and overall pain relief was not significant enough to attract attention. It was also found to be associated with adverse effects in few patients.", "To determine the effectiveness and safety of topical glyceryl trinitrate (GTN) in the management of acute anal fissure in children.\n Individual children were randomised to receive GTN paste or placebo for six weeks in addition to oral senna and lactulose. Patients took laxatives alone for a further 10 weeks. Each week a research nurse telephoned families to assess pain scores and give advice. Main outcome measures were validated standardised pain scores and time to painless defaecation.\n Forty subjects were recruited from 46 eligible children; 31 children completed the trial (13 in the GTN group and 18 in the placebo group). No differences in the proportion of those achieving pain free defaecation with relation to time were seen between the two groups. Similarly, there were no significant differences in pain scores between the two groups over the 16 week study period. However, in both groups pain scores had decreased significantly. There were no differences in the incidence of rectal bleeding, faecal soiling, presence of visible fissure, skin tag, or faecal loading at outpatient review at the time of recruitment, or at 6 weeks and 16 weeks. No serious adverse effects were observed.\n This study suggests that 0.2% GTN paste is ineffective in the treatment of acute anal fissures in childhood. However the overall fissure healing rate is high (84%) with associated reduction in pain scores, suggesting that a nurse based treatment programme can achieve a high rate of fissure healing.", "Anal fissure in children usually is treated by sitz baths, stool softeners, and analgesic ointments. However, some cases are intractable to the treatment. In recent years, it has been reported that nitric oxide donors such as local glyceryl-trinitrate (GTN) ointment causes a reversible chemical sphincterotomy. Although the GTN ointment can be an alternative therapy for adult cases, it has not yet been studied in the children who suffer from anal fissure.\n Sixty-five children with anal fissure were divided randomly into 3 groups. Each group received double-blinded a topical ointment that contained either 0.2% GTN, 10% lidocaine, or placebo. These ointments were applied to the lowest part of the anal canal twice daily. Patients were periodically reviewed, and the study was ended after 8 weeks.\n Complete healing of the fissure occurred in 26 of 31 (83.9%) patients treated with GTN, 7 of 14 (50%) patients treated with lidocaine, and 6 of 17 (35.2%) treated with placebo. In 29 of 31 (93.5%) GTN-treated patients, a total relief of symptoms was observed, whereas this occurred in 7 of 14 (50%) treated with lidocaine and 6 of 11 (35.3%) in the placebo group. The differences between the study group and control groups were highly statistically significant (P < .001).\n The majority of children suffering from anal fissure will be cured and have relief of symptoms after topical application of GTN ointment to the anal canal.", "A randomized, double-blind, placebo-controlled trial was performed to test the effect of intra-anal glyceryl trinitrate ointment in patients with chronic anal fissures that would normally have been treated by sphincterotomy. Long-term follow-up was then performed to assess fissure healing.\n Patients with chronic anal fissures were randomly assigned to 0.2 percent topical glyceryl trinitrate ointment or placebo. Anal manometry was performed before treatment, one week later, and 48 hours after treatment ceased at four weeks. Fissure healing was assessed by an observer blinded to the treatment arm. Pain was recorded on a linear analog scale. At the completion of the trial, treatment was continued with glyceryl trinitrate until fissure healing was obtained or lateral sphincterotomy was performed if required for ongoing pain. A long-term follow-up assessment was made at a mean of 29 (range, 25-33) months.\n There was a significant reduction in anal resting pressure at Week 1 with glyceryl trinitrate (P = 0.001) but not placebo, and at Week 4 there was a significant reduction in pain score with glyceryl trinitrate (P = 0.001) and placebo (P = 0.01) and a significant reduction in fissure grade with glyceryl trinitrate (P = 0.0001) and placebo (P = 0.02). Forty-six percent of fissures healed with glyceryl trinitrate and 16 percent healed with placebo (P = 0.001). At long-term follow-up in 40 of 43 patients, 14 patients (35 percent) had undergone lateral sphincterotomy, and in the remainder who were treated with glyceryl trinitrate there was a significant reduction in pain score (P = 0.0002). Seventeen patients attended for repeat manometry and fissures were healed with glyceryl trinitrate in ten (59 percent) cases. High internal sphincter pressures persisted at long-term follow-up in patients successfully treated with glyceryl trinitrate, indicating that the sphincter is the cause rather than effect of anal fissure.\n Topical glyceryl trinitrate produces a successful internal sphincterotomy, which resulted in long-term healing of 59 percent of chronic anal fissures and significant improvement in pain. Internal sphincter spasm is the cause of chronic anal fissure.", "Anal fissure is most commonly treated surgically by internal anal sphincterotomy. However, there is some concern over the effects of this procedure on continence. Nitric oxide donors such as glyceryl trinitrate (GTN) have been shown to cause a reversible chemical sphincterotomy capable of healing fissures in a small series of cases. This study reports a prospective, randomised, double-blind, placebo-controlled trial to test the hypothesis that topical GTN is the best first-line treatment for chronic anal fissure.\n 80 consecutive patients were randomised to receive treatments with topical 0.2% GTN ointment or placebo. Maximum anal resting pressure (MARP) was measured with a constantly perfused side-hole catheter before and after the first application of trial ointment. Anodermal blood flow was measured during manometry by laser Doppler flowmetry. After initial treatments, patients were given a supply of ointment (either GTN or placebo) to be applied to the lower anal canal twice daily. Patients were reviewed 2-weekly. At the initial and follow up visits patients were asked to record pain experienced on defaecation on a linear analogue pain score. Endpoints were healing of the fissure or condition after 8 weeks of treatment.\n After 8 weeks, healing was observed in 26/38 (68%) patients treated with GTN and in 3/39 (8%) patients treated with placebo (p < 0.0001, chi 2 test). Linear analogue pain score fell significantly in both groups after 2 weeks of treatment. This fall was maintained in those treated with GTN but pain scores returned to pre-treatment values by 4 weeks on treatment with placebo. MARP fell significantly from a mean of 115.9 (SD 31.6) to 75.9 (30.1) cm H2O (p < 0.001, Student's paired t-test) in patients treated with GTN but no change was seen in MARP after placebo. Anodermal blood flow measured by laser Doppler flowmetry significantly increased after application of GTN ointment but was unaffected by placebo.\n Topical GTN provides rapid, sustained relief of pain in patients with anal fissure. Over two-thirds of patients treated in this way avoided surgery which would otherwise have been required for healing. Long-term follow up is needed to assess the risk of recurrent fissure in patients with GTN.", "The aim of this prospective randomized trial was to compare the effectiveness and morbidity of surgical versus chemical sphincterotomy in the treatment of chronic anal fissure after a 3-year follow-up.\n Eighty patients with chronic anal fissure were treated by whether open lateral internal sphincterotomy (group 1) or chemical sphincterotomy with 25 U botulinum toxin injected into the internal sphincter (group 2). Clinical and manometric results were analyzed.\n Overall healing was 92.5% in the open sphincterotomy group and 45% in the toxin botulinum group (P<.001). There is a group of patients with clinical (duration of disease >12 months and presence of a sentinel pile before treatment) and manometric factors (persistently elevated mean resting pressure, % of time presence of slow waves, and number of patients or the time presence ultra slow waves after treatment) associated with a higher recurrence of anal fissure. The final percentage of incontinence was 5% in the open sphincterotomy group and 0% in the botulinum toxin group (P>.05).\n We recommend surgical sphincterotomy as the first therapeutic approach in patients with clinical and manometric factors of recurrence. We prefer the use of botulinum toxin in patients older than 50 years or with risk factors for incontinence, despite the higher rate of recurrence, since it avoids the greater risk of incontinence in the surgical group.", "This study was designed to assess the safety and efficacy of 0.2 percent glyceryl trinitrate suppository form in the healing of chronic anal fissure.\n Thirty-four patients with symptomatic chronic anal fissures were assigned to 0.2 percent glyceryl trinitrate suppository (n = 21) or placebo (n = 13) in a double blind design. Patient's symptom scores were registered at first visit. A validated daily chart was given to assess their symptoms on a daily basis. Both groups received psyllium from the beginning of the study. They were assessed at two-week intervals for six weeks. Then, they started a washout period of one month and after that were crossed over for another six weeks. Chi-squared, t-tests, and analysis of variance were used for statistical analysis.\n Complete healing at six weeks was achieved in 12 of 21 patients (57 percent) in the glyceryl trinitrate group and 5 of 13 patients (38 percent) in the placebo (P < 0.05). The overall healing rates at the end of study were 15 of 21 (71 percent) vs. 11 of 13 (84 percent) in the glyceryl trinitrate and placebo groups, respectively (P > 0.05).\n Application of 0.2 percent glyceryl trinitrate suppository form represents a new, promising, and effective treatment for chronic anal fissure.", "As lateral sphincterotomy and anal dilatation causes complications, a reversible chemical sphincterotomy method has been recently proposed as an alternative treatment in patients with anal fissure. In this study, the effect of botulinum toxin causing temporary paralysis in internal anal sphincter was compared with that of lidocaine in patients with chronic anal fissure.\n A total of 62 outpatients were randomly assigned to receive botulinum toxin or lidocaine pomade. The patients were evaluated before and after two months of treatment with physical examination and anal manometry. Pain and nocturnal pain were scored.\n In an evaluation period of two months, in 24 of 34 patients of botulinum group (70.58%), and in six of 28 patients of lidocaine group (21.42%) showed complete epithelization (p = 0.006). All patients who had previously reported nocturnal pain became symptom free in botulinum group and in four patients of lidocaine group. Pain following defecation disappeared in 24 patients of botulinum group and in 20 patients of control group (p = 0.959). There was no adverse effect in both groups. While resting anal pressure and maximum voluntary pressure were significantly low in botulinum toxin group, both parameters did not change in lidocaine group.\n Botulinum toxin is a reliable and effective method for patients with chronic anal fissure. It can be applied easily without any anesthesia and instrumentation. It is cheaper in comparison with surgical methods and it can be a good alternative treatment in patients with risk of incontinence.", "Lateral internal sphincterotomy, the most common treatment for chronic anal fissure, may cause permanent injury to the anal sphincter, which can lead to fecal incontinence. We compared two nonsurgical treatments that avert the risk of fecal incontinence. We randomly assigned 50 adults with symptomatic chronic posterior anal fissures to receive treatment with either a total of 20 U of botulinum toxin injected into the internal anal sphincter on each side of the anterior midline or 0.2 percent nitroglycerin ointment applied twice daily for six weeks.\n After two months, the fissures were healed in 24 of the 25 patients (96 percent) in the botulinum-toxin group and in 15 of the 25 (60 percent) in the nitroglycerin group (P=0.005). No patient in either group had fecal incontinence. At some time during treatment, five patients in the nitroglycerin group had transient, moderate-to-severe headaches that were related to treatment. None of the patients in the botulinum-toxin group reported adverse effects. Ten patients who did not have a response to the assigned treatment - 1 in the botulinum-toxin group and 9 in the nitroglycerin group - crossed over to the other treatment; the fissures subsequently healed in all 10 patients. There were no relapses during an average of about 15 months of follow-up.\n Although treatment with either topical nitroglycerin or botulinum toxin is effective as an alternative to surgery for patients with chronic anal fissure, botulinum toxin is the more effective nonsurgical treatment.", "The aim of this study was to compare prospectively diltiazem with GTN ointment in the treatment of anal fissure.\n Of 43 outpatients with chronic anal fissure, 22 patients were randomized to topical diltiazem (2%) ointment and 21 patients to glyceryltrinitrate (GTN) (0.5%) ointment twice daily for 8 weeks. During the course of treatment each patient was seen three times. Side-effects and healing were recorded.\n Healing occurred in 19 of 22 patients treated with diltiazem and 18 of 21 patients were cured with GTN (P = 0.95). Those who were treated with nitroglycerin ointment developed headache and dizziness developed after GTN in 33.3% of cases while no patient had any side-effects after diltiazem.\n Diltiazem and glyceryltrinitrate (GTN) were equally effective in healing anal fissure but the former resulted in fewer side-effects.", "The aim of this study was to compare the efficacy of the local application of 0.5% nifedipine ointment vs. lateral internal sphincterotomy in the healing of chronic anal fissure.\n Sixty-four patients with symptomatic chronic anal fissures were randomly assigned to 0.5% nifedipine ointment (n=32) every 8 h for 8 weeks or lateral internal sphincterotomy (n=32). Both groups received stool softeners and fiber supplements and were assessed at 2, 4, 6, and 8 weeks. Long-term outcomes were determined after a median follow-up of 19 months (nifedipine group) and 20.5 months (lateral internal sphincterotomy group).\n Complete healing at 8 weeks was achieved in 30 out of 31 patients (96.7%) in the nifedipine group and 32 out of 32 patients (100%) in the lateral internal sphincterotomy group (p=0.49). The overall healing rates at the end of follow-up were 28 out of 30 (93%) vs. 32 out of 32 (100%) in the nifedipine and sphincterotomy groups respectively (p=0.48). Two of the 30 patients in the nifedipine group relapsed whereas none in the sphincterotomy group did. Sixteen patients (50%) developed side effects in the nifedipine group, compared with six patients (18.7%) in the sphincterotomy group.\n Topical application of 0.5% nifedipine ointment represents a new, promising, easily handled, effective alternative to lateral internal sphincterotomy.", "Botulinum toxin induces healing in patients with idiopathic anal fissures.\n One hundred-fifty patients with posterior anal fissures were treated with botulinum toxin injected in the internal anal sphincter on each side of the anterior midline. Subjects were randomized into 2 treatment groups based on the number of units of botulinum toxin injected. Patients in group I were treated with 20 units of botulinum toxin and, if the fissure persisted, were retreated with 30 units. Patients in group II were treated with 30 units and retreated with 50 units, if the fissure persisted.\n The 2 groups were comparable in age, gender distribution, duration of symptoms, resting pressure, and maximum voluntary pressure at anorectal manometry. One month after the injection, examinations revealed complete healing in 55 patients (73%) from group I and 65 patients (87%) from group II (P =.04). Five patients from group II reported a mild incontinence of flatus that lasted 2 weeks after the treatment and disappeared spontaneously. The values of the resting anal pressure (P=.3) and the maximum voluntary pressure (P =.2) did not differ between the 2 groups. At 2 months' evaluation, a healing scar was found in 67 patients (89%) from group I and 72 patients (96%) from group II. A relapse of the fissure was observed in 6 patients (8%) from group I who had a healing scar at 1 month, and 2 other patients never healed. A persistent fissure was present in 3 patients from group II who had no other symptoms.\n Botulinum toxin injected into the internal anal sphincter is effective in managing anal fissures and avoiding permanent complications. All patients were treated with the active drug and healed after 1 or 2 successive treatments. The results also confirm that higher doses account for a higher success rate, with little increase in complications or side effects, which is probably related to the diffusion of the toxin to the external sphincter.", "Topical nitroglycerin has been widely used as a means for avoiding surgery in patients with anal fissure. However, nitroglycerin has not been universally accepted for this application because of inconsistency of efficacy and side effects. This study compares conventional digital application with precise intra-anal dosing of nitroglycerin using a specialized dose-delivery device and anal cannula.\n Twenty-six consecutive patients (13 males) with chronic anal fissure and no previous treatment were randomly allocated to receive 0.75 ml of 0.3 percent nitroglycerin ointment (2.25 mg nitroglycerin) t.i.d. intra-anal using the cannula (Group A) or perianally with the gloved finger (Group B). Nitroglycerin dosage was controlled in Group A by the dose-delivery device connected to the cannula and by single-dose preloaded syringes in Group B.\n Anal manometry: pressure reduction after application of nitroglycerin was 47 +/- 18.6 in Group A and 20.7 +/- 13.4 percent in Group B (P < 0.01). Headaches were reported by 1 of 10 patients in Group A and 10 of 12 patients in Group B (P = 0.0027). Seven patients of Group B had to be crossed to intra-anal treatment as a result of intensity of headaches. Pain relief was noted by 8 of 10 and 9 of 12 patients in Groups A and B, respectively (P = 0.6). Sphincterotomy was required in only 13.6 percent of all patients.\n Controlled intra-anal dosing of topical nitroglycerin produces a significantly greater reduction in sphincteric pressure and lower incidence of headaches than with perianal administration of the same dose of ointment. These results suggest a new paradigm for increasing safety and efficacy of dose-dependent prescription anal topical medications.", "Anal fissures are associated with hypertonia of the internal anal sphincter and pain. We evaluated the efficacy of local application of a combination of minoxidil and lignocaine in healing anal fissures.\n In this prospective, randomized, double-blind study, 90 patients with anal fissure were recruited. Patients received local applications of ointments containing 5% lignocaine (n=28), 0.5% minoxidil (n=36), or both (n=26). Healing of anal fissure at 6 weeks was used as the primary end-point.\n Rates of complete healing of fissure were similar in the three groups (lignocaine alone 8/27, minoxidil alone 10/34, combination 7/22; p=ns). Mean (SD) time taken for complete healing with combination treatment [1.9 (0.6) weeks] was significantly shorter than that with minoxidil alone (3.1 [1.7] weeks; p=0.001) or with lignocaine alone (3.3 [0.8] weeks; p=0.002). Rates of pain relief were similar in the three groups. Stoppage of bleeding occurred more often with combination treatment than with lignocaine alone. No patient had systemic or local side effects.\n Combination treatment with minoxidil and lignocaine helps in faster healing of anal fissures and provides better symptomatic relief than either drug alone.", "To compare a systemic transdermal therapeutic system with local application of glyceryl trinitrate ointment in the treatment of anal fissure.\n Prospective, multicentre, randomised trial.\n Three teaching hospitals, Turkey.\n 89 outpatients with chronic anal fissure were randomly assigned to be treated with either transdermal (n = 52) or 0.2% glyceryl trinitrate ointment (n = 37).\n The patients were assessed at the sixth and the twelfth week after initial evaluation by physical examination, anoscopy, and anal manometry.\n Changes in the maximal anal resting pressure, healing rate.\n Anal fissure was completely healed in 38 (73%) and 24 (64%) of the patients after 6 weeks and 48 (81%) and 27 (79%) of the patients in transdermal group and ointment group, respectively. Maximal anal resting pressure was reduced by 24% and 21% in transdermal and ointment groups, respectively.\n Systemic transdermal application of glyceryl trinitrate gave a satisfactory healing rate, which was comparable to that of local application of ointment.", "The conventional treatment of chronic anal fissure is lateral sphincterotomy (LAS). The alternative options of tailored sphincterotomy (TS) and 'chemical sphincterotomy' using medication such as nifedipine have recently become available.\n A prospective randomized trial was conducted to compare LAS with TS and oral nifedipine. The main endpoints were fissure healing, symptom relief, recurrence and continence.\n One hundred and thirty-two patients were treated and followed up for 4 months. LAS was significantly more effective than TS in providing pain relief (P = 0.004) and better patient satisfaction (P = 0.020) at 4 weeks. Surgery (LAS and TS) was associated with significantly better fissure healing rates (both P < 0.001 at 16 weeks) and less recurrence (both P = 0.003) than nifedipine. There were substantial problems with compliance in the nifedipine group (17 of 41 patients), related to side-effects and slow healing. There were no differences in continence between the three treatment groups.\n LAS was most effective in providing pain relief and allowing rapid fissure healing, with minimal recurrence and no increased risk of incontinence, in patients with good anal sphincter function.", "The present study aims to evaluate and compare the efficacy of two nitrate gels, containing isosorbide-5-mononitrate (ISMN) or glyceryl trinitrate (GTN), in the therapy of chronic anal fissure.\n The patients were randomly assigned to three groups: 0.1% ISMN gel (21 patients), 0.1% GTN gel (21 patients) and a placebo group (ten patients). The ethic committee of our hospital approved the protocol and informed consent was obtained from all participants. All patients underwent clinical examination, visual inspection of the fissure and anal manometry prior to and after therapy.\n The chronic anal fissure was completely healed in 71% of the patients treated with ISMN, 67% with GTN and in 30% from the placebo group. One patient in the ISMN group reported mild headache. Three patients in the GTN group had anal burning.\n Both topical nitrate treatments (ISMN and GTN) were effective for chronic anal fissures. The reduction of the anal pressure was slightly higher after ISMN treatment (28%) than the treatment with GTN (23%). However, the statistical difference was not significant (p>0.05).", "To compare symptomatic relief, healing, and changes in maximal anal resting pressure with the use of topical formulations in patients with chronic anal fissure.\n Sixty-four consecutive patients with chronic anal fissure were randomized into 4 groups that received, in a double-blind manner, a topical ointment that contained 0.2% nitroglycerine (GTN), 5% xylocaine, Proctosedyl (hydrocortisone acetate, heparin, framycetin sulfate, esculoside, ethoform, butoform) or petroleum jelly (Vaseline), to be applied twice daily. Patients were reviewed at 2-week intervals for 6 weeks. Anal manometry was done before, and 20 minutes after, the first application of the ointment.\n There was significant (p < 0.0001) reduction in mean anal resting pressure after application of GTN, but not any other ointment. Of 16 patients receiving GTN, complete pain relief occurred in 6 and 15 patients after 2 and 4 weeks of treatment, respectively; this was more frequent than in the other 3 groups. At 6 weeks also, complete pain relief occurred more often with GTN than with Vaseline or xylocaine. After 4 weeks of treatment, 3 patients on GTN had complete healing of fissure as compared to one each in the xylocaine and Proctosedyl groups and none in the Vaseline group. At 6 weeks, healing of fissure had occurred in 15 of 16 patients receiving GTN as compared to 4 receiving Vaseline, 11 receiving xylocaine, and 12 on Proctosedyl.\n Topical nitroglycerine produces 'chemical sphincterotomy' with reduction in mean anal resting pressure. Pain relief and healing of fissure occurred earlier with GTN than with other treatments. GTN should be considered as the treatment of choice for the non-surgical management of patients with chronic anal fissure.", "Botulinum toxin injection into the internal anal sphincter has been shown to be an effective treatment for chronic anal fissure. A randomized, prospective trial was conducted to compare botulinum toxin with lateral internal anal sphincterotomy as definitive management for chronic anal fissure.\n Patients diagnosed as having chronic anal fissure were randomly assigned to one of the two treatment arms. In the botulinum toxin group (n = 61), 20 to 30 U (approximately 0.3 U/kg) of type A botulinum toxin (Botox) was injected into the internal anal sphincter. The injection was repeated two months later if complete healing was not accomplished. Patients in the sphincterotomy group (n = 50) underwent lateral internal anal sphincterotomy. The same investigators evaluated the patients on postoperative/postinjection days 7 and 28, and then in a blinded manner at 2, 6, and 12 months.\n In the botulinum group, single injection resulted in complete healing in 45 of the 61 patients (73.8 percent) at the second month. Of the 16 failures, 6 patients refused further treatment, and 10 were treated with a second injection, which resulted in an overall healing rate of 86.9 percent (53/61) at 6 months. In the sphincterotomy group, the success rate was 82 percent (41/50) at day 28 and 98 percent (49/50) at the second month (P = 0.023 and P < 0.0001, respectively, compared with the botulinum group-single injection). At 6 months, 2 patients in the LIS group developed recurrences, and the healing rate was similar to that of the botulinum group (86.9 96.4 percent; P = 0.212). At 12 months, the success rate of the Botox group fell to 75.4 percent (46/61) with 7 recurrences, whereas it remained stable in the sphincterotomy group (94 percent, P = 0.008). Sphincterotomy was associated with a significantly higher complication rate (8 cases of anal incontinence none in the botulinum toxin group; P < 0.001). Full return to daily activities took significantly less time in the botulinum group (1 14.8 +/- 5.7 days; P < 0.0001).\n Although the healing rate of chronic anal fissure is considerably high with botulinum toxin injection with earlier recovery and less complications compared with sphincterotomy, it occasionally requires a repeat injection, and the healing is slower. The early (two months) and late (one year) healing rates are significantly higher in the sphincterotomy group, the two groups reaching similar healing rates only at six months." ]

[ "2665802" ]

[ "Ultrasound and pulsed electromagnetic energy treatment for perineal trauma. A randomized placebo-controlled trial." ]

[ "Ultrasound and pulsed electromagnetic energy therapies are increasingly used for perineal trauma sustained during childbirth. The study included 414 women with moderate or severe perineal trauma randomly allocated to receive active ultrasound, or active pulsed electromagnetic energy, or corresponding placebo therapies; the allocation was double-blind for each machine. Overall, more than 90% thought that treatment made their problem better. There were no clear differences between the groups in outcome either immediately after treatment, or 10 days or 3 months postpartum, other than more pain associated with pulsed electromagnetic energy treatment at 10 days. Bruising looked more extensive after ultrasound therapy but then seemed to resolve more quickly. Neither therapy had an effect on perineal oedema or haemorrhoids. The place of these new therapies in postnatal care should be clarified by further controlled trials before they become part of routine care." ]

[ "11306778" ]

[ "The effect of transdermal glyceryl trinitrate, a nitric oxide donor, on blood pressure and platelet function in acute stroke." ]

[ "Hypertension is a common medical complication in acute stroke and is associated with a poor outcome. However, no large trials have assessed the effect of lowering blood pressure (BP) on outcome, and it remains unclear how BP should be managed in acute stroke. We assessed, in a double-blind randomised controlled trial, whether the nitric oxide (NO) donor glyceryl trinitrate (GTN, a known systemic and cerebral vasodilator), would lower BP and alter platelet function.\n Thirty-seven patients with recent (< 5 days) ischaemic or haemorrhagic stroke were randomised by minimisation to 12 days of daily treatment with transdermal GTN or matching placebo patches. Twenty-four-hour ambulatory BP was measured before and during GTN treatment at days 0, 1 and 8. Platelet aggregation and expression of adhesion molecules were assessed at the same time points. Functional outcome (Rankin scale) and case fatality were assessed at 3 months. Analysis was by intention-to-treat.\n GTN significantly lowered BP by 13.0/5.2 mm Hg at day 1 and 9.3/5.0 mm Hg at day 8. The lesser reduction at day 8 than day 1 suggests that tolerance to GTN was developing. Non-significant falls of 0.9/0.6 and 3.8/0.0 mm Hg occurred at days 1 and 8, respectively, in the placebo group. GTN had no effect on heart rate, or platelet aggregation or expression of platelet adhesion molecules, including glycoproteins Ia, Ib, IIIa and P-selectin. Additionally, GTN did not alter case fatality or dependency, although the study was not powered for these outcomes.\n Transdermal GTN, an NO donor, lowered BP by 5-8%, a clinically significant and relevant, but not excessive, degree in patients with acute stroke. However, GTN had no effect on platelet aggregation or expression of adhesion molecules. Since NO donors increase cerebral blood flow in patients with acute ischaemic stroke, GTN may be an appropriate drug for testing the effect of lowering BP on functional outcome.\n Copyright 2001 S. Karger AG, Basel" ]

[ "3541427", "1836919", "1335647", "1665400", "7485697", "8817829", "2150529", "10418916", "3924520", "6242150", "8525690" ]

[ "Hepatitis B immunization of newborns according to a two dose protocol.", "Immune response to simultaneous administration of a recombinant DNA hepatitis B vaccine and multiple compulsory vaccines in infancy.", "Simultaneous vaccination against hepatitis A and B: results of a controlled study.", "Design and compliance of HBV vaccination trial on newborns to prevent hepatocellular carcinoma and 5-year results of its pilot study.", "Comparative study of the immunogenicity and safety of two dosing schedules of hepatitis B vaccine in neonates.", "Safety and immunogenicity of a recombinant hepatitis B vaccine administered to infants at 2, 4 and 6 months of age. The Kaiser-UCLA Vaccine Study Group.", "Immunogenicity of hepatitis B vaccine simultaneously administered with the expanded programme on immunisation (EPI).", "Long-term efficacy of plasma-derived hepatitis B vaccine: a 15-year follow-up study among Chinese children.", "Hepatitis B vaccine in neonates: induction of anti-HBs immune response and interruption of maternal HBsAg transmission.", "Immune response to hepatitis B vaccine in infants and newborns: control trial in an endemic area (Senegal).", "Newborn universal immunisation against hepatitis B: immunogenicity and reactogenicity of simultaneous administration of diphtheria/tetanus/pertussis (DTP) and oral polio vaccines with hepatitis B vaccine at 0, 2 and 6 months of age." ]

[ "Experimental hepatitis B immunization trial in newborns was carried out in Burundi. Newborns were randomly divided into vaccine and control groups. Vaccinated newborns were given two injections of hepatitis B vaccine: one at birth and another 2 months later. A booster dose was given at 12 months of age. Results obtained show that two months after the second dose of HB vaccine, 96.8% of the vaccinated babies had anti-HBs; at the age of one year this figure had fallen to 83.8%. Six months after the booster dose, 95.6% were anti-HBs positive, with a geometric mean titre of 214 mIU ml-1. The anti-HBs responses in these infants was compared to those observed in previous studies performed in Senegal in infants (same protocol) or in newborns (3 dose protocol). The anti-HBs responses were lower in terms of mean titre values in neonates who received the two dose protocol than in older children and in neonates who received three doses at one month intervals. Vaccine efficacy was monitored during a two year period in neonates both immunized and nonimmunized. Protective efficacy was found to be 100% if considering HBsAg positive events and 75% if considering all HBV events (HBsAg and/or anti-HBc positive).", "The reactogenicity and immunogenicity of simultaneous administration of recombinant DNA hepatitis B vaccine with diphtheria and tetanus toxoids (DT) and oral poliovirus vaccine (OPV) in 111 infants were compared with those of DT and OPV alone in a control group of 21 infants. All subjects received three doses of the vaccine according to one of three different schedules of vaccination. Reactions following simultaneous administration of vaccines were all but absent, with mild pain reported for four out of 111 subjects, compared with one of 21 in the control group. Seroconversion rates of 98-100% and high anti-HBs geometric mean titres (GMTs) were observed in all study groups after three doses of hepatitis B vaccine. Significantly higher anti-HBs were seen in Group III, where six months is allowed between the second and the third hepatitis B vaccine doses, compared with Group I and II, where only 1-2 months separate the second and third doses. A fourth dose of vaccine was needed in both these groups to obtain anti-HBs levels as high as seen in Group III after three vaccine doses at 3, 4 and 10 months of age. The immune response to DT and OPV was similar in the study groups and the control group. It is concluded that a course of 10 micrograms doses of recombinant hepatitis B vaccine given simultaneously with DT and OPV elicits a strong anti-HBs response and does not interfere with the immune response to the other antigens.", "Hepatitis A and hepatitis B are endemic in many countries and must be considered as serious health risks for large parts of the world population. Simultaneous or combined vaccination against these two diseases would therefore be most advantageous. In order to investigate possible interactions between these vaccines with respect to their tolerability and immunogenicity, we conducted a randomized prospective study comparing single and simultaneous administration of the two vaccines. Three groups of healthy volunteers, each with 55 persons, were included in the study. All were negative for hepatitis A and hepatitis B markers and had normal serum liver enzyme values. Group I received hepatitis A vaccine (720 ELISA units) into the left deltoid muscle, group II received hepatitis B vaccine (20 micrograms) into the right deltoid muscle and group III received hepatitis A vaccine into the left, and hepatitis B vaccine into the right deltoid muscle. Three doses of the vaccines were administered at 0, 1 and 6 months. Local and systemic reactions were monitored by means of questionnaires. Blood samples for determination of antibody to hepatitis A virus (anti-HAV) and antibody to hepatitis B surface antigen (anti-HBs) and of serum SGOT and SGPT levels were drawn at months 0, 1, 2, 6 and 7. There were no serious general and only mild local reactions. The mean serum SGOT and SGPT values remained in the normal range in all groups. The seroconversion rates and mean geometric titres of the anti-HAV and anti-HBs antibodies were similar when the vaccines were administered separately or simultaneously. There were no significant differences between the compared groups.(ABSTRACT TRUNCATED AT 250 WORDS)", "A large-scale, controlled study of universal immunization of newborns against HBV infection has been conducted in the high incidence area of hepatocellular carcinoma, Qidong County of China. This area has a stable population, standardized cancer registration system, and an epidemiological base for measurements of liver cancer prevention by vaccine. Randomization was done on the community level. The vaccination and the control group each will consist of 38,000 children by the end of 1990. It is anticipated that the design will provide high statistical power to detect 50% reduction in the prevalence rate of chronic hepatitis among the vaccinees vs. the controls at 6 to 10 years of age, and 50% reduction in the incidence rate of hepatocellular carcinoma at 35 to 40 years of age. The vaccine used is Hep-B Vax, donated by Merck and Co. through WHO. The vaccine was administered at 0, 1, and 6 months after birth, the dosage of 5 or 2.5 micrograms in the pilot study as used before 1985 and of 5 micrograms dose level during the main study starting from January 1, 1985. About 85% of the cohorts have now entered the protocol. The vaccination coverage during 1984 to 1989 was 98.0% (35,064/35,789). Follow-up of the vaccinees and the age-matched controls at 5 years has exceeded 97%. The cumulative mortality in the vaccinated group up to 1988 was 1.29% (354/27,450). No single death nor serious adverse reaction was found that was associated with vaccination. The use of HBV vaccine at a reduced dose was especially important for the developing countries at the present time in order to achieve widespread immunization. Five-year results of the pilot study of this vaccination project showed that significant protection against HBV infection was achieved with the 5 or 2.5 micrograms per dose regimen plus a booster of 5 micrograms given at 3.5 to 4 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)", "Healthy Egyptian neonates born to hepatitis B surface antigen (HBsAg)-seronegative mothers were randomly enrolled in one of three vaccination schedules. A dose of 2.5 micrograms of recombinant HB vaccine was given at birth, two, and six months of age (group A) or two, four, and nine months of age (group B). These two groups and a third control group (group C) also were given the other routine childhood vaccines (BCG, DPT, polio, and measles). Blood samples were taken one month after the third vaccine dose in groups A (seven months of age) and B (10 months of age), and a second follow-up blood sample was taken at the age of 18 months for all three groups. Sera were tested for HBsAg and antibody to hepatitis B core antigen, and quantitatively for antibody to hepatitis B surface antigen (anti-HBs) using commercial enzyme immunoassay kits. The vaccine was well tolerated and side effects were limited to local soreness, redness, or temporary swelling. Among 590 infants who were followed-up, good (51-300 mIU anti-HBs/ml) or excellent (> 300 mIU/ml) immune responses occurred in 85% of the infants in group A and in 96% in group B. Geometric mean titers of anti-HBs at the first and second follow-up were 306 and 55 mIU/ml in group A, and 1,492 and 147 mIU/ml in group B. The recombinant HB vaccine is safe and immunogenic when given in three doses of 2.5 micrograms in either regimen, but delay of the booster dose of the vaccine until nine months after birth produced a higher immune response.", "A recombinant hepatitis B vaccine was administered to over 5000 infants in a prospective, randomized and blinded study. Infants were given either recombinant hepatitis B vaccine (Engerix-B, SmithKline Beecham Pharmaceuticals, 10 micrograms dose-1) or a Haemophilus influenzae type b (Hib) conjugate vaccine at 2, 4 and 6 months of age simultaneously with diphtheria-tetanus-pertussis and oral polio vaccines. Adverse reactions were ascertained by parental reports and interviews, and review of medical records. Blood specimens collected from 269 infants given hepatitis B vaccine were assayed for antibody to hepatitis B surface antigen (anti-HBs) by enzyme immunoassay. Infants given hepatitis B vaccine experienced low rates of adverse reactions that were similar or lower than the rates in infants given Hib conjugate vaccine. The geometric mean anti-HBs concentrations were 9.6 mIU ml-1 after one dose, 333 mIU ml-1 after two doses and 1812 mIU ml-1 after three doses (99% had levels > or = 10 mIU ml-1). Antibody responses to diphtheria and tetanus toxoids were unaffected by simultaneous administration of hepatitis B or Hib conjugate vaccine. Engerix-B vaccine was safe and immunogenic when given with other routine childhood immunizations at 2, 4 and 6 months of age, and should provide long-term protection against hepatitis B virus infection.", "To assess the immunogenicity of hepatitis B vaccine simultaneously administered with the Expanded Programme on Immunisation (EPI) vaccines, a total of 300 consecutive infants, ranging in age between 6 weeks and 6 months, were alternatively assigned to the revised EPI and to EPI plus plasma-derived hepatitis B vaccine (Hevac B Pasteur). Four dosages (2 mcg or 0.5 ml each) of hepatitis B vaccine were given intramuscularly. HBsAg, anti-HBc, and anti-HBs were determined at day 0 and at day 210 in both groups by radioimmunoassay methods. The anti-HBs titre levels and geometric mean titres (GMTs) were determined at day 180 and day 210. There were three new hepatitis B virus infections in the control group and none in the study group by day 210. The seroconversion rates in the study group were 66% at day 180 and 84% at day 210, the respective GMTs being 116 and 940. Although the duration of observation is short (7 months) and the difference in the rate of infection between the two groups is not statistically significant (P greater than 0.05), the immunogenicity of the vaccine appears to be good. The simultaneous administration of hepatitis B vaccine and the EPI vaccines is logistically ideal. However, we suggest a further study using a larger dose of the Hevac B Pasteur vaccine to find out if a higher seroconversion rate than the 84% observed in this study could be achieved.", "To determine necessity and timing of booster of hepatitis B vaccine, we need to observe the duration of its protection. We report the results of a 15-year follow-up of a cohort of 649 children who participated a randomized, double blind, placebo-controlled trial on a plasma-derived hepatitis B vaccine in 1982. During the 15 years after vaccination, more vaccinated children had anti-HBs of 10 S/N ratios or over, compared with the controls, at all nine observations. At 15 years 50.0% (26/52) of the participants studied in the vaccinated group and 33.3% of the tested controls (18/54) retained anti-HBs levels of S/N ratios> or =10 (P < 0.09). However, since 5 years after vaccination, median S/N ratios of anti-HBs among the vaccinated children with detectable anti-HBs were lower than those of the controls except that detected at 15 years. 16.7% (9/54) of the tested children in the control group were HBsAg positive at 15 years after vaccination, in comparison with 1.9% (1/52) of the tested children in the vaccinated (P < 0.02). 28 chronic HBsAg carriers were identified in the control cohort over the 15 years, whereas only 1 case was noted in the vaccinated group (8.2% vs. 0.3%, P < 0.00001), corresponding to an efficacy of 96%.", "nan", "In 1978 it was suggested that hepatitis B (HB) vaccine should be used to prevent the early hepatitis B surface antigen (HBsAg) carrier state in children. Immunization was effected by 3 injections of HB vaccine at one-month intervals followed by a booster injection after one year. Children in a control group were immunized with DT-polio vaccine according to the same schedule. The anti-HBs response of the children to HB vaccination was studied in relation to their hepatitis B virus (HBV) serum markers prior to immunization. Of the seronegative children, 70.5% responded to immunization after 2 injections of 5- g doses of HB vaccine and 94% after the third injection. The efficacy of the vaccine was demonstrated by comparison of HB events after one year in 309 seronegative children immunized with HB vaccine and 252 seronegative children immunized with DT-polio vaccine, and after two years in 101 and 119 children, respectively. The incidence of the HBsAg carrier state was reduced by 80% in susceptible children. In order to eliminate the perinatal transmission occurring in newborns with HBsAg-positive mothers, a study of immunization at birth has been instituted. A total of 86 newborns responded to the vaccination as well as older children, irrespective of the HBV status of their mothers. After one year, the incidence of the HBsAg carrier state was reduced by 80%. In Africa, immunization teams have a limited amount of time to devote to each rural community. The immunogenic effect of 2 doses of HB vaccine given at an interval of 2 or 6 months has therefore been investigated. All were given a booster dose one year after the first injection of vaccine. No difference was observed in the seroconversion rate or in the anti-HBs titres as between the two protocols. These results demonstrate that 2 doses of 5 micrograms of HB vaccine are sufficient to obtain a high immunogenic effect in infants. In addition, an investigation was carried out on the immune response to HBsAg and tetanus toxoid antigen when administered simultaneously to children as HB vaccine and DT-polio vaccine. The immune response was at least equal to that observed after administration of these vaccines separately.", "The reactogenicity and immunogenicity of the administration of recombinant vaccine against hepatitis B simultaneously (but at separate sites) with diphtheria/tetanus/pertussis (DTP) and oral polio vaccines were examined. Six hundred and twenty-six children (group I) were given hepatitis B vaccine at 0, 2 and 6 months of age; the other vaccines were administered at 2, 4 and 6 months of age. A control group of 731 children (group II) received only DTP and oral polio vaccines. The results showed that 93% of the infants in group I had anti-HBs titres above the protective level ( > or = 10 mIU ml-1) after vaccination. There were no differences in the immune responses for DTP and polio between the two study groups. The vaccine efficacy against poliomyelitis was 96% for serotype I, 100% for serotype II and 97-98% for serotype III. Of the infants in both groups, 97% had antibodies against B. pertussis; all children were positive for tetanus and diphtheria. There were no differences in the incidences of general reactions between groups. Local swelling and redness were reported following 4.2 and 4.4%, respectively, of all injections of hepatitis B vaccine. These reactions were reported following 31 and 33%, respectively, of all doses of DTP vaccine. It can be concluded that the simultaneous administration of hepatitis B vaccine with the DTP and polio vaccines is well-tolerated; hepatitis B vaccine remained highly immunogenic and did not interfere with the immune response to the other antigens." ]

[ "9241305", "12080483", "15039411", "15039412", "15572496", "20159179", "16487195", "9422013", "16612101" ]

[ "Levonorgestrel-releasing intrauterine device versus hysteroscopic endometrial resection in the treatment of dysfunctional uterine bleeding.", "A randomized controlled trial of levonorgestrel releasing IUD and thermal balloon ablation in the treatment of menorrhagia.", "Effect of hysterectomy vs medical treatment on health-related quality of life and sexual functioning: the medicine or surgery (Ms) randomized trial.", "Clinical outcomes and costs with the levonorgestrel-releasing intrauterine system or hysterectomy for treatment of menorrhagia: randomized trial 5-year follow-up.", "Long-term treatment of menorrhagia with levonorgestrel intrauterine system versus endometrial resection.", "A randomized prospective trial comparing the levonorgestrel-releasing intrauterine system with thermal balloon ablation for the treatment of heavy menstrual bleeding.", "A randomised trial comparing the levonorgestrel intrauterine system and thermal balloon ablation for heavy menstrual bleeding.", "A randomised comparison of medical and hysteroscopic management in women consulting a gynaecologist for treatment of heavy menstrual loss.", "Health status function after treatment with thermal balloon endometrial ablation and levonorgestrel intrauterine system for idiopathic menorrhagia: a randomized study." ]

[ "To compare the effect of a levonorgestrel-releasing intrauterine device with that of endometrial resection on menstrual bleeding, patient satisfaction, and quality of life in menorrhagic women during 12 months of follow-up.\n Seventy premenopausal women with dysfunctional uterine bleeding were enrolled in a prospective, open, parallel-group, controlled trial. They were randomized to either insertion of an intrauterine system releasing 20 micrograms/day of levonorgestrel (n = 35) or endometrial resection (n = 35). The women were evaluated at baseline, and thereafter, uterine bleeding was assessed monthly with a pictorial blood loss assessment chart. Clinical gynecologic examination was performed bimonthly, and the hematologic variables were measured at 6 and 12 months. On the latter occasion, the women were requested to rate the degree of satisfaction with the effect of their treatment and to complete the Short Form 36 General Health Survey questionnaire.\n Recurrent menorrhagia was observed at 12 months in four women in the intrauterine device group (including two with partial expulsion of the device) and in three women in the resection group. Compared with baseline values, at 1 year, the pictorial blood loss assessment chart score was reduced by 79% in the former group and by 89% in the latter. Amenorrhea or hypomenorrhea at 12 months was reported by 65% of the women with an intrauterine device compared with 71% who underwent endometrial resection. The degree of satisfaction with treatment was high in both groups, with 29 of 34 (85%) women being satisfied or very satisfied in the intrauterine device group versus 33 of 35 (94%) in the resection group. Health-related quality of life perception was not significantly different in the two treatment groups.\n Somewhat less satisfactory results were obtained with a levonorgestrel-releasing intrauterine system compared with endometrial resection for dysfunctional uterine bleeding at 1 year of follow-up.", "Our aim was to compare the treatment of menorrhagia either with a levonorgestrel-releasing intrauterine device or with endometrial thermal balloon ablation. The primary endpoints of evaluation were menstrual blood flow reduction and the increase in hemoglobin values, while the secondary end points were adverse side effects; health related quality of life. After randomization, 36 women underwent outpatient thermal balloon ablation under local anesthesia and an intrauterine device releasing 20 microgram/day of levonorgestrel, were inserted within the first 7 days of menses to 36 women. Both techniques were found to be significantly effective in reducing the menstrual blood loss but in comparison thermal balloon ablation was more effective in Deltamean +/- SD decrease of pictorial sores (388.2 +/- 21 vs 343 +/- 27; p < 0.001). We noted a significant but similar increases in Deltamean +/- SD hemoglobin values (3.9 +/- 1.7 vs 3.7 +/- 1.4; p:.21). Patients treated by thermal balloon ablation reported fewer side effects and perceived a higher health related quality of life in physical role functioning. At one year of follow-up, the medicated device was effective but not as effective as thermal balloon ablation in reducing the menstrual blood loss. However it was found to be as effective as thermal balloon ablation in increasing the hemoglobin values. The side effect profile of the medicated device may alter its acceptability by reducing the perceived health related quality of life in menorrhagic women with no desire for further childbearing.", "Although a quarter of US women undergo elective hysterectomy before menopause, controlled trials that evaluate the benefits and harms are lacking.\n To compare the effect of hysterectomy vs expanded medical treatment on health-related quality of life.\n A multicenter, randomized controlled trial (August 1997-December 2000) of 63 premenopausal women, aged 30 to 50 years, with abnormal uterine bleeding for a median of 4 years who were dissatisfied with medical treatments, including medroxyprogesterone acetate. The participants, who were patients at gynecology clinics and affiliated practices of 4 US academic medical centers, were followed up for 2 years.\n Participants were randomly assigned to undergo hysterectomy or expanded medical treatment with estrogen and/or progesterone and/or a prostaglandin synthetase inhibitor. The hysterectomy route and medical regimen were determined by the participating gynecologist.\n The primary outcome was mental health measured by the Mental Component Summary (MCS) of the 36-Item Short-Form Health Survey (SF-36). Secondary outcomes included physical health measured by the Physical Component Summary (PCS), symptom resolution and satisfaction, body image, and sexual functioning, as well as other aspects of mental health and general health perceptions.\n At 6 months, women in the hysterectomy group had greater improvement in MCS scores than women in the medicine group (8 vs 2, P =.04). They also had greater improvement in symptom resolution (75 vs 29, P<.001), symptom satisfaction (44 vs 7, P<.001), interference with sex (41 vs 22, P =.003), sexual desire (21 vs 3, P =.01), health distress (33 vs 13, P =.009), sleep problems (13 vs 1, P =.03), overall health (12 vs 2, P =.006), and satisfaction with health (31 vs 14, P =.01). By the end of the study, 17 (53%) of the women in the medicine group had requested and received hysterectomy, and these women reported improvements in quality-of-life outcomes during the 2 years that were similar to those reported by women randomized to the hysterectomy group. Women who continued medical treatment also reported some improvements (P<.001 for within-group change in many outcomes), with the result that most differences between randomized groups at the end of the study were no longer statistically significant in the intention-to-treat analysis.\n Among women with abnormal uterine bleeding and dissatisfaction with medroxyprogesterone, hysterectomy was superior to expanded medical treatment for improving health-related quality-of-life after 6 months. With longer follow-up, half the women randomized to medicine elected to undergo hysterectomy, with similar and lasting quality-of-life improvements; those who continued medical treatment also reported some improvements.", "Because menorrhagia is often a reason for seeking medical attention, it is important to consider outcomes and costs associated with alternative treatment modalities. Both the levonorgestrel-releasing intrauterine system (LNG-IUS) and hysterectomy have proven effective for treatment of menorrhagia but there are no long-term comparative studies measuring cost and quality of life.\n To compare outcomes, quality-of-life issues, and costs of the LNG-IUS vs hysterectomy in the treatment of menorrhagia.\n Randomized controlled trial conducted between October 1, 1994, and October 6, 2002, and enrolling 236 women (mean [SD] age, 43 [3.4] years) referred to 5 university hospitals in Finland for complaints of menorrhagia.\n Participants were randomly assigned to treatment with the LNG-IUS (n = 119) or hysterectomy (n = 117) and were monitored for 5 years.\n Health-related quality of life (HRQL) as measured by the 5-Dimensional EuroQol and the RAND 36-Item Short-Form Health Survey, other measures of psychosocial well-being (anxiety, depression, and sexual function), and costs.\n After 5 years of follow-up, 232 women (99%) were analyzed for the primary outcomes. The 2 groups did not differ substantially in terms of HRQL or psychosocial well-being. Although 50 (42%) of the women assigned to the LNG-IUS group eventually underwent hysterectomy, the discounted direct and indirect costs in the LNG-IUS group (2817 dollars [95% confidence interval, 2222 dollars-3530 dollars] per participant) remained substantially lower than in the hysterectomy group (4660 dollars [95% confidence interval, 4014 dollars-5180 dollars]). Satisfaction with treatment was similar in both groups.\n By providing improvement in HRQL at relatively low cost, the LNG-IUS may offer a wider availability of choices for the patient and may decrease costs due to interventions involving surgery.", "The purpose of this study was to compare the long-term efficacy of the levonorgestrel intrauterine system and transcervical resection of the endometrium in the treatment of menorrhagia.\n This study was an open, randomized 3-year trial. Patients with menorrhagia were assigned randomly to either the levonorgestrel intrauterine system (n = 30) or endometrial resection (n = 29). Pictorial blood loss assessment charts were used to measure menstrual blood loss. A pictorial blood-loss assessment chart score exceeding 75 (representing menstrual blood loss >/=60 mL) was used to diagnosis the patient as having menorrhagia. Discontinuations and cases requiring repeat operations were evaluated.\n Pictorial blood loss scores decreased from a baseline median of 261.5 (range, 60-1503) to 7 (range, 0-101; P < .001) for the levonorgestrel intrauterine system and from 311 (range, 81-2506) to 4 (range, 0-182; P < .001) for transcervical resection of the endometrium. Nineteen women of 30 using the levonorgestrel intrauterine system completed the 3-year follow-up compared with 22 of 29 for transcervical resection of the endometrium.\n Both treatments efficiently reduced menstrual bleeding. The high continuation rate suggests that the levonorgestrel intrauterine system is comparable with transcervical resection of the endometrium.", "Use of the levonorgestrel-releasing intrauterine system (LNG-IUS) was compared with thermal balloon ablation (TBA) for the treatment of heavy menstrual bleeding (HMB).\n A prospective randomized trial comparing the LNG-IUS (n=30 women) and TBA (n=28 women).\n Hemoglobin levels increased (p<.001) and blood loss was reduced (p<.001) in both groups after 1 year of treatment. Menstrual bleeding was less in the LNG-IUS group compared to the TBA group at 6 and 12 months of treatment (p=.035 and p=.048, respectively). Intermenstrual bleeding was significantly less in the TBA group at 6 months compared to the LNG-IUS group (p=.044); however, there was no significant difference at 12 months (p=.129). No difference was found in psychological aspects between pre- and posttreatment variables in either of the groups (p=.537).\n Both the LNG-IUS and TBA appear to be effective in controlling HMB; however, posttreatment uterine bleeding patterns are different.\n Copyright (c) 2010 Elsevier Inc. All rights reserved.", "To compare the levonorgestrel intrauterine system (LNG-IUS) (Mirena); Schering Co., Turku, Finland) and thermal balloon ablation (Thermachoice; Gynecare Inc., Menlo Park, CA, USA) for the treatment of heavy menstrual bleeding.\n An open, pragmatic, prospective randomised trial.\n A menstrual disorders clinic at National Women's Hospital, Auckland, New Zealand.\n Seventy-nine women with heavy menstrual bleeding randomised to the LNG-IUS (40 women) or the thermal balloon ablation (39 women).\n Women were randomised to treatment with the LNG-IUS or thermal balloon ablation and followed up by a postal and telephone questionnaire.\n Menstrual loss measured by a pictorial bleeding assessment chart (PBAC) at 3, 6, 12 and 24 months. Patient satisfaction, quality of life and menstrual symptoms were assessed by questionnaire administered at 3, 6, 12 and 24 months. Treatment side effects and treatment failures were also recorded.\n Both the treatments resulted in a significant reduction in PBAC scores. At 12 and 24 months, median PBAC scores were significantly lower in women treated with the LNG-IUS compared with women treated by thermal balloon ablation (11.5 versus 60.0 at 12 months [P= 0.002]; 12.0 versus 56.5 [P= 0.002] at 24 months). At 24 months, nine (35%) women still using the LNG-IUS had amenorrhoea compared with one (5%) woman successfully treated by thermal balloon ablation (P = 0.025). There were no significant differences in patient satisfaction between two treatments during follow up. Treatment failed in 11 (28%) women using the LNG-IUS and in 10 (26%) women treated with thermal balloon ablation. Overall, women in both groups showed an increased quality of life as a result of the treatment, with Short Form-36 scores increasing from 63.7 at randomisation to 76.1 at 24 months.\n At 12 and 24 months of follow up, women with heavy menstrual bleeding treated with the LNG-IUS have significantly lower PBAC scores than women treated with thermal balloon ablation. Both the treatments resulted in a significant increase in overall quality of life, but there were no significant differences between either treatment in quality of life, patient satisfaction or the number of women requesting an alternative treatment during 24 months of follow up.", "To compare medical with hysteroscopic management in women referred to a gynaecologist complaining of heavy menstrual loss.\n Single-centre randomised trial.\n A teaching hospital in the United Kingdom.\n One hundred and ninety-seven women seeking specialist treatment of heavy menstrual loss for the first time and willing to accept either treatment.\n 1. Medical treatments not previously used by the women prescribed by experienced gynaecologists in standard doses and timings for a minimum of three cycles (n = 94), and 2. transcervical resection of the endometrium performed under general anaesthesia five weeks after goserelin preparation (n = 93).\n Treatment satisfaction and acceptability, relief of symptoms, change in haemoglobin, and improvement in health related quality of life, all after four months.\n Women allocated transcervical resection were more likely to be totally or generally satisfied (76% versus 27%, P < 0.001), to find the treatment acceptable (93% versus 36%, P < 0.001), and willing to have the treatment again (93% versus 31%, P < 0.001). Although pain and bleeding were significantly reduced by medical treatment this was modest in comparison with transcervical resection (P < 0.001). Haemoglobin levels were significantly increased only following transcervical resection. Short form 36 scores were also improved in both arms, although only transcervical resection returned them to normal values.\n Medical treatment was less effective than transcervical resection of the endometrium, irrespective of previous treatment or type of medical management. Early hysteroscopic endometrial surgery should be considered by such woman with the choice made by the woman after a full discussion of the advantages and disadvantages of all the options.", "To compare patients' health status function after treatment with thermal balloon endometrial ablation (TBEA) and levonorgestrel intrauterine system (LNG-IUS) for idiopathic menorrhagia.\n Forty-four patients were recruited into a randomized trial comparing their health status after treatment with TBEA or LNG-IUS for idiopathic menorrhagia.\n At 1 year follow-up, the mean haemoglobin was significantly higher in women treated with TBEA (12.6 g/dl vs. 10.3 g/dl, p = 0.018). Iron deficiency occurred in 13.3% from the TBEA arm and in 50% from the LNG-IUS arm (p = 0.026). The women's mean Short Form 36 Questionnaire general health perception scores (54.9 vs. 40.5, p = 0.024) and mental health scores (49.5 vs. 38.3, p = 0.021) in TBEA arm were significantly higher than in the LNG-IUS arm. The mental health domain score was also significantly lower in the LNG-IUS arm (46.1 vs. 38.3, p = 0.041).\n TBEA appears to offer better health status function at 1 year follow-up and to be more acceptable to our Chinese population in the treatment of idiopathic menorrhagia following failed medical treatment." ]

[ "12922085", "2316281", "16624457", "17297298", "10876850", "8994317", "1557929", "14615149", "17196713" ]

[ "Antigen dependent adverse reactions and seroconversion of a tick-borne encephalitis vaccine in children.", "A new vaccine against tick-borne encephalitis: initial trial in man including a dose-response study.", "Safety and immunogenicity of the modified adult tick-borne encephalitis vaccine FSME-IMMUN: results of two large phase 3 clinical studies.", "Tick-born encephalitis (TBE) vaccination in children: advantage of the rapid immunization schedule (i.e., days 0, 7, 21).", "[A cultured concentrated inactivated vaccine against tick-borne encephalitis studied during the immunization of children and adolescents].", "Tick-borne encephalitis: development of a paediatric vaccine. A controlled, randomized, double-blind and multicentre study.", "A randomized phase II study of a new tick-borne encephalitis vaccine using three different doses and two immunization regimens.", "Randomized, phase II dose-finding studies of a modified tick-borne encephalitis vaccine: evaluation of safety and immunogenicity.", "Tick-borne encephalitis (TBE) vaccination: applying the most suitable vaccination schedule." ]

[ "Two randomized, double blind dose comparison studies were conducted in 595 children in Austria and Germany with an albumin-free and thiomersal-free tick-borne encephalitis (TBE) vaccine. Vaccinated subjects of an age between 6 months and 12 years randomly assigned received either the full adult dose or half the adult dose. Results from vaccinated children under 1 year of age at the time of the first vaccination (159 subjects) showed an age dependent immune response. There were significantly fewer adverse systemic events (e.g. fever reactions). In children who received only half the adult dose, while seroconversion was not significantly different (93% versus 98%) after the second vaccination, and 100% for both groups after the third vaccination. Based on these results, it is recommended to vaccinate children between the ages of 1 and 12 years with half the adult dose.", "A new vaccine against tick-borne encephalitis was investigated in 56 healthy volunteers randomized for five different doses of antigen in a comparative group trial. Good tolerability and high immunogenicity were found using three different antibody test systems. The dose response study revealed that there was a strong relationship between the amount of antigen administered and the antibody response over the range of 0.03-3.0 micrograms antigen per dose.", "A prospective, randomised, multicentre, single-blind phase 3 study was performed to assess the safety of a vaccination schedule consisting of two vaccinations (21-35 days apart) with the tick-borne encephalitis (TBE) vaccine FSME-IMMUN \"adults\" (five consecutive lots) in comparison to another licensed TBE vaccine (Encepur), with polygeline) (two lots) in healthy volunteers (n=3966) aged 16-65 years. The safety of the third vaccination with FSME-IMMUN \"adults\" (6 months after the first vaccination) was investigated in a follow-up study on the same population (n=3705) and TBE antibody titres were analysed pre- and post-vaccination in a subgroup of volunteers (n=564). Following the first vaccination, the overall incidence of fever (> or =38.0 degrees C) was 0.8% in the FSME-IMMUN \"adults\" study group and 5.6% in the comparator study group; fever was mainly mild. The fever rate after the second vaccination was 0.6% and 0.5% in the two study groups, respectively. Local and systemic reactions after the first vaccination occurred with a lower frequency in the FSME-IMMUN \"adults\" study group than in the comparator group. Upon analysing the tolerability of the third vaccination with FSME-IMMUN \"adults\", similar results were determined in both study groups of volunteers previously vaccinated with FSME-IMMUN \"adults\" or with the comparator vaccine. The immunogenicity results demonstrated similar seroconversion rates (as determined by ELISA or neutralization test) before and after the third vaccination in the FSME-IMMUN \"adults\" group and in the comparator group respectively. The results of both studies demonstrate that: (1) FSME-IMMUN \"adults\" is safe and highly immunogenic, (2) all five production lots of FSME-IMMUN \"adults\" were consistent with respect to a low rate of adverse events, (3) FSME-IMMUN \"adults\" induces considerably lower adverse reaction rates than the comparator vaccine after the first vaccination, and (4) two vaccinations with the comparator vaccine can be successfully followed by a third vaccination with FSME-IMMUN \"adults\".", "Tick-borne encephalitis (TBE) is an important, vaccine-preventable arthropod-borne disease, causing severe illness in children too. In order to evaluate the immune response to different licensed primary immunization schedules, a total of 294 children aged 1 to 11 years of age were enrolled in a randomized, controlled, multi-center trial. The subjects were vaccinated with the pediatric formulation of a TBE vaccine (Encepur children) according to the conventional schedule (Group C; N = 73, vaccination on days 0, 28 and 300), the modified conventional schedule (Group M; N = 139, vaccination on days 0, 21 and 300), or the rapid schedule (Group R; N = 82, vaccination on Days 0, 7 and 21). Antibody titers as measured by neutralization-test (NT) and ELISA were determined on Days 0, 42, 180, 300, and 321. The demographic data of the study groups were similar. Most subjects (97%-100%) reached an NT titer of at least 1:10 on Day 42. On Day 42, the highest NT geometric mean titers (GMTs) were reached in Group C. In Group C and Group M, titers declined up to Day 300. Until Day 300, the highest NT-GMTs were maintained in Group R, notably without a decline compared to Day 42. Group M reached titers similar to Group R on Day 42, but these titers declined by 50% up to Day 180. Similar to the NT, on Day 42 highest geometric mean concentrations (GMCs) as measured by ELISA across all groups were reached in Group C. In all groups, titers declined until Day 300. On Day 300, GMC ELISA of Group R was higher compared to Group C and Group M. To conclude, the rapid immunization schedule in children not only provides fast protection but also leads to stable titers as measured by NT for at least 300 days after vaccination.", "The word deals with the results obtained in the study of the reactogenicity and immunological activity of concentrated and inactivated tissue-culture tick-borne encephalitis vaccine, manufactured by the Chumakov Institute of Poliomyelitis and Viral Encephalitides, in the immunization of children and adolescents. The vaccine proved to be moderately reactogenic and exhibited pronounced immunological activity. In 91.5% of the immunized children the fourfold increase of the antibody level was observed. On the basis of the data obtained in this study the tick-borne encephalitis vaccine was recommended for use in medical practice for the prophylaxis of tick-borne encephalitis among children and adolescents.", "A total of 522 children between 18 months and 14 years and 191 adults between 18 and 60 years were vaccinated with TBE-vaccine according to an abbreviated schedule (0, 7, 21). The aim of the study was to investigate whether reducing the amount of antigen in the vaccination for children would preserve an adequate immune response and decrease the rate of side-effects. Efficacy was determined on the extent to which children, vaccinated with the low doses (0.4 microgram or 0.75 microgram), reacted by developing antibodies in the same way as adults treated with the approved dose of 1.5 micrograms (equivalence of titres). The titres obtained in the children with the two lower doses were equivalent to those in the adults obtained with the standard dose. Titres decreased in the children with increasing age. Children older than 12 years in the approved dosage group had the same median titres as adults. The frequency of side-effects in the two lower dose groups, especially raised temperature, was markedly reduced. Whereas 30.1% of the children vaccinated with the approved dose had raised temperature higher than 38 degrees C only 18.8% and 18.4%, respectively, of the children vaccinated with the lower doses developed such temperatures. This improved tolerance in terms of raised temperature was also reflected in the other general reactions such as tiredness, joint pain or headache.", "A new, highly purified inactivated tick-borne encephalitis (TBE) vaccine (FSME-Vaccine Behring, BI 71.061) was recently registered in Germany. A multinational phase II study was performed in seven centres located in areas endemic for TBE. A total of 379 healthy adults were randomly allocated into three dosage groups (1.0, 1.5 and 2.0 micrograms antigen per dose, respectively) and into two immunization schedules [vaccination with one dose of 0.5 ml intramuscularly on days 0, 7 and 21 (abbreviated schedule), or on days 0, 28 and 300 (conventional schedule)]. Antibody response to vaccination was assayed by enzyme-linked immunosorbent assay (ELISA), haemagglutination inhibition test (HIT) and neutralization test (NT). Seroconversion rates in the different groups 28 days after one single dose were 75.3-83.5% in ELISA, 35.8-50.6% in HIT, and 100% in NT. All vaccinees showed seroconversion in all tests on day 42 in the conventional schedule and on day 35 in the abbreviated schedule, with the exception of one subject, who remained seronegative in HIT only. Geometric mean titres (GMT) of about 3000 in ELISA were achieved by two vaccinations in the conventional schedule and showed a booster increase to 5500-8000 GMT after revaccination on day 300. Overall frequency of adverse events (related and unrelated) was 37% (conventional schedule) and 46% (abbreviated schedule) after the first, 9% and 21% after the second, and 5% and 15% after the third vaccination, respectively. Generally, side effects were mild and transient, including mainly headache, fever, malaise and local irritation. Serious, vaccine-related side effects did not occur.(ABSTRACT TRUNCATED AT 250 WORDS)", "Two clinical studies were conducted to identify the optimal dose of a modified tick-borne encephalitis (TBE) vaccine (FSME-IMMUN \"new\") in adults. A prospective, randomised, phase II, double-blind dose-finding study with the FSME-IMMUN \"new\" vaccine was performed in volunteers aged 16-65 years (n=405) to evaluate the immunogenicity and safety of two vaccinations with three vaccine doses (0.6, 1.2 and 2.4microg antigen). The safety and immunogenicity of the third vaccination were investigated in a follow-up study on the same study population. Antibody response to vaccination was assessed by enzyme-linked immunosorbent assay (ELISA) and, after the third vaccination, by neutralisation test (NT). Seroconversion rates (ELISA) in the different dose groups (0.6, 1.2 and 2.4 microg) were 85.1, 96.2 and 97.0%, respectively, after the second vaccination, which 73% of the volunteers received only 21 days after the first vaccination. Seroconversion rates after the third vaccination were 96, 99.2 and 100% (ELISA) as well as 77, 93 and 96.6% (NT) with the 0.6, 1.2 and 2.4 microg doses, respectively. No unexpected AEs or vaccine-related serious adverse events (SAE) were observed during either study. Local and systemic reactions were mainly mild and not dose-dependent, with an overall fever rate of <1% after the first vaccination. The 2.4 microg dose is the optimal dose for the FSME-IMMUN \"new\" preparation in adults, as it was found to: (1) be non-inferior to the 1.2 microg dose with respect to fever rate after the first vaccination; (2) induce the highest seroconversion rate; and (3) be well-tolerated with respect to local and systemic reactions. The results of both studies demonstrate that the FSME-IMMUN \"new\" vaccine is safe and highly immunogenic in adults.", "Tick-borne encephalitis (TBE) is caused by an arthropod-borne virus, belonging to the family of Flaviviridae. In case of disease, which can lead to neurological sequelae or even fatal outcomes, only symptomatic treatment is available. TBE can be prevented by vaccination. Various primary immunization schedules have been developed. To identify the most suitable schedule, the present randomised, controlled study was designed to provide data on the immune response elicited by four different immunization schedules obtained by ELISA and by neutralization test (NT). A total of 398 healthy subjects aged > or =12 years were randomised to vaccination according to either the rapid schedule (Group R, vaccination on days 0, 7 and 21), the conventional schedule (Group C, vaccination on days 0, 28 and 300), the modified conventional schedule (Group M, vaccination on days 0, 21 and 300) or the accelerated conventional schedule (Group A, vaccination on days 0, 14 and 300). Within 3 weeks (i.e. by day 21) antibody levels were higher in Group R and Group A than in Group M and Group C. Group R and Group C both had higher titres on days 42, 180 and 300, than Group A and Group M. The rapid schedule thus combines the advantages of fast protection and of high titres over the observation period of 300 days." ]

[ "2879344", "6336824", "3891920", "3897808", "3520382", "3080173", "3320274", "2950392" ]

[ "[Double-blind treatment of 49 cases of chronic multiple sclerosis using hyperbaric oxygen].", "Hyperbaric-oxygen treatment of multiple sclerosis. A randomized, placebo-controlled, double-blind study.", "Hyperbaric oxygen in chronic progressive multiple sclerosis: visual evoked potentials and clinical effects.", "A double-blind trial of hyperbaric oxygen in the treatment of multiple sclerosis.", "Hyperbaric oxygen therapy in chronic stable multiple sclerosis: double-blind study.", "Hyperbaric oxygen in multiple sclerosis: a double blind trial.", "Hyperbaric oxygen and multiple sclerosis: final results of a placebo-controlled, double-blind trial.", "[Ineffectiveness of hyperbaric oxygen therapy in multiple sclerosis. A randomized placebo-controlled double-blind study]." ]

[ "Forty nine patients with a chronic form of multiple sclerosis (MS) [progressive or stable] were treated with hyperbaric oxygen (HO) in a double blind trial. Patients were divided in three groups: the first group (group I) received a course of 2.3 ATA HO with diazepam (5 mg); the second group (group II) received a course of 2 ATA HO; the third group (group III) was the control group. Each patient breathed an adapted gaseous mixture in high pressure. Each patient received 20 sessions of this procedure during 4 weeks. Patients were evaluated with clinical, neurophysiological and immunological parameters. Clinical examination consisted in the evaluation of the Kurtzke's Disability Status Scale (DSS) and Functional Status Scale (FSS). This evaluation was done in the week before the procedure, the week following the treatment, then in the third and sixth month. The neurophysiological study was a comparative analysis from the variations of visual, somesthesic and brain stem auditory potentials. The immunological study was the analysis of the lymphocyte populations (OKT4/OKT8 ratio). Each examination was carried out the week before, then the week following the procedure. We found no amelioration into three groups. Subjectively, some patients thought to be better, but this was true in the two treated groups (I, II) and in the control group (III). There was not an FSS significant variation. We also found no significant variation of evoked potentials and OKT4/OKT8 ratio. We observed some incidental effects of the treatment, particularly in group I, in which patients were treated with a higher pressure.(ABSTRACT TRUNCATED AT 250 WORDS)", "Several uncontrolled studies have suggested a beneficial effect of hyperbaric oxygen on multiple sclerosis. We studied 40 patients with advanced chronic multiple sclerosis who were randomly divided into two matching groups. The experimental group received pure oxygen, and the placebo group received a mixture of 10 per cent oxygen and 90 per cent nitrogen; both groups were treated at a pressure of 2 atmospheres absolute for 90 minutes once daily, for a total of 20 exposures. Objective improvement occurred in 12 of 17 patients treated with hyperbaric oxygen and in 1 of 20 patients treated with placebo (P less than 0.0001). Improvement was transient in seven of the patients treated with oxygen and long-lasting in five. Those with less severe forms of the disease had a more favorable and lasting response. At one year of follow-up, deterioration was noticed in 2 patients (12 per cent) in the oxygen group, neither of whom had had an initial response, and in 11 patients (55 per cent) in the placebo group, one of whom had had a positive initial response (P less than 0.0008). Minor ear problems and reversible myopia were the only side effects observed. These preliminary results suggest a positive, though transient, effect of hyperbaric oxygen on advanced multiple sclerosis, warranting further study. This therapy cannot be generally recommended without longer follow-up periods and additional confirmatory experience.", "The effects of hyperbaric oxygen at a pressure of two atmospheres absolute were studied in a group of patients with chronic progressive multiple sclerosis. A slight but statistically insignificant shortening of the visual evoked potential latencies was seen after treatment with hyperbaric oxygen as compared with placebo treatment. The treatment did not appreciably halt the progression of the disease and deferioration occurred more often among the patients in the treatment group than in the control group.", "A randomized double-blind trial of hyperbaric oxygen (2 atmospheres absolute for 20 sessions of 90 minutes, over a period of one month) demonstrated no advantage over a placebo gas mixture in the treatment of multiple sclerosis. Of 41 patients completing the trial, 21 had been treated with oxygen, eight of whom reported improvement (two confirmed objectively). Of 20 patients in the placebo group, seven claimed improvement (four confirmed objectively). Even when patients with mild disease were considered separately, or when functional systems were assessed individually, no benefit could be shown to result from hyperbaric oxygen therapy.", "We carried out a randomized, double-blind, placebo-controlled trial of hyperbaric oxygen therapy (HBO) in patients with chronic stable MS. Eighty-two patients were treated in a multiplace hyperbaric chamber with gas supplied by mask. Forty-one patients received 20 consecutive daily treatments of 100% O2 followed by 7 \"booster\" treatments in the next 6 months; 41 control patients received \"air\" (12.5% O2 at 1.75 atmospheres absolute). There was no significant difference in treatment and control groups in the Extended Kurtzke Disability scores, Kurtzke Functional scores, magnetic resonance imaging, or evoked potentials after the initial 20 treatments or after the boosters. HBO is not effective in treating chronic stable MS.", "Eighty four patients with multiple sclerosis were treated in monoplace chambers with either hyperbaric oxygen at 2 atmospheres absolute or placebo. Comprehensive double blind assessment was carried out before, immediately after, and one month after treatment. There was no clinically important or significant benefit in any of the four major criteria of outcome--namely, the patient's subjective opinion, the examiner's opinion, the score on the Kurtzke disability status scale, or the time taken to walk 50 m. Out of 40 other clinical variables assessed, two (the sensory scale and timed writing with the left hand) showed a significant improvement without any subjective clinical correlate or change in any of seven other tests of left hand function. No group of symptoms was perceived by the patients as having improved more after treatment with hyperbaric oxygen than placebo. It is concluded that there is no basis for recommending hyperbaric oxygen in the treatment of multiple sclerosis.", "The long term results are reported of a trial involving 120 patients with chronic multiple sclerosis who were randomised to receive either 100% oxygen at 2 atmospheres absolute (ATA) for 90 minutes daily for 20 sessions or placebo therapy with air using a simulated compression procedure. The previous finding of subjective improvement in bowel/bladder function at the end of treatment was not confirmed by objective urodynamic assessment. The treatment did not alter disease progression as measured by the Kurtzke disability status scale nor did it alter the rate of acute relapse. There was less deterioration in cerebellar function at one year in the treated patients as measured by the Kurtzke functional systems scale. No other differences were found between the two groups. Psychometric tests and measurements of lymphocyte sub-populations showed no treatment related effects. Evoked potential studies showed no improvements but there was a significant reduction in amplitude of the visual evoked potential in the treated patients at the end of therapy. This might indicate a reversible degree of retinal damage induced by oxygen toxicity.", "Seventeen patients with definite and progressive multiple sclerosis entered a double-blind randomized placebo-controlled therapeutic trial of hyperbaric oxygen (HBO). Exposure in monoplace chamber was 90 minutes long each time, 5 days a week, for 4 weeks. The treatment and placebo groups received 100% oxygen at 1.5 bar constant pressure or normal air at 0.1-0.2 bar, respectively. The clinical status of the patients in both groups were compared until one year after treatment. There was no benefit of HBO versus placebo according to the Kurtzke disability status scale. A lesser proportion of patients with deterioration of bowel/bladder function 12 months after therapy was the only benefit of HBO versus placebo according to Kurtzke functional systems scales. On the whole however, HBO is useless in the management of progressive forms of multiple sclerosis." ]

[ "20574649", "10075615", "9920948", "17158431", "18794178", "15001324", "18704426", "18635256", "11096165" ]

[ "Etanercept (ETN) with methotrexate (MTX) is better than ETN monotherapy in patients with active rheumatoid arthritis despite MTX therapy: a randomized trial.", "Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial.", "A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate.", "Randomized phase 2 trial of anti-tumor necrosis factor therapy for cachexia in patients with early rheumatoid arthritis.", "Efficacy, safety and patient-reported outcomes of combination etanercept and sulfasalazine versus etanercept alone in patients with rheumatoid arthritis: a double-blind randomised 2-year study.", "Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial.", "A comparison study of a recombinant tumor necrosis factor receptor:Fc fusion protein (rhTNFR:Fc) and methotrexate in treatment of patients with active rheumatoid arthritis in China.", "Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial.", "A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis." ]

[ "The superiority of the combination therapy of methotrexate (MTX) and anti-tumor necrosis factor (TNF) biological agents over anti-TNF monotherapy in MTX-naïve patients with rheumatoid arthritis (RA) has been demonstrated. We investigated the efficacy and safety of continuation versus discontinuation of MTX at the commencement of etanercept (ETN) in patients with active RA despite MTX therapy. In total, 151 patients with active RA despite treatment with MTX were randomized to either ETN 25 mg twice a week and MTX 6-8 mg/week (the E + M group) or ETN alone (the E group). Co-primary endpoints included the European League Against Rheumatism (EULAR) good response rate and the American College of Rheumatology (ACR) 50 response rate at week 24. Demographic and clinical features between groups at baseline were similar. The EULAR good response rates were significantly higher in the E + M group (52%) than in the E group (33%) at week 24 (p = 0.0001). Although the ACR50 response rate, one of the co-primary endpoints, and the ACR70 response rate at week 24 were not significantly greater in the E + M group (64 and 38%, respectively) than in the E group (48 and 26%, respectively), the ACR20 response rate was significantly greater in the E + M group (90%) than in the E group (64%; p = 0.0002). Safety profiles were similar for the groups. Thus, MTX should be continued at the commencement of ETN therapy, even in RA patients who show an inappropriate response to MTX.", "In a phase II study, etanercept (recombinant human tumor necrosis factor receptor [p75]:Fc fusion protein) safely produced rapid, dose-dependent improvement in rheumatoid arthritis over 3 months.\n To confirm the benefit of etanercept therapy of longer duration and simplified dosing in patients with rheumatoid arthritis.\n Randomized, double-blind, placebo-controlled trial with blinded joint assessors.\n 13 North American centers.\n 234 patients with active rheumatoid arthritis who had an inadequate response to disease-modifying antirheumatic drugs.\n Twice-weekly subcutaneous injections of etanercept, 10 or 25 mg, or placebo for 6 months.\n The primary end points were 20% and 50% improvement in disease activity according to American College of Rheumatology (ACR) responses at 3 and 6 months. Other end points were 70% ACR responses at 3 and 6 months and other measures of disease activity at 3 and 6 months.\n Etanercept significantly reduced disease activity in a dose-related fashion. At 3 months, 62% of the patients receiving 25 mg of etanercept and 23% of the placebo recipients achieved 20% ACR response (P < 0.001). At 6 months, 59% of the 25-mg group and 11% of the placebo group achieved a 20% ACR response (P < 0.001); 40% and 5%, respectively, achieved a 50% ACR response (P < 0.01). The respective mean percentage reduction in the number of tender and swollen joints at 6 months was 56% and 47% in the 25-mg group and 6% and -7% in the placebo group (P < 0.05). Significantly more etanercept recipients achieved a 70% ACR response, minimal disease status (0 to 5 affected joints), and improved quality of life. Etanercept was well tolerated, with no dose-limiting toxic effects.\n Etanercept can safely provide rapid, significant, and sustained benefit in patients with active rheumatoid arthritis.", "Patients treated with methotrexate for rheumatoid arthritis often improve but continue to have active disease. This study was undertaken to determine whether the addition of etanercept, a soluble tumor necrosis factor receptor (p75):Fc fusion protein (TNFR:Fc), to methotrexate therapy would provide additional benefit to patients who had persistent rheumatoid arthritis despite receiving methotrexate.\n In a 24-week, double-blind trial, we randomly assigned 89 patients with persistently active rheumatoid arthritis despite at least 6 months of methotrexate therapy at a stable dose of 15 to 25 mg per week (or as low as 10 mg per week for patients unable to tolerate higher doses) to receive either etanercept (25 mg) or placebo subcutaneously twice weekly while continuing to receive methotrexate. The primary measure of clinical response was the American College of Rheumatology criteria for a 20 percent improvement in measures of disease activity (ACR 20) at 24 weeks.\n The addition of etanercept to methotrexate therapy resulted in rapid and sustained improvement. At 24 weeks, 71 percent of the patients receiving etanercept plus methotrexate and 27 percent of those receiving placebo plus methotrexate met the ACR 20 criteria (P<0.001); 39 percent of the patients receiving etanercept plus methotrexate and 3 percent of those receiving placebo plus methotrexate met the ACR 50 criteria (for a 50 percent improvement) (P<0.001). Patients receiving etanercept plus methotrexate had significantly better outcomes according to all measures of disease activity. The only adverse events associated with etanercept were mild injection-site reactions, and no patient withdrew from the study because of adverse events associated with etanercept.\n In patients with persistently active rheumatoid arthritis, the combination of etanercept and methotrexate was safe and well tolerated and provided significantly greater clinical benefit than methotrexate alone.", "Tumor necrosis factor (TNF) is an important mediator of cachexia, and its blockade prevents catabolism in animal models. However, little evidence shows that anti-TNF therapy is effective in treating cachexia in humans.\n The main aim of this study was to investigate the effect of etanercept, a synthetic soluble TNF receptor, on body composition in patients with early rheumatoid arthritis (RA).\n Twenty-six patients were randomly assigned to 24 wk of treatment with etanercept or methotrexate; the latter is the first-line therapy for RA. Body composition, physical function, disease activity, systemic inflammation, and the circulating insulin-like growth factor (IGF) system were measured at baseline (week 0) and at follow-up (weeks 12 and 24). Twelve patients in each treatment group (9 F, 3 M) completed the study.\n Overall, no important changes in body composition were observed, despite a transient increase in IGF-I at week 12 (P < 0.01). However, the secondary analysis of those patients (6/treatment group) who gained weight during follow-up showed a significant effect of etanercept on the composition of the weight gained: 44% of weight gained in the etanercept group was fat-free mass, as compared with only 14% in the methotrexate group (P = 0.04). Etanercept and methotrexate were equally effective in controlling the disease and improving physical function.\n Anti-TNF therapy with etanercept is not superior to that with methotrexate for the treatment of rheumatoid cachexia over a period of 6 mo. However, TNF blockade seems to normalize the anabolic response to overfeeding and, if these findings are confirmed, may be useful in conditions characterized by anorexia and weight loss.", "To determine the efficacy and safety of etanercept and etanercept plus sulfasalazine versus sulfasalazine in patients with rheumatoid arthritis (RA) despite sulfasalazine therapy.\n Patients were randomly assigned to etanercept (25 mg twice weekly; sulfasalazine was discontinued at baseline), etanercept plus sulfasalazine (unchanged regimen of 2-3 g/day) or sulfasalazine in a double-blind, randomised, 2-year study in adult patients with active RA despite sulfasalazine therapy. Efficacy was assessed using the American College of Rheumatology criteria, disease activity scores (DAS) and patient-reported outcomes (PRO).\n Demographic variables and baseline disease characteristics were comparable among treatment groups; mean DAS 5.1, 5.2 and 5.1 for etanercept (n = 103), etanercept plus sulfasalazine (n = 101) and sulfasalazine (n = 50), respectively. Withdrawal due to lack of efficacy was highest with sulfasalazine (26 (52%) vs 6 (6%) for either etanercept group, p<0.001). Patients receiving etanercept or etanercept plus sulfasalazine had a more rapid initial response, which was sustained at 2 years, than those receiving sulfasalazine: mean DAS 2.8, 2.5 versus 4.5, respectively (p<0.05); ACR 20 response was achieved by 67%, 77% versus 34% of patients, respectively (p<0.01) Overall, PRO followed a similar pattern; a clinically significant improvement in health assessment questionnaire was achieved by 76%, 78% versus 40% of patients, respectively (p<0.01). Commonly reported adverse events occurring in the etanercept groups were injection site reactions and pharyngitis/laryngitis (p<0.01).\n Etanercept and etanercept plus sulfasalazine are efficacious for the long-term management of patients with RA. The addition of etanercept or substitution with etanercept should be considered as treatment options for patients not adequately responding to sulfasalazine.", "Etanercept and methotrexate are effective in the treatment of rheumatoid arthritis but no data exist on concurrent initiation or use of the combination compared with either drug alone. We aimed to assess combination treatment with etanercept and methotrexate versus the monotherapies in patients with rheumatoid arthritis.\n In a double-blind, randomised, clinical efficacy, safety, and radiographic study, 686 patients with active rheumatoid arthritis were randomly allocated to treatment with etanercept 25 mg (subcutaneously twice a week), oral methotrexate (up to 20 mg every week), or the combination. Clinical response was assessed by criteria of the American College of Rheumatology (ACR). The primary efficacy endpoint was the numeric index of the ACR response (ACR-N) area under the curve (AUC) over the first 24 weeks. The primary radiographic endpoint was change from baseline to week 52 in total joint damage and was assessed with the modified Sharp score. Analysis was by intention to treat.\n Four patients did not receive any drug; thus 682 were studied. ACR-N AUC at 24 weeks was greater for the combination group compared with etanercept alone and methotrexate alone (18.3%-years [95% CI 17.1-19.6] vs 14.7%-years [13.5-16.0], p<0.0001, and 12.2%-years [11.0-13.4], p<0.0001; respectively). The mean difference in ACR-N AUC between combination and methotrexate alone was 6.1 (95% CI 4.5-7.8, p<0.0001) and between etanercept and methotrexate was 2.5 (0.8-4.2, p=0.0034). The combination was more efficacious than methotrexate or etanercept alone in retardation of joint damage (mean total Sharp score -0.54 [95% CI -1.00 to -0.07] vs 2.80 [1.08 to 4.51], p<0.0001, and 0.52 [-0.10 to 1.15], p=0.0006; respectively). The mean difference in total Sharp score between combination and methotrexate alone was -3.34 (95% CI -4.86 to -1.81, p<0.0001) and between etanercept and methotrexate was -27 (-3.81 to -0.74, p=0.0469). The number of patients reporting infections or adverse events was similar in all groups.\n The combination of etanercept and methotrexate was significantly better in reduction of disease activity, improvement of functional disability, and retardation of radiographic progression compared with methotrexate or etanercept alone. These findings bring us closer to achievement of remission and repair of structural damage in rheumatoid arthritis.", "The objective of this study is to evaluate the efficacy and safety of rhTNFR:Fc: a recombinant tumor necrosis factor receptor:Fc fusion protein compared with methotrexate (MTX) in patients with rheumatoid arthritis in China. We treated 238 patients with active rheumatoid arthritis with either twice weekly subcutaneous injection rhTNFR:Fc (25 mg) or weekly oral MTX (mean 15 mg per week) for 24 weeks (registration number: 2003L01264). Clinical responses were defined as the percent improvement in disease activity according to the criteria of the American College of Rheumatology (ACR-N). As compared with MTX-treated patients, more patients who received rhTNFR:Fc had ACR20 improvement in disease activity during the first 2 weeks (P < 0.05). Similarly, more patients treated with rhTNFR:Fc having ACR20, ACR50, ACR70 improvement in disease activity during 8 weeks (P < 0.05). At the end of 12-week treatment, patients received rhTNFR:Fc also had significant improvement at ACR20 (P < 0.05). Compared with oral MTX, patients received rhTNFR:Fc also had significant improvement at ACR70 at the end of 24 weeks treatment (P < 0.05). In conclusion, compared with oral MTX subcutaneous injection, rhTNFR:Fc acted more rapidly to release symptoms and signs of active RA in Chinese patients, and well tolerated in patients with rheumatoid arthritis in China.", "Remission and radiographic non-progression are goals in the treatment of early rheumatoid arthritis. The aim of the combination of methotrexate and etanercept in active early rheumatoid arthritis (COMET) trial is to compare remission and radiographic non-progression in patients treated with methotrexate monotherapy or with methotrexate plus etanercept.\n 542 outpatients who were methotrexate-naive and had had early moderate-to-severe rheumatoid arthritis for 3-24 months were randomly assigned to receive either methotrexate alone titrated up from 7.5 mg a week to a maximum of 20 mg a week by week 8 or methotrexate (same titration) plus etanercept 50 mg a week. Coprimary endpoints at 52 weeks were remission measured with the disease activity score in 28 joints (DAS28) and radiographic non-progression measured with modified total Sharp score. Treatment was allocated with a computerised randomisation and enrolment system, which masked both participants and carers. Analysis was done by modified intention to treat with last observation carried forward for missing data. This study is registered with ClinicalTrials.gov, number NCT00195494).\n 274 participants were randomly assigned to receive combined treatment and 268 methotrexate alone. 132 of 265 (50%, 95% CI 44-56%) patients who took combined treatment and were available for assessment achieved clinical remission compared with 73 of 263 (28%, 23-33%) taking methotrexate alone (effect difference 22.05%, 95%CI 13.96-30.15%, p<0.0001). 487 evaluable patients had severe disease (DAS28>5.1). 196 of 246 (80%, 75-85%) and 135 of 230 (59%, 53-65%), respectively, achieved radiographic non-progression (20.98%, 12.97-29.09%, p<0.0001). Serious adverse events were similar between groups.\n Both clinical remission and radiographic non-progression are achievable goals in patients with early severe rheumatoid arthritis within 1 year of combined treatment with etanercept plus methotrexate.\n Wyeth Research.", "Etanercept, which blocks the action of tumor necrosis factor, reduces disease activity in patients with long-standing rheumatoid arthritis. Its efficacy in reducing disease activity and preventing joint damage in patients with active early rheumatoid arthritis is unknown.\n We treated 632 patients with early rheumatoid arthritis with either twice-weekly subcutaneous etanercept (10 or 25 mg) or weekly oral methotrexate (mean, 19 mg per week) for 12 months. Clinical response was defined as the percent improvement in disease activity according to the criteria of the American College of Rheumatology. Bone erosion and joint-space narrowing were measured radiographically and scored with use of the Sharp scale. On this scale, an increase of 1 point represents one new erosion or minimal narrowing.\n As compared with patients who received methotrexate, patients who received the 25-mg dose of etanercept had a more rapid rate of improvement, with significantly more patients having 20 percent, 50 percent, and 70 percent improvement in disease activity during the first six months (P<0.05). The mean increase in the erosion score during the first 6 months was 0.30 in the group assigned to receive 25 mg of etanercept and 0.68 in the methotrexate group (P= 0.001), and the respective increases during the first 12 months were 0.47 and 1.03 (P=0.002). Among patients who received the 25-mg dose of etanercept, 72 percent had no increase in the erosion score, as compared with 60 percent of patients in the methotrexate group (P=0.007). This group of patients also had fewer adverse events (P=0.02) and fewer infections (P= 0.006) than the group that was treated with methotrexate.\n As compared with oral methotrexate, subcutaneous [corrected] etanercept acted more rapidly to decrease symptoms and slow joint damage in patients with early active rheumatoid arthritis." ]

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[ "A prospective study of green tea consumption and cancer incidence, Hiroshima and Nagasaki (Japan).", "A multi-institute case-control study on the risk factors of developing pancreatic cancer.", "Diet and gastric cancer: a casecontrol study in Fujian Province, China.", "A prospective study of green tea consumption and oral cancer incidence in Japan.", "Coffee, tea, colas, and risk of epithelial ovarian cancer.", "Green tea consumption and the risk of pancreatic cancer in Japanese adults.", "Preventive effects of drinking green tea on cancer and cardiovascular disease: epidemiological evidence for multiple targeting prevention.", "Green tea and black tea consumption in relation to colorectal cancer risk: the Singapore Chinese Health Study.", "No association between green tea and prostate cancer risk in Japanese men: the Ohsaki Cohort Study.", "Green tea and the risk of colorectal cancer: pooled analysis of two prospective studies in Japan.", "Reduced risk of esophageal cancer associated with green tea consumption.", "Green tea consumption and mortality due to cardiovascular disease, cancer, and all causes in Japan: the Ohsaki study.", "Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study.", "Green tea and the prevention of breast cancer: a case-control study in Southeast China.", "Prospective cohort study of green tea consumption and colorectal cancer risk in women.", "Dietary habits and gastro-intestinal cancers: a comparative case-control study of stomach and large intestinal cancers in Nagoya, Japan.", "A prospective study of stomach cancer death in relation to green tea consumption in Japan.", "Protective effect of green tea on the risks of chronic gastritis and stomach cancer.", "[A case control study of cancer of the pancreas].", "Green tea consumption and subsequent risk of gastric cancer by subsite: the JPHC Study.", "Life-style and subsite of gastric cancer--joint effect of smoking and drinking habits.", "Green tea consumption, genetic susceptibility, PAH-rich smoky coal, and the risk of lung cancer.", "A comparative case-control analysis of stomach cancer and atrophic gastritis.", "A comparative case-control study of colorectal cancer and adenoma.", "A case-control study of diet and prostate cancer in Japan: possible protective effect of traditional Japanese diet.", "A prospective study of diet, smoking, and lower urinary tract cancer.", "Tea and coffee consumption and the risk of digestive tract cancers: data from a comparative case-referent study in Japan.", "Diet habits, alcohol drinking, tobacco smoking, green tea drinking, and the risk of esophageal squamous cell carcinoma in the Chinese population.", "Green tea and the risk of breast cancer: pooled analysis of two prospective studies in Japan.", "Green tea and the risk of gastric cancer in Japan.", "Green tea intake, MTHFR/TYMS genotype and breast cancer risk: the Singapore Chinese Health Study.", "No association between green tea and the risk of gastric cancer: pooled analysis of two prospective studies in Japan.", "Tea and lycopene protect against prostate cancer.", "Green tea consumption and prostate cancer risk in Japanese men: a prospective study.", "A case-control study of gastric cancer and diet in northern Kyushu, Japan.", "Soya foods and breast cancer risk: a prospective study in Hiroshima and Nagasaki, Japan.", "Tea consumption and ovarian cancer risk: a case-control study in China.", "Green tea consumption and lung cancer risk: the Ohsaki study.", "Smoking, alcohol drinking, green tea consumption and the risk of esophageal cancer in Japanese men.", "Effect of life styles on the risk of subsite-specific gastric cancer in those with and without family history.", "[A case-control study on the dietary risk factors of upper digestive tract cancer].", "The influence of cigarette smoking, alcohol, and green tea consumption on the risk of carcinoma of the cardia and distal stomach in Shanghai, China.", "Green tea consumption and the risk of pancreatic and colorectal cancers.", "Green-tea consumption and risk of stomach cancer: a population-based case-control study in Shanghai, China.", "Green tea and risk of breast cancer in Asian Americans.", "A population-based case-control study of lung cancer and green tea consumption among women living in Shanghai, China.", "Prospective study of educational background and stomach cancer in Japan.", "Foods and beverages in relation to urothelial cancer: case-control study in Japan.", "Intakes of selected foods and beverages and the incidence of gastric cancer among the Japanese residents of Hawaii: a prospective study.", "Green tea and coffee intake and risk of pancreatic cancer in a large-scale, population-based cohort study in Japan (JPHC study).", "[A case-control study on drinking green tea and decreasing risk of cancers in the alimentary canal among cigarette smokers and alcohol drinkers]." ]

[ "Laboratory and animal studies have shown a protective effect of green tea on cancer of different sites, but epidemiological evidence is limited and inconclusive. This prospective study in Japan examined the association between green tea consumption and cancer incidence.\n Subjects were 38,540 people (14,873 men, mean age 52.8 years; 23,667 women, mean age 56.8 years) who responded to a mail survey carried out between 1979 and 1981. A self-administered questionnaire ascertained consumption frequency of green tea using precoded answers (never, once per day, twice to four times per day, and five or more times per day). Follow-up continued until 31 December 1994. The study analyzed solid cancers (n = 3881); hematopoietic cancers (188); cancers of all sites combined (4069); and cancer of specific sites with more than 100 cases, i.e. stomach (901), colon (432), rectum (193), liver (418), gallbladder (122), pancreas (122), lung (436), breast (281), and bladder (122). Poisson regression was used to allow for city, gender, age, radiation exposure, smoking status, alcohol drinking, body-mass index, education level, and calendar time.\n Green tea consumption was virtually unrelated to incidence of cancers under study. The relative risks of all cancers for those consuming green tea twice to four times per day and five or more times per day were 1.0 (95% confidence interval 0.91-1.1) and 0.98 (0.88-1.1), respectively, as compared with those consuming green tea once per day or less.\n Our findings do not provide evidence that regular green tea consumption is related to reduced cancer risks.", "A multi-institute, hospital-based, case-control study on pancreatic cancer was carried out to examine its association with preceding diseases, cigarette smoking, alcohol drinking and dietary factors. Analyses were based on 124 newly diagnosed exocrine pancreatic cancer cases and sex-, age- and institute-matched hospital controls in seven hospitals in Japan. Cigarette smoking showed a positive association with the risk of developing pancreatic cancer. Especially among smokers, a risk enhancing effect of involuntary/passive smoking prior to twenty years of age was observed (P < 0.05). No consistent associations were found with coffee, black tea or alcohol consumption. Among dietary factors, favoring food of a salty taste and drinking green tea five cups per day or more were positively associated with the risk. Drinking milk and eating fish everyday were inversely associated with the risk.", "AIM:To explore the relationship between consumption of fish sauce, other dietary factors, living habits and the rish kf gastric cancer.METHODS:From May 1994 to July 1995, a population-based 1 2 case-control study was in Carried out inhigh-risk areas of gastric cancer, Changle and Fuqing cities, Fujian Province. Totally 272 cases and 544 age, gender-matched controls were included. Risk state analyses were made by ASRS package.RESULTS:Risk state single-factor analysis indicated that gastric cancer risk rose with high intake of fish sauce(OR =2.57), salted vegetables (OR =1.41), salted/fried fish and small shrimps (OR =1.57), low consumption of fresh vegetables (OR =1.95), fresh citrus fruits (OR =1.41), other fresh fruits (OR =1.31), green tea (OR =1.72), exposure to moldy foods (OR =2.32), irregular dinners (OR =5.47) and familial history of malignancy (OR =3.27).No significant relationship was observed between smoking, drinking, salt intake, use of refrigerator and gastric cancer rish. The results of rish state conditional Logistic regression showed that fish sauce, salted/dried fish and small shrimps, irregular dinners, familial history of malignancy were included in the best rish set. The summary ARS for the four factors was 75.49%.CONCLUSION:High intake of fish sauce, salted foods, moldy foods, irregular dinners and familial history of malignancy were possible risk factors for gastric cancer, whereas fresh vegetables and fruits.and green tea might have protective effects for gastric cancer.", "To examine the relation of green tea consumption with oral carcinogenesis, we prospectively analyzed data from a nationwide large-scale cohort study in Japan.\n A total of 20,550 men and 29,671 women aged 40-79 years, without any history of oral and pharyngeal cancer at baseline survey, were included in the present study. During a mean follow-up period of 10.3 years, 37 oral cancer cases were identified. The Cox proportional hazard model was used to estimate the hazard ratio (HR) and 95% confidence interval (95% CI) for oral cancer according to green tea consumption by sex, while adjusting for age, smoking, alcohol drinking, and other dietary factors.\n For women, the HRs of oral cancer for green tea consumption of 1-2, 3-4, and 5 or more cups per day were 0.51 (95% CI: 0.10-2.68), 0.60 (95% CI: 0.17-2.10), and 0.31 (95% CI: 0.09-1.07), respectively, compared with those who drank less than one cup per day (p for trend, 0.08). For men, no such trends were observed.\n Our findings did not suggest a prominent inverse association of green tea consumption with oral cancer, although there was a tendency for a reduced risk in women.", "Associations of coffee, tea, and other caffeinated beverages with ovarian cancer risk remain uncertain. In a population-based study in Washington State, 781 women with epithelial ovarian cancer diagnosed in 2002 to 2005 and 1,263 controls completed self-administered questionnaires detailing consumption of caffeinated and noncaffeinated coffee, teas, and colas and in-person interviews regarding reproductive and hormonal exposures. We assessed risk associated with coffee, tea, and cola drinking and with total caffeine consumption using logistic regression to calculate odds ratios and 95% confidence intervals. Neither caffeinated nor decaffeinated coffees were associated with ovarian cancer risk; also, we observed no association of total caffeine with risk using a combined index that summed intake from coffee, tea, and carbonated soft drinks. Among teas, neither herbal/decaffeinated nor black teas were associated with risk; however, women who reported drinking >or=1 cup/d of green tea had a 54% reduction in risk (P trend = 0.01). Associations of green tea with risk were similar when invasive and borderline cases were considered separately and when Asian women were excluded from analysis. Green tea, which is commonly consumed in countries with low ovarian cancer incidence, should be further investigated for its cancer prevention properties.", "Green tea polyphenols have been shown to inhibit tumor growth in animal and in vitro studies. We examined the relationship between green tea consumption and the risk of death from pancreatic cancer in a large Japanese cohort.\n At baseline (1988-1990), study participants reported the frequency and amount of green tea consumption during the past year. They were followed-up for mortality until December 31, 2003. Relative risk and 95% confidence intervals were calculated from Cox proportional hazard models.\n During an average follow-up of 13 years, we observed 292 pancreatic cancer deaths. In men and women combined, the relative risk was 1.23 (95% confidence interval, 0.84-1.80) for participants who consumed 7 or more cups of green tea per day as compared with those who consumed less than 1 cup per day, after adjustment for potential confounding factors. No significant trend in risk reduction was noted, with increasing consumption of green tea. We found no inverse association between cups of green tea consumed per day and the risk of pancreatic cancer in either men or women.\n Our findings do not support the hypothesis that green tea consumption is associated with decreased risk of pancreatic cancer in humans.", "The significance of drinking green tea in prevention of two of the main lifestyle-related diseases, cancer and cardiovascular disease, was demonstrated in terms of a prospective cohort study on a total of 8,552 general residents in Saitama Prefecture, Japan. On the basis of the follow-up study, we revealed decreased relative risk of cancer incidence for those consuming over 10 cups a day, compared with those consuming below 3 cups: 0.54 (95% confidence interval, 0.22-1.34) for men, 0.57 (0.34-0.98) for women, and 0.59 (0.35-0.98) for both sexes. Furthermore, a significant delay in cancer onset was associated with increased consumption of green tea. Next, decreased relative risk of death from cardiovascular disease was 0.58 (0.34-0.99) for men, 0.82 (0.49-1.38) for women, and 0.72 (0.60-1.04) for members of both sexes consuming over 10 cups a day. Finally, we evaluated the life-prolonging effects of drinking green tea on cumulative survival, using the life table.", "The relationships between green tea and black tea consumption and colorectal cancer risk were examined within the Singapore Chinese Health Study, a prospective cohort study of diet and cancer involving >60,000 men and women. Intake of green tea and black tea was assessed through in-person interviews. Incident cancer cases and deaths among cohort members were identified through record linkage of the cohort database with respective databases from the nationwide Singapore Cancer Registry and the Singapore Registry of Births and Deaths. The proportional hazard regression method was used to examine the associations between intake of green and black tea separately and colorectal cancer risk with adjustment for potential confounders. After an average of 8.9 years of follow-up, 845 colorectal cancer cases were identified. Subjects who drank green tea exhibited a statistically non-significant increase in risk [relative risk (RR) = 1.12, 95% confidence interval (CI) = 0.97-1.29] relative to non-drinkers of green tea. This risk increase was mainly confined to men (RR = 1.31, 95% CI = 1.08-1.58); the comparable RR in women was 0.89 (95% CI = 0.71-1.12). In men, the green tea-colorectal cancer association was noted mainly in those with advanced disease (Duke C or D) (RR = 1.53, 95% CI = 1.19-1.97), and the association was dose dependent (P for trend = 0.0002). This latter association was especially strong within the colon subsite (RR = 1.75, 95% CI = 1.24-2.46; P for trend < 0.0001). Irrespective of gender, intake of black tea was not associated with risk of colorectal cancer (RR = 0.92, 95% CI = 0.79-1.07) in this Asian population.", "In a prospective study of 19,561 Japanese men, green-tea intake was not associated with a lower risk of prostate cancer (110 cases), the multivariate hazard ratio for men drinking > or =5 cups compared with <1 cup per day being 0.85 (95% confidence interval 0.50-1.43, trend P = 0.81).", "Although laboratory experiments suggest protective effects of green tea against colorectal cancer, few prospective cohort studies have been conducted.\n We conducted a pooled analysis of two prospective cohort studies among residents in Miyagi Prefecture in rural northern Japan. The first study started in 1984 and included 26,311 subjects. The second study started in 1990 and included 39,604 subjects. The subjects responded to a self-administered questionnaire including an item on green tea consumption. With 7 to 9 years of follow-up, 305 colon and 211 rectal cancers were identified in the two cohorts through record linkage to a regional cancer registry. We used Cox regression to estimate the hazard ratio (HR) of colorectal cancer according to the consumption of green tea with adjustment for potential confounders, and pooled the estimates obtained from each cohort by general variance-based method.\n Multivariate pooled HRs for colon cancer associated with drinking 1-2, 3-4, and 5 or more cups of green tea per day, as compared with less than 1 cup per day, were 1.06 (95% confidence interval [CI]=0.74-1.52), 1.10 (0.78-1.55), 0.97 (0.70-1.35), respectively (trend p=0.81). Corresponding HRs for rectal cancer were 0.85 (95% CI=0.56-1.29), 0.70 (0.45-1.08), 0.85 (0.58-1.23), respectively (trend p=0.31).\n Consumption of green tea was not associated with lower risk of colorectal cancer.", "Studies in laboratory animals have suggested inhibitory effects of green tea on the induction of some cancers, notably, esophageal cancer. However, only a few epidemiologic studies have evaluated green tea as a potential inhibitor of human esophageal cancer.\n Our purpose was to evaluate the relationship between green tea consumption and the risk of esophageal cancer.\n This esophageal cancer study was part of a larger multicenter, case-control study that included three other gastrointestinal sites (pancreas, colon, and rectum). Medical records of patients aged 30-74 years old who were diagnosed with esophageal cancer from October 1, 1990, through January 31, 1993, were identified from the Shanghai Cancer Registry, which covers 6.8 million people in the urban area of Shanghai, People's Republic of China. During the ascertainment period, records of 1016 eligible cases of esophageal cancer were identified. Control subject records were selected by frequency matching in accordance with the age-sex distribution of the four gastrointestinal cancers ascertained by the cancer registry during 1986-1987. Patient interviews were then conducted using a structured, standardized questionnaire to obtain information on demographic characteristics, residential history, height and weight, diet, smoking, alcohol and tea drinking, medical history, family history of cancer, occupation, physical activity, and reproductive history.\n Of the 902 patients interviewed, 734 (81.4%) had their disease pathologically confirmed. There were 1552 control subjects interviewed, including 240 alternates. All analyses of tea effects were conducted separately among men and women and all were adjusted for age. After further adjustment for other known confounders, a protective effect of green tea drinking on esophageal cancer was observed among women (odds ratio [OR] = 0.50; 95% confidence interval [CI] = 0.30-0.83), and this risk decreased (P for trend < or = .01) as tea consumption increased. Among men, the ORs were also below 1.00, although not statistically significant. ORs for green tea intake were estimated among those persons who neither smoked nor drank alcohol. In this subset, statistically significant decreases in risk among tea drinkers were observed for both men (OR = 0.43; 95% CI = 0.22-0.86; P for trend = .05) and women (OR = 0.40; 95% CI = 0.20-0.77; P for trend < .001).\n This population-based, case-control study of esophageal cancer in urban Shanghai suggests a protective effect of green tea consumption. Although these findings are consistent with studies in laboratory animals, indicating that green tea can inhibit esophageal carcinogenesis, further investigations are definitely needed.", "Green tea polyphenols have been extensively studied as cardiovascular disease and cancer chemopreventive agents in vitro and in animal studies. However, the effects of green tea consumption in humans remain unclear.\n To investigate the associations between green tea consumption and all-cause and cause-specific mortality.\n The Ohsaki National Health Insurance Cohort Study, a population-based, prospective cohort study initiated in 1994 among 40,530 Japanese adults aged 40 to 79 years without history of stroke, coronary heart disease, or cancer at baseline. Participants were followed up for up to 11 years (1995-2005) for all-cause mortality and for up to 7 years (1995-2001) for cause-specific mortality.\n Mortality due to cardiovascular disease, cancer, and all causes.\n Over 11 years of follow-up (follow-up rate, 86.1%), 4209 participants died, and over 7 years of follow-up (follow-up rate, 89.6%), 892 participants died of cardiovascular disease and 1134 participants died of cancer. Green tea consumption was inversely associated with mortality due to all causes and due to cardiovascular disease. The inverse association with all-cause mortality was stronger in women (P = .03 for interaction with sex). In men, the multivariate hazard ratios of mortality due to all causes associated with different green tea consumption frequencies were 1.00 (reference) for less than 1 cup/d, 0.93 (95% confidence interval [CI], 0.83-1.05) for 1 to 2 cups/d, 0.95 (95% CI, 0.85-1.06) for 3 to 4 cups/d, and 0.88 (95% CI, 0.79-0.98) for 5 or more cups/d, respectively (P = .03 for trend). The corresponding data for women were 1.00, 0.98 (95% CI, 0.84-1.15), 0.82 (95% CI, 0.70-0.95), and 0.77 (95% CI, 0.67-0.89), respectively (P<.001 for trend). The inverse association with cardiovascular disease mortality was stronger than that with all-cause mortality. This inverse association was also stronger in women (P = .08 for interaction with sex). In women, the multivariate hazard ratios of cardiovascular disease mortality across increasing green tea consumption categories were 1.00, 0.84 (95% CI, 0.63-1.12), 0.69 (95% CI, 0.52-0.93), and 0.69 (95% CI, 0.53-0.90), respectively (P = .004 for trend). Among the types of cardiovascular disease mortality, the strongest inverse association was observed for stroke mortality. In contrast, the hazard ratios of cancer mortality were not significantly different from 1.00 in all green tea categories compared with the lowest-consumption category.\n Green tea consumption is associated with reduced mortality due to all causes and due to cardiovascular disease but not with reduced mortality due to cancer.", "Green tea catechins (GTCs) proved to be effective in inhibiting cancer growth in several experimental models. Recent studies showed that 30% of men with high-grade prostate intraepithelial neoplasia (HG-PIN) would develop prostate cancer (CaP) within 1 year after repeated biopsy. This prompted us to do a proof-of-principle clinical trial to assess the safety and efficacy of GTCs for the chemoprevention of CaP in HG-PIN volunteers. The purity and content of GTCs preparations were assessed by high-performance liquid chromatography [(-)-epigallocathechin, 5.5%; (-)-epicatechin, 12.24%; (-)-epigallocatechin-3-gallate, 51.88%; (-)-epicatechin-3-gallate, 6.12%; total GTCs, 75.7%; caffeine, <1%]. Sixty volunteers with HG-PIN, who were made aware of the study details, agreed to sign an informed consent form and were enrolled in this double-blind, placebo-controlled study. Daily treatment consisted of three GTCs capsules, 200 mg each (total 600 mg/d). After 1 year, only one tumor was diagnosed among the 30 GTCs-treated men (incidence, approximately 3%), whereas nine cancers were found among the 30 placebo-treated men (incidence, 30%). Total prostate-specific antigen did not change significantly between the two arms, but GTCs-treated men showed values constantly lower with respect to placebo-treated ones. International Prostate Symptom Score and quality of life scores of GTCs-treated men with coexistent benign prostate hyperplasia improved, reaching statistical significance in the case of International Prostate Symptom Scores. No significant side effects or adverse effects were documented. To our knowledge, this is the first study showing that GTCs are safe and very effective for treating premalignant lesions before CaP develops. As a secondary observation, administration of GTCs also reduced lower urinary tract symptoms, suggesting that these compounds might also be of help for treating the symptoms of benign prostate hyperplasia.", "Breast cancer is the most common malignancy in women worldwide. Tea has anticarcinogenic effects against breast cancer in experimental studies. However, epidemiologic evidence that tea protects against breast cancer has been inconsistent. A case-control study was conducted in Southeast China between 2004 and 2005. The incidence cases were 1009 female patients aged 20-87 years with histologically confirmed breast cancer. The 1009 age-matched controls were healthy women randomly recruited from breast disease clinics. Information on duration, frequency, quantity, preparation, type of tea consumption, diet and lifestyle were collected by face-to-face interview using a validated and reliable questionnaire. Conditional logistic regression analyses were used to estimate odds ratios (ORs) and associated 95% confidence intervals. Compared with non-tea drinkers, green tea drinkers tended to reside in urban, have better education and have higher consumption of coffee, alcohol, soy, vegetables and fruits. After adjusting established and potential confounders, green tea consumption was associated with a reduced risk of breast cancer. The ORs were 0.87 (0.73-1.04) in women consuming 1-249 g of dried green tea leaves per annum, 0.68 (0.54-0.86) for 250-499 g per annum, 0.59 (0.45-0.77) for 500-749 g per annum and 0.61 (0.48-0.78) for >or=750 g per annum, with a statistically significant test for trend (P < 0.001). Similar dose-response relationships were observed for duration of drinking green tea, number of cups consumed and new batches prepared per day. We conclude that regular consumption of green tea can protect against breast cancer. More research to closely examine the relationship between tea consumption and breast cancer risk is warranted.", "Tea and its constituents have shown anticarcinogenic activities in in vitro and animal studies. Epidemiologic studies, however, have been inconsistent. We prospectively evaluated the association between green tea consumption and colorectal cancer (CRC) risk in a cohort of 69,710 Chinese women aged 40 to 70 years. Information on tea consumption was assessed through in-person interviews at baseline and reassessed 2 to 3 years later in a follow-up survey. During 6 years of follow-up, 256 incident cases of CRC were identified. The multivariate relative risk of CRC was 0.63 (95% confidence interval, 0.45-0.88) for women who reported drinking green tea regularly at baseline compared with nonregular tea drinkers. A significant dose-response relationship was found for both the amount of tea consumed (Ptrend = 0.01) and duration in years of lifetime tea consumption (Ptrend = 0.006). The reduction in risk was most evident among those who consistently reported to drink tea regularly at both the baseline and follow-up surveys (relative risk, 0.43; 95% confidence interval, 0.24-0.77). The inverse association with regular tea drinking was observed for both colon and rectal cancers. This study suggests that regular consumption of green tea may reduce CRC risk in women.", "A simultaneous case-control study on stomach cancer and colo-rectal cancer involving 93 cases with stomach cancer, 93 cases with colo-rectal cancer and 186 controls was conducted using a common questionnaire at the Aichi Cancer Center Hospital in 1981-83. A fondness for salty tastes, especially salted foods such as pickled hakusai (vegetable) and dried & salted fishes, which are typical traditional Japanese foods showed a significantly positive association with stomach cancer (relative risk(RR) = 2.60, P less than 0.01). On the other hand, the habit of eating a western-style breakfast, particularly for 10 years or more made a significant contribution to the risk of colon cancer (RR = 2.24, P less than 0.05) but conversely decreased the risk of stomach cancer (RR = 0.50, not significant (NS)) and rectal cancer (RR = 0.40, NS). In this study, relatively frequent intakes (4 times/week) of some vegetables, i.e. pumpkin, green pepper, onion and cabbage, showed high relative risks for both stomach and colon cancers, contrary to the findings of previous epidemiological studies. Cigarette smoking increased the risk of stomach cancer (RR = 1.99, NS) but decreased that of colon cancer (RR = 0.61, NS). There was no positive relation between drinking and cancer at any site. Some other factors with opposite effects on the two contrasting cancers and some independent factors were identified in this comparative case-control study.", "To evaluate whether green tea consumption provides protection against stomach cancer death, relative risks were calculated using Cox proportional hazards regression analysis in the Japan Collaborative Study for Evaluation of Cancer Risk, sponsored by the Ministry of Health and Welfare (JACC Study). The study was based on 30 370 men and 42 481 women aged 40-79. After adjustment for age, smoking status, history of peptic ulcer, family history of stomach cancer along with certain dietary items, the risks associated with drinking one or two, three or four, five to nine, and 10 or more cups of green tea per day, relative to those of drinking less than one cup per day, were 1.6 (95% CI: 0.9-2.9), 1.1 (95% CI: 0.6-1.9), 1.0 (95% CI: 0.5-2.0), and 1.0 (95% CI: 0.5-2.0), respectively, in men (P for trend=0.669), and 1.1 (95% CI: 0.5-2.5), 1.0 (95% CI: 0.5-2.5), 0.8 (95% CI: 0.4-1.6), and 0.8 (95% CI: 0.3-2.1), respectively, in women (P for trend=0.488). We found no inverse association between green tea consumption and the risk of stomach cancer death.\n Copyright 2002 Cancer Research UK", "Despite the declining trend, stomach cancer remains the second most common cancer worldwide. We examined the role of green tea consumption on chronic gastritis and stomach cancer risks. A population-based case-control study was conducted in Yangzhong, China, with 133 stomach cancer cases, 166 chronic gastritis cases, and 433 healthy controls. Epidemiologic data were collected by standard questionnaire and odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models in SAS. Inverse association was observed between green tea drinking and chronic gastritis and stomach cancer risks. After adjusting for age, gender, education, body mass index, pack-years of smoking and alcohol drinking, ORs of green tea drinking were 0.52 (95% CI: 0.29-0.94) and 0.49 (95% CI: 0.31-0.77) for stomach cancer and chronic gastritis, respectively. In addition, dose-response relationships were observed with years of green tea drinking in both diseases. The results provide further support on the protective effect of green tea against stomach cancer. This is the first time that green tea drinking was found to be protective against chronic gastritis, which may be of importance when designing intervention strategies for stomach cancer and its pre-malignant lesions in the high-risk population.", "We report the findings of a case-control study of cancer of the pancreas, which was conducted in Hokkaido Prefecture. Seventy-one patients with pancreatic cancer were matched on sex and age (+/- 3 years) to 142 community-based controls. The latter had telephone interviews. We questioned all subjects about demographic factors, diet, beverage consumption, and medical and surgical history. Significantly decreased risks were associated with consumption of raw vegetables and green tea. The risk increased significantly with consumption of the fat of meat, boiled fish, coffee, black tea and alcoholic beverages.", "To investigate the relationship between green tea consumption and subsequent risk of gastric cancer at different anatomical subsites in a population-based prospective study.\n The Japan Public Health Center-based prospective study (JPHC Study) was established in 1990 for Cohort I and in 1993 for Cohort II. Among 72,943 subjects (34,832 men and 38,111 women), 892 gastric cancer cases (665 men and 227 women) were identified from 1990 to 2001.\n While no association between green tea consumption and gastric cancer was observed among men, a decreased risk of gastric cancer was observed among women after adjustment for potential confounding factors. This result was more remarkable when only the tumors in the distal portion were analyzed; for that subsite, the relative risk was 0.51 (95% confidence interval 0.30-0.86) in the highest category of green tea consumption (5 or more cups per day versus less than 1 cup per day) (p for trend = 0.01). The null association for upper-third gastric cancer was consistent for both sexes.\n An inverse association between green tea consumption and distal gastric cancer was observed among women. More prospective studies with detailed information are needed to confirm the role of green tea in the occurrence of gastric cancer.\n Copyright 2004 Kluwer Academic Publishers", "To clarify the effects of life-style on gastric cancer by subsite focusing on the proximal part (cardia and fundus) and the distal part (pyloric antrum), a case-control study was conducted at the Aichi Cancer Center in Nagoya, Japan from 1988-1991. This study compared 668 histologically confirmed gastric cancer cases [123 cardia, 218 middle (body), 256 antrum, and 71 unclassified] with 668 controls using a common questionnaire about life-styles as related to smoking, drinking, dietary habits and frequency of food intake. Controls were selected from among outpatients of the same hospital. Controls free of cancer and other specific diseases were matched with cases for sex, age (within 2 years), and time of hospital visit (within 2 months). A Western-style breakfast decreased the risk of antrum cancer, while consumption of greasy food increased the risk of cardia cancer. Fresh vegetables decreased the risk of cancer in both cardia and antrum. Habitual smoking is associated with increased risk of gastric cancer and it is more prominent in cardia cancer, especially in those who are drinkers. Results obtained from this study suggest that risk factors and relative risks of gastric cancer varied by subsite to a considerable degree. Furthermore, the joint effect of smoking and drinking may play an important role in the development of gastric cancer, especially of cardia cancer.", "Experimental evidence suggests that green tea (Camellia sinesis) may reduce the risk of lung cancer through several hypothesized mechanisms including scavenging oxidative radicals, inhibition of tumor initiation, and modulation of detoxification enzymes. However, epidemiologic results have not been consistent as to the relationship between green tea consumption and lung caner prevention. We employed a population-based case-control study of 122 cases and 122 controls to investigate the effect that green tea consumption may have on the risk of lung cancer and whether polymorphisms in 8-oxoguanine-DNA glycosylase (OGG1), glutathione-S-transferase M1 (GSTM1), and aldo-keto reductase 1C3 (AKR1C3) modify such an association. Daily green tea consumption was associated with a non-significant reduction in lung cancer risk. However, the effect of smoky coal exposure was higher for non-drinkers (odds ratio (OR)=4.93; 95% confidence interval (95% CI)=1.27-19.13) than for drinkers (OR=1.88; 95% CI=1.01-3.48). Further, among individuals with the OGG1 Cys(326) allele, daily consumption was associated with a 72% reduction (95% CI=0.09-0.94). Among GSTM1 null homozygotes, those who consumed green tea daily had a non-significant reduction in risk compared with non-consumers. Green tea consumption had no effect among OGG1 Ser(326) homozygotes or GSTM1 carriers. In addition, AKR1C3 genotype did not modulate the effect of green tea consumption. The chemopreventive effects of green tea in this population may be restricted to individuals who are particularly susceptible to oxidative stress and oxidative DNA damage.", "We conducted a comparative case-control analysis of stomach cancer and atrophic gastritis involving 427 cases with stomach cancer, 1414 cases with atrophic gastritis, and 3014 control subjects based on a questionnaire survey conducted for the subjects who received gastroscopic examination at Aichi Cancer Center Hospital from April 1985 to March 1989. The risk of atrophic gastritis in both males and females was not associated with any environmental factors. The risk of stomach cancer compared with the control subjects was positively associated with an intake of salted fish guts or cod roe [relative risk (RR) = 1.52, 95% confidence interval (CI) = 1.08-2.15] and smoking (RR for 20 or more cigarettes per day = 2.84; 95% CI = 1.79-4.51) and inversely associated with Western-style breakfast (RR = 0.68; 95% CI = 0.48-0.96) in males. Additionally, the risk of stomach cancer was inversely associated with a daily intake of raw vegetables (RR = 0.56; 95% CI = 0.34-0.94) in males when compared with the patients with atrophic gastritis as controls. Several environmental factors, such as intake of green-yellow vegetables, fruit, and meat, and a family history of stomach cancer, were only associated with intestinal types of cancer in females, whereas a clear difference between diffuse and intestinal types was not observed in males. The results of the present study suggest that risk factors for stomach cancer may be different from those for premalignant lesions.", "We conducted a comparative case-control study of colorectal cancer and adenoma involving 221 cases with colorectal cancer, 525 cases with colorectal adenoma and 578 neighborhood controls. Daily vegetables intake was associated with lower risks of distal colon adenoma (relative risks (RR) = 0.59, 95% confidence interval (CI): 0.39-0.89) and rectal cancer (RR = 0.46, 95% CI: 0.25-0.84). Daily beans intake was associated with lower risk of colon adenoma (RR = 0.58, 95% CI: 0.37-0.91 for the proximal colon and RR = 0.63, 95% CI: 0.45-0.88 for the distal colon) and daily intake of seaweeds was associated with lower risk of rectal cancer (RR = 0.42, 95% CI: 0.22-0.82). Daily intake of fish and shellfish also showed an inverse association with the risk of colon adenoma (RR = 0.67, 95% CI: 0.45-0.99 for the proximal colon and RR = 0.70, 0.52-0.94 for the distal colon). Generally, intakes of animal or vegetable fat-rich foods, especially meats, were associated with decreases in risks of both adenoma and cancer, though the association of cancer was not statistically significant. Other than dietary factors, daily alcohol drinking was associated with an increased risk of adenoma in the proximal colon (RR = 1.95, 95% CI: 1.15-3.29) and ex-drinkers showed higher risks for colon adenoma and colorectal cancer. Sports or occupational activities and coffee drinking were inversely associated and family history of colorectal cancer was positively associated with the risk of both colorectal adenoma and cancer.", "The age-adjusted incidence of prostate cancer is low in Japan, and it has been suggested that the traditional Japanese diet, which includes many soy products, plays a preventive role against prostate cancer. We performed a case-control study on dietary factors and prostate cancer in order to assess the hypothesis that the traditional Japanese diet reduces the risk of prostate cancer. Four geographical areas (Ibaraki, Fukuoka, Nara, and Hokkaido) of Japan were selected for the survey. Average daily intake of food from 5 years before the diagnosis was measured by means of a semi-quantitative food frequency questionnaire. We studied 140 cases and 140 individually age ( +/- 5 years)-matched hospital controls for analysis. Estimates of age-adjusted odds ratios (ORs) and linear trends were calculated by conditional logistic regression models with adjustment for cigarette smoking and total energy intake as confounding factors. Consumption of fish, all soybean products, tofu (bean curds), and natto (fermented soybeans) was associated with decreased risk. ORs of the fourth vs. first quartile and 95% confidence intervals (95%CIs) were 0.45 (0.20-1.02) for fish, 0.53 (0.24-1.14) for all soybean products, 0.47 (0.20-1.08) for tofu, and 0.25 (0.05-1.24) for natto. Consumption of fish and natto showed significantly decreasing linear trends for risk (P < 0.05). Consumption of meat was significantly associated with increased risk (the OR of the second vs. first quartile was 2.19, 95%CI 1.00-4.81). Consumption of milk, fruits, all vegetables, green-yellow vegetables, and tomatoes showed no association. Our results provide support to the hypothesis that the traditional Japanese diet, which is rich in soybean products and fish, might be protective against prostate cancer.", "The association of diet and smoking with bladder cancer was investigated in a cohort study conducted in Hawaii. The study included 7995 Japanese-American men who were born between 1900 and 1919, and were examined from 1965 to 1968. After 22 years of follow-up, 96 incident cases of bladder cancer were diagnosed. Current cigarette smokers had a 2.9-fold risk of bladder cancer, compared with nonsmokers. A direct dose-response relation was observed, based on pack-years of cigarette smoking. Consumption of fruit was inversely associated with the risk of bladder cancer (P = 0.038). The relative risk was 0.6 among subjects who had the most frequent (> or = 5 times/wk) intake of fruits compared to those with the least intake (< or = 1 time/wk). A weaker inverse association with milk intake was also observed (P = 0.07). Frequent consumption of fried vegetables, pickles, or coffee increased the risk of bladder cancer, but none of these foods showed a significant dose-response relationship. There was no association of other selected foods, alcohol, total calories, protein, fat, or carbohydrates with bladder cancer risk.", "The purpose of this study was to examine the hypothesis that tea and coffee consumption have a protective effect against development of digestive tract cancers.\n A comparative case-referent study was conducted using Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC) data from 1990 to 1995 in Nagoya, Japan. This study comprised 1,706 histologically diagnosed cases of digestive tract cancers (185 esophagus, 893 stomach, 362 colon, 266 rectum) and a total of 21,128 non-cancer outpatients aged 40 years and over. Logistic regression was used to analyze the data, adjusting for gender; age; year and season at hospital-visit; habitual smoking and alcohol drinking; regular physical exercise; fruit, rice, and beef intake; and beverage intake.\n The odds ratio (OR) of stomach cancer decreased to 0.69 (95 percent confidence interval [CI] = 0.48-1.00) with high intake of green tea (seven cups or more per day). A decreased risk was also observed for rectal cancer with three cups or more daily intake of coffee (OR = 0.46, CI = 0.26-0.81).\n The results suggest the potential for protective effect against site-specific digestive tract cancer by consumption of green tea and coffee, although most associations are limited only to the upper category of intake and have no clear explanation for site-specificity.", "This study aims to investigate the risk of esophageal squamous cell carcinoma in relation to exogenous factors in a rural area of China with a high incidence of esophageal squamous cell carcinoma.\n A population-based case-control study was conducted in Yangzhong County, Jiangsu Province, China, with 355 histologically confirmed esophageal squamous cell carcinoma cases recruited between 1 January 2004 and 28 February 2006 and 408 controls matched by sex and age, randomly selected from the local population.\n Stratified logistic regression analysis by sex revealed that hot-temperature food items, pork braised in brown sauce and old stocked rice intake could increase the risk of esophageal squamous cell carcinoma with odds ratio of 2.127 (95% confidence interval: 1.394-3.245), 2.059 (95% confidence interval: 1.417-2.993) and 9.059 (95% confidence interval: 5.930-13.840), respectively, in men and 3.048 (95% confidence interval: 1.733-5.364), 1.914 (95% confidence interval: 1.159-3.162) and 14.532 (95% confidence interval: 7.816-27.019), respectively, in women, whereas diet high in salt and chili, tobacco smoking and alcohol drinking only showed possible risk effects in men with odds ratio 2.338 (95% confidence interval: 1.568-3.485), 3.378 (95% confidence interval: 2.117-5.389), 1.976 (95% confidence interval: 1.337-2.921) and 2.197 (95% confidence interval: 1.510-3.195), respectively. Green tea drinking showed a protective effect in women (odds ratio=0.257; 95% confidence interval: 0.070-0.941).\n Findings from this study provided evidence that dietary habits, tobacco-smoking and alcohol drinking contribute to the etiology of esophageal squamous cell carcinoma. A healthy dietary habit, with smoking cessation and alcohol controlling is of a great importance in the prevention of esophageal cancer.", "In a pooled analysis of two prospective studies with 35004 Japanese women, green-tea intake was not associated with a lower risk of breast cancer (222 cases), the multivariate relative risk for women drinking >or=5 cups compared with <1 cup per day being 0.84 (95% confidence interval 0.57-1.24, Trend P=0.69).", "Although laboratory experiments and case-control studies have suggested that the consumption of green tea provides protection against gastric cancer, few prospective studies have been performed.\n In January 1984, a total of 26,311 residents in three municipalities of Miyagi Prefecture, in northern Japan (11,902 men and 14,409 women 40 years of age or older), completed a self-administered questionnaire that included questions about the frequency of consumption of green tea. During 199,748 person-years of follow-up, through December 1992, we identified 419 cases of gastric cancer (in 296 men and 123 women). We used Cox regression to estimate the relative risk of gastric cancer according to the consumption of green tea.\n Green-tea consumption was not associated with the risk of gastric cancer. After adjustment for sex, age, presence or absence of a history of peptic ulcer smoking status, alcohol consumption, other dietary elements, and type of health insurance, the relative risks associated with drinking one or two, three or four, and five or more cups of green tea per day, as compared with less than one cup per day, were 1.1 (95 percent confidence interval, 0.8 to 1.6), 1.0 (95 percent confidence interval, 0.7 to 1.4), and 1.2 (95 percent confidence interval, 0.9 to 1.6), respectively (P for trend=0.13). The results were similar after the 117 cases of gastric cancer that were diagnosed in the first three years of follow-up had been excluded, with respective relative risks of 1.2 (95 percent confidence interval, 0.8 to 1.8) 1.0 (95 percent confidence interval, 0.7 to 1.5), and 1.4 (95 percent confidence interval, 1.0 to 1.9) (P for trend=0.07).\n In a population-based, prospective cohort study in Japan, we found no association between green-tea consumption and the risk of gastric cancer.", "The tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) has been reported to act as a cancer preventive agent through folate pathway inhibition in experimental studies. We hypothesized that if folate pathway inhibition is the mechanism of cancer preventive activities of EGCG, then the protective effect against breast cancer would be stronger among women with low dietary folate intake and the high-activity methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TYMS) genotypes. In a nested case-control study of 380 women with incident breast cancer and 662 controls within the Singapore Chinese Health Study, we found no association between either green tea intake or gene polymorphisms of MTHFR (C677T and A1298C) and TYMS (1494 ins/del) and breast cancer risk. However, among women with low folate intake (<133.4 microg/day), weekly/daily green tea intake was inversely associated with breast cancer risk compared with less green tea intake [odds ratio (OR) = 0.45, 95% confidence interval (CI) = 0.26-0.79, P for interaction = 0.02]. Among women with high folate intake (>or=133.4 microg/day), green tea intake was not associated with breast cancer. Similarly, among women possessing the high-activity MTHFR/TYMS genotypes (0-1 variant allele), weekly/daily versus less frequent green tea intake was associated with lower breast cancer risk (OR = 0.66, 95% CI = 0.45-0.98), which was observed even more strongly among those who also had low folate intake (OR = 0.44, 95% CI = 0.22-0.89) than high folate intake (OR = 0.92, 95% CI = 0.55-1.54). This association was not observed among women possessing the low-activity genotypes (2-4 variant alleles). Our findings suggest that folate pathway inhibition may be one mechanism through which green tea protects against breast cancer in humans.", "nan", "Prostate cancer is the most common male cancer in developed countries and is increasing in the developing world. Its long latency and geographical variation suggest the possibility of prevention or postponement of onset by dietary modification. To investigate the possible joint effect of lycopene and green tea on prostate cancer risk, a case-control study was conducted in Hangzhou, China, with 130 prostate cancer patients and 274 hospital controls. Information on tea and dietary intakes, and possible confounders was collected using a structured questionnaire. The risk of prostate cancer for the intake of tea and lycopene and their joint effect were assessed using multivariate logistic regression models. Prostate cancer risk was reduced with increased consumption of green tea. The protective effect of green tea was significant (odds ratio 0.14, 95% CI: 0.06-0.35) for the highest quartile relative to the lowest after adjusting for total vegetables and fruits intakes and other potential confounding factors. Intakes of vegetables and fruits rich in lycopene were also inversely associated with prostate cancer risk (odds ratio 0.18, 95% CI 0.08-0.39). Interaction analysis showed that the protective effect from tea and lycopene consumption was synergistic (p<0.01). This study suggests that habitual drinking tea and intakes of vegetables and fruits rich in lycopene could lead to a reduced risk of prostate cancer in Chinese men. Together they have a stronger preventive effect than either component taken separately. This is the first epidemiological study to investigate the joint effect between tea drinking and lycopene intake.", "The incidence of prostate cancer is much lower in Asian than Western populations. Given that environmental factors such as dietary habits may play a major role in the causation of prostate cancer and the high consumption of green tea in Asian populations, this low incidence may be partly due to the effects of green tea. The JPHC Study (Japan Public Health Center-based Prospective Study) was established in 1990 for cohort I and in 1993 for cohort II. The subjects were 49,920 men aged 40-69 years who completed a questionnaire that included their green tea consumption habit at baseline and were followed until the end of 2004. During this time, 404 men were newly diagnosed with prostate cancer, of whom 114 had advanced cases, 271 were localized, and 19 were of an undetermined stage. Green tea was not associated with localized prostate cancer. However, consumption was associated with a dose-dependent decrease in the risk of advanced prostate cancer. The multivariate relative risk was 0.52 (95% confidence interval: 0.28, 0.96) for men drinking 5 or more cups/day compared with less than 1 cup/day (p(trend) = 0.01). Green tea may be associated with a decreased risk of advanced prostate cancer.", "A case-control study of gastric cancer was done in a rural area of northern Kyushu, Japan, in relation to dietary habits especially focusing on the relationship with the consumption of broiled fish. The study was based upon 139 cases of newly diagnosed gastric cancer at a single institution, 2,574 hospital controls and 278 controls sampled randomly from the residents of the study area (with sex and year of birth matched). No association was observed between the consumption of broiled fish and gastric cancer risk whether three types of broiled fish (raw fish, dried fish and salted fish) were analyzed separately or as a single category. However, consistently in the comparisons with both sets of controls, the risk of gastric cancer was inversely related with the consumption of fruits and positively associated with cigarette smoking. A decreased risk of gastric cancer was also noted among those with high consumption of green tea (10 or more cups per day).", "The association between soya foods and breast cancer risk was investigated in a prospective study of 34759 women in Hiroshima and Nagasaki, Japan. Women completed dietary questionnaires in 1969-1970 and/or in 1979-1981 and were followed for incident breast cancer until 1993. The analysis involved 427 cases of primary breast cancer in 488989 person-years of observation. The risk for breast cancer was not significantly associated with consumption of soya foods: for tofu, relative risks adjusted for attained age, calendar period, city, age at time of bombings and radiation dose to the breast were 0.99 (95% CI 0.80-1.24) for consumption two to four times per week and 1.07 (0.78-1.47) for consumption five or more times per week, relative to consumption once a week or less; for miso soup, relative risks were 1.03 (0.81-1.31) for consumption two to four times per week and 0.87 (0.68-1.12) for consumption five or more times per week, relative to consumption once a week or less. These results were not materially altered by further adjustments for reproductive variables and were similar in women diagnosed before age 50 and at ages 50 and above. Among 17 other foods and drinks examined only dried fish (decrease in relative risk with increasing consumption) and pickled vegetables (higher relative risk with higher consumption) were significantly related to breast cancer risk; these associations were not prior hypotheses and, because of the large number of comparisons made, they may be due to chance.", "To investigate whether tea consumption has an etiological association with ovarian cancer, a case-control study was conducted in China during 1999-2000. The cases were 254 patients with histologically confirmed epithelial ovarian cancer. The 652 controls comprised 340 hospital visitors, 261 non-neoplasm hospital outpatients, and 51 women recruited from the community. Information on the frequency, type, and duration of tea consumption was collected by personal interview using a validated questionnaire. The risk of ovarian cancer for tea consumption was assessed using adjusted odds ratios based on multivariate logistic regression analysis, accounting for confounding demographic, lifestyle, and familial factors including hormonal status and family ovarian cancer. The ovarian cancer risk declined with increasing frequency and duration of overall tea consumption. The adjusted odds ratio was 0.39 for those drinking tea daily and 0.23 for those drinking tea for >30 years, compared with nontea drinkers. The dose response relationships were significant, and the inverse association with ovarian cancer was observed for green tea consumption. We concluded that increasing frequency and duration of tea drinking, especially green tea, can reduce the risk of ovarian cancer. However, the protective effects of black tea and Oolong tea need to be additionally investigated.", "We examined the risk of lung cancer in relation to green tea consumption in a population-based cohort study in Japan among 41,440 men and women, aged 40-79 years, who completed a questionnaire in 1994 regarding green tea consumption and other health-related lifestyle factors. During the follow-up period of 7 years (from 1995 to 2001), 302 cases of lung cancer were identified, and the Cox proportional hazards regression model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). The multivariable-adjusted HRs of lung cancer incidence for green tea consumption of 1 or 2, 3 or 4, and 5 or more cups/day as compared to less than 1 cup/day were 1.14 (95% CI: 0.80-1.62), 1.18 (95% CI: 0.83-1.66), and 1.17 (95% CI: 0.85-1.61), respectively (P for trend=0.48). This cohort study has found no evidence that green tea consumption is associated with lung cancer.", "Although smoking and alcohol drinking are established risk factors of esophageal cancer, their public health impact is unclear. Furthermore, the effect of green tea is controversial.\n The present study was based on a pooled analysis of two prospective cohort studies. A self-administered questionnaire about health habits was distributed to 9,008 men in Cohort 1 and 17,715 men in Cohort 2, aged 40 years or older, with no previous history of cancer. We identified 38 and 40 patient cases with esophageal cancer among the subjects in Cohort 1 (9.0 years of follow-up) and Cohort 2 (7.6 years of follow-up), respectively. Cox proportional hazards regression was used to estimate hazard ratios (HRs) of the risk of esophageal cancer incidence.\n Cigarette smoking, alcohol drinking and green tea consumption were significantly associated with an increased risk of esophageal cancer. Compared with men who had never smoked, never drunk alcohol or green tea, the pooled multivariate HRs (95% confidence intervals) were 5.09 (1.80-14.40) (p for trend <0.0001), 2.73 (1.55-4.81) (p for trend=0.0002), or 1.67 (0.89-3.16) (P for trend=0.04) for men who were currently smoking > or =20 cigarettes/day, drinking alcohol daily, or drinking > or =5 cups green tea/day, respectively. The population attributable fractions of esophageal cancer incidence that was attributable to smoking, alcohol drinking and green tea consumption were 72.0%, 48.6%, and 22.1%, respectively.\n Among the variables studied, smoking has the largest public health impact on esophageal cancer incidence in Japanese men, followed by alcohol drinking and green tea drinking.", "To evaluate a combined effect of gastric cancer family history (GCFH) and selected living habits on the subsite-specific of gastric cancer, a hospital-based case-referent study was conducted in Tokai area of Japan. The study subjects were 850 newly diagnosed gastric cancer (GC) patients and 28,619 cancer-free first-visit outpatients. Odds ratios (ORs) of all subsites of GC in subjects with both GCFH and habitual smoking were significantly higher (OR = 4.22) compared with those with merely GCFH (OR = 1.81) or habitual smoking (OR = 2.83). When positive GCFH subjects frequently consumed raw vegetable, the risk of GC decreased in cardia (OR = 0.68), antrum (OR = 0.43) and all subsites (OR = 0.74). Our findings provided evidence that GCFH and habitual smoking increased the risk of GC with family history, while frequent intake of raw vegetable decreased the risk and it was modified by other environmental factors.", "To understand the effect of dietary factors in Yangzhong, Jiangsu Province-a high prevalence area in China.\n A case-control study on 209 cases of upper digestive tract cancer was conducted. There were 68 cases of esophageal cancer, 69 cases of cardiac cancer and 72 cases of other gastric cancers including 129 males and 80 females aged 35-79 under the study.\n It is revealed that intake of pickled vegetables increases the ORs of esophageal, cardiac and other gastric cancers (OR = 2.82, OR = 5.17, OR = 2.92, respectively). It is also concluded that the intake of leftovers can elevate the ORs of esophageal and cardiac gastric cancer (OR = 1.88 and OR = 1.90) and over consumption of salt also elevates the OR of cardiac cancer (OR = 1.87). However, drinking green tea may decrease the ORs of esophageal and other gastric cancers (OR = 0.20 and OR = 0.28) while fruits consumption may reduce the OR of esophageal cancers (OR = 0.51).\n Tumors from upper digestive tract have some relations with diet factors but the effects vary with the differences of tumor sites, dose of exposure and area, etc.", "The divergent incidence patterns of gastric cardia and distal stomach cancer may suggest different etiologies. This study examined the role of cigarette smoking, alcohol drinking, and green tea consumption as risk factors for carcinoma by anatomic subsite of stomach.\n Newly-diagnosed stomach carcinoma patients (n = 1124) and frequency-matched population controls (n = 1451) were interviewed in person. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models.\n Excess risks associated with cigarette smoking and alcohol consumption were observed largely among men. The adjusted ORs for all stomach cancer combined were 1.35 (CI: 1.06-1.71) for current smokers, and 1.26 (CI: 0.86-1.84) for ex-smokers. For tumors of the distal stomach, statistically significant positive dose-response trends were found for the number of cigarettes smoked per day, the duration and pack-years of smoking, and inverse trends for years of stopped smoking. For tumors of the gastric cardia, however, a monotonic association was found only for the number of cigarettes smoked per day (P=0.06). Alcohol consumption was not related to the risk of cardia cancer, while a moderate excess risk of distal stomach cancer (OR: 1.55; CI: 1.07-2.26) was observed among heavy alcohol drinkers. Green tea drinking was inversely associated with risk of stomach cancer arising from either subsite, with ORs of 0.77 (CI: 0.52-1.13) among female heavy drinkers, and 0.76 (CI: 0.55-1.27) among male heavy drinkers.\n Our findings provide further evidence that cigarette smoking and, possibly, alcohol consumption increase the risk of stomach carcinoma, notably of the distal segment. An inverse association with green tea drinking was also observed.", "The effect of green tea drinking in reducing human cancer risk is unclear, though a protective effect has been reported in numerous animal studies and several epidemiologic investigations. Herein the hypothesis that green tea consumption may reduce the risk of cancers of the colon, rectum and pancreas is examined in a large population-based case-control study conducted in Shanghai, China. Newly diagnosed cancer cases (931 colon, 884 rectum and 451 pancreas) during 1990-1993 among residents 30-74 years of age were included. Controls (n = 1,552) were selected among Shanghai residents and frequency-matched to cases by gender and age. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) of each cancer associated with green tea consumption were derived after adjustment for age, income, education and cigarette smoking. Additional adjustment for dietary items and body size was found to have minimal impact. An inverse association with each cancer was observed with increasing amount of green tea consumption, with the strongest trends for rectal and pancreatic cancers. For men, compared with non-regular tea drinkers, ORs among those in the highest tea consumption category (> or = 300 g/month) were 0.82 for colon cancer, 0.72 for rectal cancer and 0.63 for pancreatic cancer, with p values for trend being 0.38, 0.04 and 0.04, respectively. For women, the respective ORs for the highest consumption category (> or = 200 g/month) were 0.67, 0.57 and 0.53, with the respective p values for trend being 0.07, 0.001 and 0.008. Our findings provide further evidence that green tea drinking may lower the risk of colorectal and pancreatic cancers.", "The effect of drinking Chinese green tea on the risk of stomach cancer was evaluated in a population-based case-control study conducted in Shanghai, China, from October 1991 to December 1993. Eligible cases were incident cases of primary stomach cancer diagnosed during the study period among residents of Hongkou district and Nanhui county aged under 80 years. Controls were selected from the same street or commune where the case resided and were matched to the cases on age (within three years) and gender. A total of 711 cases and 711 matched controls, more than 90 percent of the eligible subjects, completed the interview. Information was obtained on the types of tea used, age when habitual tea drinking started, frequency of new batches of tea leaves used per day, number of cups brewed from each batch, total duration of drinking for each batch, strength and temperature of the tea consumed. Statistical analysis was based on modelling through conditional logistic regression. After adjusting for age, gender, place of residence, education, birthplace, alcohol consumption, and cigarette smoking, the odds ratio (OR) comparing drinkers of green tea with nondrinkers was 0.71 (95 percent confidence interval = 0.54-0.93). The adjusted OR decreased with increasing number of new batches of the green tea consumed each day (P value trend = 0.006). With the largest series of stomach cancer cases to date, this study found green-tea consumption associated with lower risk of stomach cancer. Among drinkers of green tea, the risk of stomach cancer did not depend on the age when habitual green-tea drinking started. Green tea may disrupt gastric carcinogenesis at both the intermediate and the late stages.", "There is substantial in vitro and in vivo evidence implicating tea polyphenols as chemopreventive agents against various cancers. However, epidemiologic data obtained from mainly Western populations are not supportive of a protective role of tea, mainly black tea, in the etiology of breast cancer. Much less is known about the relationship between green tea and breast cancer risk. During 1995-1998, we conducted a population-based, case-control study of breast cancer among Chinese, Japanese and Filipino women in Los Angeles County and successfully interviewed 501 breast cancer patients and 594 control subjects. Detailed information on menstrual and reproductive factors; dietary habits, including intake of black and green tea; and other lifestyle factors was collected. Risk of breast cancer was not related to black tea consumption. In contrast, green tea drinkers showed a significantly reduced risk of breast cancer, and this was maintained after adjusting for age, specific Asian ethnicity, birthplace, age at menarche, parity, menopausal status, use of menopausal hormones, body size and intake of total calories and black tea. Compared to women who did not drink green tea regularly (i.e., less than once a month), there was a significant trend of decreasing risk with increasing amount of green tea intake, adjusted odds ratios being 1.00, 0.71 (95% confidence interval [CI] 0.51-0.99) and 0.53 (95% CI 0.35-0.78), respectively, in association with no, 0-85.7 and >85.7 ml of green tea per day. The significant inverse association between risk of breast cancer and green tea intake remained after further adjustment for other potential confounders, including smoking; alcohol, coffee and black tea intake; family history of breast cancer; physical activity; and intake of soy and dark green vegetables. While both green tea and soy intake had significant, independent protective effects on breast cancer risk, the benefit of green tea was primarily observed among subjects who were low soy consumers. Similarly, the protective effect of soy was primarily observed among subjects who were nondrinkers of green tea. In summary, our results point to an important role of both green tea and soy intake in relation to breast cancer risk in Asian-American women.\n Copyright 2003 Wiley-Liss, Inc.", "Epidemiologic evidence regarding the association between the consumption of green tea and lung cancer is limited and inconclusive, although experimental studies have shown consistently that tea preparations and tea polyphenols may inhibit the induction of a variety of cancers, including lung cancer. In this population-based case-control study, we examined the association between past consumption of green tea and the risk of lung cancer. We identified 649 incident cases of primary lung cancer among women diagnosed from February 1992 through January 1994 using the population-based Shanghai Cancer Registry. We randomly selected a control group of 675 women from the Shanghai Residential Registry, frequency-matched to the expected age distribution of the cases. Green tea consumption was ascertained through face-to-face interviews. We estimated adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) using unconditional logistic regression. Among nonsmoking women, consumption of green tea was associated with a reduced risk of lung cancer (OR = 0.65; 95% CI = 0.45-0.93), and the risks decreased with increasing consumption. We found little association, however, among women who smoked (OR = 0.94; 95% CI = 0.40-2.22). The inconsistency in the association between drinking tea and the risk of lung cancer reported in previous studies may in part be due to inadequate control of confounding of active smoking.", "Different lifestyle choices are commonly regarded as a reflection of socioeconomic status, and the latter is inversely correlated with the risk of developing stomach cancer. However, the details of this association are still unclear in terms of the degree to which lifestyle factors are having impact. To explain the correlation between socioeconomic status and stomach cancer, we therefore examined the roles played by different lifestyle factors.\n A prospective cohort study of diet and cancer was initiated in Japan during 1988. Data were collected by means of a self-administered questionnaire. A follow-up survey was conducted annually, and the cause of death was recorded from the death certificate. The total of 127,477 study participants resided in 45 areas of Japan, and we retrieved data for 18,746 men and 26,184 women for the present analysis. After 328,030 person-years of follow-up, 379 deaths from stomach cancer were detected: 261 in men and 118 in women.\n For men, the age-adjusted relative risk was lowest in the highly educated group (relative risk = 0.72, 95% CI: 0.50-1.04). Relative risk after adjustment for age and dietary choices (including pickles, vegetables, fruit, green tea, and preference for salty foods) was the same as the age-adjusted relative risk (relative risk = 0.72, 95% CI: 0.50-1.04).\n The expected inverse correlation between education level and death from stomach cancer was observed in men. However, this association could not be explained by differences in dietary habits, smoking, or alcohol consumption associated with socioeconomic status.", "The roles of several foods and beverages in the development of bladder cancer remain unclear.\n We undertook a hospital-based case-control study at Aichi Cancer Center Hospital, Japan. Subjects included 124 men and women (bladder cancer cases) with newly diagnosed cancers of the renal pelvis (n = 5), ureter (n = 6) or bladder (n = 113) and 620 age- and sex-matched, cancer-free outpatients (controls) presenting at the hospital in the period from 1994 to 2000. Smoking-adjusted odds ratios (OR) were estimated to assess the strength of associations between self-reported intake of foods or drinks and bladder cancer risk, using conditional logistic models.\n We found a decreased risk in relation to frequent intake of green-yellow vegetables; the OR for the highest intake score compared with the lowest was 0.54 (95% confidence interval [CI] 0.29-0.99). The OR for carrot intake of >/=5 times/week compared with </=1-3 times/month was 0.41 (95% CI 0.16-1.01) and a decreasing risk with increasing consumption of green vegetables was also detected (P for trend = 0.063). Inverse associations between black tea, eggs and meat and risk were also suggested, whereas moderate drinkers of green tea (5-9 cups/day) showed an elevated risk. Coffee and milk consumption did not appear to exert any influence.\n Those with an increased risk of bladder cancer, such as smokers, may benefit from increasing their consumption of green-yellow vegetables.", "We report on the associations between the intake of certain foods and beverages and the incidence of gastric cancer in a cohort of 11,907 randomly selected Japanese residents of Hawaii (6297 women and 5610 men).\n The daily intake of six beverages, cigarettes and alcohol and the weekly frequency of intake of 13 foods and food groups was estimated with a short food frequency questionnaire. Over an average follow-up period of 14.8 years, 108 cases of gastric cancer (44 women, 64 men) were identified via linkage to the Hawaii Tumor Registry.\n In gender-combined proportional hazards analyses, the consumption of fresh fruit seven or more times per week was associated with a significantly reduced risk of gastric cancer, compared to lower levels of consumption (relative hazard (RH): 0.6, 95% confidence interval (CI): 0.4-1.0, P = 0.03). The combined intake of fresh fruit and raw vegetables was inversely associated with the risk of gastric cancer in the total cohort, and among the men (P < 0.05). No significant relationships were found between gastric cancer incidence and the intake of pickled vegetables, miso soup, dried or salted fish, or processed meats among either gender. Compared to non-drinkers, men who drank one cup of coffee per day had a significantly elevated risk of gastric cancer (RH: 2.5, 95% CI: 1.0-6.1, P = 0.05), but there was no evidence of a dose-response relationship. Cigarette smoking and consumption of alcohol were not related to gastric cancer, in analyses restricted to the men.\n The results related to fruit and vegetable intake are consistent with an anti-nitrosating effect of these foods, while the unexpected association between coffee consumption and gastric cancer is difficult to explain and may represent a chance finding.", "Pancreatic cancer is one of the most aggressive and treatment-refractory malignancies in humans. The most effective means of reducing pancreatic cancer mortality may be primary prevention. Although laboratory studies have demonstrated that green tea possesses anticancer activities, results from epidemiological studies have failed to show a consistent cancer-preventive effect. In addition, there is a lingering concern that coffee mighty increase the risk of pancreatic cancer although the most recent epidemiological studies showed no overall association between coffee and risk. Here, we examined the association between the drinking of green tea or coffee and the risk of pancreatic cancer in a large population-based cohort study in Japan (JPHC study). In total, 102 137 participants were followed for an average of 11 years through to the end of 2003. A total of 233 incident cases of pancreatic cancer were identified among 1 116 945 person-years of follow-up. Overall, the risk of pancreatic cancer was not associated with either green tea or coffee intake in our population, although a reduced risk was apparent among men who drank at least three cups of coffee per day compared with those who did not drink any or only rarely drank coffee. In conclusion, our findings support the idea that green tea or coffee consumption does not have a substantial impact on pancreatic cancer risk in general.", "To explore the role of green tea in decreasing the risks of gastric cancer, liver cancer, esophageal cancer among alcohol drinkers or cigarette smokers.\n A population based case-control study was conducted in Taixing, Jiangsu province.\n In Taixing city, identified cases of stomach, liver and esophageal cancers were chosen with informed consent. The numbers were 206, 204, 218 respectively. Controls were chosen from normal population having lived in the area for longer than 10 years, also with informed consent. Green tea drinking seemed to have decreased 81%, 78%, 39% risk for the development of gastric cancer, liver cancer and esophageal cancer among alcohol drinkers. It might also have decreased 16%, 43%, 31% on the risks of developing the three kinds of cancers among cigarette smokers. Interaction assessment showed that drinking green tea could significantly decrease the risk of gastric cancer and liver cancer among alcohol drinkers, with ORs of interaction item 0.23 (95% CI: 0.10 - 0.55) and 0.25 (95% CI: 0.11 - 0.57) respectively.\n Habit of drinking green tea seemed to have significant protective effects on the development of both gastric and liver cancer among alcohol drinkers while, green tea also having some protective effect on esophageal cancer among alcohol drinkers and on three kinds of cancers among cigarette smokers." ]

[ "14592306", "12684301", "9741373", "14572126" ]

[ "A prospective 8 week trial of nasal interfaces vs. a novel oral interface (Oracle) for treatment of obstructive sleep apnea hypopnea syndrome.", "Clinical outcomes related to interface type in patients with obstructive sleep apnea/hypopnea syndrome who are using continuous positive airway pressure.", "Comparison of nose and face mask CPAP therapy for sleep apnoea.", "A randomized crossover efficacy trial of oral CPAP (Oracle) compared with nasal CPAP in the management of obstructive sleep apnea." ]

[ "To compare efficacy, compliance rates, and side effects of a new strapless oral interface, the Oracle, with available nasal masks over 8 weeks of use for the treatment of obstructive sleep apnea hypopnea syndrome (OSAHS).\n A total of 38 patients with OSAHS (respiratory disturbance index (RDI) >/=15/h) were enrolled after the diagnostic polysomnogram for subsequent continuous positive airway pressure (CPAP) therapy. After randomization, therapeutic pressures during a titration study were determined for 21 patients in the oral group and 17 patients in the nasal group. Comparisons for nasal and oral interfaces were made for baseline patient characteristics, average hours of CPAP use, side effects from therapy, and among questionnaires evaluating patients' subjective responses to therapy at months 1 and 2.\n No significant difference was observed in the average hours of CPAP use between the oral (4.5+/-2.1; 5.5+/-2.6) and nasal groups (4.0+/-2.6; 4.8+/-2.5) for either month 1 or 2 (P>0.05). The dropout rates were similar for both groups after 8 weeks of therapy. However, patients in the nasal group had higher occurrences of side effects such as nasal congestion, dryness, and air leaks, whereas patients in the oral group experienced more oral dryness and gum pain.\n Oral delivery of CPAP with the Oracle is an effective and suitable alternative for patients with OSAHS.", "To evaluate the effect of interface on objective compliance, patient satisfaction, adverse effects, quality of life, and residual sleep-disordered breathing in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS) using continuous positive airway pressure (CPAP).\n Randomized, cross-over.\n Two suburban community-based hospital sleep laboratories.\n Data were collected on 39 patients with OSAHS (mean age, 48.7 years), in whom CPAP was a novel treatment.\n Interventions were nasal pillows (Breeze; Mallinckrodt Corporation; Minneapolis, MN) and nasal mask (Contour; Respironics; Murrysville, PA).\n Outcomes assessed at the completion of each 3-week treatment period were objective compliance, adverse effects, and satisfaction with CPAP (CPAP questionnaire), daytime sleepiness (Epworth sleepiness scale [ESS]), quality of life (Functional Outcomes of Sleep Questionnaire [FOSQ]), sleep diary, and residual sleep-disordered breathing (apnea-hypopnea index [AHI]). Patients were randomly assigned to use the nasal pillows or the nasal mask following laboratory titration and initiated on CPAP (pressure range, 5 to 14 cm H(2)O). The percentage of days utilized favored the nasal pillows (94.1% vs 85.7%; p = 0.02), but minutes of use per night did not differ (nasal pillows, 223 min; nasal mask, 288 min). ESS scores were lower and the FOSQ total scores were higher following CPAP treatment (p < 0.001), but no differential treatment effects were noted. Fewer adverse effects, less trouble getting to sleep and staying asleep, and less air leak were reported with nasal pillows (p < 0.04). The mean +/- SD pretreatment AHI (47.1 +/- 35.1/h) was significantly lower following treatment with CPAP for both types of interface (nasal pillows, 10.2 +/- 9.8/h; nasal mask, 7.0 +/- 7.7/h; p < 0.001).\n Nasal pillows are a well-tolerated and effective interface for OSAHS patients receiving CPAP at < or = 14 cm H(2)O. Use of nasal pillows was associated with fewer adverse effects and better sleep quality during the first 3 weeks of CPAP therapy. Further investigation is needed to determine whether interface type affects long-term CPAP use.", "Many patients with sleep apnoea/hypopnoea syndrome (SAHS) find nasal continuous positive airway pressure (CPAP) treatment unsatisfactory due to side effects related to mouth air leakage. A study was performed to compare side effects with face mask and nose mask CPAP therapy in patients with SAHS, with and without uvulopalatopharyngoplasty (U3P).\n Twenty newly diagnosed patients with SAHS took part in a randomised double limb trial of face or nose mask CPAP therapy (four weeks per limb) in which CPAP compliance in terms of machine run time was measured and patients answered a symptom questionnaire on side effects resulting from the mask. Ten patients with SAHS with U3P (SAHS/U3P) who were already regular users of nasal CPAP were also given a four week trial of face mask CPAP to compare compliance and symptoms. Ten patients with SAHS were matched with the 10 SAHS/U3P patients for body mass index, age, apnoea/hypopnoea index, and CPAP pressure. Long term compliance was estimated one year after the mask comparison studies.\n For patients with SAHS nightly compliance was higher with a nose mask (mean (SE) 5.3 (0.4) hours/night CPAP) than with a face mask (4.3 (0.5) hours/night CPAP), p = 0.01 (mean difference 1.0 hour/night, 95% CI 1.8 to 0.3). Nose masks were rated more comfortable by 19 of 20 patients (p < 0.001) despite more mouth leak related symptoms. For SAHS/U3P patients compliance was marginally higher with nose masks (5.1 (0.7) hours/night CPAP) than with face masks (4.0 (0.8) hours/night CPAP), p = 0.07 (mean difference 1.1 hour/night, 95% CI 2.1 to 0.1). Nose masks were rated more comfortable by seven of 10 patients. There were no significant differences in side effect scores with face and nose masks. At one year nine of 10 SAHS patients and nine of 10 SAHS/U3P patients were still using CPAP. Compliance was 5.4 (0.6) hours/night for the SAHS patients and 3.5 (0.4) hours/night for the SAHS/U3P patients, p = 0.02 (mean difference 1.9 hour/night, 95% CI 3.6 to 0.3).\n Compliance is greater with nose mask CPAP than with face mask CPAP because the overall comfort is better and compensates for increased symptoms associated with mouth leakage. Improved face mask design is needed.", "To determine the therapeutic efficacy and viability of a novel oral interface for continuous positive airway pressure (CPAP) compared with conventional nasal interfaces.\n A randomized single-blind crossover study.\n Hospital-based sleep laboratory.\n 21 CPAP-naïve patients with obstructive sleep apnea (baseline apnea-hypopnea index, 85 +/- 36) Interventions: Nasal CPAP and oral CPAP MEASUREMENTS AND RESULTS: Patients were each treated for two 4-week periods using nasal CPAP and oral CPAP. The CPAP titrations were undertaken at the start of each treatment arm. Outcome measures were recorded at baseline and at the end of each treatment arm. These included polysomnography variables, CPAP compliance, subjective sleepiness, obstructive sleep apnea symptom ratings, and adverse effects. There were no significant differences between oral and nasal interfaces for the on-CPAP frequency of apneas and hypopneas (mean difference, nasal-oral [95%CI] = -4.6[-10.1-1.0]/h; P = 0.06) or arousals (-3.0 [-7.8-1.8]/h; P = 0.23). There were also no statistically significant differences between interfaces for scores on the Epworth Sleepiness Scale (-0.7 [-3.1-1.7]; P = 0.20), obstructive sleep apnea symptoms (-7.7 [-17.7-2.4]; P = 0.052), CPAP compliance (0.3 [-0.5-1.1] h/night; P = 0.50), CPAP pressure (0.05 [-0.66-0.76] cmH20; P = 0.73), CPAP side effects scores (-2.0 [-5.3-1.4]; P = 0.23), or mask preference (P = 0.407). In addition, both nasal and oral interfaces significantly improved polysomnographic variables, Epworth Sleepiness Scale scores, obstructive sleep apnea symptoms, and CPAP compliance from baseline (all P < 0.05).\n This preliminary study indicates that oral CPAP has similar efficacy to traditionally applied nasal CPAP in treating obstructive sleep apnea. Additional large studies are required to determine the range of clinical situations where oral CPAP is indicated." ]

[ "12734132", "17456286", "17346614", "16045371", "14751328", "11817917", "12683740", "17500622" ]

[ "Impact of electron beam tomography, with or without case management, on motivation, behavioral change, and cardiovascular risk profile: a randomized controlled trial.", "Showing smokers with vascular disease images of their arteries to motivate cessation: a pilot study.", "Information given to postmenopausal women on coronary computed tomography may influence cardiac risk reduction efforts.", "Using UV photography to reduce use of tanning booths: a test of cognitive mediation.", "Patient adherence to skin self-examination. effect of nurse intervention with photographs.", "Improved smoking cessation in smokers given ultrasound photographs of their own atherosclerotic plaques.", "Effects of appearance-based interventions on sun protection intentions and self-reported behaviors.", "Long-term effects of appearance-based interventions on sun protection behaviors." ]

[ "Although the use of electron beam tomography (EBT) as a motivational tool to change behavior is practiced, its efficacy has not been studied.\n To assess the effects of incorporating EBT as a motivational factor into a cardiovascular screening program in the context of either intensive case management (ICM) or usual care by assessing its impact over 1 year on a composite measure of projected risk.\n Randomized controlled trial with a 2 x 2 factorial design and 1 year of follow-up.\n A consecutive sample of 450 asymptomatic active-duty US Army personnel aged 39 to 45 years stationed within the Washington, DC, area and scheduled to undergo a periodic Army-mandated physical examination were enrolled between January 1999 and March 2001 (mean age, 42 years; 79% male; 66 [15%] had coronary calcification; mean [SD] predicted 10-year coronary risk, 5.85% [3.85%]).\n Patients were randomly assigned to 1 of 4 intervention arms: EBT results provided in the setting of either ICM (n = 111) or usual care (n = 119) or EBT results withheld in the setting of either ICM (n = 124) or usual care (n = 96).\n The primary outcome measure was change in a composite measure of risk, the 10-year Framingham Risk Score (FRS).\n Comparing the groups who received EBT results with those who did not, the mean absolute risk change in 10-year FRS was +0.30 vs +0.36 (P =.81). Comparing the groups who received ICM with those who received usual care, the mean absolute risk change in 10-year FRS was -0.06 vs +0.74 (P =.003). Improvement or stabilization of cardiovascular risk was noted in 157 patients (40.2%). In multivariable analyses predicting change in FRS, after controlling for knowledge of coronary calcification, motivation for change, and multiple psychological variables, only the number of risk factors (odds ratio, 1.42; 95% confidence interval, 1.16-1.75 for each additional risk factor) and receipt of ICM (odds ratio, 1.62; 95% confidence interval, 1.04-2.52) were associated with improved or stabilized projected risk.\n Using coronary calcification screening to motivate patients to make evidence-based changes in risk factors was not associated with improvement in modifiable cardiovascular risk at 1 year. Case management was superior to usual care in the management of risk factors.", "To examine the potential impact of visual personalized biomarker feedback on intention to stop smoking and to evaluate possible underlying causal pathways.\n This study is a pilot for a randomized controlled trial. Outcome measures were assessed immediately after the intervention and at 4 weeks follow-up.\n Twenty-three smokers attending a cardiovascular outpatient clinic in London were randomly allocated to one of two groups: to either receive a print-out of an ultrasound image of their carotid artery showing atherosclerotic plaque alongside an image of a disease-free artery, or to receive routine verbal feedback.\n The intervention significantly increased perceptions of susceptibility to smoking-related diseases (Cohen's h=0.99) and led to increases both in engagement in smoking cessation behaviours (Cohen's h=0.79) and intentions to stop smoking (Cohn's d=0.44). The latter was moderated by self-efficacy: the intervention increased intention to stop smoking only in people with higher levels of self-efficacy with regard to stopping smoking.\n This study provides preliminary support for the potential effectiveness of personalized biomarker feedback to increase intentions to stop smoking. It also highlights the need to target and increase self-efficacy in smoking cessation interventions.", "Cardiovascular disease (CVD) is largely preventable through appropriate risk-factor modification. We sought to compare effects of comprehensive cardiac risk factor screening with and without computed tomography (CT) imaging of the coronary arteries on behavior change related to cardiac risk in postmenopausal women.\n 56 postmenopausal women were randomized to alternative screening programs and followed for 1 year.\n Subjects randomized (n=26) to the CT imaging group were shown images of their coronary arteries and received an interpretation from a radiologist. Most subjects in the CT group had a very low-risk (73.1%) coronary calcification score at baseline. Systolic blood pressure, total cholesterol, triglyceride, LDL, and cholesterol/HDL ratio declined significantly in the conventional screening group, but not in the CT imaging group (P<0.05). As compared to baseline values, study participation lead to significant reductions in total cholesterol, HDL, LDL, and blood pressure at 6 months (P<0.05) and triglyceride (P<0.05) at 12 months.\n CVD risk-screening programs can facilitate cardiac risk reduction in women, but these data do not support an independent benefit of coronary CT imaging in a low-to-moderate risk group. The possibility of a deleterious effect of imaging on patient commitment to lifestyle changes is suggested.", "Two laboratory studies were conducted in which a new type of intervention was used to reduce ultraviolet radiation (UV) exposure from tanning booth use among college students (Time 1 Ns=70 and 134). The intervention uses UV photography to highlight the damage to facial skin caused by previous UV exposure. When the authors controlled for baseline measures of booth use, students in both studies who viewed their UV photographs reported less booth use at a follow-up session 3-4 weeks later than did students not shown a copy of their photograph. Also, in both studies, the decline in use was significantly mediated by a Tanning Cognition Index composed of variables suggested by the prototype-willingness (prototype) model of health risk: tanning attitudes, tanner prototypes, and willingness to engage in risky UV exposure.", "Results from a single case-control study suggest that skin self-examination (SSE) has the potential to reduce mortality from melanoma by 63%. Despite these encouraging results, SSE rates are low. Few prospective studies of interventions to increase SSE in high-risk cohorts have been performed. The purpose of this study was to assess the impact of a brief nurse-delivered intervention using digital photographs on patients' adherence to performing SSE. DESIGN SETTING/PARTICIPANTS: Patients at high risk for melanoma skin cancer (five or more dysplastic nevi) (N=100) were recruited from the outpatient Pigmented Lesion Clinic at Memorial Sloan-Kettering Cancer Center. All participants had baseline whole-body digital photography as part of their clinical evaluation.\n Patients were randomized: Group A (n =49) received a teaching intervention (physician and nurse education module) with a photo book (personal whole-body photographs compiled in the form of a booklet, with nurse instruction on how to use the photographs); and Group B (n =51) received the teaching intervention only without a photo book. MAIN OUTCOMES/MEASURES: Self-administered questionnaires were provided at three intervals: baseline, post-teaching intervention, and at the 4-month post-baseline visit. To assess adherence with SSE, patients were asked, \"How many times in the past 4 months did you (or someone else) usually, thoroughly examine your skin?\"\n In Group A (teaching intervention with photo book), 10.2% of the patients at baseline reported skin examination three or more times during the past 4 months, while 61.2% reported skin examination three or more times at the 4-month follow-up (p =0.039 for paired comparison). In Group B (teaching intervention only), nearly 20% of the patients at baseline reported skin examination three or more times during the past 4 months, while 37% reported skin examination three or more times at the 4-month follow-up (p =0.63). The increase in reported skin examination was compared between the two groups (>51% v >17.6%, p =0.001).\n The results suggest that a brief nurse-delivered intervention is effective at increasing patient adherence with SSE. Utilizing digital photographs as an adjunct to screening appeared to increase patient adherence to performing SSE.", "We examined whether making smokers aware that they had developed peripheral atherosclerosis would improve smoking cessation.\n Smokers selected from the general population were randomly allocated to undergo high-resolution B-mode ultrasonography of their carotid and femoral arteries. All smokers received quit-smoking counseling. Smokers with > or =1 atherosclerotic plaque were given two photographs of a plaque with a relevant explanation. Quit rates were assessed by telephone 6 months later.\n Seventy-nine smokers did not undergo ultrasonography (A). Among the 74 smokers submitted to ultrasonography, 20 had no plaque (B) and 54 had > or =1 plaque (C). Quit rates were, respectively, 6.3, 5.0, and 22.2% in groups A, B, and C. Quit rates were higher in smokers submitted to ultrasonography (B + C vs A; P = 0.031) and in those receiving photographs (C vs A + B; P = 0.003). Smoking cessation was independently associated with intervention C (OR = 6.2; 95% CI = 1.8-21) and a white-collar job but not with age or gender.\n Providing smokers with photographs demonstrating atherosclerosis on their own person was an effective adjunct to physician's advice to quit smoking. Since ultrasonography is used increasingly often in clinical practice for cardiovascular risk stratification, this can provide an additional opportunity and means to deter smokers from smoking.\n Copyright 2002 American Health Foundation and Elsevier Science (USA).", "Two appearance-based interventions designed to increase sun protection intentions and behaviors were evaluated. Sixty-eight college students in Experiment 1 and 76 beachgoers in Experiment 2 were randomly assigned to receive or not receive a photoaging (premature wrinkling and age spots) information intervention and, separately, to receive or not receive a novel ultraviolet (UV) photo intervention that makes the negative-appearance consequences of UV exposure more salient. Both experiments indicated that the UV photo intervention significantly increased intentions to use sunscreen in the future. A follow-up conducted with the beach sample indicated that UV photo information also produced greater protective behaviors for incidental sun exposure and that the combination of UV photo and photoaging information resulted in substantially lower reported sunbathing.", "To examine the longer term efficacies of exposure to UV photographs and photoaging information (e.g., wrinkles and age spots) for increasing sun protection intentions and behaviors of young adults.\n Randomized controlled trial with 4- to 5-month and 12-month follow-ups.\n Participants' self-reported sun protection intentions assessed immediately after the interventions, and both self-reported sun protection behaviors and an objective assessment (via spectrophotometry) of skin color change measured at the end of summer (4-5 months following interventions) and 1 year following interventions.\n Both interventions resulted in immediate positive effects on future sun protection intentions. Both interventions showed objective evidence of less skin darkening at the postsummer follow-up, with those in the photoaging information condition also reporting more sun protective behavior and continuing to show less skin darkening 1 year after intervention. There was also evidence that effects of photoaging information on subsequent skin color change were mediated by the earlier positive effect photoaging information had on participants' intentions to sun protect and their subsequent sun protection behaviors.\n UV photo and photoaging-information interventions each show promise as a brief and relatively inexpensive approach for motivating sun protection practices that may reduce skin cancer risk.\n Copyright (c) 2007 APA, all rights reserved." ]

[ "14665488", "19017587", "15172892", "1731596", "15786890", "7808991", "9834911", "22410137", "22150035", "14733856" ]

[ "Initial experience on rifampin and pyrazinamide vs isoniazid in the treatment of latent tuberculosis infection among patients with silicosis in Hong Kong.", "Adverse events with 4 months of rifampin therapy or 9 months of isoniazid therapy for latent tuberculosis infection: a randomized trial.", "Treatment completion and costs of a randomized trial of rifampin for 4 months versus isoniazid for 9 months.", "A double-blind placebo-controlled clinical trial of three antituberculosis chemoprophylaxis regimens in patients with silicosis in Hong Kong. Hong Kong Chest Service/Tuberculosis Research Centre, Madras/British Medical Research Council.", "Is the combination of pyrazinamide plus rifampicin safe for treating latent tuberculosis infection in persons not infected by the human immunodeficiency virus?", "[Compliance and tolerance of new antitubercular short-term chemopreventive regimens in childhood--a pilot project].", "[Compliance, tolerance and effectiveness of a short chemoprophylaxis regimen for the treatment of tuberculosis].", "Latent tuberculosis infection treatment for prison inmates: a randomised controlled trial.", "Three months of rifapentine and isoniazid for latent tuberculosis infection.", "[Treatment of latent tuberculosis among homeless population. Comparison between wo therapeutic approaches]." ]

[ "To compare the adverse effects and treatment adherence between 2 months of rifampin plus pyrazinamide (2RZ) and 6 months of isoniazid (6H).\n Patients with silicosis in Hong Kong are at high risk of acquiring tuberculosis. A previous study showed that treatment with 6H reduced the risk of silico-tuberculosis by one half.\n Patients with silicosis and a Mantoux skin test reaction > or =10 mm were randomized to receive either 2RZ or 6H daily. Liver function testing was done monthly during the initial 2 months. The adverse effects and treatment adherence were compared between the two regimens.\n Forty patients (mean age, 61.6 +/- 9.1 years) and 36 patients (mean age, 57.6 +/- 9.7 years) were randomized to the 2RZ and 6H arms, respectively (p > 0.05) [+/- SD]. Baseline characteristics were comparable. Nineteen patients in the 2RZ arm had peak alanine transaminase (ALT) levels > 1.5 times the upper limit of normal (ULN) in comparison with only five study subjects of the 6H arm (47.5% vs 13.9%, p < 0.01). Fourteen patients (35%) in the 2RZ arm and 1 patient (2.8%) in the 6H arm had peak ALT levels more than five times the ULN (p < 0.001). Only seven patients had symptoms suggestive of hepatitis; none of the patients had jaundice. All recovered after withholding treatment. In the 2RZ study arm, none of the baseline characteristics predicted hepatotoxicity. Other adverse effects were generally mild and comparable between both study arms. Treatment was stopped prematurely in 45% and 36.1% of patients in the 2RZ and 6H arms, respectively (p = 0.43). The main reasons were hepatotoxicity for the 2RZ arm and voluntary withdrawal after experiencing other minor adverse effects for the 6H arm.\n A higher incidence of hepatotoxicity was associated with rifampin plus pyrazinamide than isoniazid in the treatment of latent tuberculosis infection among patients with silicosis in Hong Kong.", "Treatment of latent tuberculosis infection with isoniazid for 9 months is complicated by poor patient adherence and the need for close follow-up of side effects, especially hepatotoxicity. Shorter and safer regimens are needed.\n To compare the frequency of adverse events and treatment completion in 2 treatment regimens for latent tuberculosis infection.\n Multicenter, randomized, open-label trial.\n Tuberculosis clinics located in university hospitals in Canada, Brazil, and Saudi Arabia.\n 847 patients without a contraindication for rifampin and requiring treatment for latent tuberculosis infection.\n Four months of daily rifampin therapy or 9 months of daily isoniazid therapy.\n Grade 3 to 4 drug-related adverse events resulting in drug discontinuation (primary outcome), and on-time treatment completion, grade 1 to 2 drug-related adverse events, and changes in liver enzymes and hematologic variables (secondary outcomes).\n Seventeen of 422 participants who started isoniazid therapy developed grade 3 to 4 adverse events compared with 7 of 418 who started rifampin therapy (risk difference [rifampin minus isoniazid], -2.3% [95% CI, -5% to -0.1%]; P = 0.040). Grade 3 or 4 hepatitis occurred in 16 of 422 isoniazid recipients compared with 3 of 418 rifampin recipients (risk difference, -3.1% [CI, -5% to -1%]; P = 0.003). Grade 1 or 2 adverse events attributed to study drugs occurred with similar frequency. Asymptomatic reduction in platelet and leukocyte counts were more frequent in rifampin recipients. More patients completed rifampin treatment (78%) than isoniazid treatment (60%) (difference, 18% [CI, 12% to 24%]; P < 0.001]).\n The study did not measure efficacy, and the open-label design may increase the chance of bias in ascertainment of adverse events.\n Treatment of latent tuberculosis with 4 months of rifampin leads to fewer serious adverse events and better adherence than 9 months of isoniazid. These findings justify a large-scale trial to compare the efficacy of rifampin with that of isoniazid.", "There is little published information regarding treatment completion, safety, and efficacy of rifampin administered daily for 4 months-a recommended alternative to 9 months of isoniazid for therapy of latent tuberculosis infection. In an open-label randomized trial at a university-affiliated respiratory hospital, consenting patients whose treating physician had recommended therapy for latent tuberculosis infection were randomized to daily self-administered rifampin for 4 months or daily self-administered isoniazid for 9 months. Of 58 patients randomized to rifampin, 53 (91%) took 80% of doses, and 50 (86%) took more than 90% of doses within 20 weeks compared with 44 (76%) and 36 (62%) who took 80 and 90%, respectively, of doses of isoniazid within 43 weeks (relative risks: 80% of doses, 1.2 [95% confidence interval: 1.02, 1.4]; 90% of doses, 1.4 [1.1, 1.7]). Adverse events resulted in permanent discontinuation of therapy for two (3%) patients taking rifampin, and for eight (14%) patients taking isoniazid. Three patients developed drug-induced hepatitis--all were taking isoniazid. Total costs of therapy were significantly higher for isoniazid. In conclusion, completion of therapy was significantly better with 4 months of rifampin and major side effects were somewhat lower. Further studies are needed to assess the safety and efficacy of the 4-month rifampin regimen.", "A double-blind placebo-controlled trial of antituberculosis chemoprophylaxis was undertaken in sillicotic subjects in Hong Kong where there is a high prevalence of both silicosis and tuberculosis. During 1981 to 1987, 679 Chinese men with silicosis, with no history of previous antituberculosis chemotherapy and no evidence of active tuberculosis, were admitted to the trial and have been studied for between 2 and 5 yr. They were allocated at random to four series-rifampin for 12 wk (R3), isoniazid and rifampin for 12 wk (HR3), isoniazid alone for 24 wk (H6), or placebo (Pl)--in a double-blind design with matching placebos for isoniazid and rifampin as appropriate. Active pulmonary tuberculosis developed more frequently during the 5 yr in the placebo series than in the three chemoprophylaxis series (p less than 0.01, log-rank test), but there were no significant differences between the chemoprophylaxis series. The estimated proportions of patients with active pulmonary disease in the placebo series were 9% at 2 yr, 15% at 3 yr, 20% at 4 yr, and 27% at 5 yr. In contrast, in the three chemoprophylaxis series combined they were 5, 8, 10, and 13%, respectively. Thus, although chemoprophylaxis halved the proportion of patients in whom tuberculosis developed, this proportion was still substantial. There was no evidence that chemoprophylaxis led to the selection of drug-resistant strains of bacilli. Adverse effects were reported with a similar frequency in all four series, suggesting that few were drug related. During the first 12 wk, hepatic toxicity was reported in 8 (1%) patients (3 HR3, 3 H6, and 2 Pl), but only 1 (H6) had symptomatic hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)", "Nine public health care centres in four Spanish cities.\n To evaluate the efficacy and safety of 2 months of rifampicin (R) plus pyrazinamide (Z) therapy (2RZ) compared with a 6-month course of isoniazid therapy (6H) for treating latent tuberculosis infection (LTBI).\n Multicentered, randomised, comparative and prospective trial conducted in HIV-seronegative contacts of infectious pulmonary TB cases.\n Of 352 individuals, 199 received 6H and 153 2RZ; 73% of contacts receiving 6H and 71% receiving 2RZ completed treatment (P = 0.73). Treatment interruption due to hepatotoxicity (ALT/AST > 5 times upper limit of normal) was observed in 10% of contacts in the 2RZ group and in 2.5% of the 6H group (P = 0.007). This higher than expected rate of hepatotoxicity in the 2RZ arm led to premature termination of the study. Severe or fatal liver injury was not detected. Liver function tests normalised after discontinuation of treatment. We conclude that the use of RZ should only be considered when other regimens are unsuitable and intensive monitoring of liver function is feasible.", "Efficacy of preventive chemotherapy in tuberculosis-infected children depends to a great extend on medical compliance and drug tolerability. Two new short-course chemoprevention-regimes of tuberculosis--four months Rifampin (A) and two months Rifampin plus Pyrazinamide (B)--were compared with the well established regimen of six months Isoniacid (C). 150 children (mean age 3.6 years with Tb conversion) were randomly allocated to these three regimens. 13 patients were non-compliant, in terms of interview, urinary INH-test strips, urine colour and prescription frequency: 7 in group C and 3 in group A and B, respectively. Adverse effects were observed in 5 patients: 3 in group C and 1 in group A and B. 1 child (group B) developed tuberculosis two years after stopping short course chemoprevention. Good compliance (94%) as well as neglectable risks of adverse effects (2%) justify further controlled studies to evaluate the efficacy of short course chemoprevention in childhood.", "To evaluate compliance, side effects and the efficacy of a short course of chemoprophylaxis for tuberculosis with isoniazid plus rifampin during 3 months, compared with the classic course of isoniazid for 9 months.\n Prospective, comparative, randomized and open study of patients with the suitable criteria for chemoprophylaxis, in accordance with the guidelines of the Centers for Disease Control of 1990. Patients were divided into 2 groups: the group of isoniazid plus rifampin, received isoniazid (300 mg per day) plus rifampin (600 mg per day) for 3 months, and the group of isoniazid, that received isoniazid at a dose of 300 mg per day for 9 months.\n 238 patients were included, of which 42 refused chemoprophylaxis. Of the remaining 196 patients, 98 were included in each group. Both groups were comparable at base level. The side effects, neither light nor severe showed significant differences. The appearance of adverse effects obliged the suspension of treatment in 7 patients in group isoniazid and of 9 patients in group isoniazid plus rifampin. Three patients in group isoniazid plus rifampin and 11 in group isoniazid stopped treatment (OR 4.14, 95% CI 1.02-19.45; p = 0.04). Efficacy was comparable in the two groups; only one case of tuberculosis was detected in a patient who gave up chemoprophylaxis at day 30.\n Tolerance in group isoniazid plus rifampin compared with group I was similar. Compliance was better in the short-term group with a lower percentage of abandonment. On comparing, both groups have shown similar efficacy in preventing the appearance of tuberculosis.", "A prison in northern Taiwan.\n To compare safety and the completion rate of the 4-month daily rifampicin regimen (4R) vs. the standard 6-month daily isoniazid regimen (6H) for latent tuberculosis infection (LTBI) in prison inmates.\n This was an open-label randomised trial among human immunodeficiency virus negative male inmates. Inmates without active tuberculosis (TB) who tested positive for both the tuberculin skin test and QuantiFERON®-TB Gold In-Tube were eligible, but those with baseline glutamic pyruvic transaminase (GPT) levels ≥ 120 U/l, bilirubin levels ≥ 2.4 U/l or a platelet count < 150 k/mm(3) were excluded. The primary endpoint was any adverse event that resulted in discontinuation of LTBI treatment.\n Participants (n = 373; 14% hepatitis B surface antigen positive, 21% anti-hepatitis C virus [HCV] positive) were randomised (stratified by hepatitis B virus, HCV status and 2-year prison term) to receive either 4R or 6H under directly observed treatment. The 4R group (n = 190) was less likely to experience an adverse event leading to discontinuation of treatment (2% vs. 12%, P < 0.001 for all adverse events; 0% vs. 8%, P < 0.001 for hepatotoxicity), and more likely to complete LTBI treatment (86% vs. 78%, P = 0.041), compared with the 6H group (n = 183).\n 4R is safer and has a higher completion rate than 6H as treatment for LTBI among male prison inmates.", "Treatment of latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control and elimination. The current standard regimen of isoniazid for 9 months is efficacious but is limited by toxicity and low rates of treatment completion.\n We conducted an open-label, randomized noninferiority trial comparing 3 months of directly observed once-weekly therapy with rifapentine (900 mg) plus isoniazid (900 mg) (combination-therapy group) with 9 months of self-administered daily isoniazid (300 mg) (isoniazid-only group) in subjects at high risk for tuberculosis. Subjects were enrolled from the United States, Canada, Brazil, and Spain and followed for 33 months. The primary end point was confirmed tuberculosis, and the noninferiority margin was 0.75%.\n In the modified intention-to-treat analysis, tuberculosis developed in 7 of 3986 subjects in the combination-therapy group (cumulative rate, 0.19%) and in 15 of 3745 subjects in the isoniazid-only group (cumulative rate, 0.43%), for a difference of 0.24 percentage points. Rates of treatment completion were 82.1% in the combination-therapy group and 69.0% in the isoniazid-only group (P<0.001). Rates of permanent drug discontinuation owing to an adverse event were 4.9% in the combination-therapy group and 3.7% in the isoniazid-only group (P=0.009). Rates of investigator-assessed drug-related hepatotoxicity were 0.4% and 2.7%, respectively (P<0.001).\n The use of rifapentine plus isoniazid for 3 months was as effective as 9 months of isoniazid alone in preventing tuberculosis and had a higher treatment-completion rate. Long-term safety monitoring will be important. (Funded by the Centers for Disease Control and Prevention; PREVENT TB ClinicalTrials.gov number, NCT00023452.).", "We aimed to compare treatment adherence and toxicity of isoniazide (H) (6 months) compared with rifampicine (R) + pirazinamide (Z) (2 months) in homeless patients in latent tuberculous infection (LTBI).\n Randomized and controlled prospective study.\n We included 172 patients (116 males and 56 females) with an age average of 42.3 (12.8) years; 31 (18%) had recent conversion and 72 (41.8%) had some risk factor of hepatotoxicity. Both bivariate and multivariate analysis (p < 0.001; OR = 5.15 [2.34-11.35]) showed that the treatment was completed by 61.5% of patients administered the R+Z regimen, while it was completed only by 28.2% of those administered H for 6 months. Moreover, treatment was completed by 48.4% of Spanish or foreign patients with legal residence, while it was completed only by 28.6% of immigrant patients with no legal residence (p = 0.044 in bivariate analysis).\n The R+Z regimen for 2 months as treatment of LTBI in homeless patients displays a higher adherence than H for 6 months. There were no differences in toxicity." ]

[ "15889312", "8287317", "15040822", "16826020", "19452097", "16133653", "11484097", "1922205", "17103296", "7484282", "19252142", "17768587", "11149482", "1435170", "2671517", "12919708", "12110425", "19020919", "17291843", "15977465", "8213255", "1611221", "14669194", "19603365", "19521657", "18978624", "15129394", "7990242", "12879220", "8931030", "11079527", "9271287", "12450060", "8369985", "1566165", "12844212", "8592957", "7710725", "8675921", "15040821" ]

[ "Effect of impact exercise on bone mineral density in elderly women with low BMD: a population-based randomized controlled 30-month intervention.", "One-year psoas training can prevent lumbar bone loss in postmenopausal women: a randomized controlled trial.", "Effect of 6-month whole body vibration training on hip density, muscle strength, and postural control in postmenopausal women: a randomized controlled pilot study.", "Effect of exercise on bone mineral density and lean mass in postmenopausal women.", "[Effects of a combined weight-bearing and non-weight-bearing ( warm water) exercise program on bone mass and quality in postmenopausal women with low bone-mineral density].", "A 1-year combined weight-bearing training program is beneficial for bone mineral density and neuromuscular function in older women.", "Effect of exercise training and detraining on bone mineral density in postmenopausal women with osteoporosis.", "Prevention of postmenopausal osteoporosis. A comparative study of exercise, calcium supplementation, and hormone-replacement therapy.", "A multi-component exercise regimen to prevent functional decline and bone fragility in home-dwelling elderly women: randomized, controlled trial.", "The effects of calcium supplementation (milk powder or tablets) and exercise on bone density in postmenopausal women.", "Strength training preserves the bone mineral density of postmenopausal women without hormone replacement therapy.", "Physical training preserves bone mineral density in postmenopausal women with forearm fractures and low bone mineral density.", "Resistance training over 2 years increases bone mass in calcium-replete postmenopausal women.", "Bone density in postmenopausal women: high impact vs low impact exercise.", "Efficacy of nonloading exercises in prevention of vertebral bone loss in postmenopausal women: a controlled trial.", "Effect of alendronate and exercise on bone and physical performance of postmenopausal women: a randomized controlled trial.", "Change in bone mass distribution induced by hormone replacement therapy and high-impact physical exercise in post-menopausal women.", "Effect of antioxidants combined to resistance training on BMD in elderly women: a pilot study.", "The effects of hormone replacement therapy and resistance training on spine bone mineral density in early postmenopausal women.", "Effect of whole-body vibration exercise on lumbar bone mineral density, bone turnover, and chronic back pain in post-menopausal osteoporotic women treated with alendronate.", "Effects of aerobic training on bone mineral density of postmenopausal women.", "The effects of calcium supplementation and exercise on bone density in elderly Chinese women.", "High-frequency vibration training increases muscle power in postmenopausal women.", "[Effect of whole body vibration exercise on osteoporotic risk factors].", "Unipedal standing exercise and hip bone mineral density in postmenopausal women: a randomized controlled trial.", "Physiological adaptations to strength and circuit training in postmenopausal women with bone loss.", "A randomized, prospective study of the effects of Tai Chi Chun exercise on bone mineral density in postmenopausal women.", "Effects of high-intensity strength training on multiple risk factors for osteoporotic fractures. A randomized controlled trial.", "Efficacy of home-based exercise for improving quality of life among elderly women with symptomatic osteoporosis-related vertebral fractures.", "The effects of a community exercise program on fracture risk factors in older women.", "Musculoskeletal responses to high- and low-intensity resistance training in early postmenopausal women.", "Randomized placebo-controlled trial of brisk walking in the prevention of postmenopausal osteoporosis.", "The effect of strength training combined with bisphosphonate (etidronate) therapy on bone mineral, lean tissue, and fat mass in postmenopausal women.", "The effects of walking at the anaerobic threshold level on vertebral bone loss in postmenopausal women.", "The effect of high-intensity trunk exercise on bone mineral density of postmenopausal women.", "Effects of exercise on bone mineral density in calcium-replete postmenopausal women with and without hormone replacement therapy.", "Effects of a one-year high-intensity versus low-intensity resistance training program on bone mineral density in older women.", "Therapeutic exercise in the prevention of bone loss. A controlled trial with women after menopause.", "Impact of a 12-month exercise program on the physical and psychological health of osteopenic women.", "Prevention of postmenopausal bone loss by a low-magnitude, high-frequency mechanical stimuli: a clinical trial assessing compliance, efficacy, and safety." ]

[ "Evidence of the effect of exercise on bone loss comes mainly from studies in voluntary postmenopausal women, and no population-based, long-term interventions have been performed. The purpose of this population-based, randomized, controlled trial was to determine the effect of long-term impact exercise on bone mass at various skeletal sites in elderly women with low bone mineral density (BMD) at the radius and hip. Participants (n=160) were randomly assigned to 30 months either of supervised and home-based impact exercise training or of no intervention. The primary outcome measures were femoral neck, trochanter and total hip BMD, and the secondary outcomes were bone density measures at the radius and calcaneum. Outcomes were assessed at baseline, 12 months and 30 months using blinded operators. The analyses were performed on an intention-to-treat analysis. Mean femoral neck and trochanter BMD decreased in the control group [-1.1%, 95% confidence interval (CI) -0.1% to -2.1% and -1.6%, 95% CI -0.4% to -2.7%], while no change occurred in the exercise group. Mean trochanter BMC decreased more in the control group (-7.7%, 95% CI -9.7% to -5.6% vs. -2.9%, 95% CI -5.3 to -0.9). There were six falls that resulted in fractures in the exercise group and 16 in the control group during the 30-month intervention (P=0.019). A significant bone loss occurred in both groups at the radius and calcaneum. In multivariate analysis, weight gain was associated with increased BMD and BMC at all femur sites both in the exercise group and in the pooled groups. In conclusion, impact exercise had no effect on BMD, while there was a positive effect on BMC at the trochanter. Exercise may prevent fall-related fractures in elderly women with low bone mass.", "On the premise that bone response to exercise is locally controlled, we conducted a randomized trial to evaluate the effects of a 1-year training of psoas muscles (treatment group: TG) versus a 1-year training of deltoid muscles (control group: CG) on the lumbar trabecular bone mineral density (TBMD). TBMD was measured with computed tomography scan. Seventy-eight subjects were included and 67 completed the study. Intention to treat analysis revealed no significant change in TBMD from 0 to 12 months. Data analysis in the 67 remaining women, including both assiduous and nonassiduous subjects, revealed greater bone loss in CG than in TG although the difference was not significant. Similar analysis in a subgroup of subjects who performed the exercises assiduously (TG: n = 23, CG: n = 26) showed that the mean bone loss of all four vertebrae from 0 to 12 months was significantly greater in the CG (-8.87 +/- 12.75 mg/cm3, mean +/- SD) than in the TG (0.14 +/- 11.21 mg/cm3, mean +/- SD, P = 0.01). These results suggest that continuous 1-year psoas training can prevent lumbar bone loss in postmenopausal women and support the hypothesis of local action of physical activity.", "High-frequency mechanical strain seems to stimulate bone strength in animals. In this randomized controlled trial, hip BMD was measured in postmenopausal women after a 24-week whole body vibration (WBV) training program. Vibration training significantly increased BMD of the hip. These findings suggest that WBV training might be useful in the prevention of osteoporosis.\n High-frequency mechanical strain has been shown to stimulate bone strength in different animal models. However, the effects of vibration exercise on the human skeleton have rarely been studied. Particularly in postmenopausal women-who are most at risk of developing osteoporosis-randomized controlled data on the safety and efficacy of vibration loading are lacking. The aim of this randomized controlled trial was to assess the musculoskeletal effects of high-frequency loading by means of whole body vibration (WBV) in postmenopausal women.\n Seventy volunteers (age, 58-74 years) were randomly assigned to a whole body vibration training group (WBV, n = 25), a resistance training group (RES, n = 22), or a control group (CON, n = 23). The WBV group and the RES group trained three times weekly for 24 weeks. The WBV group performed static and dynamic knee-extensor exercises on a vibration platform (35-40 Hz, 2.28-5.09g), which mechanically loaded the bone and evoked reflexive muscle contractions. The RES group trained knee extensors by dynamic leg press and leg extension exercises, increasing from low (20 RM) to high (8 RM) resistance. The CON group did not participate in any training. Hip bone density was measured using DXA at baseline and after the 6-month intervention. Isometric and dynamic strength were measured by means of a motor-driven dynamometer. Data were analyzed by means of repeated measures ANOVA.\n No vibration-related side effects were observed. Vibration training improved isometric and dynamic muscle strength (+15% and + 16%, respectively; p < 0.01) and also significantly increased BMD of the hip (+0.93%, p < 0.05). No changes in hip BMD were observed in women participating in resistance training or age-matched controls (-0.60% and -0.62%, respectively; not significant). Serum markers of bone turnover did not change in any of the groups.\n These findings suggest that WBV training may be a feasible and effective way to modify well-recognized risk factors for falls and fractures in older women and support the need for further human studies.", "To evaluate the effects of physical activity on bone mineral density, bone mineral content, and lean mass in postmenopausal, overweight/obese women.\n We conducted a 12-month randomized controlled aerobic exercise intervention versus control in 173 sedentary, overweight/obese, postmenopausal women, aged 50-75 yr. The exercise prescription consisted of >or=45 min of moderate-intensity aerobic exercise (60-75% of maximal heart rate), 5 d.wk for 12 months. Control participants attended 45-min stretching sessions once a week. Ninety-eight percent (N=170) completed the trial. Exercisers averaged 172 min.wk (SD=89) of exercise and expended 3828 kJ.wk (SD=2053). We assessed body fat, total lean mass, and total body bone mineral density and content using dual-energy x-ray absortiometry (DXA). We compared baseline with 12-month changes in exercisers versus controls.\n Exercisers lost significantly more weight than stretchers (1.3-kg loss vs 0.1-kg gain, P=0.01). However, no differences between exercisers and controls in the change from baseline to 12 months were detected: exercisers' average bone mineral density increased by 0.005 g.cm and controls' by 0.003 g.cm (P=0.61). Similarly, no significant differences were detected for bone mineral content. Lean mass increased by 0.2 kg in both groups (P=0.84).\n Overall, the results from this randomized controlled study suggest that a yearlong moderate-intensity aerobic exercise intervention does not affect total body bone mineral density, bone mineral content, or lean mass in overweight/obese postmenopausal women.", "To evaluate the effects of a combined weight- and non weight-bearing (water) exercise program on bone mass and quality in postmenopausal women with low bone mineral density.\n 125 post-menopausal women with osteopenia/osteoporosis underwent a bone mass (Dual-Energy X-ray Absorbimetry, DEXA) and bone tissue quality (phalangeal osteosonography) evaluation. 58 of the participants took part in an 11-month specific exercise program (E). The other represented a control group (C) that did not exercise. At the end of the exercise program all the participants were re-evaluated.\n Concerning bone mass, within and between groups data analysis showed that t-score, measured at neck of femur, significantly increased in E (p < 0.05). No differences were instead detected for all the other parameters. With respect to osteosonography, group C showed a significant decrease of all bone quality parameters (p < 0.05), whereas E showed no differences after the exercise program.\n The results showed that a specific exercise program targeting osteoporosis is useful to reduce the physiological bone loss and to maintain a good bone quality in a group of postmenopausal women with low bone mineral density.", "Forty-eight community living women 66-87 years old volunteered to participate in a 12-month prospective, randomized, controlled, trial. The aim was to determine if a combined weight-bearing training program twice a week would be beneficial to bone mineral density and neuromuscular function. The participants were pairwise age-matched and randomly assigned to either an exercise group (n=24) or a control group (n=24). Twenty-one subjects in the intervention group and 19 in the control group completed the study. The exercise program lasted for 50 min and consisted of a combination of strengthening, aerobic, balance and coordination exercises. The mean percentage of scheduled sessions attended for the exercise group was 67%. At the completion of the study, the intervention group showed significant increments in bone mineral density of the Ward's triangle (8.4%, P<0.01) as well as improvement in maximum walking speed (11.4%, P<0.001) and isometric grip strength (9.9%, P<0.05), as compared to the control group. The conclusion was that a combined weight-bearing training program might reduce fracture risk factors by improving bone density as well as muscle strength and walking ability. This program could be suitable for older community living women in general, and might, therefore, have important implications for fracture prevention.", "We examined the effect of exercise training and detraining on bone mineral density (BMD) in postmenopausal women with osteoporosis. Thirty-five postmenopausal women with osteoporosis, aged 53-77 years, were randomly assigned to three groups: a control group (n = 20), a 2-year exercise training group (n = 8), and an 1-year exercise training plus 1-year detraining group (n = 7). Exercise training consisted of daily brisk walking and gymnastic training. Calcium lactate, 2.0 g, and 1alpha-hydroxyvitamin D3, 1 microg were supplied daily to all subjects. No significant differences in initial lumbar BMD, measured by dual-energy X-ray absorptiometry (DXA) were found among the three groups. The mean percent change in BMD compared with the baseline was significantly higher at 1 and 2 years in the exercise training group and at 1 year in the detraining group than in the control group, and did not differ significantly at 2 years between the detraining and control groups. These findings indicate that our exercise training program led to a significant increase in lumbar BMD in postmenopausal women with osteoporosis compared with the control, but that the BMD reverted toward a level that was not significantly different from the control with detraining. Continued exercise training is needed to maintain the bone mass gained through exercise training.", "Osteoporosis among older women is a major public health problem. We studied the effects of three approaches to the prevention of osteoporosis in women with low bone density.\n One hundred twenty postmenopausal women (mean [+/- SD] age, 56 +/- 4) who were selected because they had low forearm bone density were enrolled in a double-blind, placebo-controlled, randomized study comparing the effects of an exercise regimen (exercise group, n = 41), exercise plus dietary calcium supplementation (exercise-calcium group, n = 39), and exercise plus continuous replacement of estrogen and progesterone (exercise-estrogen group, n = 40). Periodically during the two-year study period, we measured the women's bone density at three forearm sites, measured indexes of calcium metabolism, and recorded symptom scores. A comparison group of 42 women (mean age, 55.5 +/- 3.1) with normal bone density was also followed for two years.\n Significant bone loss in the distal forearm occurred in the group with normal bone density (control group) and the exercise group (change, -2.7 percent and -2.6 percent of the base-line value per year, respectively). Bone loss at the distal forearm site was significantly lower in the exercise-calcium group (-0.5 percent of the base-line value per year), and bone density increased at this site in the exercise-estrogen group (+2.7 percent of the base-line value per year). Bone loss at the median forearm site was significantly lower in the exercise-calcium group (-1.3 percent of the base-line value per year) than in the exercise group (-2.4 percent), and bone density at this site increased significantly in the exercise-estrogen group (+0.8 percent of the base-line value per year). Breast tenderness occurred in 47 percent of the women in the exercise-estrogen group but in only 20 percent in the other two treatment groups. Vaginal bleeding occurred at some time in 52 percent of the women who had not had a hysterectomy in the exercise-estrogen group, as compared with 11 percent and 12.5 percent, respectively, in the exercise and exercise-calcium groups.\n In postmenopausal women with low bone density, bone loss can be slowed or prevented by exercise plus calcium supplementation or estrogen-progesterone replacement. Although the exercise-estrogen regimen was more effective than exercise and calcium supplementation in increasing bone mass, it also caused more side effects.", "Summary: This study showed that combination of strength, balance, agility and jumping training prevented functional decline and bone fragility in home-dwelling elderly women. The finding supports the idea that it is possible to maintain good physical functioning by multi-component exercise program and thus postpone the age-related functional problems.\n This 1-year randomized, controlled exercise intervention trial assessed the effects of two different training programs and their combination on physical functioning and bone in home-dwelling elderly women.\n One hundred and forty-nine healthy women aged 70-78 years were randomly assigned into: group 1-resistance training (RES), group 2-balance-jumping training (BAL), group 3-combination of resistance and balance-jumping training (COMB), and group 4-controls (CON). Self-rated physical functioning, leg extensor force, dynamic balance, and bone mass and structure were measured.\n Self-rated physical functioning improved in the COMB group, but was reduced in the CON group; the mean inter-group difference was 10% (95% CI: 0-22%). Mean increase in the leg extensor force was higher in the RES (14%; 4-25%) and COMB (13%; 3-25%) compared with the CON groups. Dynamic balance improved in the BAL (6%; 1-11%) and in the COMB (8%; 3-12%) groups. There were no inter-group differences in BMC at the proximal femur. In those COMB women who trained at least twice a week, the tibial shaft structure weakened 2% (0-4%) less than those in the CON group.\n Strength, balance, agility, and jumping training (especially in combination) prevented functional decline in home-dwelling elderly women. In addition, positive effects seen in the structure of the loaded tibia indicated that exercise may also play a role in preventing bone fragility.", "The etiology of age-related bone loss is unclear but both lack of exercise and dietary calcium deficiency have been implicated in its causation. This 2-year randomized placebo-controlled study was designed to examine the effects of increased dietary calcium and exercise in 168 women who were more than 10 years postmenopausal. The subjects were randomized into one of 4 groups: placebo, milk powder containing 1 g of calcium, calcium tablets 1 g/night, and calcium tablets 1 g/night and an exercise regimen. The exercise group aimed to undertake 4 h of extra weight-bearing exercise per week and were undertaking 10% more activity than other groups at 2 years. Bone mineral density at the lumbar spine, three hip sites, and two sites of the tibia close to the ankle joint were measured at 6 month intervals. Dietary intake was evaluated by a weighed food record, exercise was evaluated by an exercise diary, and blood and urine samples were obtained to examine effects on calcium homeostasis. Individual data points were compared using repeated measures ANOVA and least squares regression. Calcium supplementation by either the calcium tablets or the milk powder resulted in cessation of bone loss at the intertrochanteric hip site (placebo, calcium tablets, calcium and exercise, milk powder -0.81, +0.17, +0.23, and +0.07% per year, respectively; p < 0.05 for all supplementation groups compared with placebo) with similar results at the trochanteric hip site. The calcium and exercise group had less bone loss at the femoral neck site when compared with calcium supplementation alone (placebo, calcium tablets, calcium and exercise, milk powder -0.67, -0.18, +0.28, and -0.18% per year, respectively; p < 0.05 for calcium and exercise compared with calcium alone). There was a significant reduction in the rate of bone loss at the ultradistal site of the tibia (placebo, calcium tablets, calcium and exercise, milk powder -2.5, -1.6, -1.0, and -1.5% per year, respectively; p < 0.05 for all supplementation groups compared with placebo). There was no significant bone loss at the spine site in any group.(ABSTRACT TRUNCATED AT 250 WORDS)", "The study was designed to evaluate the effects of strength training (ST) on the bone mineral density (BMD) of postmenopausal women without hormone replacement therapy.\n Subjects were randomized into untrained (UN) or trained (TR) groups. The TR group exercised three ST sessions per week for 24 weeks, and body composition, muscular strength, and BMD of the lumbar spine and femur neck were evaluated.\n Body weight, mass index, and fat percentage were lower after 24 weeks only in the TR group (p < .05). SR also improved the one repetition maximum test in 46% and 39% of upper and lower limbs, respectively. The percentage of demineralization was higher in the UN group than in the TR group at the lumbar spine and femoral neck (p < .05).\n Results indicated that 24 weeks of ST improved body composition parameters, increased muscular strength, and preserved BMD in postmenopausal women.", "One hundred and twelve postmenopausal women with low bone mineral density (BMD) and forearm fractures were randomized to physical training or control group. After one year the total hip BMD was significantly higher in the women in the physical training group. The results indicate a positive effect of physical training on BMD in postmenopausal women with low BMD.\n The fivefold increase in hip fracture incidence since 1950 in Sweden may partially be due to an increasingly sedentary lifestyle. Our hypothesis was that physical training can prevent bone loss in postmenopausal women.\n One hundred and twelve postmenopausal women 45 to 65 years with forearm fractures and T-scores from -1.0 to -3.0 were randomized to either a physical training or control group. Training included three fast 30-minute walks and two sessions of one-hour training per week. Bone mineral density (BMD) was measured in the hip and the lumbar spine at baseline and after one year.\n A per protocol analysis was performed, including 48 subjects in the training group and 44 subjects in the control group. The total hip BMD increased in the training group +0.005 g/cm2 (+/-0.018), +0.58%, while it decreased -0.003 g/cm2 (+/-0.019), -0.36%, (p = 0.041) in the control group. No significant effects of physical training were seen in the lumbar spine. A sensitivity intention to treat analysis, including all randomized subjects, showed no significant effect of physical training on BMD at any site.\n The results indicate a small but positive effect of physical exercise on hip BMD in postmenopausal women with low BMD.", "Understanding the stress/strain relationship between exercise and bone is critical to understanding the potential benefit of exercise in preventing postmenopausal bone loss. This study examined the effect of a 2-year exercise intervention and calcium supplementation (600 mg) on bone mineral density (BMD) in 126 postmenopausal women (mean age, 60 +/- 5 years). Assignment was by block randomization to one of three groups: strength (S), fitness (F), or nonexercise control (C). The two exercise groups completed three sets of the same nine exercises, three times a week. The S group increased the loading, while the F group had additional stationary bicycle riding with minimal increase in loading. Retention at 2 years was 71% (59% in the S group, 69% in the F group, and 83% in the C group), while the exercise compliance did not differ between the exercise groups (S group, 74 +/- 13%; F group, 77 +/- 14%). BMD was measured at the hip, lumbar spine, and forearm sites every 6 months using a Hologic 4500. Whole body BMD also was measured every 6 months on a Hologic 2000. There was no difference between the groups at the forearm, lumbar spine, or whole body sites. There was a significant effect of the strength program at the total (0.9 +/- 2.6%; p < 0.05) and intertrochanter hip site (1.1 +/- 3.0%; p < 0.01). There was a significant time and group interaction (p < 0.05) at the intertrochanter site by repeated measures. This study shows the effectiveness of a progressive strength program in increasing bone density at the clinically important hip site. We concluded that a strength program could be recommended as an adjunct lifestyle approach to osteoporosis treatment or used in combination with other therapies.", "This 1 year study examined the effect of high impact and low impact activities on bone mineral density (BMD) at the lumbar vertebrae (L2-L4) in healthy, sedentary, early postmenopausal women. Fifteen subjects whose postmenopausal status was verified by the blood levels of follicle stimulating hormone (FSH) and estradiol were chosen. These subjects were tested on the following variables: BMD via dual photon absorptiometry, heart rate response to the Balke treadmill test, percent fat via skinfolds, and a 3-d dietary analysis. Subjects were matched and then assigned randomly to one of three groups: (a) a control nonexercising group, (b) a low impact exercise group, and (c) a high impact exercise group. The control nonexercising group experienced a significant linear decrease in BMD during the study (F = 12.63, P = 0.002). Both the low and high impact exercise groups maintained BMD during the study (F = 0.04, P = 0.85; F = 1.08, P = 0.31, respectively). The difference in BMD between the low impact and the high impact exercise groups was not significant (F = 0.36, P = 0.55). In conclusion, 20 min of moderate intensity low impact or high impact exercise 3 d.wk-1 for 1 yr is effective in maintaining BMD in early postmenopausal women.", "A considerable increase in muscle strength and bone mass can be achieved in young adults through athletic exercise programs. We studied a less demanding nonloading exercise program for the back extensor muscles in postmenopausal women who were not on estrogen therapy. We randomly assigned 65 healthy Caucasian women without evidence of or risk factors for osteoporosis into an exercise group and a control group. The strength of the back extensor muscles and bone mineral density of the lumbar spine were measured at baseline and every 6 months for 2 years. In addition, a physical activity score was determined. Compliance was assessed by regular interviews and review of diaries. During the 2-year study, the mean rates of bone loss in the two groups were not statistically different. The strength of the back extensor muscles increased in both groups but significantly more (P = 0.002) in the exercise group. We conclude that postmenopausal bone loss is unaffected by a modest exercise program despite an increase in muscle strength. Nonloading muscle exercise may be ineffective in retarding vertebral bone loss in ambulatory, healthy postmenopausal women.", "In this randomized, double-blind, placebo-controlled 12-month trial we evaluated effects of weight- bearing jumping exercise and oral alendronate, alone or in combination, on the mass and structure of bone, risk factors for falling (muscle strength and power, postural sway, and dynamic balance), and cardiorespiratory fitness in postmenopausal women. A total of 164 healthy, sedentary, early postmenopausal women were randomly assigned to one of four experimental groups: (1) 5 mg of alendronate daily plus progressive jumping exercise, (2) 5 mg alendronate, (3) placebo plus progressive jumping exercise, or (4) placebo. The primary endpoint was 12-month change in bone mass and geometry (measured with dual-energy X-ray absorptiometry and peripheral computed tomography at several axial and limb sites) and physical performance; the secondary endpoint was change in biochemical markers of bone turnover. The jumping exercise was conducted an average 1.6 +/- 0.9 (mean +/- SD) times a week. Alendronate daily was effective in increasing bone mass at the lumbar spine (alendronate vs placebo 3.5%; 95% CI, 2.2-4.9%) and femoral neck (1.3%; 95% CI, 0.2-2.4%) but did not affect other bone sites. Exercise alone had no effect on bone mass at the lumbar spine or femoral neck; it had neither an additive nor an interactive effect with alendronate at these bone sites. However, at the distal tibia the mean increase of 3.6% (0.3-7.1%) in the section modulus (that is, bone strength) and 3.7% (0.1-7.3%) increase in the ratio of cortical bone to total bone area were statistically significant in the exercise group compared to the nonexercise group, indicating exercise-induced thickening of the bone cortex. Bone turnover was reduced in alendronate groups only. Alendronate had no effect on physical performance while the jumping exercise improved leg extensor power, dynamic balance, and cardiorespiratory fitness. As conclusion Alendronate is effective in increasing bone mass at the lumbar spine and femoral neck, while exercise is effective in increasing the mechanical properties of bone at some of the most loaded bone sites, as well as improving the participants' muscular performance and dynamic balance. Together alendronate and exercise may effectively decrease the risk of osteoporotic fractures.", "The purpose of this intervention trial was to determine whether changes in bone mass distribution could be observed in postmenopausal women following hormone replacement therapy (HRT) and/or high-impact physical exercise. Eighty healthy women, aged 50-57 years, at <5 years after the onset of menopause and with no previous use of HRT, were randomly assigned to one of four groups: HRT; exercise (Ex); HRT + Ex (ExHRT); and control (Co). HRT administration was conducted in a double-blind manner for 1 year using estradiol plus noretisterone acetate (Kliogest). The exercise groups participated in a 1 year progressive training program consisting of jumping and bounding activities. Subjects participated in two supervised sessions per week and were asked to perform a series of exercises at home 4 days/week. Bone measurements using a quantitative computed tomography scanner (Somatom DR, Siemens) were obtained from the proximal femur, midfemur, proximal tibia, and tibial shaft. Data were analyzed with a software program (BONALYSE 1.3) calculating density (g/cm(3)), cross-sectional area (CSA; mm(2)), and moments of inertia (I(max), I(min), I(polar)). In addition, the bone mass spectrum was determined as a function of the angular distribution around the bone mass center (polar distribution) and the distance from the bone mass center through the diaphyseal wall (radial distribution). After the 1 year period, there was an overall interaction of group x time in bone mineral density (BMD) at the proximal femur (p = 0.05) and tibial shaft (p = 0.035). Women in the ExHRT and HRT groups had increased proximal femur and tibial shaft BMD when compared with the change observed in the Co group (p = 0.024-0.011). The change was more pronounced in the cortical tibia, wherein the ExHRT group also differed from the Ex group (p = 0.038). No significant changes were found in bone CSA at any of the measured sites. The radial distribution indicated an increase of BMD in the endocortical part of the measured sites in the HRT and ExHRT groups and in the proximal tibia in the Ex group. The polar distribution showed that bone mass was redistributed in the anteroposterior direction. The changes in I(max), I(min), and I(polar) in the HRT and ExHRT groups differed from those in the Co group at the proximal femur, midfemur, and proximal tibia (p = 0.047-0.001). The Ex group also differed from the Co group in I(max) and I(polar) at the proximal tibia (p = 0.018 and 0.039, respectively). These results support the idea that HRT acts primarily at the bone-marrow interface. The exercise intervention chosen for this study contributed to the maintenance of bone mass. Our results suggest that both HRT and exercise have local effects on bone mass. The change in bone mass distribution induced by HRT and exercise may play an important role in the alteration of bone strength.", "We determined the effect of antioxidants and resistance training on bone mineral density of postmenopausal women. After 6 months, we observed a significant decrease in the lumbar spine BMD of the placebo group while other groups remained stable. Antioxidants may offer protection against bone loss such as resistance training.\n The purpose of this pilot study was to determine the effects of antioxidant supplements combined to resistance training on bone mineral density (BMD) in healthy elderly women.\n Thirty-four postmenopausal women (66.1 +/- 3.3 years) were randomized in four groups (placebo, n = 7; antioxidants, n = 8; exercise and placebo, n = 11; and exercise and antioxidants, n = 8). The 6-month intervention consisted in antioxidant supplements (600 mg vitamin E and 1,000 mg vitamin C daily) or resistance exercise (3x/week). Femoral neck and lumbar spine BMD (DXA) and dietary intakes (3-day food record) were measured before and after the intervention. A repeated measure ANOVA and non-parametric Mann-Whitney U tests were used.\n We observed a significant decrease in the placebo group for lumbar spine BMD (pre, 1.01 +/- 0.17 g/cm(2); post, 1.00 +/- 0.16 g/cm(2); P < 0.05 respectively) while it remained stable in all other groups. No changes were observed for femoral neck BMD.\n Antioxidant vitamins may offer some protection against bone loss in the same extent as resistance exercise although combining both does not seem to produce additional effects. Our results suggest to further investigate the impact of antioxidant supplements on the prevention of osteoporosis.", "This study evaluated the additive effects of hormone replacement therapy (HRT) and a 1-year site-specific resistance-training (RT) program involving two free weight exercises (i.e., squat and deadlift) 2 days/week as a strategy to reverse or attenuate bone loss at the lumbar spine in early postmenopausal women. Participants from a group of self-selected HRT or non-HRT (N=141) users were randomly assigned to RT (exercise) or no training, creating four groups: 1) non-HRT plus RT [NHRT plus exercise (n=35)]; 2) HRT plus RT [HRT plus exercise (n=37)]; 3) HRT no resistance training [HRT no exercise (n=35)]; or 4) control [non-HRT no resistance training group (n=34)]. Mean age and months past menopause did not differ between groups (52.1+/-3.0 years and 52.8+/-9.9 months, respectively). Post-menopausal status was confirmed by follicle-stimulating hormone levels > or =40 mIU/mL. Bone mineral density (BMD) of the spine was assessed by Dual Energy X-ray Absorptiometry (Hologic), at baseline and month 12. Data were analyzed using a 4 (experimental condition) x 2 (time) repeated measures multivariate analysis of variance to determine the effects of RT on HRT and non-HRT in early postmenopausal women. The main effects for group (P<0.007), time (P<0.001), and the group by time interaction (P<0.001) were each significant. Control participants experienced an average of -3.6% reduction of BMD at the spine. HRT treatment with no exercise showed bone loss of -0.66%. One year of RT produced increases in spine BMD of +0.43% and +0.70%, respectively for the NHRT plus exercise, and HRT plus exercise groups with no differences between the NHRT and HRT exercise groups. In conclusion, RT alone was as effective as HRT in preventing bone loss at the spine and was more effective than HRT alone in attenuating bone loss at the spine. Moreover, there was no additional benefit in combining HRT with RT for preventing bone loss at the spine in this group of early postmenopausal women.", "Exercise may enhance the effect of alendronate on bone mineral density (BMD) and reduce chronic back pain in elderly women with osteoporosis. The aim of this study was to determine whether whole-body vibration exercise would enhance the effect of alendronate on lumbar BMD and bone turnover, and reduce chronic back pain in postmenopausal women with osteoporosis.\n Fifty post-menopausal women with osteoporosis, 55-88 years of age, were randomly divided into two groups of 25 patients each: one taking alendronate (5 mg daily, ALN) and one taking alendronate plus exercise (ALN+EX). Exercise consisted of whole-body vibration using a Galileo machine (Novotec, Pforzheim, Germany), at an intensity of 20 Hz, frequency once a week, and duration of exercise 4 minutes. The study lasted 12 months. Lumbar BMD was measured by dual energy X-ray absorptiometry (Hologic QDR 1500W). Urinary cross-linked N-terminal telopeptides of type I collagen (NTX) and serum alkaline phosphatase (ALP) levels were measured by enzyme-linked immunosorbent assay and standard laboratory techniques, respectively. Chronic back pain was evaluated by face scale score at baseline and every 6 months.\n There were no significant differences in baseline characteristics, including age, body mass index, years since menopause, lumbar BMD, urinary NTX and serum ALP levels, or face scale score between the two groups. The increase in lumbar BMD and the reduction in urinary NTX and serum ALP levels were similar in the ALN and ALN+EX groups. However, the reduction in chronic back pain was greater in the ALN+EX group than in the ALN group.\n The results of this study suggest that whole-body vibration exercise using a Galileo machine appears to be useful in reducing chronic back pain, probably by relaxing the back muscles in post-menopausal osteoporotic women treated with alendronate.", "A total of 76 women were enrolled and 55 naturally postmenopausal women completed a 12 month study investigating the effects of aerobic training plus calcium supplementation on lumbar (L2-4) bone mineral density (BMD) and forearm BMD. Training was conducted on treadmills at 70-85% of maximal heart rate for 30 or 45 minutes, three times per week for 12 months. Lumbar BMD was measured with dual-photon absorptiometry and forearm BMD with single-photon absorptiometry. Groups were similar with respect to age, weight, months since menopause, height, maximal oxygen uptake (VO2max), and lumbar and forearm BMD upon entering the study. Following training, percentage changes in VO2max were significantly different between the control and exercise groups but not between exercise groups. ANOVA evaluating lumbar BMD revealed a nonsignificant interaction effect and no significant changes (p > 0.05) between groups or times. The control (N = 19), 30 minute (N = 20), and 45 minute (N = 16) groups percentage lumbar BMD changes (X +/- SD) over 12 months were -0.61 +/- 3.40, -0.48 +/- 3.63, and 0.81 +/- 4.53%, respectively. The 95% confidence limits for percentage changes in lumbar BMD for the control, 30 minute, and 45 minute groups were -2.25 to 1.02, -2.18 to 1.22, and -1.16 to 3.22%, respectively. Forearm BMD changes were also not significant. Improvement in lumbar BMD was weakly but positively correlated with improvements in VO2max, r = 0.28, p < 0.05. Women < or = 6 years of the onset of menopause had an accelerated lumbar BMD loss compared to subjects who were > 6 years postmenopausal, and this subset's BMD changes were examined.(ABSTRACT TRUNCATED AT 250 WORDS)", "A randomized controlled trial was carried out to determine whether calcium supplementation and load-bearing exercise can increase or maintain bone mass in the elderly. Fifty Chinese women, aged 62-92 years, living in a hostel for the elderly in Hong Kong were randomized to enter one of four treatment groups: (I) calcium supplementation of 800 mg (as calcium lactate gluconate) daily; (II) load-bearing exercise four times a week plus a daily placebo tablet; (III) calcium supplementation daily and load-bearing exercise four times a week; (IV) a placebo tablet daily. The interventions went on for 10 months. The bone mineral density (BMD) was measured at three sites in the hip (femoral neck, Ward's triangle and intertrochanteric area) and the L2-4 level of the spine. The percentage change in BMD in 10 months was used as the main outcome measurement. The parathyroid hormone level and indices of bone metabolism were also measured before and after 10 months of intervention. The BMD at Ward's triangle and the intertrochanteric area increased significantly in subjects on calcium supplement (p less than 0.05), but there was no significant change at the spine and femoral neck. Exercise had no effect on bone loss at any site. However, the results of two-way analysis of variance showed a significant joint effect of calcium supplements and exercise at the femoral neck (p less than 0.05), but not at the other sites. The parathyroid hormone levels fell significantly in subjects on calcium supplements (p less than 0.01). Calcium supplement in the form of calcium lactate gluconate was adequately absorbed in elderly Chinese women with a calcium intake of less than 300 mg per day. It was effective in reducing bone loss at the hip, and there may be interaction effects with exercise in maintaining bone density.", "To test whether training on a high-frequency (28Hz) vibrating platform improves muscle power and bone characteristics in postmenopausal women.\n Randomized controlled trial with 6-month follow-up.\n Outpatient clinic in a general hospital in Italy.\n Twenty-nine postmenopausal women (intervention group, n=14; matched controls, n=15).\n Participants stood on a ground-based oscillating platform for three 2-minute sessions for a total of 6 minutes per training session, twice weekly for 6 months. The controls did not receive any training. Both groups were evaluated at baseline and after 6 months.\n Muscle power, calculated from ground reaction forces produced by landing after jumping as high as possible on a forceplate, cortical bone density, and biomarkers of bone turnover.\n Over 6 months, muscle power improved by about 5% in women who received the intervention, and it remained unchanged in controls (P=.004). Muscle force remained stable in both the intervention and control groups. No significant changes were observed in bone characteristics.\n Reflex muscular contractions induced by vibration training improve muscle power in postmenopausal women.", "Whole body vibration (WBV) training is a new approach which is currently discussed in the context of reducing the risk of osteoporotic fractures. The study was undertaken to determine the effect of one-year WBV exercise on bone mineral density (BMD) and the number of falls.\n 151 postmenopausal women (68.5 +/- 3.1 years) were randomly assigned to three groups: (1) conventional (multifunctional) training (TG); (2) multifunctional training including WBV (VTG); (3) wellness-control group (CG). The training groups performed multifunctional training twice weekly (60 min; dancing aerobics, balance training, functional strength training). In the last 15 min of each session, leg strength exercises on vibration platforms were performed. The plates were switched on only in the VTG. The CG performed a low intensity gymnastic and relaxation programme (4 x 10 sessions of 60 min). BMD was measured at the hip and lumbar spine at baseline and after 12 months with the DXA method. Falls were recorded daily with the calendar method in a fall log.\n An increase in BMD at the lumbar spine was measured after one year in both training groups (VTG: + 1.17 +/- 2.4 % vs. TG: + 1.73 +/- 2.4 %). The difference between the TG and the CG was significant (p < .05). Regarding the hip region a loss was noted in the CG (- 0.9 +/- 2.5), whereas the BMD stayed stable in the training groups (TG: - 0.3 %; VTG: + 0.1 %). The fall rate was significantly lower in VTG compared to CG (0.43 falls/person/year (VTG) vs. 1.14 (CG).\n The multifunctional training resulted in a gain of BMD at the lumbar spine. Vibration training did not enhance the effect on bone but significantly reduced falls.", "The aim of this study was to test the effect of unipedal standing exercise on bone mineral density (BMD) of the hip in postmenopausal women. Japanese postmenopausal women (n = 94) were assigned at random to an exercise or control group (no exercise). The 6-month exercise program consisted of standing on a single foot for 1 min per leg 3 times per day. BMD of the hip was measured by dual-energy X-ray absorptiometry. There was no significant difference in age and baseline hip BMD between the exercise group (n = 49) and control group (n = 45). Exercise did not improve hip BMD compared with the control group. Stepwise regression analysis identified old age as a significant determinant (p = 0.034) of increased hip total BMD at 6 months after exercise. In 31 participants aged >/=70 years, the exercise group (n = 20) showed significant increase in the values of hip BMD at the areas of total (p = 0.008), intertrochanteric (p = 0.023), and Ward's triangle (p = 0.032). The same parameters were decreased in the control group (n = 11). The percent changes in hip BMD of the exercise group were not significantly different from those of the control group either in the participants with low baseline hip total BMD (<80% of the young adult mean) or high baseline hip total BMD (> or =80% of the young adult mean). In conclusion, unipedal standing exercise for 6 months did not improve hip BMD in Japanese postmenopausal women. Effect of exercise on hip total BMD was age dependent. In participants aged > or =70 years, the exercise significantly increased hip total BMD.", "Strength training (ST; high intensity/low volume/long rest) has been used in several populations, including children, young adults, and older adults. However, there is no information about circuit weight training (CWT; low intensity/high volume/short rest) in apparently healthy postmenopausal women. The purpose of the present study was to analyze the effects of high-intensity ST and circuit training on isometric strength (IS), upper limb dynamic strength (ULS) and lower limb dynamic strength (LLS), muscle activation of quadriceps (EMG quad), maximal oxygen uptake (VO2 max), time to exhaustion (TE), and bone mineral density (BMD). Twenty-eight postmenopausal women were divided into 3 groups: 1) ST group (STG, n = 9, 45-80% 1 repetition maximum (1RM), 2-4 sets, 20-6 reps), 2) circuit training group (CTG, n = 10, 45-60% 1RM, 2-3 sets, 20-10 reps), and 3) a control group (CON, n = 9, no exercise). Significance level was defined as p <or= 0.05 for all analyses. After 24 weeks of training, increases were observed in STG and CTG. However, whereas in the STG, the IS (32.7%), ULS (28.7%), LLS (39.4%), EMG quad (50.7%), VO2 max (22%), and TE (19.3%) increased, CTG showed changes only in IS (17.7%), ULS (26.4%), LLS (42.2%), VO2 max (18.6%), and TE (16.8%). BMD did not change in any experimental group. In the CON, there were no changes in the variables analyzed. Our results suggest that ST and circuit training positively affect postmenopausal women's muscular strength, muscular activation, and cardiorespiratory fitness, with no changes in BMD.", "To evaluate the potential benefits of programmed Tai Chi Chun (TCC) exercise on the weight-bearing bones of early postmenopausal women.\n Age-matched and randomized prospective intervention.\n University medical school.\n One hundred thirty-two healthy postmenopausal women (mean age, 54.0+/-3.5y) within 10 years of menopause onset were recruited and randomized into the TCC exercise group (n=67) or the sedentary control group (n=65).\n Supervised TCC exercise was performed by the TCC group for 45 minutes a day, 5 days a week, for 12 months; control subjects retained a sedentary life style. Main outcome measures Bone mineral density (BMD) was measured in the lumbar spine and proximal femur by using dual-energy x-ray absorptiometry and in the distal tibia by using multislice peripheral quantitative computed tomography (pQCT). All BMD measurements were repeated after 12 months in both groups. Fracture rate was also documented.\n Baseline measurements showed homogeneity in age, anthropometric variables, and menstruation status between the TCC and control groups. Exactly 81.6% of the subjects in the TCC group and 83.1% of subjects in the control group completed the 12-month follow-up study. BMD measurements revealed a general bone loss in both TCC and sedentary control subjects at all measured skeletal sites, but with a reportedly slower rate in the TCC group. A significant 2.6- to 3.6-fold retardation of bone loss (P<.01) was found in both trabecular and cortical compartments of the distal tibia in the TCC group as compared with the controls, as measured by pQCT. A total of 4 fracture cases were documented during follow-up, including 3 subjects in the control group and 1 in the TCC group.\n This is the first prospective and randomized study to show that a programmed TCC exercise intervention is beneficial for retarding bone loss in weight-bearing bones in early postmenopausal women. Long-term follow-up is needed to substantiate the role of TCC exercise in the prevention of osteoporosis and its related fracture.", "To determine how multiple risk factors for osteoporotic fractures could be modified by high-intensity strength training exercises in postmenopausal women.\n Randomized controlled trial of 1-year duration.\n Exercise laboratory at Tufts University, Boston, Mass.\n Forty postmenopausal white women, 50 to 70 years of age, participated in the study; 39 women completed the study. The subjects were sedentary and estrogen-deplete.\n High-intensity strength training exercises 2 days per week using five different exercises (n = 20) vs untreated controls (n = 19).\n Dual energy x-ray absorptiometry for bone status, one repetition maximum for muscle strength, 24-hour urinary creatinine for muscle mass, and backward tandem walk for dynamic balance.\n Femoral neck bone mineral density and lumbar spine bone mineral density increased by 0.005 +/- 0.039 g/cm2 (0.9% +/- 4.5%) (mean +/- SD) and 0.009 +/- 0.033 g/cm2 (1.0% +/- 3.6%), respectively, in the strength-trained women and decreased by -0.022 +/- 0.035 g/cm2 (-2.5% +/- 3.8%) and -0.019 +/- 0.035 g/cm2 (-1.8% +/- 3.5%), respectively, in the controls (P = .02 and .04). Total body bone mineral content was preserved in the strength-trained women (+2.0 +/- 68 g; 0.0% +/- 3.0%) and tended to decrease in the controls (-33+77 g; -1.2% +/- 3.4%, P = .12). Muscle mass, muscle strength, and dynamic balance increased in the strength-trained women and decreased in the controls (P = .03 to < .001).\n High-intensity strength training exercises are an effective and feasible means to preserve bone density while improving muscle mass, strength, and balance in postmenopausal women.", "This randomized controlled trial was designed to investigate the effect of a 6-month home-based exercise program versus control (usual activities) on quality of life for postmenopausal women with osteoporosis who had at least one vertebral fracture. Twelve-month assessments of outcomes were completed to determine if women would continue exercising with minimal supervision and if benefit could be sustained. The home exercise program followed a \"lifestyle exercise\" approach where participants completed exercises 60 min per day, 3 days a week and could complete exercises in small periods of time throughout the day. Exercise activities included stretching, strength training and aerobics (i.e. walking). Participants were assessed at baseline, 6 months, and 12 months using the Osteoporosis Quality of Life Questionnaire (OQLQ), the Sickness Impact Profile (SIP), a balance test, and the Timed Up And Go test. Bone mineral density was assessed at baseline and 12 months for both the lumbar spine and femoral neck. Quality of life (OQLQ) improved over 6 months in the exercise group compared to the control group in the domains of symptoms (P=0.003), emotion (P=0.01) and leisure (P=0.03). Results from the balance test indicated a greater effect in the exercise group over 12 months (P<0.05). There were no significant differences between groups in measures of Timed Up and Go, SIP at 6 and 12 months, and femoral neck and lumbar spine bone mineral density at 12 months. Home-based exercise with minimal supervision improves quality of life in elderly women with vertebral fractures. Future research is needed to determine if home exercise programs reduce falls and fall-related injuries in the elderly.", "One hundred and seventy-nine women aged 60-85 years (mean age 71.6 years, SD 5.3 years) were randomly recruited from the community to participate in a 12-month randomized controlled trial to determine whether a program of twice-weekly structured exercise has beneficial effects on three factors associated with osteoporotic fractures: quadriceps strength, postural sway and bone density. At initial testing, there were no significant differences in the strength, sway and bone density measures (assessed at the hip and lumbar spine) between the exerciser and control groups. The exercise classes included strengthening, coordination and balance exercises, and approximately 35 min of each class comprised weight-bearing exercise. The mean number of classes attended for the 68 exercisers who completed the program was 59.8 of the 82 classes (72.9%). At the completion of the trial, the intervention group showed significant improvements in quadriceps strength and sway but not bone mineral density when compared with the control group. Indices of fracture risk, indicated by (i) the sum of standard score results and (ii) the sum of quartile grades of the femoral neck bone density, sway and strength measures, decreased significantly in the exercisers at the end of the trial compared with the controls. In conclusion, the program of general aerobic exercise may have reduced overall fracture risk, even though it did not significantly increase bone density. Further long-term studies are required that include acceptable weight-loaded exercises to determine optimal programs for reducing fracture risk factors by improving bone density as well as strength and balance.", "The purpose of this study was to compare the effects of a high-load (80%, 1-repetition maximum (RM), 8 reps) and a high-repetition (40%, 1-RM, 16 reps) resistance training protocol on muscular strength and bone mineral density (BMD) in early postmenopausal, estrogen-deficient women. The 6-month programs were matched initially for training volume (3 sets, 3 d x wk(-1)) for 12 exercises selected to specifically load the spine and hip.\n Subjects included 25 women (41-60 yr) who were matched by spine BMD then randomly assigned to either the high-load (HL, N = 10), high-repetition (HR, N = 7), or control (C, N = 8) groups. Dietary calcium intakes were supplemented to approximately 1500 mg x d(-1). Total body, spine, and hip BMD (DXA, Lunar Model DPX-IQ), upper and lower body muscular strength, and biochemical markers of bone turnover were measured at baseline and after 6 months of training.\n There were no group differences in the baseline measures. Both training groups showed similar increases in biceps (20%) and rectus femoris (28-33%) cross-sectional areas, in lower body strength (approximately 30%) and in hip strength (37-40%). HL showed greater improvements in upper body strength (HL 25%, HR 16%). Neither training group experienced significant increases in spine or hip BMD, although the HL total body BMD tended to decrease (-1.1%+/-0.4, P = 0.054) after training. Osteocalcin tended to increase (P = 0.08) in all groups after training, and the % change in osteocalcin was positively related to % changes in the total hip (r = 0.41, P = 0.048) and the trochanter (r = 0.42, P = 0.04) BMD.\n The high-load and high-repetition resistance training protocols were both effective in improving muscular strength and size in postmenopausal women, indicating low-intensity resistance training can be beneficial for the muscular fitness in women for whom high-intensity exercise is contraindicated.", "to evaluate the effects of brisk walking on bone mineral density in women who had suffered an upper limb fracture.\n randomized placebo-controlled trial. Assessments of bone mineral density were made before and at 1 and 2 years after intervention. Standardized and validated measures of physical capacity, self-rated health status and falls were used.\n district general hospital outpatient department.\n 165 women drawn from local accident and emergency departments with a history of fracture of an upper limb in the previous 2 years. Women were randomly allocated to intervention (self-paced brisk walking) or placebo (upper limb exercises) groups.\n both groups were seen at 3-monthly intervals to assess progress, measure physical capacity and maintain enthusiasm. The brisk-walking group were instructed to progressively increase the amount and speed of walking in a manner that suited them. The upper limb exercise placebo group were asked to carry out a series of exercises designed to improve flexibility and fine hand movements, appropriate for a past history of upper limb fracture.\n drop-outs from both intervention and placebo groups were substantial (41%), although there were no significant differences in bone mineral density, physical capacity or health status between drop-outs and participants. At 2 years, among those completing the trial, bone mineral density at the femoral neck had fallen in the placebo group to a greater extent than in the brisk-walking group [mean net difference between intervention and placebo groups 0.019 g/cm2, 95% confidence interval (CI) -0.0026 to +0.041 g/cm2, P = 0.056]. Lumbar spine bone mineral density had increased to a similar extent (+0.017 g/cm2) in both groups. The cumulative risk of falls was higher in the brisk-walking group (excess risk of 15 per 100 person-years, 95% CI 1.4-29 per 100 person-years, P < 0.05). There were no significant differences in clinical or spinal x-ray fracture risk or self-rated health status between intervention and placebo groups.\n the promotion of exercise through brisk-walking advice given by nursing staff may have a small, but clinically important, impact on bone mineral density but is associated with an increased risk of falls. Self-paced brisk walking is difficult to evaluate in randomized controlled trials because of drop-outs, placebo group exercise, limited compliance and lack of standardization of the duration and intensity of walking. Further work is needed to evaluate the best means of safely achieving increased activity levels in different groups, such as older women and those at high risk of fractures.", "The combined and separate effects of exercise training and bisphosphonate (etidronate) therapy on bone mineral in postmenopausal women were compared. Forty-eight postmenopausal women were randomly assigned (double blind) to groups that took intermittent cyclical etidronate; performed strength training (3 d/week) and received matched placebo; combined strength training with etidronate; or took placebo and served as nonexercising controls. Bone mineral, lean tissue, and fat mass were assessed by dual-energy X-ray absorptiometry before and after 12 months of intervention. After removal of outlier results, changes in bone mineral density (BMD) of the lumbar spine and bone mineral content (BMC) of the whole body were greater in the subjects given etidronate (+2.5 and +1.4%, respectively) compared with placebo (-0.32 and 0%, respectively) (p < 0.05), while exercise had no effect. There was no effect of etidronate or exercise on the proximal femur and there was no interaction between exercise and etidronate at any bone site. Exercise training resulted in significantly greater increases in muscular strength and lean tissue mass and greater loss of fat mass compared with controls. We conclude that etidronate significantly increases lumbar spine BMD and whole-body BMC and that strength training has no additional effect. Strength training favourably affects body composition and muscular strength, which may be important for prevention of falls.", "The purpose of this study was to determine the optimal intensity of exercise necessary to prevent the postmenopausal bone loss on the basis of anaerobic threshold (AT). Thirty-three postmenopausal women were randomized to control (group C: n = 12) or two exercise groups (group H and group M). All women performed a treadmill exercise test, and the AT was measured by expired gas analysis. The exercise regimen consisted mainly of walking at a speed that kept the exercise heart rate above the AT (group H: n = 12) or below the AT (group M: n = 9). Exercise was performed for 30 minutes, three times a week for 7 months. The bone mineral density (BMD) of the lumbar vertebrae was measured using dual energy X-ray absorptiometry. The BMD level in group C decreased by 1.7 +/- 2.7%, but there was a significant increase of 1.1 +/- 2.9% in group H. In group M there was a decrease of 1.0 +/- 3.1% which did not differ from group C. In group C, serum osteocalcin and urinary hydroxyproline excretion were significantly increased, but no changes were seen in either of the exercise groups. Urinary calcium significantly decreased in the exercise groups. We conclude that short-term (7 months) exercise with intensity above the AT is safe and effective in preventing postmenopausal bone loss.", "The purpose of this study was to determine the effect of a 1-year trunk resistive exercise program on bone mineral density at the lumbar spine and hip in postmenopausal women. Forty-nine subjects were divided into exercise and control groups. Dual photon absorptiometry was used to measure bone mineral density and the Muscle Examination and Exercise Dosimeter 3000 system was used to assess trunk muscle strength. Resistive exercise target levels for the exercise group were based on the results of the trunk muscle strength tests. The exercise group performed 3 sets of 10 repetitions for each of the sit-up, prone trunk extension, and double leg flexion exercises. The subjects were seen once per month and performed the exercises a minimum of three times per week. The bone mineral density and strength tests were done at baseline, at 6 months and at 12 months. The results of the study showed that 1) the dual photon absorptiometry method and the Muscle Examination and Exercise Dosimeter 3000 system were highly reliable in measuring bone mineral density and trunk muscle strength, respectively; and 2) no significant differences were found between the exercise and control groups at lumbar vertebrae L2, L3, L4, L2-L4, and the femoral neck, Ward's triangle, and trochanteric region of the proximal femur at baseline, 6-month, and 12-month evaluation sessions.", "Osteoporosis is a major public health concern. The combination of exercise, hormone replacement therapy, and calcium supplementation may have added benefits for improving bone mineral density compared to a single intervention. To test this notion, 320 healthy, non-smoking postmenopausal women, who did or did not use hormone replacement therapy (HRT), were randomized within groups to exercise or no exercise and followed for 12 months. All women received 800 mg calcium citrate supplements daily. Women who exercised performed supervised aerobic, weight-bearing and weight-lifting exercise, three times per week in community-based exercise facilities. Regional bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry. Women who used HRT, calcium, and exercised increased femoral neck, trochanteric and lumbar spine bone mineral density by approximately 1-2%. Trochanteric BMD was also significantly increased by approximately 1.0% in women who exercised and used calcium without HRT compared to a negligible change in women who used HRT and did not exercise. The results demonstrate that regional BMD can be improved with aerobic, weight-bearing activity combined with weight lifting at clinically relevant sites in postmenopausal women. The response was significant at more sites in women who used HRT, suggesting a greater benefit with hormone replacement and exercise compared to HRT alone.", "The purpose of this study was to determine the effects of a 12-month resistance training program, of two different intensities, on bone mineral density (BMD) in healthy, older women. Twenty-six Caucasian women (aged 65-79 years) completed the study. Subjects were randomly assigned to one of three groups: high-intensity (HI; n = 8), low-intensity (LI; n = 7), and control (CON; n = 11). The active groups performed 10 exercises, 3 days/week under supervision. Exercise intensity was maintained at 80% of one-repetition maximum (1-RM) for the HI groups, and at 40% 1-RM for the LI group. The volume of work was maintained constant between the two groups by assigning the LI group twice as many repetitions for each exercise. Maximal muscular strength and BMD of the lumbar spine and total hip were measured at baseline and at 12 months. Strength was evaluated using the 1-RM method, and BMD was determined by dual-energy X-ray absorptiometry. Exercise session attendance was similar for the two groups (81.0% HI; 76.8% LI). Muscular strength improved in the exercisers compared with the CON group (p < or = 0.05). Percentage change in lumbar spine BMD was 0.7 +/- 1.9%, 0.5 +/- 2.4%, and -0.1 +/- 2.3% for the HI, LI, and CON groups, respectively. Percentage change in total hip BMD was 0.8 +/- 2.3% (HI), 1.0 +/- 1.7% (LI), and 0.9 +/- 1.3% (CON). Group differences in BMD change were not significant (p > 0.05). These findings suggest that high-intensity and low-intensity resistance training regimens effectively increase muscular strength, but not lumbar spine or total hip BMD, in healthy, older women.", "To evaluate the efficacy of therapeutic exercises in the prevention of bone loss, 146 untrained healthy postmenopausal women were prospectively controlled for (mean +/- SD) 3.0 +/- 1.3 yr. Eighty-two subjects aged (mean +/- SD) 61.5 +/- 6.1 yr participated in an exercise program (group 1) and sixty-four aged (mean +/- SD) 59.1 +/- 7.4 yr served as controls (group 2). Periodically during the study period, we measured women's bone density at two forearm sites and recorded their physical activities. Because bone loss differed insignificantly between the groups, group 1 was retrospectively subdivided into group 1a (regular exercise) and group 1b (nonregular exercise). The results showed that only 39 women (48 percent) of group 1 (group 1a) performed the exercise program regularly for the prescribed time. Regression slopes of forearm bone density (distal and proximal scans) v time were significantly less negative (P < 0.05) in group 1a (distal, -0.3 percent and proximal, -0.7 percent per year) than in group 1b (distal, -1.8 percent and proximal -1.6 percent per year) or group 2 (distal, -1.7 percent and proximal, -1.9 percent per year). We conclude that in untrained elderly women, poor compliance with regular physical activities is a main factor, explaining the lack of response to exercise treatment in prevention of osteoporosis.", "To describe the effect of a supervised physical activity program on the physical and psychological health of osteopenic women.\n A randomized controlled trial.\n Sherbrooke, Quebec, Canada.\n A total of 124 community-living postmenopausal women, between 50 and 70 years of age, with low bone mass took part in the study.\n Subjects allocated to the experimental group performed weight-bearing exercises (walking, stepping up and down from benches), aerobic dancing, and flexibility exercises for 60 minutes, three times a week, over a period of 12 months. All subjects were invited to attend bi-monthly educational seminars covering topics related to osteoporosis.\n Spinal and femoral bone mineral density (BMD), functional fitness (flexibility, coordination, agility, strength/endurance, cardiorespiratory endurance), psychological well-being, back pain intensity, and self-perceived health.\n Spinal BMD stabilized in the exercisers while decreasing significantly in the controls (P = .031). No change in femoral BMD was observed in either group (P = .597). Four of the five parameters chosen to evaluate functional fitness, namely flexibility, agility, strength, and endurance, were affected positively by the exercise program (all P < .01). Adjusting for prescores by means of an analysis of covariance revealed a significant difference between the groups in psychological well-being, which favored the exercisers (P = .012). After 12 months, back pain reported by exercisers was lower than that reported by controls (P = .008). Finally, self-perceived health increased in the exercise group, whereas no difference was observed in the control group (P = .790).\n These results suggest that after 12 months, exercising can produce a significant increase above initial levels in the functional fitness, well-being, and self-perceived health of osteopenic women. Intensity of back pain can also be lowered by exercise. The exercise program succeeded in stabilizing spinal BMD but had no effect on femoral BMD.", "A 1-year prospective, randomized, double-blind, and placebo-controlled trial of 70 postmenopausal women demonstrated that brief periods (<20 minutes) of a low-level (0.2g, 30 Hz) vibration applied during quiet standing can effectively inhibit bone loss in the spine and femur, with efficacy increasing significantly with greater compliance, particularly in those subjects with lower body mass.\n Indicative of the anabolic potential of mechanical stimuli, animal models have demonstrated that short periods (<30 minutes) of low-magnitude vibration (<0.3g), applied at a relatively high frequency (20-90 Hz), will increase the number and width of trabeculae, as well as enhance stiffness and strength of cancellous bone. Here, a 1-year prospective, randomized, double-blind, and placebo-controlled clinical trial in 70 women, 3-8 years past the menopause, examined the ability of such high-frequency, low-magnitude mechanical signals to inhibit bone loss in the human.\n Each day, one-half of the subjects were exposed to short-duration (two 10-minute treatments/day), low-magnitude (2.0 m/s2 peak to peak), 30-Hz vertical accelerations (vibration), whereas the other half stood for the same duration on placebo devices. DXA was used to measure BMD at the spine, hip, and distal radius at baseline, and 3, 6, and 12 months. Fifty-six women completed the 1-year treatment.\n The detection threshold of the study design failed to show any changes in bone density using an intention-to-treat analysis for either the placebo or treatment group. Regression analysis on the a priori study group demonstrated a significant effect of compliance on efficacy of the intervention, particularly at the lumbar spine (p = 0.004). Posthoc testing was used to assist in identifying various subgroups that may have benefited from this treatment modality. Evaluating those in the highest quartile of compliance (86% compliant), placebo subjects lost 2.13% in the femoral neck over 1 year, whereas treatment was associated with a gain of 0.04%, reflecting a 2.17% relative benefit of treatment (p = 0.06). In the spine, the 1.6% decrease observed over 1 year in the placebo group was reduced to a 0.10% loss in the active group, indicating a 1.5% relative benefit of treatment (p = 0.09). Considering the interdependence of weight, the spine of lighter women (<65 kg), who were in the highest quartile of compliance, exhibited a relative benefit of active treatment of 3.35% greater BMD over 1 year (p = 0.009); for the mean compliance group, a 2.73% relative benefit in BMD was found (p = 0.02). These preliminary results indicate the potential for a noninvasive, mechanically mediated intervention for osteoporosis. This non-pharmacologic approach represents a physiologically based means of inhibiting the decline in BMD that follows menopause, perhaps most effectively in the spine of lighter women who are in the greatest need of intervention." ]

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[ "A prospective randomized comparison of conventional mechanical ventilation and very early high frequency oscillatory ventilation in extremely premature newborns with respiratory distress syndrome.", "Inhaled nitric oxide in premature infants with the respiratory distress syndrome.", "A prospective, randomized, multicenter trial of high-frequency oscillatory ventilation compared with conventional ventilation in preterm infants with respiratory distress syndrome receiving surfactant.", "High-frequency oscillatory ventilation versus conventional mechanical ventilation for very-low-birth-weight infants.", "Volume guarantee versus high-frequency ventilation: lung inflammation in preterm infants.", "The Provo multicenter early high-frequency oscillatory ventilation trial: improved pulmonary and clinical outcome in respiratory distress syndrome.", "HFOV in premature neonates: effects on pulmonary mechanics and epithelial lining fluid cytokines. A randomized controlled trial.", "Randomized comparison of high-frequency ventilation with high-rate intermittent positive pressure ventilation in preterm infants with respiratory failure.", "Effects of pressure support ventilation plus volume guarantee vs. high-frequency oscillatory ventilation on lung inflammation in preterm infants.", "High-frequency oscillatory ventilation for the prevention of chronic lung disease of prematurity.", "Prospective randomized multicenter comparison of high-frequency oscillatory ventilation and conventional ventilation in preterm infants of less than 30 weeks with respiratory distress syndrome.", "Early high-frequency oscillatory ventilation versus synchronized intermittent mandatory ventilation in very low birth weight infants: a pilot study of two ventilation protocols." ]

[ "To compare the effectiveness and safety of very early high-frequency oscillatory ventilation (HFOV) with conventional mechanical ventilation (CMV) in treatment of the respiratory distress syndrome (RDS) and to evaluate their impact on the incidence of chronic pulmonary disease and early and late morbidity of very low-birthweight neonates.\n A prospective randomized clinical trial.\n Tertiary neonatal intensive care unit in the Perinatology Center in Prague.\n 43 premature newborns, delivered in the Department of Obstetrics in the Perinatology Center, were randomly divided into two groups (HFOV and CMV) immediately after delivery; 2 patients in each group died, 2 fulfilled crossover criteria from CMV to HFOV, and 2 were excluded because of congenital malformations. Nineteen patients treated with HFOV were therefore compared with 18 infants in the CMV group.\n The two contrasting modes of ventilation were introduced immediately after intubation. Maintenance of optimal lung volume in HFOV to optimize oxygenation and the therapeutic administration of surfactant after fulfilling defined criteria are important points of the strategy and design of the study.\n Except for a higher proportion of males in the HFOV group (p<0.02), the basic clinical characteristics (gestational age, birthweight, Apgar score at 5 min, umbilical arterial pH), the two groups were similar. In the acute stage of RDS, infants treated with HFOV had higher proximal airway distending pressure with HFOV for 6 h after delivery (p<0.05). For a period of 12 h after delivery lower values for the alveolar-arterial oxygen difference (p<0.03) were noted. The number of patients who did not require surfactant treatment was higher in the HFOV group (11 vs. 1, p<0.001). In the HFOV group the authors found a lower roentgenographic score at 30 days of age (p<0.03) and a lower clinical score in the 36th postconceptional week (p<0.05), using these two scoring systems for assessing chronic lung disease according to Toce scale. The incidence of pneumothorax, pulmonary interstitial emphysema, intraventricular hemorrhage and retinopathy of prematurity in both groups was the same.\n HFOV, when applied early and when the clinical strategy of maintenance of optimal lung volume is used, improves oxygenation in the acute stage of RDS, reduces the need of surfactant administration, and can decrease the injury to lung tissue even in extremely immature newborns to whom surfactant is administered therapeutically.", "Inhaled nitric oxide improves gas exchange, decreases pulmonary vascular lability, and reduces pulmonary inflammation. We hypothesized that the use of inhaled nitric oxide would decrease the incidence of chronic lung disease and death in premature infants with the respiratory distress syndrome.\n We conducted a randomized, double-blind, placebo-controlled study of the effect of inhaled nitric oxide during the first week of life on the incidence of chronic lung disease and death in premature infants (less than 34 weeks' gestation) who were undergoing mechanical ventilation for the respiratory distress syndrome. Infants were randomly assigned to receive inhaled nitric oxide (10 ppm on day 1, followed by 5 ppm for six days) or inhaled oxygen placebo for seven days. We further randomly assigned the infants in each group to receive intermittent mandatory or high-frequency oscillatory ventilation.\n A total of 207 premature infants were enrolled. In the group given inhaled nitric oxide, 51 infants (48.6 percent) died or had chronic lung disease, as compared with 65 infants (63.7 percent) in the placebo group (relative risk, 0.76; 95 percent confidence interval, 0.60 to 0.97; P=0.03). There was no significant difference between the nitric oxide and placebo groups in the overall incidence of intraventricular hemorrhage and periventricular leukomalacia (33.3 percent and 38.2 percent, respectively), but the group given inhaled nitric oxide had a lower incidence of severe intraventricular hemorrhage and periventricular leukomalacia (12.4 percent vs. 23.5 percent; relative risk, 0.53; 95 percent confidence interval, 0.28 to 0.98; P=0.04). The type of ventilation had no significant effect on the outcome.\n The use of inhaled nitric oxide in premature infants with the respiratory distress syndrome decreases the incidence of chronic lung disease and death.\n Copyright 2003 Massachusetts Medical Society", "To compare high-frequency oscillatory ventilation (HFOV) and intermittent positive pressure ventilation (IPPV) as a primary ventilation mode in preterm infants with respiratory distress syndrome. Primary end points were survival and maintenance of the randomized ventilation mode.\n Prospective, multicenter, randomized clinical trial.\n Level III neonatal intensive care units at three university children's hospitals.\n Ninety-six premature infants (gestational age < 32 weeks) randomly assigned to HFOV or IPPV within the first 2 hours of life. All patients received a natural surfactant. No differences were found between the study groups with respect to the demographic data or the severity of respiratory distress syndrome. Infants were stratified at randomization, by birth weight, into two groups: 750 to 1000 gm (n = 32) and 1001 to 1500 gm (n = 64). The centers involved complied with a study protocol that planned a reduction in respiratory pressures when the infant's oxygen requirement had reached a fractional concentration of inspired oxygen of 0.6.\n Five patients in the HFOV group died, and eight patients did not respond to the randomized ventilation mode; whereas four patients in the IPPV group died, and nine were switched to HFOV. No differences were found in gas exchange or ventilator support over the first 72 hours. Premature infants with a birth weight < 1000 gm had a significantly shorter course to reach fractional concentration of inspired oxygen of 0.21 while receiving IPPV than those receiving HFOV (9.3+/-4.5 days vs 27.5+/-10.2 days, p = 0.01). No differences were found between the groups in extraalveolar air (HFOV seven; IPPV, seven) and intracranial bleeding (HFOV, nine; IPPV, eight).\n After surfactant treatment, HFOV, as a primary ventilation mode in premature infants with respiratory distress syndrome, is as safe and efficacious as conventional ventilation.", "The efficacy and safety of early high-frequency oscillatory ventilation as compared with conventional synchronized intermittent mandatory ventilation for the treatment of infants with very low birth weight have not been established.\n We conducted a randomized, multicenter clinical trial to determine whether infants treated with early high-frequency oscillatory ventilation were more likely than infants treated with synchronized intermittent mandatory ventilation to be alive without requiring supplemental oxygen at 36 weeks of postmenstrual age. Eligible infants weighed 601 to 1200 g at birth, were less than four hours of age, had received one dose of surfactant, and required ventilation with a mean airway pressure of at least 6 cm of water and a fraction of inspired oxygen of at least 0.25. Infants were stratified according to birth weight and exposure to prenatal corticosteroids and then randomly assigned to high-frequency oscillatory ventilation or synchronized intermittent mandatory ventilation. Ventilation was managed according to protocols designed to optimize lung inflation and blood gas values.\n Five hundred infants were enrolled in the study. Infants randomly assigned to high-frequency oscillatory ventilation were successfully extubated earlier than infants assigned to synchronized intermittent mandatory ventilation (P<0.001). Of infants assigned to high-frequency oscillatory ventilation, 56 percent were alive without a need for supplemental oxygen at 36 weeks of postmenstrual age, as compared with 47 percent of those receiving synchronized intermittent mandatory ventilation (P=0.046). There was no difference between the groups in the risk of intracranial hemorrhage, cystic periventricular leukomalacia, or other complications.\n There was a small but significant benefit of high-frequency oscillatory ventilation in terms of the pulmonary outcome for very-low-birth-weight infants without an increase in the occurrence of other complications of premature birth.\n Copyright 2002 Massachusetts Medical Society", "Appropriate ventilation together with improvement of clinical care of premature babies can contribute to reducing lung inflammation, known to represent the \"primum movens\" of bronchopulmonary dysplasia (BPD). High-frequency oscillatory ventilation (HFOV) and volume-guarantee (VG) ventilation are effective in the treatment of neonatal respiratory distress syndrome (RDS).\n To assess the potential of HFOV and VG to prevent BPD in the acute phase of RDS, by a randomised clinical study evaluating lung inflammation in premature infants. Study design: Forty infants (gestational age 25-32 weeks) with RDS were assigned to assist-control ventilation plus VG (Vt = 5 ml/kg) or HFOV (both with a Dräger Babylog 8000 plus ventilator). Levels of interleukin (IL) 6, IL8 and tumour necrosis factor were determined in tracheal aspirate on days 1, 3 and 7 of life.\n In the HFOV group IL6 levels were significantly higher on day 3 (0.5 (0.2) vs assisted-control ventilation plus VG group 0.1 (0.2) ng/ml) and oxygen dependency was significantly longer (36 (23) vs assisted-control ventilation plus VG group 19 (11) days).\n VG ventilation is an effective lung-protective strategy to be used in acute RDS, inducing a lower expression of early inflammation markers than HFOV. Whether the use of this initial ventilatory strategy contributes to the prevention of BPD requires further studies.", "To compare the hospital course and clinical outcome of preterm infants with respiratory distress syndrome treated with surfactant and managed with high-frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation (CV) as their primary mode of ventilator support.\n A prospective randomized clinical trial.\n Three community-based level III neonatal intensive care units.\n A total of 125 neonates who were 35 weeks or less estimated gestation requiring intubation and assisted ventilation for respiratory distress syndrome with arterial to alveolar oxygen ratio less than .50.\n Patients were randomized to continue CV (61 patients) or be changed to HFOV (64 patients) after exogenous surfactant administration (100 mg/kg). HFOV was used in a strategy to promote lung recruitment and maintain lung volume. Protocol respiratory care guidelines were followed; otherwise routine care was provided by each neonatal intensive care unit.\n No differences were noted in demographic features between the two study groups. The study population birth weight was 1.51 +/- .47 kg (mean +/- SD), gestational age was 30.9 +/- 2.5 weeks, and study entry age was 2 to 3 hours. Patients randomized to HFOV demonstrated the following significant findings compared with CV-treated patients: vasopressor support was less intensive; surfactant redosing was not as frequent; oxygenation improved more rapidly and remained higher during the first 7 days; fewer infants required prolonged supplemental oxygen or ventilator support; treatment failure was reduced; more patients survived without chronic lung disease at 30 days; need for continuous supplemental oxygen at discharge was less; frequency of necrotizing enterocolitis illness was lower; there were fewer abnormal hearing tests; and hospital costs were decreased. No differences were seen between the two study groups in the frequency or severity of patent ductus arteriosus, air leak, retinopathy of prematurity, or intraventricular hemorrhage. Length of hospital stay and survival to discharge were similar for HFOV- and CV-treated infants.\n When used early with a lung recruitment strategy, HFOV after surfactant replacement resulted in clinical outcomes consistent with a reduction in both acute and chronic lung injury. Benefit was evident for preterm infants both less than or equal to 1 kg and more than 1 kg. In addition, early HFOV treatment may have had a more global effect on patient health throughout the hospitalization, resulting in reduced morbidity and decreased health care cost.", "Ventilation strategies for preterm neonates may influence the severity of pulmonary dysfunction and later development of chronic lung disease. The objective of this report is to compare the effects of high-frequency oscillatory ventilation (HFOV) versus synchronized intermittent mandatory ventilation (sIMV) from the points of views of biochemical and functional variables.\n Randomized controlled trial.\n Third level NICU.\n Forty preterm neonates with a gestational age of 24-29 weeks were randomly assigned to one of the two above-mentioned ventilation strategies within 30 min from birth.\n At 1, 3, 5, and 7 days, the babies were monitored by means of ventilator indices, pulmonary function, and eight pro-inflammatory or anti-inflammatory cytokines measured in bronchoalveolar lavage fluid. The neonates assigned to the HFOV procedure benefited from early and sustained improvement in pulmonary mechanics and gas exchange-significantly higher dynamic respiratory compliance values, significantly lower expiratory airway resistance and oxygenation index values-with earlier extubation as compared to the neonates assigned to sIMV treatment, and showed significantly lower transforming growth factor-beta1 concentrations in bronchoalveolar lavage fluid.\n The results of this randomized clinical trial support the hypothesis that early and exclusive use of HFOV, combined with optimum volume strategy, has a beneficial effect during the acute phase of lung injury.", "In a randomized, controlled, multicenter trial, we tested the hypothesis that high-frequency ventilation (HFV) with a high lung volume strategy results in fewer treatment failures than intermittent positive pressure ventilation (IPPV) with high rates and low peak inspiratory pressures.\n Infants with a gestational age between >/=24 weeks and <30 weeks, requiring mechanical ventilation within 6 hours of birth, were randomly assigned to receive either IPPV or HFV until 240 hours after randomization, extubation, or meeting treatment failure criteria. Treatment failure, the primary end point, was determined when air leaks, an oxygenation index >35 to 45 (depending on gestational age), death, or chronic lung disease occurred. Chronic lung disease was defined as persistent requirement of mechanical ventilation, continuous positive airway pressure, or supplemental oxygen at a postmenstrual age of 36 weeks. Secondary end points included the incidence of intracranial hemorrhage.\n The third scheduled interim analysis led to termination of the trial after recruitment of 284 infants. Treatment failure criteria were met by 46% of infants receiving IPPV and 54% of infants receiving HFV (1-tailed primary hypothesis, P =.92; 2-tailed chi2 test, P =.15). Air leaks occurred in 31% and 42% (P =.042), CLD in 23% and 25%, and grade 3-4 intracranial hemorrhage in 13% and 14% of IPPV-treated and HFV-treated patients, respectively. The mortality rate before discharge was 10% in both groups.\n HFV with a high lung volume strategy did not cause less lung injury in preterm infants than IPPV with a high rate and low peak inspiratory pressures.", "The aim of the present study was to evaluate if high-frequency oscillatory ventilation (HFOV) might reduce lung inflammation in preterm infants with infant respiratory distress syndrome (RDS) in comparison with the early application of another potentially lung-protective ventilation strategy, such as pressure support ventilation plus volume guarantee (PSV + VG). Infants at less than 30 weeks of gestation with RDS were enrolled consecutively in the study if they required mechanical ventilation, and were randomly allocated to receive HFOV or PSV + VG. Bronchial aspirate samples for the measurement of interleukin (IL)-1beta, IL-8, and IL-10 were obtained before surfactant treatment (T1), after 6-18 hr of ventilation (T2), after 24-48 hr of ventilation (T3), and before extubation (T4). Thirteen patients were enrolled in the HFOV group, and 12 in the PSV + VG group. The mean values of IL-1beta, IL-8, and IL-10 at T4 were lower in the HFOV group than in the PSV + VG group. The present study demonstrates that early treatment with HFOV is associated with a reduction of lung inflammation in comparison with PSV + VG in preterm infants with RDS.\n (c) 2005 Wiley-Liss, Inc.", "There remains uncertainty concerning the safety and efficacy of high-frequency oscillatory ventilation as compared with those of conventional ventilation for the respiratory support of very preterm infants. We conducted a multicenter trial to determine whether early intervention with high-frequency oscillatory ventilation reduced mortality and the incidence of chronic lung disease among newborns with a gestational age of 28 weeks or less.\n We randomly assigned preterm infants with a gestational age of 23 to 28 weeks to either conventional ventilation or high-frequency oscillatory ventilation within one hour after birth. Randomization was stratified according to center and gestational age (23 to 25 weeks or 26 to 28 weeks).\n A total of 400 infants were assigned to high-frequency oscillatory ventilation, and 397 were assigned to conventional ventilation. The composite primary outcome (death or chronic lung disease, diagnosed at 36 weeks of postmenstrual age) occurred in 66 percent of the infants assigned to receive high-frequency oscillatory ventilation and 68 percent of those in the conventional-ventilation group (relative risk in the group assigned to high-frequency oscillatory ventilation, 0.98; 95 percent confidence interval, 0.89 to 1.08). Similar proportions of infants died or had chronic lung disease in each gestational-age group. In both treatment groups treatment failure occurred in 10 percent of infants (relative risk in the group assigned to high-frequency oscillatory ventilation, 0.99; 95 percent confidence interval, 0.66 to 1.50). There were no significant differences between the groups in a range of other secondary outcome measures, including serious brain injury and air leak.\n The results obtained with high-frequency oscillatory ventilation and conventional ventilation do not differ significantly in the early treatment of respiratory disease in very preterm infants. Assessment of long-term effects will require additional follow-up.\n Copyright 2002 Massachusetts Medical Society", "Early use of high-frequency ventilation and exogenous surfactant is proposed as the optimal mode of ventilatory support in infants with respiratory distress syndrome. In very premature infants, we tested the hypothesis that high-frequency versus conventional ventilation could decrease exogenous surfactant requirements and improve pulmonary outcome, without altering the complication rate, including that of severe intraventricular hemorrhage.\n Preterm infants with a postmenstrual age of 24 to 29 weeks, presenting with respiratory distress syndrome were randomly assigned to high-frequency oscillatory ventilation (lung volume recruitment strategy) or conventional ventilation.\n Two hundred seventy-three infants were enrolled. One hundred fifty-three had a postmenstrual age of 24 to 27 weeks, and 143 had a birth weight </=1000 g. One hundred thirty-four infants were randomized at 142 minutes of life (median) to receive conventional ventilation (mean postmenstrual age at birth: 27. 6 +/- 1.5 weeks; mean birth weight: 997 +/- 245 g); and 139 infants were randomized at 145 minutes of life to receive high-frequency ventilation (mean postmenstrual age at birth: 27.5 +/- 1.4 weeks; mean birth weight: 976 +/- 219 g). High-frequency ventilation, compared with conventional ventilation, was associated with a twofold reduction in the requirement for >/=2 instillations of exogenous surfactant (30% vs 62%; odds ratio:.27; 95% confidence interval:.16-.44) and no difference in pulmonary outcome. The incidence of severe intraventricular hemorrhage was 24% in the high-frequency group and 14% in the conventional ventilation group (adjusted odds ratio: 1.50; 95% confidence interval:.68-3.30).\n Early use of high-frequency oscillatory ventilation in very premature infants decreases exogenous surfactant requirements, does not improve the pulmonary outcome, and may be associated with an increased incidence of severe intraventricular hemorrhage.", "To evaluate the feasibility of conducting a prospective, randomized trial comparing early high-frequency oscillatory ventilation (HFOV) to synchronized intermittent mandatory ventilation (SIMV) in very low birth weight (VLBW) premature infants. This pilot study evaluated two ventilator management protocols to determine how well they could be implemented in a multicenter clinical trial. Although this pilot study was not powered to detect differences in outcome, we also collected outcome data.\n Prospective, multicenter, randomized pilot study.\n Seven tertiary-level intensive care nurseries with previous experience with both HFOV and flow-triggered SIMV.\n Fifty infants weighing 501 to 1200 g, less than 4 hours of age, who had received one dose of surfactant and required ventilation with mean airway pressure > or =6 cm H2O and F(I)O2 > or =0.25, and had an anticipated duration of ventilation greater than 24 hours.\n Patients were stratified by birth weight and prenatal steroid status, then randomized to either HFOV or SIMV with tidal volume monitoring. Ventilator management for patients in both study arms was strictly governed by protocols that included optimizing lung inflation and blood gases, weaning strategies, and extubation criteria.\n Data were collected using the tools planned for the larger collaborative study. Protocol compliance was closely monitored, with successive changes in the protocol made as necessary to improve clarity and increase compliance. The incidence of major neonatal adverse outcomes was recorded.\n Data are presented for 24 HFOV and 24 SIMV infants (two infants, twins, were withdrawn from the study at parent's request). Nineteen of the 24 HFOV infants and 20 of the 24 SIMV infants survived to 36 weeks corrected age. Age at final extubation for survivors was 16+/-16 (mean+/-SD) days for HFOV infants and 24+/-24 days for SIMV infants. At 36 weeks corrected age, 14 of the 19 HFOV survivors were extubated and in room air, whereas 5 required supplemental oxygen. In comparison, 6 of the 20 SIMV survivors were extubated and in room air, whereas 14 required supplemental oxygen. Grade III/IV IVH and/or periventricular leukomalacia occurred in 2 HFOV and 2 SIMV patients. Overall compliance with the ventilator protocols was 82% for the SIMV protocol, and 88% for the HFOV protocol.\n The preliminary outcome data supports conducting the large randomized trial, which began in July of 1998. The protocols for the ventilator management of VLBW infants, both with HFOV and with SIMV were easily implemented and consistently followed, and are presented here." ]

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[ "Exercise in a behavioural weight control programme for obese patients with Type 2 (non-insulin-dependent) diabetes.", "Men gain additional psychological benefits by adding exercise to a weight-loss program.", "Plasma leptin in moderately obese men: independent effects of weight loss and aerobic exercise.", "The influence of a 1-year programme of brisk walking on endurance fitness and body composition in previously sedentary men aged 42-59 years.", "Effects of an ad libitum low-fat, high-carbohydrate diet on body weight, body composition, and fat distribution in older men and women: a randomized controlled trial.", "The effects on plasma lipoproteins of a prudent weight-reducing diet, with or without exercise, in overweight men and women.", "Effect of exercise on total and intra-abdominal body fat in postmenopausal women: a randomized controlled trial.", "Improved carbohydrate metabolism after physical training and dietary intervention in individuals with the \"atherothrombogenic syndrome'. Oslo Diet and Exercise Study (ODES). A randomized trial.", "Effects of diet and exercise in men and postmenopausal women with low levels of HDL cholesterol and high levels of LDL cholesterol.", "Training-induced changes in serum lipids, fat tolerance, and adipose tissue metabolism in patients with hypertriglyceridemia.", "Effects of lifestyle activity vs structured aerobic exercise in obese women: a randomized trial.", "Effect of exercise duration and intensity on weight loss in overweight, sedentary women: a randomized trial.", "Effects of exercise training on gallbladder function in an obese female population.", "Changes in plasma lipids and lipoproteins in overweight men during weight loss through dieting as compared with exercise.", "Effects of an energy-restrictive diet with or without exercise on abdominal fat, intermuscular fat, and metabolic risk factors in obese women.", "The independent effects of dietary weight loss and aerobic training on high density lipoproteins and apolipoprotein A-I concentrations in obese men.", "Effect of exercise training at different intensities on fat metabolism of obese men.", "Independent and additive effects of energy restriction and exercise on glucose and insulin concentrations in sedentary overweight men.", "Immune response to exercise training and/or energy restriction in obese women.", "A worksite program for overweight middle-aged men achieves lesser weight loss with exercise than with dietary change.", "Lifestyle intervention in overweight individuals with a family history of diabetes.", "Effects of cross-training on markers of insulin resistance/hyperinsulinemia.", "Physical activity within a community-based weight control program: program evaluation and predictors of success.", "Exercise and weight control in sedentary overweight men: effects on clinic and ambulatory blood pressure.", "The effect of weight loss with or without exercise training on large artery compliance in healthy obese men.", "Prescribing exercise in multiple short bouts versus one continuous bout: effects on adherence, cardiorespiratory fitness, and weight loss in overweight women.", "Moderate exercise improves glucose metabolism in uncontrolled elderly patients with non-insulin-dependent diabetes mellitus.", "Use of personal trainers and financial incentives to increase exercise in a behavioral weight-loss program.", "Influence of diet and exercise on skeletal muscle and visceral adipose tissue in men.", "Effect of an energy-restrictive diet, with or without exercise, on lean tissue mass, resting metabolic rate, cardiovascular risk factors, and bone in overweight postmenopausal women.", "The effect of intensity controlled aerobic dance exercise on aerobic capacity of middle-aged, overweight women.", "Comparison of single versus multiple lifestyle interventions: are the antihypertensive effects of exercise training and diet-induced weight loss additive?", "Diet and exercise are equally effective in reducing risk for cardiovascular disease. Results of a randomized controlled study in men with slightly to moderately raised cardiovascular risk factors.", "Effects of a resistive training program on lipoprotein--lipid levels in obese women.", "Short-term effects of weight loss with or without low-intensity exercise training on fat metabolism in obese men.", "Exercise training and severe caloric restriction: effect on lean body mass in the obese.", "Exercise in the treatment of obesity: effects of four interventions on body composition, resting energy expenditure, appetite, and mood.", "The effect of low-intensity exercise training on fat metabolism of obese women.", "Does the amount of endurance exercise in combination with weight training and a very-low-energy diet affect resting metabolic rate and body composition?", "Physical activity and weight loss: does prescribing higher physical activity goals improve outcome?" ]

[ "Two studies were conducted to determine whether adding exercise to a diet programme promotes weight loss or glycaemic control in Type 2 (non-insulin-dependent) diabetic subjects. In Study 1, 25 subjects were randomly assigned to diet plus moderate exercise or diet plus placebo exercise. All subjects exercised twice a week as a group and once a week on their own; the diet plus moderate exercise group walked a 3-mile route at each session while the diet plus placebo exercise group did very low intensity exercises such as stretching and light calisthenics. All subjects followed a calorie-counting diet and were taught behaviour modification strategies. Weight losses and improvements in glycaemic control did not differ significantly between the two treatment groups at the end of the 10-week treatment or at 1-year follow-up. In Study 2, more extreme conditions were compared: a diet only group and a diet plus exercise group. The diet plus exercise group walked a 3-mile route with the group 3 times/week and once a week on their own, while the diet only group was instructed to maintain their current low level of activity. Both groups received comparable diet and behaviour modification instruction and therapist contacts. The diet plus exercise group had significantly (p less than 0.01) better weight losses than the diet only condition at the end of the 10 week programme (-9.3 kg vs -5.6 kg) and at 1 year follow-up (-7.9 kg vs -3.8 kg).(ABSTRACT TRUNCATED AT 250 WORDS)", "Adding exercise to a comprehensive weight-loss program might not only attenuate any psychological distress associated with weight-loss attempts but also may provide psychological benefits. This study examined whether a diet-plus-exercise weight-loss program improved psychological outcomes more than a diet-only weight-loss program or an assessment-only control group.\n This study was part of a larger 1-year randomized weight-loss trial examining the effects of diet and exercise on cardiovascular disease risk factors in 264 overweight adults. Psychological measures specific to weight control (e.g., cognitive restraint, disinhibition, hunger, and body dissatisfaction) as well as traditional measures of psychological distress (e.g., symptoms of depression, anxiety, and stress) were obtained at baseline and 1 year.\n Men and women in either weight-loss program reported greater restraint, less disinhibition, and less hunger at 1 year than those in no program. Men in the diet-plus-exercise program experienced additional increases in restraint and decreases in hunger than did men in the diet-only program. Women in the diet-plus-exercise program did not experience additional psychological benefits specific to weight control than those in the diet-only program, despite increases in aerobic capacity.\n The pattern seen for overweight men in the diet-plus-exercise program at 1 year-greater restraint, less disinhibition, and less hunger-is similar to the pattern seen in successful weight maintainers. These results underscore the need for innovative strategies that will enhance and sustain the pattern of psychological benefits specific to weight control associated with successful weight loss, especially for overweight women.", "The independent effects of weight loss and exercise on plasma leptin and total (AT), subcutaneous (SAT), and visceral (VAT) adipose tissue were investigated in 52 obese men. Subjects were randomly assigned to four 12-wk protocols: 1) control (C, n = 8), 2) diet-induced weight loss (DWL, n = 14), 3) exercise-induced weight loss (EWL, n = 14), and 4) exercise with weight maintenance (EWS, n = 16). Plasma leptin was unchanged in C (from 7.8 +/- 1.3 to 7.7 +/- 1.0 ng/ml). Equivalent weight loss (7.5 kg) decreased leptin significantly but similarly (DWL, from 8.5 +/- 1.0 to 4.8 +/- 0.6 ng/ml; EWL, from 10.1 +/- 1.0 to 5.0 +/- 0.6 ng/ml). Exercise in the absence of weight loss did not alter leptin levels (from 10.1 +/- 1. 3 to 9.2 +/- 1.2 ng/ml). Changes in leptin correlated with changes in AT and SAT (both P < 0.05) but not in VAT. We conclude that reduction in adipose tissue after weight loss results in a collateral decrease in circulating leptin, and exercise, independent of its effects on weight loss, has no profound influence on leptin secretion.", "This study examined the influence of a 1-year brisk walking programme on endurance fitness and the amount and distribution of body fat in a group of formerly sedentary men. Seventy-two males, aged 42-59 years, body mass index 25.2 (0.3) kg.m-2 [mean (SEM)], were randomly allocated to either a walking group (n = 48) or control group (n = 24). Brisk walking speed was evaluated using a 1.6-km track walk. Changes in endurance fitness were assessed by measuring blood lactate concentration and heart rate during submaximal treadmill walking. Body composition was determined by hydrostatic weighing and anthropometry; energy intake was assessed from 7-day weighed food inventories. Differences in the response of walkers and controls were examined using two-way analyses of variance. Forty-two walkers (87.5%) completed the study and averaged 27.9 (1.4%) min.day-1 of brisk walking (range 11-46). Brisk walking speed averaged 1.95 (0.03) m.s-1 and elicited approximately 68 (1) % of maximum heart rate. Heart rate and blood lactate concentration during submaximal treadmill walking were significantly reduced in the walkers after 3, 6 and 12 months and the oxygen uptake at a reference blood lactate concentration of 2 mmol.l-1 was increased by 3.2 ml.kg-1.min-1 (14.9%) in the walkers at 6 months (P < 0.01). Although skinfold thicknesses at anterior thigh and medial calf sites decreased significantly for the walkers, the response of the two groups did not differ significantly for other body composition variables or for energy intake.", "The efficacy of ad libitum low-fat diets in reducing body weight and fat in overweight and obese adults remains controversial.\n We examined the effect of a 12-week low-fat, high-complex carbohydrate diet alone (HI-CHO) and in combination with aerobic exercise training (HI-CHO + EX) on body weight and composition in 34 individuals with impaired glucose tolerance (20 women and 14 men; mean +/- SEM age, 66 +/- 1 years). Participants were randomly assigned to a control diet (41% fat, 14% protein, 45% carbohydrates, and 7 g of fiber per 1000 kcal), a HI-CHO diet (18% fat, 19% protein, 63% carbohydrates, and 26 g of fiber per 1000 kcal), or a HI-CHO diet plus endurance exercise 4 d/wk, 45 min/d, at 80% peak oxygen consumption (HI-CHO + EX). Participants were provided 150% of estimated energy needs and were instructed to consume food ad libitum. Total food intake, body composition, resting metabolic rate, and substrate oxidation were measured.\n There was no significant difference in total food intake among the 3 groups and no change in energy intake over time. The HI-CHO + EX and HI-CHO groups lost more body weight (-4.8 +/- 0.9 kg [P=.003] and -3.2 +/- 1.2 kg [P=.02]) and a higher percentage of body fat (-3.5% +/- 0.7% [P=.01] and -2.2% +/- 1.2% [P=.049]) than controls (-0.1 +/- 0.6 kg and 0.2% +/- 0.6%). In addition, thigh fat area decreased in the HI-CHO (P=.003) and HI-CHO + EX (P<.001) groups compared with controls. High carbohydrate intake and weight loss did not result in a decreased resting metabolic rate or reduced fat oxidation.\n A high-carbohydrate diet consumed ad libitum, with no attempt at energy restriction or change in energy intake, results in losses of body weight and body fat in older men and women.", "The National Cholesterol Education Program (NCEP) recommends a low-saturated-fat, low-cholesterol diet, with weight loss if indicated, to correct elevated plasma cholesterol levels. Weight loss accomplished by simple caloric restriction or increased exercise typically increases the level of high-density lipoprotein (HDL) cholesterol. Little is known about the effects on plasma lipoproteins of a hypocaloric NCEP diet with or without exercise in overweight people.\n We tested the hypothesis that exercise (walking or jogging) will increase HDL cholesterol levels in moderately overweight, sedentary people who adopt a hypocaloric NCEP diet. We randomly assigned 132 men and 132 women 25 to 49 years old to one of three groups: control, hypocaloric NCEP diet, or hypocaloric NCEP diet with exercise. One hundred nineteen of the men and 112 of the women returned for testing after one year.\n After one year, the subjects in both intervention groups had reached or closely approached NCEP Step 1 dietary goals and reduced their mean body fat significantly (range of reduction in mean fat weight, 4.0 to 7.8 kg). Weight loss on the NCEP diet alone did not significantly change HDL cholesterol levels in either the men or the women as compared with the subjects in the control group. Plasma levels of HDL cholesterol increased significantly more in the men who exercised and dieted (mean [+/- SE] change, +13 +/- 3 percent) than in the men who only dieted (+2 +/- 3 percent, P less than 0.01) or the men who acted as controls (-4 +/- 2 percent, P less than 0.001). HDL cholesterol levels remained about the same in the women who exercised and dieted (+1 +/- 2 percent); they were higher than in the women who only dieted (-10 +/- 3 percent, P less than 0.01), but not higher than in the controls (-3 +/- 3 percent).\n Regular exercise in overweight men and women enhances the improvement in plasma lipoprotein levels that results from the adoption of a low-saturated-fat, low-cholesterol diet.", "The increasing prevalence of obesity is a major public health concern. Physical activity may promote weight and body fat loss.\n To examine the effects of exercise on total and intra-abdominal body fat overall and by level of exercise.\n Randomized controlled trial conducted from 1997 to 2001.\n A total of 173 sedentary, overweight (body mass index > or =24.0 and >33% body fat), postmenopausal women aged 50 to 75 years who were living in the Seattle, Wash, area.\n Participants were randomly assigned to an intervention consisting of exercise facility and home-based moderate-intensity exercise (n = 87) or a stretching control group (n = 86).\n Changes in body weight and waist and hip circumferences at 3 and 12 months; total body, intra-abdominal, and subcutaneous abdominal fat at 12 months.\n Twelve-month data were available for 168 women. Women in the exercise group participated in moderate-intensity sports/recreational activity for a mean (SD) of 3.5 (1.2) d/wk for 176 (91) min/wk. Walking was the most frequently reported activity. Exercisers showed statistically significant differences from controls in baseline to 12-month changes in body weight (-1.4 kg; 95% confidence interval [CI], -2.5 to -0.3 kg), total body fat (-1.0%; 95% CI, -1.6% to -0.4%), intra-abdominal fat (-8.6 g/cm2; 95% CI, -17.8 to 0.9 g/cm2), and subcutaneous abdominal fat (-28.8 g/cm2); 95% CI, -47.5 to -10.0 g/cm2). A significant dose response for greater body fat loss was observed with increasing duration of exercise.\n Regular exercise such as brisk walking results in reduced body weight and body fat among overweight and obese postmenopausal women.", "To compare the single and joint effect of 1-year diet and exercise intervention on carbohydrate metabolism and associated coronary risk variables.\n Unmasked, randomized, 2 x 2 factorial intervention trial with 1-year duration for each participant.\n The participants were recruited from a screening examination of 40-year-old persons in Oslo, Norway.\n Two hundred and nineteen sedentary men and women, with diastolic blood pressure 86-99 mmHg, HDL cholesterol < 1.20 mmol L-1, triglycerides > 1.4 mmol L-1, total cholesterol 5.20-7.74 mmol L-1 and BMI > 24. Participants were randomly allocated to control (n = 43), diet (n = 55), exercise (n = 54) and diet+exercise (n = 67).\n Exercise: supervised endurance exercise three times a week. Diet: reduce weight, increase the intake of fish and reduce total fat intake.\n One-year changes in insulin and glucose before and after a standardized glucose load.\n As compared with controls fasting insulin in pmol L-1 decreased significantly in the combined diet and exercise group (3.9 +/- 6.2 versus -22.6 +/- 4.7 respectively, P = 0.003). Insulin in pmol L-1 after glucose load decreased significantly in all intervention groups compared to controls (diet: -82.2 +/- 49.9 P = 0.02; exercise: -92.4 +/- 60.1 P = 0.03; diet + exercise: -179.6 +/- 46.1 P = 0.0004). Fasting glucose in mmol L-1 decreased significantly in the diet alone group (0.21 +/- 0.07 P = 0.006) and in the diet+exercise group (-0.26 +/- 0.08 P = 0.005). In a subgroup analysis of the good responders, the observed changes with respect to total cholesterol (-0.76 mmol L-1), HDL cholesterol (0.16 mmol L-1), triglycerides (-0.72 mmol L-1), systolic and diastolic blood pressure (-8.5/ -6.8 mmHg) were all statistically significant compared to the control with P < 0.001).\n Exercise and diet intervention and in particular the combination of the two, were effective in improving carbohydrate metabolism. Associated risk factors were also affected in a beneficial direction.", "Guidelines established by the National Cholesterol Education Program (NCEP) promote exercise and weight loss for the treatment of abnormal lipoprotein levels. Little is known, however, about the effects of exercise or the NCEP diet, which is moderately low in fat and cholesterol, in persons with lipoprotein levels that place them at high risk for coronary heart disease.\n We studied plasma lipoprotein levels in 180 postmenopausal women, 45 through 64 years of age, and 197 men, 30 through 64 years of age, who had low high-density lipoprotein (HDL) cholesterol levels (< or =59 mg per deciliter in women and < or =44 mg per deciliter in men) and moderately elevated levels of low-density lipoprotein (LDL) cholesterol (>125 mg per deciliter but <210 mg per deciliter in women and >125 mg per deciliter but <190 mg per deciliter in men). The subjects were randomly assigned to aerobic exercise, the NCEP Step 2 diet, or diet plus exercise, or to a control group, which received no intervention.\n Dietary intake of fat and cholesterol decreased during the one-year study (P<0.001), as did body weight, in women and men in either the diet group or the diet-plus-exercise group, as compared with the controls (P<0.001) and the exercise group (P<0.05), in which dietary intake and body weight were unchanged. Changes in HDL cholesterol and triglyceride levels and the ratio of total to HDL cholesterol did not differ significantly among the treatment groups, for subjects of either sex. The serum level of LDL cholesterol was significantly reduced among women (a decrease of 14.5+/-22.2 mg per deciliter) and men (a decrease of 20.0+/-17.3 mg per deciliter) in the diet-plus-exercise group, as compared with the control group (women had a decrease of 2.5+/-16.6 mg per deciliter, P<0.05; men had a decrease of 4.6+/-21.1 mg per deciliter, P<0.001). The reduction in LDL cholesterol in men in the diet-plus-exercise group was also significant as compared with that among the men in the exercise group (3.6+/-18.8 mg per deciliter, P<0.001). In contrast, changes in LDL cholesterol levels were not significant among the women (a decrease of 7.3+/-18.9 mg per deciliter) or the men (10.8+/-18.8 mg per deciliter) in the diet group, as compared with the controls.\n The NCEP Step 2 diet failed to lower LDL cholesterol levels in men or women with high-risk lipoprotein levels who did not engage in aerobic exercise. This finding highlights the importance of physical activity in the treatment of elevated LDL cholesterol levels.", "Ten males (mean age 44 years) with primary hypertriglyceridemia were trained for 4 months 3 times/week for 1-h sessions. Eleven patients with similar physical characteristics and hypertriglyceridemia served as controls. Serum was assayed for TG and cholesterol (CH) and the various lipoprotein fractions, apoprotein A-I, glucose, insulin, and C-peptide. The removal of TG from the circulation was estimated by the Intralipid test. An open fat biopsy was taken and the incorporation and esterification of [14C]palmitate and glycerol release were measured in vitro. Following endurance physical training, serum TG and VLDL-TG decreased by 25 and 27%, respectively. No changes were observed in total CH and CH in the lipoprotein fractions or in apoprotein A-I. Fat tolerance increased slightly (+8%) whereas the incorporation of labelled palmitate into adipose tissue was reduced by 16%. The diminished incorporation was concomitant with a reduction in the esterification of fatty acids to TG (-29%). Enhanced removal of TG may contribute to the lowering of serum TG. The skeletal muscle is probably responsible for this adaptation, whereas the uptake of TG into adipose tissue is diminished.", "Physical inactivity contributes to weight gain, but only 22% of Americans are regularly active.\n To examine short- and long-term changes in weight, body composition, and cardiovascular risk profiles produced by diet combined with either structured aerobic exercise or moderate-intensity lifestyle activity.\n Sixteen-week randomized controlled trial with 1-year follow-up, conducted from August 1995 to December 1996.\n Forty obese women (mean body mass index [weight in kilograms divided by the square of height in meters], 32.9 kg/m2; mean weight, 89.2 kg) with a mean age of 42.9 years (range, 21-60 years) seen in a university-based weight management program.\n Structured aerobic exercise or moderate lifestyle activity; low-fat diet of about 1200 kcal/d.\n Changes in body weight, body composition, cardiovascular risk profiles, and physical fitness at 16 weeks and at 1 year.\n Mean (SD) weight losses during the 16-week treatment program were 8.3 (3.8) kg for the aerobic group and 7.9 (4.2) kg for the lifestyle group (within groups, P<.001; between groups, P = .08). The aerobic group lost significantly less fat-free mass (0.5 [1.3] kg) than the lifestyle group (1.4 [1.3] kg; P = .03). During the 1-year follow-up, the aerobic group regained 1.6 [5.5] kg, while the lifestyle group regained 0.08 (4.6) kg. At week 16, serum triglyceride levels and total cholesterol levels were reduced significantly (P<.001) from baseline (16.3% and 10.1% reductions, respectively) but did not differ significantly between groups and were not different from baseline or between groups at week 68.\n A program of diet plus lifestyle activity may offer similar health benefits and be a suitable alternative to diet plus structured aerobic activity for obese women.", "A higher duration and intensity of exercise may improve long-term weight loss.\n To compare the effects of different durations and intensities of exercise on 12-month weight loss and cardiorespiratory fitness.\n Randomized trial conducted from January 2000 through December 2001 involving 201 sedentary women (mean [SD] age, 37.0 [5.7] years; mean [SD] body mass index, 32.6 [4.2]) in a university-based weight control program.\n Participants were randomly assigned to 1 of 4 exercise groups (vigorous intensity/high duration; moderate intensity/high duration; moderate intensity/moderate duration; or vigorous intensity/moderate duration) based on estimated energy expenditure (1000 kcal/wk vs 2000 kcal/wk) and exercise intensity (moderate vs vigorous). All women were instructed to reduce intake of energy to between 1200 and 1500 kcal/d and dietary fat to between 20% and 30% of total energy intake.\n Body weight, cardiorespiratory fitness, and exercise participation.\n After exclusions, 184 of 196 randomized participants completed 12 months of treatment (94%). In intention-to-treat analysis, mean (SD) weight loss following 12 months of treatment was statistically significant (P <.001) in all exercise groups (vigorous intensity/high duration = 8.9 [7.3] kg; moderate intensity/high duration = 8.2 [7.6] kg; moderate intensity/moderate duration = 6.3 [5.6] kg; vigorous intensity/moderate duration = 7.0 [6.4] kg), with no significant difference between groups. Mean (SD) cardiorespiratory fitness levels also increased significantly (P =.04) in all groups (vigorous intensity/high duration = 22.0% [19.9%]; moderate intensity/high duration = 14.9% [18.6%]; moderate intensity/moderate duration = 13.5% [16.9%]; vigorous intensity/moderate duration = 18.9% [16.9%]), with no difference between groups. Post hoc analysis revealed that percentage weight loss at 12 months was associated with the level of physical activity performed at 6 and 12 months. Women reporting less than 150 min/wk had a mean (SD) weight loss of 4.7% [6.0%]; inconsistent (other) pattern of physical activity, 7.0% [6.9%]; 150 min/wk or more, 9.5% [7.9%]; and 200 min/wk or more of exercise, 13.6% [7.8%].\n Significant weight loss and improved cardiorespiratory fitness were achieved through the combination of exercise and diet during 12 months, although no differences were found based on different exercise durations and intensities in this group of sedentary, overweight women.", "Aerobic exercise may influence gallstone disease pathogenesis through its effect on gallbladder motility. The purpose of this investigation was to examine the effects of exercise training on gallbladder emptying in obese women.\n Twenty-seven obese subjects were randomized into one of two groups: exercise (E) (five 45-min brisk walking sessions per week at 75.2 +/- 0.5% of maximum heart rate) and controls (C). Gallbladder function via cholescintigraphy, cardiorespiratory fitness, and body composition were measured in all subjects before and after a 12-wk intervention period. In each cholescintigraphy trial subjects ingested an 8-oz liquid meal 45 min after injection of 99mTc disofenin to promote gallbladder emptying. Gallbladder areas were then scanned for 60 s and then every 5 min for 60 min.\n VO2max increased significantly by 9% for E when compared with that for C (P < 0.001). Within E postprandial gallbladder ejection fraction (EF) increased significantly after training (39.5 +/- 4.9% to 54.7 +/- 6.5%, P < 0.05); however, this 15.2% increase in EF was not significantly greater than the change reported in the controls.\n Results indicate that 12 wk of moderate exercise training does improve cardiorespiratory fitness but does not significantly effect gallbladder emptying in obese women.", "We studied separately the influence of two methods for losing fat weight on the levels of plasma lipids and lipoproteins in overweight sedentary men--decreasing energy intake without increasing exercise (diet), and increasing energy expenditure without altering energy intake (exercise, primarily running)--in a one-year randomized controlled trial. As compared with controls (n = 42), dieters (n = 42) had significant loss of total body weight (-7.8 +/- 0.9 kg [mean +/- SE]), fat weight (-5.6 +/- 0.8 kg), and lean (non-fat) weight (-2.1 +/- 0.5 kg) (P less than 0.001 for each variable), and exercisers (n = 47) had significant loss of total body weight (-4.6 +/- 0.8 kg) and fat weight (-3.8 +/- 0.7 kg) (P less than 0.001 for both variables) but not lean weight (-0.7 +/- 0.4 kg). Fat-weight loss did not differ significantly between dieters and exercisers. All subjects were discouraged from altering their diet composition; however, dieters and exercisers had slight reductions in the percentage of kilojoules derived from fat. As compared with the control group, both weight-loss groups had significant increases (P less than 0.01) in plasma concentrations of high-density lipoprotein (HDL) cholesterol (diet vs. exercise, 0.13 +/- 0.03 vs. 0.12 +/- 0.03 mmol per liter), HDL2 cholesterol (0.07 +/- 0.02 vs. 0.07 +/- 0.02 mmol per liter), and HDL3 cholesterol (0.07 +/- 0.02 vs. 0.06 +/- 0.02 mmol per liter) and significant decreases (P less than 0.05) in triglyceride levels (diet vs. exercise, -0.35 +/- 0.14 vs. -0.24 +/- 0.12 mmol per liter). Levels of total and low-density lipoprotein cholesterol were not significantly changed, relative to values in controls. None of these changes were significantly different between dieters and exercisers. Thus, we conclude that fat loss through dieting or exercising produces comparable and favorable changes in plasma lipoprotein concentrations.", "The primary objective was to examine whether the combination of diet and aerobic exercise (DA) or diet and resistance exercise (DR) is associated with greater improvements in metabolic risk factors by comparison to diet only (DO) in obese women. A second objective considered whether reductions in metabolic risk factors are related to concurrent changes in abdominal and/or intermuscular fat distribution.\n A total of 38 premenopausal obese women were randomly assigned to one of three 16-week treatments: DO (n=13), DA (n=11), or DR (n=14). Plasma glucose, insulin, and lipid levels were measured in a fasting state and after a 75-g oral glucose challenge (oral glucose tolerance test [OGTT]). Total, abdominal subcutaneous, visceral, and intermuscular fat were measured by magnetic resonance imaging.\n Significant reductions (P < 0.02) in body weight (approximately 10 kg or 10%) and in total, abdominal subcutaneous, visceral, and intermuscular fat were observed within each group. Fasting and OGTT insulin, total cholesterol, LDL cholesterol, and apolipoprotein B also decreased within each group (P < or = 0.02). The changes in the body fat and metabolic variables were not different across treatment (P > 0.05). Visceral fat alone was related to the metabolic risk factors both before and after the treatment.\n Weight loss was associated with reductions in metabolic risk factors in obese women. The improvement in the metabolic profile was not enhanced by the addition of aerobic or resistance exercise. The findings reinforce the importance of diminished visceral fat in the treatment of insulin resistance.", "Several studies have demonstrated that high density lipoprotein cholesterol (HDL-C) is increased after either dietary weight loss or aerobic exercise training, but it is unclear whether the effects of these two interventions are separate and independent, or just related to the amount of weight or fat lost. The effect of dietary weight loss or aerobic training on apolipoprotein A1 (Apo-A-I) has not been extensively studied. In the present study we evaluated the effects of either dietary weight loss or aerobic exercise training on lipoproteins and Apo A-I, and assessed whether they are related to changes in body composition. Twenty-six obese, otherwise healthy, untrained, nonsmoking, male subjects were weight stabilized for ten days, during which maximal aerobic capacity, body composition, and fat cell size were measured. At the end of this ten-day period lipoproteins and Apo A-I were measured. Subjects were then randomized into either a dietary weight loss (n = 12) or aerobic exercise group (n = 14). At the end of three months the groups were restabilized and restudied. Although both groups lost weight, the weight loss was greater in the diet group (-13.1 v -2.8 kg, P less than 0.001). Important differences in body composition were also detected after the two interventions with 25% of the total weight loss in the diet group coming from fat free mass. Significant decrements in triglyceride (-54 +/- 67 mg/dL, P less than 0.05), total cholesterol (-29 +/- 27 mg/dL, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)", "The present study investigated the effect of exercise training at different intensities on fat oxidation in obese men. Twenty-four healthy male obese subjects were randomly divided in either a low- [40% maximal oxygen consumption (VO(2 max))] or high-intensity exercise training program (70% VO(2 max)) for 12 wk, or a non-exercising control group. Before and after the intervention, measurements of fat metabolism at rest and during exercise were performed by using indirect calorimetry, [U-(13)C]palmitate, and [1,2-(13)C]acetate. Furthermore, body composition and maximal aerobic capacity were measured. Total fat oxidation did not change at rest in any group. During exercise, after low-intensity exercise training, fat oxidation was increased by 40% (P < 0.05) because of an increased non-plasma fatty acid oxidation (P < 0.05). High-intensity exercise training did not affect total fat oxidation during exercise. Changes in fat oxidation were not significantly different among groups. It was concluded that low-intensity exercise training in obese subjects seemed to increase fat oxidation during exercise but not at rest. No effect of high-intensity exercise training on fat oxidation could be shown.", "Overweight and inactivity are associated with impaired glucose tolerance, reduced insulin sensitivity, and diabetes. Few controlled trials have assessed the independent and combined effects of energy restriction and exercise on the prevention of these conditions.\n The objective was to evaluate the independent and additive effects of 16 wk of energy restriction and exercise on glucose and insulin concentrations.\n Sixty nonsmoking, overweight, sedentary men aged 20-50 y were randomly assigned to either maintain or restrict their energy intake (4186-6279 kJ/d). Within each of these arms, the subjects were further randomly assigned to either a light-intensity (control) or a vigorous-intensity exercise program for 30 min 3 times/wk.\n Fifty-one subjects completed the study. Maximal oxygen uptake increased ( approximately 24%; P < 0.001) with vigorous but not with light exercise. Significant weight loss was observed with energy restriction (x: 10.12 kg; 95% CI: 8.02, 12.22 kg; P < 0.001) but not with exercise. Vigorous exercise reduced fasting glucose and glucose and insulin areas under the curve (AUCs) by 13% (P = 0.01) and 20% (P = 0.02), respectively. Exercise effects were independent of weight change. Energy restriction resulted in a 40% reduction in the insulin AUC (P = 0.01). Vigorous exercise and energy restriction were additive in reducing the insulin AUC.\n Energy restriction and vigorous exercise independently and additively reduce glucose and insulin concentrations in response to an oral-glucose-tolerance test. Both of these lifestyle interventions provide a potent strategy that should be an integral part of any program to reduce the risk of impaired glucose tolerance, insulin resistance, and diabetes in overweight and sedentary persons.", "The effect of exercise training (five 45-min walking sessions/wk at 60-75% maximum heart rate) and/or moderate energy restriction (4.19-5.44 MJ or 1,200-1,300 kcal x d(-1)) on innate and adaptive immunity (including mitogen-stimulated lymphocyte proliferation (MSLP), natural killer cell activity (NKCA), and monocyte and granulocyte phagocytosis and oxidative burst (MGPOB) was studied in obese women (N = 91, age 45.6 +/- 1.1 yr, body mass index 33.1 +/- 0.6 kg x m(-2)) randomized to one of four groups: control (C), exercise (E), diet (D), exercise, and diet (ED).\n Aerobic power, body composition, and immune function were measured in all subjects before and after a 12-wk diet intervention period, with data analyzed using a 4 x 2 repeated measures design. All subjects self-reported symptoms of sickness in health logs using a precoded checklist. Statistical significance was set at P < or = 0.05.\n Data from this study indicate that although exercise training was unrelated to any significant changes in resting immune function, the number of days with symptoms of upper respiratory tract infection (URTI) was reduced relative to subjects in the nonexercise groups (5.6 +/- 0.9 and 9.4 +/- 1.1 sickness days, respectively, P < 0.05). Energy restriction and weight loss (7.9 +/- 0.7 kg) was associated with a significant decrease in MSLP, but no change in NKCA, MGPOB, or URTI.\n The data are consistent the viewpoint that weight loss, even at a moderate rate, is associated with a decrease in mitogen-stimulated lymphocyte proliferation without a change in various measures of innate immunity of the blood compartment.", "To compare changes in total and regional body composition using dual energy X-ray absorptiometry (DEXA) after subjects lost weight through change in diet or exercise.\n A 12-month, randomized, controlled study of two weight-loss interventions-low-fat diet ad libitum or moderate, unsupervised exercise-in free-living, middle-aged men. Compliance was determined at monthly measurement sessions through food records and activity logs; DEXA scans were performed every 3 months.\n Fifty-eight overweight men (mean body mass index = 29.0 +/- 2.6; mean age = 43.4 +/- 5.7 years) recruited from a national corporation were assigned randomly to diet, exercise, or control groups.\n One group reduced dietary fat to 26.4% of energy intake but kept activity unchanged; another group self-selected aerobic exercise (three sessions per week at 65% to 75% maximum heart rate) but kept diet unchanged. A control group maintained weight.\n At 12 months, measurements of weight, total and regional fat mass and lean mass, energy intake, and percentage dietary fat; physical activity indexes.\n Results were analyzed using paired t tests and analysis of variance.\n Mean weight loss was 6.4 +/- 3.3 kg in dieters and 2.6 +/- 3.0 kg in exercisers; control subjects maintained weight. DEXA scans revealed that 40% of dieters' weight loss was lean tissue; more than 80% of weight lost by exercisers was fat. Exercisers maintained limb lean tissue and lost fat mass.\n Greater total weight and lean tissue loss occurred when subjects lost weight through a low-fat diet consumed ad libitum than when subjects participated in unsupervised aerobic exercise. Use of DEXA enabled identification of progressive total and regional changes in fat and lean tissue.", "To assess the effect of lifestyle intervention over 2 years on changes in weight, coronary heart disease (CHD) risk factors, and incidence of diabetes in overweight individuals with a parental history of diabetes.\n Participants (n = 154), who were 30-100% over ideal body weight, had one or both parents with diabetes, and were currently nondiabetic, were randomly assigned to 2-year treatments focused on diet (decreasing calories and fat intake), exercise (goal of 1,500 kcal/week of moderate activity), or the combination of diet plus exercise or to a no-treatment control group. Subjects were reassessed at 6 months, 1 year, and 2 years.\n At 6 months, the groups differed significantly on measures of eating, exercise, and fitness; weight losses in the diet and diet-plus-exercise groups were significantly greater than in the exercise and control conditions. Weight losses were associated with positive changes in CHD risk factors. After 6 months, there was gradual deterioration of behavioral and physiological changes, so that at 2 years, almost no between-group differences were maintained. Differences between groups in risk of developing diabetes were of borderline significance (P = 0.08). Strongest predictors were impaired glucose tolerance at baseline, which was positively related to risk of developing diabetes, and weight loss from baseline to 2 years, which was negatively related; in all treatment groups, a modest weight loss of 4.5 kg reduced the risk of type 2 diabetes by approximately 30% compared with no weight loss.\n Although initially successful, the interventions studied here were not effective in producing long-term changes in behavior, weight, or physiological parameters. However, weight loss from 0 to 2 years reduced the risk of developing type 2 diabetes. Since modest weight loss significantly reduced risk of type 2 diabetes, further research is needed to determine how best to increase the percentage of subjects achieving at least a modest weight loss.", "This study examined, through a randomized controlled trial, the effects of cross-training (combined resistance and endurance exercise) on markers of insulin resistance, (e.g., dyslipidemia, intra-abdominal obesity, hyperinsulinemia, and hypertension), body composition, and performance in hyperinsulinemic individuals. Sedentary adult males characterized as hyperinsulinemic (fasting insulin > 2 OuU.mL-1), randomly assigned to two groups (N = 8 each), completed 14 wk of training at 3 d.wk-1. An endurance-only (E) group performed both continuous cycle exercise and walking (30 min each at 60-70% heart rate reserve). A cross-training (C) group performed both endurance and resistance exercise (8 exercises, 4 sets/exercise, 8-12 repetitions/set) in a single session. Both E and C groups demonstrated similar increases in VO2max (25% and 27%) while only C demonstrated an increase in 1 RM bench press (19%) and leg press (25%). The changes induced by C training were significantly greater than those from E training alone in percent fat (6.9 +/- 1.3 vs 1.4 +/- 1.4), insulin concentration (8.5 +/- 2.7 vs 3.0 +/- 1.3 uU.mL-1), glucose levels (11.1 +/- 2.9 vs 5.9 +/- 2.6 mg.dL-1), HDL-C levels (5.1 +/- 1.3 vs 2.9 +/- 1.6 mg.dL-1), triglyceride concentration (43.8 +/- 13.6 mg.dL-1), and systolic blood pressure (14.6 +/- 5.5 vs 8.3 +/- 6.8 mm Hg). Results indicate that the addition of resistance training to an endurance training program will induce significantly greater differences in markers of insulin resistance and body composition in individuals with hyperinsulinemia than endurance training alone.", "To assess the feasibility and effectiveness of adding physical activity sessions to a weight control program in a community health center and to identify individuals suitable for outpatient group treatment with and without physical activity.\n The study population included 42 overweight women who were randomly divided into treatment groups. Both treatment groups received guidance in nutrition and behavior modification and the exercise group also participated in physical activity sessions. Both treatments included 20 sessions and participants were followed up for eight months.\n In both treatments, significant improvements were seen in physical fitness, anthropometric measurements, nutritional knowledge, food consumption, and eating behaviors. Weight loss following three months of weekly sessions did not differ by treatment group. At follow-up there was a trend towards increased maintenance of weight loss in the exercise group, however differences were not statistically significant. Attrition rates were low in both treatments and participant satisfaction was high. Lower baseline BMI predicted larger weight losses, in particular in the exercise group. Other predictors of weight loss included poorer baseline eating behaviors and employment outside of the home. Perceived spouse support predicted continual participation.", "To examine whether restriction of caloric intake and exercise of vigorous intensity can independently and additively influence clinic and ambulatory blood pressures in sedentary overweight men.\n Sixty subjects aged 20-50 years were randomly allocated either to continue their normal caloric intake or to restrict it by 4186-6279 kl/day, with 15% provided by protein, 30% by fat and 55% by carbohydrate, for 16 weeks. Within each of these groups subjects were further randomly allocated either to a control light intensity programme of exercise or to a vigorous intensity programme of exercise for 30 min three times a week. The light exercise group performed stationary cycling against no resistance, flexibility exercises and slow walking. The vigorous intensity group cycled on an ergometer at 60-70% of maximum their workload.\n Fifty-one subjects completed the study. Their maximal oxygen uptake was increased by approximately 24% with vigorous exercise but did not change with light exercise. Caloric intake restriction led to a significant loss of body mass of 9.5 kg (95% confidence interval 7.6-11.3), whereas vigorous exercise had no effect. Restriction of caloric intake reduced supine clinic systolic and diastolic blood pressures significantly by 5.6 (2.3-8.9) and 2.4 mmHg (0.4-4.2), respectively. Relative to the control light exercise group, exercise of vigorous intensity exercise had no significant effect on clinic blood pressure. In contrast, time series analysis revealed that both caloric intake restriction and vigorous exercise were associated with lower daytime ambulatory systolic blood pressure, the reduction in systolic blood pressure being sustained throughout the 24 h period when vigorous exercise and caloric intake restriction were combined.\n Compared with the effects of caloric intake restriction, the effects of a vigorous exercise programme on blood pressure are inconsistent, there being no influence on clinic blood pressure but a reduction in daytime ambulatory blood pressure. However, when combined with caloric intake restriction, regular vigorous exercise exhibits a synergistic effect in reducing ambulatory blood pressure throughout a 24 h period.", "Obesity is an independent risk factor for cardiovascular morbidity and mortality. Large artery compliance is thought to be associated with cardiovascular risk. The effect of weight loss on large artery compliance is not yet clarified.\n To investigate the effect of weight loss, with or without exercise, on vessel wall properties in healthy obese men.\n This was a pair-matched randomized intervention study. All subjects were on an energy-restricted diet. One subject from each pair was also on an exercise programme. Measurements were performed before and at the end of the study period. The study lasted for 3 months.\n The vessel wall properties of the brachial and common carotid artery were assessed using a vessel wall movement detector system in combination with applanation tonometry.\n The mean body mass index was 32.3+/-0.4 kg/m2 and decreased (P < 0.001) to 27.6+/-0.4 kg/mm2 during the study. The mean blood pressure decreased (P < 0.001) by 6%. At operating pressures, carotid artery distensibility was 27.5+/-1.7 x 10(-3)/kPa at the start of the study and 31.1+/-1.8 x 10(-3)/kPa (P < 0.04) at the end of the study. Brachial and carotid artery compliances were 0.11+/-0.01 and 1.35+/-0.08 mm2/kPa at the start of the study and tended to increase to 0.12+/-0.001 (P = 0.06) and 1.48+/-0.08 mm2/kPa (P = 0.057), respectively, at the end of the study. Isobaric compliance did not change. The diet-and-exercise group did not differ statistically from the only-diet group in the effects on weight loss, blood pressure and arterial compliance.\n This study shows that weight loss increased carotid artery distensibility at operating pressures, but not under isobaric conditions. This increase is probably due to the decrease in blood pressure. The addition of exercise did not result in an additional effect within 3 months.", "To investigate whether prescribing exercise in several short-bouts versus one long-bout per day would enhance exercise adherence, cardiorespiratory fitness, and weight loss in overweight adult females in a behavioral weight control program.\n Randomized controlled trial with subjects randomized to either a short-bout exercise group (SB, n = 28, age = 40.4 +/- 5.9 yrs) or a long-bout exercise group (LB, n = 28, age = 40.9 +/- 7.3 yrs), with subjects followed for a period of 20 weeks. Both groups were instructed to exercise 5 days per week with exercise duration progressing from 20 to 40 min per day. The LB group performed one exercise bout per day, whereas the SB group performed multiple 10 min bouts of exercise per day. The recommended caloric intake for all subjects was 5022-6277 kJ/day (1200-1500 kcal/day), with fat reduced to 20% of caloric intake.\n Fifty-six obese, sedentary females (BMI = 33.9 +/- 4.1 kg/m2).\n Exercise participation was assessed from self-reported diaries and Tri-Trac Accelerometers. Cardiorespiratory fitness was assessed using a submaximal cycle ergometer test.\n Exercising in multiple short-bouts per day improved adherence to exercise: the SB group reported exercising on a greater number of days (mean +/- s.d. = 87.3 +/- 29.5 days vs 69.1 +/- 28.9 days; P < 0.05) and for a greater total duration (223.8 +/- 69.5 min/week vs 188.2 +/- 58.4 min/week; P = 0.08) than the LB group. Predicted VO2Peak increased by 5.6% and 5.0% for the LB and SB groups, respectively (P < 0.05). There was a trend for the weight loss to be greater in the SB group (-8.9 +/- 5.3 kg) compared to the LB group (-6.4 +/- 4.5 kg; P < 0.07).\n These results suggest that short-bouts of exercise may enhance exercise adherence. Short-bouts of exercise may also enhance weight loss and produce similar changes in cardiorespiratory fitness when compared to long-bouts of exercise. Thus, short-bouts of exercise may be preferred when prescribing exercise to obese adults.", "Exercise should be an integral part of the treatment in non-insulin-dependent (NIDDM) diabetic patients, yet most of these patients' performance is low, mainly because of their obesity and concomitant macrovascular disease. We studied the influence of a moderate exercise training on parameters of glucose control in NIDDM patients. Forty patients aged 56.6 +/- 6.6 years were assigned randomly according to age and sex into exercise and control groups. The exercise group trained for 45 min 3 times weekly for 12 weeks, while the control group did not change their lifestyle. At the end of the study the exercise group had a significant reduction in plasma levels of triglycerides, fructosamine and glycohemoglobin. The improvement in metabolic control persisted significantly in patients who continued to exercise at varying levels at home during 1 year of follow-up.", "Exercise is the best predictor of long-term weight loss. This study evaluated two strategies for improving exercise adherence and long-term weight loss in obese outpatients. Obese men and women (N = 193) were randomized to 1 of 5 treatment groups for 18 months: standard behavior therapy (SBT); SBT with supervised walks (SW) 3 times per week; SBT + SW with personal trainers (PT), who walked with participants, made phone reminders, and did make-up SW; SBT + SW with monetary incentives (I) for completing SW; and SBT + SW + PT + I. Both PT and I enhanced attendance at SWs, the combination producing the best adherence. Increased walk attendance did not result in higher overall energy expenditure, however, and long-term weight loss was also not improved. Post hoc analyses suggest that the level of exercise needed for successful long-term weight loss is much higher than that usually recommended in behavioral treatment programs.", "The effects of diet only (DO) and diet combined with either aerobic (DA) or resistance (DR) exercise on subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), lean tissue (LT), and skeletal muscle (SM) tissue were evaluated in 33 obese men (DO, n = 11; DA, n = 11; DR, n = 11). All tissues were measured by using a whole body multislice magnetic resonance imaging (MRI) model. Within each group, significant reductions were observed for body weight, SAT, and VAT (P < 0.05). The reductions in body weight (approximately 10%) and SAT (approximately 25%) and VAT volume (approximately 35%) were not different between groups (P > 0.05). For all treatments, the relative reduction in VAT was greater than in SAT (P < 0.05). For the DA and DR groups only, the reduction in abdominal SAT (approximately 27%) was greater (P < 0.05) than that observed for the gluteal-femoral region (approximately 20%). Conversely, the reduction in VAT was uniform throughout the abdomen regardless of treatment (P > 0.05). MRI-LT and MRI-SM decreased both in the upper and lower body regions for the DO group alone (P < 0.05). Peak O2 uptake (liters) was significantly improved (approximately 14%) in the DA group as was muscular strength (approximately 20%) in the DR group (P < 0.01). These findings indicate that DA and DR result in a greater preservation of MRI-SM, mobilization of SAT from the abdominal region, by comparison with the gluteal-femoral region, and improved functional capacity when compared with DO in obese men.", "To study the effect of exercise added to an energy-restrictive diet in overweight postmenopausal women.\n In a longitudinal clinical study, 121 healthy, overweight postmenopausal women (age 53.8 +/- 2.5 years, body mass index: 29.7 +/- 3.1 kg/m2) were randomly assigned to 3 groups: controls, a 4,200 kJ/d diet, or a 4,200 kJ/d diet with combined aerobic and anaerobic exercise. Body composition (measured by dual-energy x-ray absorptiometry), fat distribution, resting metabolic rate, blood pressure, serum lipids and lipoproteins, bone mineral densities, and markers of collagen and bone turnover were measured before and after 12 weeks of intervention.\n One hundred eighteen women completed the study. The mean loss of body weight (9.5 kg versus 10.3 kg, NS) was similar in the intervention groups, but compared with the diet-only group, the diet-plus-exercise group lost more fat (7.8 kg versus 9.6 kg, p < 0.001) and no lean tissue mass (1.2 kg versus -0.0 kg, p < 0.001). The resting metabolic rate (per kg wt) was increased in the diet-plus-exercise group compared with the control group (11% versus 4%, p < 0.009). The levels of serum triglycerides, total cholesterol, low-density lipoprotein, and very-low-density lipoprotein decreased, and the ratio of high-density lipoprotein to low-density lipoprotein increased by 20% to 30% in both intervention groups compared with the control group (p < 0.001). The systolic blood pressure dropped, and the waist-to-hip circumference ratio and abdominal-to-total body fat decreased in both intervention groups compared with the control group (10%, p < 0.003, and 3.5%, p < 0.0001). There were no consistent, major differences between the groups in terms of changes in total body, spinal, or forearm bone mineral densities, or in markers of collagen and bone turnover.\n Overweight postmenopausal women benefit from addition of combined aerobic and anaerobic exercise to an energy-restrictive diet. The diet itself has a positive effect on cardiovascular risk factors.", "The purpose of this study was to determine the effect of intensity controlled exercise on the aerobic capacity of overweight, middle-aged women. Thirty-eight moderately overweight women, ages 35-57, participated in a 16-week dance-exercise program. Random assignment was made to an experimental group (n = 20) in which intensity of exercise was controlled and prescribed, and a control group (n = 18) in which exercise was of an intensity typical to commercial aerobic classes. Prior to the onset of training, and at the completion of 16 weeks, the following fitness tests were administered: Aerobic capacity expressed as VO2 max, body composition analysis, blood chemistry, blood pressure, resting heart rate, muscular endurance, and flexibility. T-tests, ANCOVA, and gain-score analyses were utilized to evaluate data. Both groups showed small changes in weight, percent fat, resting systolic and diastolic blood pressure, resting heart rate, high density lipoprotein-cholesterol (HDL-C), muscular endurance, and flexibility, but these changes were statistically nonsignificant. The VO2 max for the experimental group increased 41%, while the VO2 max for the control group increased 22% (p less than 0.05). The results suggest that the cardiovascular fitness changes for overweight, middle-aged women are greater when exercise intensity and progression are tailored to their age and fitness level.", "Although aerobic exercise training and diet-induced weight loss each have been shown to individually lower elevated blood pressure (BP), it is currently not known whether their combined use produces an additive antihypertensive effect. In this randomized clinical trial we therefore compared the effect on resting BP of exercise training only and dietary modification only with that of exercise training plus dietary modification in 55 sedentary, overweight patients with high normal BP or stage 1 or 2 hypertension. After baseline testing, patients were randomized to 1 of the following 3 interventions for 12 weeks: exercise training only (aerobic exercise; 30 to 45 minutes; 3 to 5 days/week; 60% to 85% of maximal heart rate), dietary modification only (aimed primarily at weight loss via restriction of energy intake and dietary fat), or exercise training plus dietary modification. Forty-eight patients completed the study. In these patients, exercise training plus dietary modification elicited a greater reduction (p < or = 0.001) in body weight (-7.1 +/- 2.9 vs -1.0 +/- 1.8 kg) than exercise training only, and a greater increase (p < or = 0.05) in maximal oxygen uptake (4.3 +/- 2.6 vs 1.9 +/- 2.0 ml/kg/min) versus dietary modification only. However, the reduction in BP with exercise training plus dietary modification (-12.5 +/- 6.3/7.9 +/- 4.3 mm Hg) did not differ significantly from that with exercise training only (-9.9 +/- 6.4/5.9 +/- 4.6 mm Hg) or dietary modification only (-11.3 +/- 12.1/7.5 +/- 4.3 mm Hg). These data indicate that the antihypertensive effects of exercise training and diet-induced weight loss are not additive. This finding has important public health and clinical implications for the millions of overweight persons with high normal BP or stage 1 or 2 hypertension.", "To study the impact of diet and exercise and the combination thereof on cardiovascular risk factors, 157 healthy men aged 35-60 years (mean +/- S.D.; 46.2 +/- 5.0) with slightly to moderately raised cardiovascular risk factors, were randomized to 4 groups, diet (D, n = 40), exercise (E, n = 39), diet plus exercise (DE, n = 39), and no active intervention (controls (C, n = 39)), and investigated at baseline and after 6 months. BMI was significantly reduced in Groups E and DE (mean difference and 95% confidence intervals (CI), -0.3 (-0.5, -0.01) and -0.6 (-0.9, -0.3) kg/m2, respectively). Waist circumference was reduced in all 3 intervention groups (D, E, and DE), -1.3 (-2.5, -0.1), -2.2 (-3.2, -1.3) and -3.0 (-3.9, -2.0) cm, but not in the control group. Blood pressure (BP) was reduced in all 3 intervention groups, systolic BP 4-7 mmHg and diastolic BP 2-6 mmHg. Serum cholesterol was reduced in Group DE, -0.45 (-0.77, -0.13) mmol/l. VLDL-cholesterol was reduced in Groups E and DE, -0.14 (-0.26, -0.03) and -0.09 (-0.18, -0.01) mmol/l, whereas LDL-cholesterol was reduced in Groups D and DE -0.30 (-0.54, -0.06) and -0.35 (-0.64, -0.05) mmol/l. In contrast, neither HDL-cholesterol nor serum triglycerides were influenced by the interventions. According to the coronary risk profile derived from the Framingham study, all 3 intervention groups (D, E, and DE) significantly reduced their estimated 10-year risk (-13, -12, and -14%, respectively). We conclude that even with rather moderate changes in diet and exercise, several important cardiovascular risk factors can be affected and that diet and exercise were about equally effective in reducing cardiovascular risk.", "The purpose of this study was to determine the effects of a resistive training program on the time course of changes in strength, body mass index, lipids, lipoproteins, and apolipoproteins in sedentary obese women. Sixteen sedentary obese women strength trained 3 times . wk-1 for 12 wk performing three sets of six to eight repetitions per set with sets 1 and 2 at 60-70% of one-repetition maximum. During set 3, the subjects used the greatest weight possible so that failure occurred between six to eight repetitions. Six sedentary obese women served as controls. Blood samples for serum total cholesterol (TC), high-density lipoproteins (HDL-C), low-density lipoproteins (LDL-C), triglycerides (TG), TC/HDL-C ratio, apolipoprotein A-I (apo A-I), and apolipoprotein B-100 (apo B-100) were obtained pre, and after 4, 8, and 12 wk of training and approximately 3-4 d following the last training session. A 3-d dietary record was obtained on all subjects pre and post, and subjects were instructed not to alter their diet. The 12 wk of resistive training did not result in a significant change in body weight, BMI, or total kilocalories consumed per day but did show a mean improvement of 58% in muscular strength (P less than 0.05). The training program did not significantly alter the TC, HDL-C, LDL-C, TG, TC/HDL-C ratio, apo A-I, or apo B-100 levels, which suggests that this increase in strength owing to resistive training in the absence of body weight loss did not alter the lipid profiles in these sedentary obese women.", "Energy restriction is known to induce a decline in fat oxidation during the postdiet period. Reduced fat oxidation may contribute to weight regain.\n The present study investigated the effect of the addition of low-intensity exercise training to energy restriction on postdiet fat oxidation and on the contribution of the sympathetic nervous system to fat oxidation.\n Forty obese men were divided randomly into 2 groups: diet (D) and diet plus exercise (DE). Both groups followed an energy restriction program for 10 wk. Subjects in the DE group also participated in a low-intensity exercise training program [40% maximal oxygen uptake (VO2max)] for 12 wk. Before the intervention and after 12 wk, with subjects at stable body weights, we measured body composition, VO2max, and substrate oxidation at rest, during exercise at 50% VO2max, and during recovery. Measurements were made with and without administration of the beta-adrenergic antagonist propranolol.\n Both interventions led to significant decreases in body weight, fat mass, and fat-free mass (P < 0.001); these decreases did not differ significantly between the D and DE groups. Neither intervention significantly affected VO2max. The effect of the intervention on the respiratory exchange ratio differed significantly between the D and DE groups [two-way analysis of variance (ANOVA), P < 0.05]. The effect on the beta-adrenergic-mediated respiratory exchange ratio tended to be different between the 2 groups (two-way ANOVA, P = 0.09).\n Addition of low-intensity exercise training to energy restriction counteracts the decline in fat oxidation during the postdiet period.", "The purpose of this study was to investigate the effects of exercise intensity on the body composition of obese subjects during severe caloric restriction. Forty obese subjects (33 women, 7 men; 41 +/- 7.7 years; 106 +/- 26kg; body fat > 25% men, > 30% women) on a commercially prepared OPTIFAST 420kcal/day supplemented fast were randomized into groups that exercised at target heart rates corresponding to 40% and 60% of the heart rate reserve (HRR) at the start of the program. Training volume was similar for both groups at approximately 300kcal per session three times per week for 12 weeks. Body weight, body fat, and lean weight were similar for both exercise intensity groups at week one. Overall, body weight decreased by 15.3 +/- 6.7 kg (p < or = .05), and body fat decreased by 14.9 +/- 5.0 kg (p < or = .05) for the 40 subjects, whereas lean weight remained unchanged. No significant differences in body weight, body fat, or lean weight were observed between the two groups. The results of the current study indicated that while on a supplemented 420-kcal/day fast, exercise at 40% and 60% of the HRR affected body composition similarly when total training volume was held constant at 900kcal/week. Lean weight remained unchanged and accompanied a 14.9 +/- 5.0-kg decrease in body fat, which may have resulted when the volume of exercise (ie, 900kcals/wk) was factored into the exercise prescriptions. These results suggest that exercising at 60% of the HRR offers no advantages for body composition changes over those obtained from exercising at 40% of HRR when the total volume of exercise training is controlled.", "This study investigated changes in body composition, resting energy expenditure (REE), appetite, and mood in 128 obese women who were randomly assigned to 1 of 4 treatment conditions: diet alone, diet plus aerobic training, diet plus strength training, or diet combined with aerobic and strength training (i.e., combined training). All women received the same 48-week group behavioral program and were prescribed the same diet. Exercising participants were provided 3 supervised exercise sessions per week for the first 28 weeks and 2 sessions weekly thereafter. Participants across the 4 conditions achieved a mean weight loss of 16.5 +/- 6.8 kg at Week 24, which decreased to 15.1 +/- 8.4 kg at Week 48. There were no significant differences among conditions at any time in changes in weight or body composition. Women who received aerobic training displayed significantly smaller reductions in REE at Week 24 than did those who received strength training. There were no other significant differences among conditions at any time on this variable or in changes in appetite and mood.", "Previous studies have shown that fat metabolism is different in upper body (UB) and lower body (LB) obese women. The present study investigated whether the effect of low-intensity exercise training on fat metabolism is different in UB and LB obese premenopausal women.\n Twenty-one healthy, premenopausal women with either LB obesity (waist-to-hip ratio of < or =0.79; n = 8) or UB obesity (waist-to-hip ratio of > or =0.85; n = 13) participated in the present study. The UB obese women were matched and randomly divided in an exercise training group (UB) and a nonexercising control group (UB-C). Subjects in the UB and LB groups participated in a low-intensity exercise training program (40% VO2max) three times per week for 12 weeks. Before and after the intervention, measurements of fat metabolism at rest and during exercise, body composition, and maximal aerobic capacity were performed.\n Exercise training did not change the respiratory exchange ratio at rest in the UB and LB groups. During exercise, relative fat oxidation increased in the UB group by 19% (p < 0.05), whereas no change in the LB and UB-C groups was found. Plasma free fatty acid oxidation did not change by exercise training, and nonplasma fatty acid oxidation tended to increase in the UB group compared with the UB-C group (p = 0.08).\n Low-intensity exercise training increased the contribution of fat oxidation to total energy expenditure during exercise but not at rest in UB obese women. Exercise training had no significant effect on fat metabolism in the LB obese women.", "Effects of large (LA; 400 min/wk) and moderate (MA; 200 min/wk) amounts of endurance exercise in combination with weight training (3 d/wk) were compared with the effects of no exercise (C) in 23 obese females after a 12-wk, 3360-kJ/d very-low-energy diet (VLED). The LA group lost 6.5 kg more weight, mainly as fat (6.4 kg), than the C group (P < 0.05). No measurable differences were found among groups for decreases in resting metabolic rate (-729 to -1233 kJ/d; NS) or fat-free mass (-2.9 to -3.9 kg; NS). No improvements in aerobic capacity were achieved with the addition of exercise to a VLED (-0.079 to -0.037 L/min; NS). Strength indexes were improved (+16 to +5 kg; P < 0.05) or maintained with exercise (-3 kg; NS) whereas a loss (-9.3 kg; P < 0.05) or maintenance (+4.5 kg; NS) was found for VLED alone. Large amounts of endurance exercise in combination with weight training added to a VLED appear to improve weight and fat loss compared with a VLED alone.", "Recommending increased physical activity facilitates long-term weight loss, but the optimal level of physical activity to recommend is unknown.\n The objective of the study was to evaluate the efficacy for long-term weight loss of recommendations for much higher physical activity than those normally used in behavioral treatments.\n Overweight men and women (n = 202) were randomly assigned to either a standard behavior therapy (SBT) for obesity, incorporating an energy expenditure (EE) goal of 1000 kcal/wk, or to a high physical activity (HPA) treatment, in which the goal was an EE of 2500 kcal/wk. To help HPA treatment group participants achieve this high exercise goal, their treatment included encouragement to recruit 1-3 exercise partners into the study, personal counseling from an exercise coach, and small monetary incentives.\n The HPA treatment group reported achieving higher mean (+/- SD) physical activity levels than did the SBT group at 6 mo (EE of 2399 +/- 1571 kcal/wk compared with 1837 +/- 1431 kcal/wk), 12 mo (EE of 2249 +/- 1751 kcal/wk compared with 1565 +/- 1309 kcal/wk), and 18 mo (EE of 2317 +/- 1854 kcal/wk compared with 1629 +/- 1483 kcal/wk) (all P < 0.01). Mean (+/- SEM) cumulative weight losses at 6, 12, and 18 mo in the HPA treatment group were 9.0 +/- 7.1, 8.5 +/- 7.9, and 6.7 +/- 8.1 kg, respectively. In the SBT group, the corresponding weight losses were 8.1 +/- 7.4, 6.1 +/- 8.8, and 4.1 +/- 7.3 kg, respectively. Between-group differences in weight loss were significant at 12 and 18 mo.\n These results suggest that recommendations of higher levels of physical activity (EE of 2500 kcal/wk) promote long-term weight loss better than do conventional recommendations." ]

[ "12829988", "12451727", "14988824", "8938532", "12948399", "11008222", "9097265", "9252161", "8720287", "9862245", "9695995" ]

[ "Maintenance therapy with ribavirin in patients with chronic hepatitis C who fail to respond to combination therapy with interferon alfa and ribavirin.", "Evaluation of ribavirin efficacy and tolerance in subjects with chronic hepatitis C virus infection.", "Antiviral action of ribavirin in chronic hepatitis C.", "Ribavirin treatment for patients with chronic hepatitis C: results of a placebo-controlled study.", "Retreatment of hepatitis C non-responsive to interferon. A placebo controlled randomized trial of ribavirin monotherapy versus combination therapy with Ribavirin and Interferon in 121 patients in the Benelux [ISRCTN53821378].", "A prospective and randomized study using ribavirin as monotherapy for the treatment of naïve patients with chronic hepatitis C.", "Modulation of hepatitis C virus quasispecies heterogeneity by interferon-alpha and ribavirin therapy.", "Tolerance and efficacy of oral ribavirin treatment of chronic hepatitis C: a multicenter trial.", "The effect of interferon alfa and ribavirin combination therapy in naive patients with chronic hepatitis C.", "Ribavirin and interferon alfa-2b in chronic hepatitis C: assessment of possible pharmacokinetic and pharmacodynamic interactions.", "Sequential versus concomitant administration of ribavirin and interferon alfa-n3 in patients with chronic hepatitis C not responding to interferon alone: results of a randomized, controlled trial." ]

[ "To assess the efficacy and safety of maintenance therapy with ribavirin alone in chronic hepatitis C, 108 patients were treated with the combination of interferon alfa and ribavirin for 24 weeks; those who failed to have a virologic response were offered enrollment in a randomized, double-blind, controlled trial of ribavirin (1,000-1,200 mg daily) versus placebo for the subsequent 48 weeks. Patients were monitored at regular intervals with symptom questionnaires, serum aminotransferase levels, hepatitis C virus (HCV) RNA levels, and complete blood counts and underwent liver biopsy at the completion of therapy. Among 108 patients, 50 were still HCV RNA positive after 24 weeks of treatment, of whom 34 agreed to be randomized to continue either ribavirin monotherapy or placebo. Among 17 patients who received placebo, there was no overall improvement in symptoms, serum alanine aminotransferase (ALT) levels, HCV RNA levels, or hepatic histology. Among the 17 patients who received ribavirin, serum ALT levels and necroinflammatory features of liver histology were improved, whereas symptoms, HCV RNA levels, and hepatic fibrosis scores were not changed significantly from baseline. Responses to ribavirin seemed to be categorical, such that 8 patients (47%) had definite improvement in liver histology. Patients with improved histology had improvements in serum ALT levels both on combination therapy and after switching to ribavirin monotherapy. In conclusion, continuation of ribavirin monotherapy may maintain serum biochemical improvements that occur during interferon-ribavirin combination therapy in some patients and that these improvements are often associated with decreases in necroinflammatory changes in the liver. Whether these improvements will ultimately result in prevention of progression of hepatitis C requires further study.", "Reports by hepatologists indicated that anti-HCV antibodies might be detected in 71% to 84% of cases of post-transfusion hepatitis and in up to 50% of cases of sporadic non-A non-B hepatitis. Anti-HCV antibodies were detected in 0.05-1% of blood donors with normal alanine transaminase (ALT) levels and negative anti-HBc screening. Anti-HCV antibodies were found in 67% of patients with a history of intravenous drug abuse or autoimmune hepatitis, and in 10-30% of patients with hepatocellular carcinoma. This indicated that hepatitis C virus was a major cause of the acute and chronic hepatitis throughout the world.\n This was a multicenteric, international, double-blind, randomized, placebo-controlled study. After the eight-week screening period, patients were randomized to receive daily ribavirin 1200 mg or placebo, during the 48-week treatment period. Follow-up observations were performed during a 16 week post-treatment period. Up to 80 male and female outpatients with mild to moderate chronic active hepatitis C virus infection were enrolled in this study.\n During the treatment period ALT values were significantly lower in the ribavirin group. Neither in the ribavirin group, nor in the placebo group significant statistical differences of the HCV RNA values were found. Significantly lower portal inflammation was noticed in ribavirin group after the treatment. Analysis of laboratory data demonstrated that ribavirin therapy was associated with mild to moderate reversible anemia. Investigator's evaluation of the effect of the therapy on patient's well being showed statistically significant differences in the benefit of the ribavirin group.\n In this study ribavirin was more effective than placebo in reducing ALT levels during the treatment period of the applied therapy in patients with chronic active hepatitis C.", "In the patients with chronic hepatitis C, the addition of ribavirin to interferon (IFN)-alpha significantly increases the virologic responses. Our aim was to assess the antiviral action of ribavirin on hepatitis C virus (HCV) as a function of ribavirin pharmacokinetics and to evaluate the influence of this antiviral effect on IFN-alpha efficacy.\n Forty-five patients with chronic hepatitis C (genotype 1b) received various schedules of IFN-alpha and/or ribavirin administration. Frequent blood sampling was performed for HCV RNA kinetics and ribavirin pharmacokinetics assessment.\n Ribavirin monotherapy induced a significant, moderate, early, and transient viral load decrease in approximately half of the patients. The occurrence of this effect was associated with longer ribavirin clearance half-lives and higher serum ribavirin concentrations. Ribavirin antiviral effect partly reduced the rebound preceding the second IFN-alpha injection in patients receiving standard IFN-alpha 3 times per week plus ribavirin. The magnitude of the rebound was inversely related to ribavirin concentrations. These patients subsequently experienced a slow, but significant, second slope of viral decrease and cleared HCV RNA. The addition of ribavirin to daily IFN-alpha monotherapy did not have any impact on the second phase of viral decline.\n Ribavirin exerts a significant, moderate, and transient antiviral effect in a significant proportion of patients with chronic hepatitis C. The antiviral effect of ribavirin correlates with ribavirin pharmacokinetics and is partly responsible for the improved efficacy of the combination of standard IFN-alpha and ribavirin compared with IFN-alpha monotherapy by increasing the incidence of the initial response.", "Small, uncontrolled studies of ribavirin for patients with chronic hepatitis C have reported efficacy in chronic hepatitis C. We have evaluated the efficacy and safety of a 24-week course of oral ribavirin in patients with chronic hepatitis C, compared to placebo.\n A total of 114 patients were randomised to ribavirin or placebo. Ribavirin was administered in doses of 1000 or 1200 mg/day for 24 weeks. Efficacy was determined in the intention-to-treat population: 76 received ribavirin and 38 placebo.\n Ribavirin was significantly more effective than placebo in reducing and normalising serum ALT levels: 42/76 (55%) of ribavirin-treated patients vs 2/38 (5%) placebo recipients had either normalisation of the ALT levels or a reduction from baseline of at least 50% (p < 0.001). ALT levels were normal in 22/76 (29%) of ribavirin-treated patients vs 0/38 placebo recipients (p < 0.001). Twenty-four weeks after stopping ribavirin, the majority of patients had abnormal ALT levels. There was no difference between the treatment groups in reduction or disappearance of HCV-RNA levels. HCV RNA disappeared during treatment in 3% of ribavirin-treated patients and 3% of placebo recipients. More ribavirin than placebo patients showed improvement in total Knodell score (45% vs 31%), but these differences were not statistically significant. Analysis of each component of a histology activity index revealed no statistically significant differences between treatment groups. Ribavirin patients had fewer lymphoid aggregates than did placebo recipients at the post-treatment assessment (p = 0.05). Ribavirin was associated with reversible haemolytic anaemia: a fall in haemoglobin occurred in 3% of placebo- and 32% (25/78) of ribavirin-treated patients, respectively (p < 0.001).\n These data indicate that ribavirin was no more effective than placebo in reducing or eliminating HCV-RNA levels, and was not significantly more effective than placebo in improving hepatic histology after 6 months of treatment. The role of a 6-month treatment of chronic hepatitis C with ribavirin alone, without a significant effect on HCV RNA, is therefore limited.", "Evidence based medicine depends on unbiased selection of completed randomized controlled trials. For completeness it is important to publish all trials. This report describes the first large randomised controlled trial where combination therapy was compared to placebo therapy and to ribavirin monotherapy, which has not been published until now.\n One hundred and twenty one patients with chronic hepatitis C and elevated transaminases who did not respond to previous treatment with standard interferon monotherapy, were included from 16 centers in Belgium, the Netherlands and Luxembourg between 1992 and 1996. Patient poor-response characteristics were: genotype 1 (69%), HCV RNA above 2 x 10(6) copies/ml (55%) and cirrhosis (38%). Patients were randomized to 6 months combination therapy with interferon alpha-2b (3 MU tiw) and ribavirin (1000-1200 mg/day), 6 months ribavirin monotherapy (1000-1200 mg/day) or 6 months ribavirin placebo. The study was double blinded for the ribavirin/placebo component. One patient did not fit the entry criteria, and 3 did not start. All 117 patients who received at least one dose of treatment were included in the intention to treat analysis.\n At the end of treatment, HCV RNA was undetectable in 35% of patients on combination therapy and in none of the patients treated with ribavirin monotherapy or placebo. The sustained virological response rate at 6 months after therapy was 15% for patients treated with interferon and ribavirin. During the 6 months treatment period 13% of patients on interferon ribavirin combination therapy, 13% of patients on ribavirin monotherapy and 11% of patients on placebo withdrew due to side effects or noncompliance. At 24 weeks of treatment the mean Hb level was 85% of the baseline value, which means a mean decrease from 9.1 mmol/l to 7.8 mmol/l. The Hb levels at the end of treatment were not significantly different from patients treated with ribavirin monotherapy (p = 0.76). End of treatment WBC was significantly lower in patients treated with combination therapy, compared to ribavirin (p < 0.01) as well as for patients treated with ribavirin monotherapy compared to placebo (p < 0.01).\n This belated report on the only placebo controlled study of interferon ribavirin combination therapy in non responders to standard doses of interferon monotherapy documents the effectiveness, be it limited, of this approach as well as the dynamics of the effects on blood counts.", "In order to evaluate the response to ribavirin in previously untreated patients with chronic hepatitic C, 39 patients were selected for a double-blind prospective and randomized trial, and divided into two groups: ribavirin-group (19 patients) and placebo-group (20 patients). Ribavirin was administered orally for 24 weeks (600 mg/day, followed by 1,000 mg/day and 1,200 mg/day each one for 8 weeks). After 3 months of drug administration, the patients were evaluated by measuring biochemical, virologic and histologic responses. After this phase, ribavirin was offered to the patients who had received placebo (second phase). The results showed that the patients who received ribavirin showed a higher reduction in serum alanine aminotransferase (ALT) activity than patients in the placebo group. Among the patients in the ribavirin-group, a complete biochemical response (ALT levels normalized) was observed in 3 patients (16%), and a partial response (reduction greater than 50% of the initial value of ALT activity) in 4 (21%). In the 20 patients in the placebo group, only 1 showed a partial response (5%). In the second phase of the study, among 16 patients who received ribavirin, 4 (25%) showed a complete and 5 (31%) a partial biochemical response. HCV-RNA did not become negative in any patient during the two phases. A reduction in the score of portal and lobular activity was observed in patients who received ribavirin, but statistical analysis did not identify differences. This study showed that ribavirin alone induces a biochemical response (ALT reduction) in some patients with chronic hepatitis C, which may be associated with a reduction in hepatic inflammatory activity reduction, but the changes are not sufficient to recommend initial monotherapy with ribavirin.", "To determine the effects of interferon-alpha (IFN-alpha) and ribavirin therapy on hepatitis C virus (HCV) quasispecies heterogeneity, 29 patients with chronic HCV infection treated with either IFN-alpha (n = 15), ribavirin (n = 7) or placebo (n = 7) were studied. HCV quasispecies heterogeneity was determined by single-strand conformational polymorphism (SSCP) analysis of the HCV E2 hypervariable region 1 (HVR1). For patients receiving IFN-alpha, HVR1 was amplified in 14 of 15 patients before, and in six of seven patients after therapy. After controlling the amount of amplicon loaded, a reduction in the number of SSCP bands was observed with IFN-alpha therapy (median number of SSCP bands per patient was eight before therapy and two after therapy). In the seven patients within each of the ribavirin- and placebo-treated groups, there was no significant difference in the viraemia level, number of SSCP bands per patient or the SSCP band pattern, before and after therapy. These findings suggest that at the doses given, IFN-alpha, but not ribavirin, exerts a selective pressure on HCV quasispecies heterogeneity.", "Hepatitis C is a common cause of chronic liver disease that may progress to cirrhosis. We conducted a multicenter double-blind placebo-controlled trial of ribavirin 600 mg given orally twice daily for 36 weeks with follow-up off therapy for an additional 16 weeks. Fifty-nine patients with compensated chronic hepatitis C were entered. Efficacy was measured at the end of therapy and after follow-up by normalization of alanine aminotransferase (ALT), improvement in liver histology, reduction in hepatitis C virus (HCV) RNA level and improvement of symptoms. Among the ribavirin recipients, 12 of 29 (41.4%) had normal ALT values at 36 weeks compared with only 1 of 30 (3.3%) placebo recipients (P < .001). No patient maintained a normal ALT when therapy was stopped. No significant decrease in level of HCV RNA was observed during the study. Histological improvement among subjects who normalized ALT (-1.67 Knodell index) was significantly greater than that in other treated patients (+0.33 Knodell index; P < .05). Fatigue improved in 19.2% of ribavirin-treated subjects and in 8.3% of placebo recipients whereas no worsening of fatigue was reported by ribavirin recipients compared with 16.7% of controls. This difference in fatigue was significant at weeks 36 and 52 (P < .05; .02, respectively). Adverse events were generally comparable between treatment groups except for a reversible hemolytic anemia experienced by ribavirin recipients. Chest pain was noted in four patients on ribavirin. Ribavirin was well tolerated and improved aminotransferase values and reduced fatigue in patients with hepatitis C viral infection while treatment was being administered. Because this action was produced without change in viral level, the mechanism of action of this agent requires further investigation.", "Chronic hepatitis C may lead to cirrhosis and hepatocellular carcinoma in a subset of patients. Because response rates with interferon alfa therapy are unsatisfactory, new therapies are needed.\n We conducted a three-arm, randomized trial in 45 interferon-naive men (mean age 40.6 +/- 12 years) with chronic hepatitis C to compare treatments: group A, ribavirin alone (15 mg/kg daily for 6 months); group B, interferon alone (3 MU thrice weekly for 6 months); and group C, interferon plus ribavirin at the above doses. Histologic outcomes of therapy were assessed by pretreatment and post-treatment liver biopsies.\n In group A, alanine aminotransferase levels normalized during therapy in 66% of those with HCV-1b and 34% of those with HCV-2a, but all patients relapsed after treatment ended. In group B, alanine aminotransferase levels normalized during treatment in 66%, 75%, and 100% of patients infected with HCV-1b, HCV-2a, and HCV-3, respectively; however, a sustained response was noted in only 25% of those with HCV-3. In group C, a sustained normalization of alanine aminotransferase with negative serum HCV RNA was seen in 20% of those with HCV-1b, 40% of those with HCV-2a, and 75% of those with HCV-3 12 months after therapy. One year after therapy ended, group C demonstrated a significant sustained response (47%) as well as a significant reduction in piecemeal necrosis and portal inflammation (p < 0.05).\n Combination therapy was significantly superior to ribavirin or interferon monotherapy in producing a sustained response in interferon-naive patients with chronic hepatitis C (p < 0.05). The results of our study suggest that ribavirin potentiates the effect of interferon therapy in chronic hepatitis C.", "The primary objective of this study was to determine whether pharmacokinetic interactions occurred between interferon alpha-2b (IFN) and ribavirin in patients with chronic hepatitis C infections. Additionally this study assessed the single and multiple-dose pharmacokinetics of ribavirin and IFN, and compared the safety, tolerability and antiviral pharmacodynamics of IFN plus ribavirin compared with either drug alone.\n In this open label parallel group study, patients with chronic hepatitis C were randomized to receive IFN 3 million IU thrice weekly s.c. alone, ribavirin 600 mg twice daily p.o. alone or both drugs in combination over 6 weeks. Single and multiple dose pharmacokinetics and indices of antiviral pharmacodynamics were assessed during weeks 1 and 6, along with safety assessments during the study.\n The range of mean ribavirin terminal phase half-lives after single doses was 44-49 h. Comparison of week 1 and week 6 AUC(0,12h) values showed accumulation in plasma of approximately 6-fold. The range of mean washout half-lives after week 6 was 274-298 h, reflecting release of ribavirin from deep compartment stores. The range of single and multiple dose IFN terminal phase half-lives was 5-7 h. IFN demonstrated an increase in bioavailability (approximately 2-fold) upon multiple dose administration. Ribavirin and IFN pharmacokinetic parameters for combined ribavirin and IFN were similar to those during monotherapy with either compound, although the power of this study to detect differences was low. Serum HCV-RNA titers and ALT concentrations were reduced by IFN alone, ribavirin alone reduced ALT concentrations only, and combined IFN plus ribavirin produced numerically greater falls in both measurements than either treatment alone. Serum concentrations of neopterin and activity of 2',5'-oligoadenylate synthetase (2'5'-OAS) were increased by IFN alone and in combination with ribavirin, whereas serum 2'5'-OAS activity was decreased and neopterin concentrations unaltered by ribavirin monotherapy. IFN and ribavirin monotherapy produced characteristic changes in safety laboratory tests (IFN--reductions in white cells, neutrophils and platelets; ribavirin--reduced haemoglobin) and characteristic adverse event profiles (IFN--headache, flu-like symptoms, fatigue, anorexia, nausea, myalgia, and insomnia; ribavirin--headache, fatigue, myalgia, and pruritus). There was no additive effect of combination therapy on safety laboratory tests or reported adverse events. All changes were fully reversible upon treatment cessation.\n There was no evidence of pharmacokinetic interactions between IFN and ribavirin in this study. There were numerical trends indicating that the combination of IFN and ribavirin reduced titers of HCV-RNA to a greater extent than did either treatment alone, and the safety profile of combination therapy was similar to those of both monotherapy treatments.", "We conducted a three-arm, randomized trial in 96 patients with chronic hepatitis C who did not respond to interferon alfa to compare treatments. Group 1 (33 patients) received ribavirin alone (1,000 mg/daily for 6 months) followed by interferon alfa n-3 alone (3 MU thrice weekly for 6 months); group 2 (33 patients) received ribavirin plus interferon alfa n-3 for 6 months at the above doses; and group 3 (30 patients) received interferon alfa n-3 alone (3 MU thrice weekly for 6 months). At the end of treatment, 3 patients (10%) in group 1, 13 (41%) in group 2, and 5 (17%) in group 3 had normal alanine transaminase (ALT) levels (group 2 vs. groups 1 and 3, P = .008). After 6 months of follow-up, only 4 patients (12.5%) in group 2 still had normal ALT values (P = .03). At the end of therapy, hepatitis C virus (HCV) RNA was no longer detectable by polymerase chain reaction in 4 (13%), 9 (27%), and 2 (7%) patients, respectively, in groups 1, 2, and 3 (P = NS). Six months posttherapy, only 5 (15%) patients in group 2 were still HCV RNA negative (P = .02). At the time of follow-up liver biopsy, performed 6 months after the end of treatment, a significant improvement of the necroinflammatory scores was observed among group 2 patients (P = .01) but not in the other two groups. Side effects reflected the profile of each drug as monotherapy; mild hemolytic anemia was the most frequent side effect caused by ribavirin. In conclusion, concomitant administration of ribavirin and interferon alfa n-3 was significantly superior to the sequential schedule or interferon alfa n-3 monotherapy in inducing a sustained response in patients with chronic hepatitis C who had not responded to interferon alone. However, combination therapy at the dose and duration adopted in this study is capable of modifying the natural course of the disease in only a minority of these patients." ]

[ "3220789" ]

[ "Effectiveness of single versus double volume exchange transfusion in newborn infants with AB0 hemolytic disease." ]

[ "The effectiveness of early single volume exchange transfusion (ET; 80 ml/kg) was compared with that of early double volume exchange transfusion (160 ml/kg) for treatment of hemolytic disease of the newborn caused by AB0 incompatibility. Twenty full-term infants with AB0 hemolytic disease were randomized into the two treatment groups. The groups were comparable for gestational age, body weight, hemoglobin values, reticulocyte count, maximum serum bilirubin levels, rate of rise of serum bilirubin before ET, antibody titer, and age at time of ET (all p greater than 0.05). The efficacy of treatment was similar in both groups taking into account the mean bilirubin level after ET, post-ET bilirubin, duration of phototherapy following ET, and frequency of second ET (all p greater than 0.05). However, platelet count immediately after ET was lower in the double volume ET group as compared to the single volume ET group (p less than 0.01). Hemoglobin values immediately after ET were higher in the double volume ET group (p less than 0.01). At ten days of life no differences were detectable. The results of this study indicate that the effectiveness of single volume ET for treatment of full-term infants with jaundice due to AB0 incompatibility is at least comparable to that of double exchange ET. Furthermore, the lesser aggressive approach determines less complications such as a decrease of platelet count." ]

[ "2145136", "2879458" ]

[ "A comparison of the effects of ipratropium bromide and metaproterenol sulfate in acute exacerbations of COPD.", "Nebulized anticholinergic and sympathomimetic treatment of asthma and chronic obstructive airways disease in the emergency room." ]

[ "Thirty-two patients presenting with acute exacerbations of chronic obstructive pulmonary disease were entered into the following double-blind, crossover study. First (time 0), patients inhaled either ipratropium bromide (54 micrograms) or metaproterenol sulfate (1.95 mg) via a metered dose inhaler (MDI) attached to a device (Inspirease) (phase 1). After 90 minutes, they inhaled whichever of the two medications they had not received in phase 1. This is referred to as phase 2. Pulmonary function (FEV1 and FVC) was measured at time 0, and at 30, 60, and 90 minutes following phase 1 treatment, and at 30, 60, and 90 minutes following phase 2 treatment (120, 150, and 180 minutes from the start of the study). Arterial blood gas samples (n = 20) were obtained at entry into the study and 30 and 90 minutes after phase 1 medication. The groups did not differ in age, degree of airway obstruction, hypoxemia, or theophylline usage at the start of the study. In phase 1, at 90 minutes, pulmonary function in both groups significantly and similarly improved. For ipratropium, FEV1 improved from 0.62 +/- 0.08 L to 0.88 +/- 0.11 L (p less than 0.01) and for metaproterenol FEV1 improved from 0.69 +/- 0.06 to 0.92 +/- 0.09 L (p less than 0.01). There was no further improvement with phase 2 treatment for either group. Thirty minutes after inhaling ipratropium, there was a small but significant rise in PO2 (5.8 +/- 3.0 mm Hg; p less than 0.05) while metaproterenol inhalation resulted in a 6.2 +/- 1.2 mm Hg decline in PO2 (p less than 0.05). These changes were not sustained at 90 minutes. We concluded that for acute exacerbations of COPD, both ipratropium and metaproterenol are effective medications when administered via an MDI attached to a device (Inspirease). However, ipratropium may be a safer choice as it initially did not cause a decline in blood oxygenation.", "The effectiveness of nebulized anticholinergic and sympathomimetic regimens was evaluated in a double-blind study of 199 patients with acute airways obstruction. Patients were assigned to one of three treatment regimens according to a randomized schedule: 0.5 mg of ipratropium bromide, 1.25 mg of fenoterol hydrobromide, and 0.5 mg of ipratropium plus 1.25 mg of fenoterol. In 148 patients with acute exacerbations of asthma (mean one-second forced expiratory volume, 1.18 +/- 0.64 liters), all three regimens produced significant improvement in one-second forced expiratory volume (p less than 0.001). The greatest improvement followed treatment with the ipratropium-fenoterol combination (0.53 +/- 0.40 liters at 45 minutes; 0.57 +/- 0.51 liters at 90 minutes) and was significantly greater than that following either ipratropium alone (p less than 0.001) or fenoterol alone (p less than 0.05). In 51 patients with acute exacerbations of chronic obstructive pulmonary disease (mean one-second forced expiratory volume, 0.67 +/- 0.29 liter), each regimen produced significant improvement in one-second forced expiratory volume at both 45 and 90 minutes (for all, p less than 0.05), but there was no significant difference among the three treatment regimens. It is concluded that, in patients with acute asthma, combination therapy with sympathomimetic and anticholinergic agents is more efficacious than either one alone. In patients with acute exacerbations of chronic obstructive pulmonary disease, although either sympathomimetic or anticholinergic therapy provides bronchodilatation, no further benefit could be demonstrated from combination therapy." ]

[ "17509808" ]

[ "The effects of a shared decision-making intervention in primary care of depression: a cluster-randomized controlled trial." ]

[ "Patient-centred depression care approaches should better address barriers of insufficient patient information and involvement in the treatment decision process. Additional research is needed to test the effect of increased patient participation on outcomes. The aim of this study was to assess, if patient participation in decision-making via a shared decision-making intervention leads to improved treatment adherence, satisfaction, and clinical outcome without increasing consultation time.\n Cluster-randomized controlled intervention study based on physician training and patient-centered decision aid compared to usual care in primary care settings in Südbaden region of Germany. Twenty-three primary care physicians treating 405 patients with newly diagnosed depression were enrolled. Patient involvement was measured with the patient perceived involvement in care scale (PICS) and a patient participation scale (MSH-scale). Patient satisfaction was measured by the CSQ-8 questionnaire. Treatment adherence was evaluated by patient and provider self-report. Depression severity and remission outcomes were assessed with the Brief PHQ-D.\n Physician facilitation of patient participation improved significantly and to a greater extent in the intervention compared to the control group. There was no intervention effect for depression severity reduction. Doctor facilitation of patient participation, patient-rated involvement, and physician assessment of adherence improved only in the intervention group. Patient satisfaction at post-intervention was higher in the intervention group compared to the control group. The consultation time did not differ between groups.\n A shared decision-making intervention was better than usual care for improving patient participation in treatment decision-making, and patient satisfaction without increasing consultation time. Additional research is needed to model causal linkages in the decision-making process in regard to outcomes.\n The study results encourage the implementation of patient participation in primary care of depression." ]

[ "9836655", "1437515", "12701949", "11237924", "15318916", "16100321", "16085190", "12902966", "15649836", "16230312" ]

[ "Review of the usefulness of contacting other experts when conducting a literature search for systematic reviews.", "The comprehensiveness of Medline and Embase computer searches. Searches for controlled trials of homoeopathy, ascorbic acid for common cold and ginkgo biloba for cerebral insufficiency and intermittent claudication.", "Beyond Medline: reducing bias through extended systematic review search.", "Lessons for search strategies from a systematic review, in The Cochrane Library, of nutritional supplementation trials in patients after hip fracture.", "Developing methods for systematic reviewing in health services delivery and organization: an example from a review of access to health care for people with learning disabilities. Part 1. Identifying the literature.", "Systematic reviews of health effects of social interventions: 1. Finding the evidence: how far should you go?", "Searching one or two databases was insufficient for meta-analysis of observational studies.", "Spinal palpation: The challenges of information retrieval using available databases.", "Searching multiple databases for systematic reviews: added value or diminishing returns?", "Effectiveness and efficiency of search methods in systematic reviews of complex evidence: audit of primary sources." ]

[ "nan", "To assess the comprehensiveness of Medline and Embase computer searches for controlled trials.\n Comparison of articles found after an exhaustive search of the literature with the yield of a Medline or Embase search. This was performed for controlled clinical trials on the efficacy of three interventions: homoeopathy, ascorbic acid for common cold, and ginkgo biloba for intermittent claudication and cerebral insufficiency. The number of controlled trials found by exhaustive search of the literature was 107, 61 and 45, respectively.\n For homoeopathy, ascorbic acid and ginkgo the proportion of all trials found by Medline was 17%, 36% and 31% respectively and for Embase 13%, 25% and 58% respectively. After checking of the references in the Medline articles 44%, 79% and 76% of all trials were identified. After checking of the references in the Embase articles 42%, 72% and 93% of all trials were identified. About 20% of the articles was not correctly indexed. Of the best trials 68%, 91% and 83% could be found with Medline and 55%, 82% and 92% of the best trials were identified through Embase.\n For the topics mentioned, Medline and Embase searches are sufficient to get an impression of the evidence from controlled trials, but only if references in the articles are followed for further evidence. If one wants to get a more complete picture, additional search strategies make sense. Of course, this picture may be different for other topics.", "To evaluate the sensitivity and precision of various extended search methods in identifying randomized controlled trials (RCTs) for systematic reviews.\n Prospective analysis of extended search methods (specialized databases or trial registries, reference lists, hand-searching, personal communication, and Internet) used in two systematic reviews of RCTs. The gold standard was the total number of RCTs identified by major databases (MEDLINE, EMBASE, etc.) and extended search strategies combined. Sensitivity was the proportion of all known RCTs identified by any extended search method. Precision reflected the proportion of all items uncovered by any extended search method that actually were RCTs.\n The extended search identified 94 additional RCTs for the systematic reviews beyond those identified with the major databases. Specialized databases and trial registries had the highest sensitivity and precision for the lipid-lowering project (13.6% and 52.7%, respectively; p < .05) followed by scanning of reference lists (7.2% sensitivity and 41.9% precision; p <.05). Hand-searching was more effective than personal communication and Internet searching (1.7% sensitivity and 12.2% precision; p < .05). The acupuncture project had slightly different results, with the specialized databases and trial registries tied with the review of reference lists for highest sensitivity (14.2%). The precision followed the same trend as the lipid-lowering project (17.6% specialized databases; 8.3% reference lists; p < .05). A post-hoc analysis showed that 75 of the 94 RCTs were indexed in the major databases but missed by the major database search.\n Extended searching identified additional RCTs for the systematic reviews beyond those found in major databases. Specialized databases and trial registries were most effective. An important number of RCTs were missed by the major database search. Timing and accuracy of indexing may explain this finding. The definitive measure, whether there is an association between the method used to uncover RCTs, the quality of the items uncovered and their impact on systematic review results, is yet to be determined.", "A key aim when conducting systematic reviews of randomized controlled trials (RCTs) is to include all of the evidence, if possible. Serious bias may result if trials are missed through inadequate search strategies.\n The objective was to evaluate the search plan for identifying RCTs in nutrition as part of a systematic review, in The Cochrane Library, of nutritional supplementation trials in patients after hip fracture.\n We identified potential studies by searching the electronic databases BIOSIS, CABNAR, CINAHL, EMBASE, HEALTHSTAR, and MEDLINE; reference lists in trial reports; and other relevant articles. We also contacted investigators and other experts for information and searched 4 nutrition journals by hand.\n We identified 15 RCTs that met the predefined inclusion criteria. The search plan identified 8 trials each in EMBASE, HEALTHSTAR, and MEDLINE and 7 in BIOSIS and CABNAR. BIOSIS was the only electronic database source of 2 trials. Eleven trials were identified by searching electronic databases and 2 unpublished trials were identified via experts in the field. We found one trial, published only as a conference abstract, by searching nutrition journals by hand. After publication of the protocol for the review in The Cochrane Library, we were informed of another unpublished trial.\n We found that a limited search plan based on only MEDLINE or one of the other commonly available databases would have failed to locate nearly one-half of the studies. To protect against bias, the search plan for a systematic review of nutritional interventions should be comprehensive.", "Our objectives were to identify literature on: (i) theory, evidence and gaps in knowledge relating to the help-seeking behaviour of people with learning disabilities and their carers; (ii) barriers experienced by people with learning disabilities in securing access to the full range of health services; (iii) interventions which improve access to health services by people with learning disabilities.\n twenty-eight bibliographic databases, research registers, organizational websites or library catalogues; reference lists from identified studies; contact with experts; current awareness and contents alerting services in the area of learning disabilities.\n Inclusion criteria were English language literature from 1980 onwards, relating to people with learning disabilities of any age and all study designs. The main criteria for assessment was relevance to the Guilliford et al. model of access to health care (Gulliford et al. Access to health care. Report of a Scoping Exercise for the National Co-ordinating Centre for NHS Service Delivery and Organisation R & D (NCCSDO). London: NCCSDO, 2001), which was modified to the special needs of people with learning disabilities. Inclusion criteria focused on relevance to the model with initial criteria revised in light of literature identified and comments from a consultation exercise with people with learning disabilities, family and paid carers and experts in the field. Data abstraction was completed independently and selected studies were evaluated for scientific rigour and the results synthesized.\n In total, 2221 items were identified as potentially relevant and 82 studies fully evaluated.\n The process of identifying relevant literature was characterized by a process of clarifying the concept under investigation and sensitive search techniques which led to an initial over-identification of non-relevant records from database searches. Thesaurus terms were of limited value, forcing a reliance on using free-text terms and alternative methods of identifying literature to supplement and improve the recall of the database searches. A key enabler in identifying relevant literature was the depth and breadth of knowledge built up by the reviewers whilst engaged in this process.", "There is little guidance on how to identify useful evidence about the health effects of social interventions. The aim of this study was to assess the value of different ways of finding this type of information.\n Retrospective analysis of the sources of studies for one systematic review.\n Case study of a systematic review of the effectiveness of interventions in promoting a population shift from using cars towards walking and cycling.\n Only four of the 69 relevant studies were found in a \"first-line\" health database such as Medline. About half of all relevant studies were found through the specialist Transport database. Nine relevant studies were found through purposive internet searches and seven relevant studies were found by chance. The unique contribution of experts was not to identify additional studies, but to provide more information about those already found in the literature.\n Most of the evidence needed for this review was not found in studies indexed in familiar literature databases. Applying a sensitive search strategy across multiple databases and interfaces is very labour intensive. Retrospective analysis suggests that a more efficient method might have been to search a few key resources, then to ask authors and experts directly for the most robust reports of studies identified. However, internet publications and serendipitous discoveries did make a significant contribution to the total set of relevant evidence. Undertaking a comprehensive search may provide unique evidence and insights that would not be obtained using a more focused search.", "To address methodologic issues in searching for observational studies by presenting database search methods and results.\n Results of two literature searches for publications reporting on observational studies of alcohol consumption and the risk of breast cancer and large bowel cancer were compared, to evaluate the sensitivity of various bibliographic databases and search strategies, including hand-searching reviews and meta-analyses.\n The target sensitivity of 90% of publications in the breast cancer search was achieved by starting with Medline, then adding Biosis, Embase, and SCI EXPANDED-SSCI, which provided a total of 72 (91%) of the 79 relevant publications. To reach a similar 89% sensitivity for large bowel cancer, at least Biosis, Dissertation Abstracts Online, Embase, ETOH, and Medline had to be searched, with the addition of hand search of reviews and meta-analyses.\n Limiting a search to one or two databases when conducting meta-analyses of observational studies will not provide a thorough summary of the existing literature. The findings support recommendations to implement a comprehensive search of electronic databases and the reference lists of recent review articles and meta-analyses.", "This study addressed 2 questions: first, what is the yield of PubMed MEDLINE for complementary and alternative medicine (CAM) studies compared to other databases; second, what is an effective search strategy to answer a sample research question on spinal palpation?\n We formulated the following research question: \"What is the reliability of spinal palpation procedures?\" We identified specific Medical Subject Headings (MeSH) and key terms as used in osteopathic medicine, allopathic medicine, chiropractic, and physical therapy. Using PubMed, we formulated an initial search template and applied it to 12 additional selected databases. Subsequently, we applied the inclusion criteria and evaluated the yield in terms of precision and sensitivity in identifying relevant studies.\n The online search result of the 13 databases identified 1189 citations potentially addressing the research question. After excluding overlapping and nonpertinent citations and those not meeting the inclusion criteria, 49 citations remained. PubMed yielded 19, while MANTIS (Manual Alternative and Natural Therapy Index System), a manual therapy database, yielded 35 citations. Twenty-six of the 49 online citations were repeatedly indexed in 3 or more databases. Content experts and selective manual searches identified 11 additional studies. In all, we identified 60 studies that addressed the research question. The cost of the databases used for conducting this search ranged from free-of-charge to $43,000 per year for a single network subscription.\n Commonly used databases often do not provide accurate indexing or coverage of CAM publications. Subject-specific specialized databases are recommended. Access, cost, and ease of using specialized databases are limiting factors.", "To explore whether searching specialised bibliographic databases identified additional relevant papers to those located by a Medline search for a systematic review of exercise therapy.\n Searches were performed in Medline, two further generalised medical databases (Embase, Cochrane Library) and four specialised databases (CancerLit, Cinahl, PsychInfo, SportDiscus) to identify controlled trials of exercise interventions for cancer patients.\n A total of 749 different publications were located through the search, of which 18 met inclusion criteria. Fifteen (83%) of these were identified through Medline and three (17%) from three individual specialised databases. A further seven studies meeting inclusion criteria were located through reference lists and contact with experts.\n In this example, searching Medline and additional specialised databases along with checking reference lists and contacting experts was the most effective means of ensuring that all relevant papers were included in the review. Searching Medline alone for systematic reviews of exercise or other unconventional therapies is likely to be inadequate.", "To describe where papers come from in a systematic review of complex evidence. Method Audit of how the 495 primary sources for the review were originally identified.\n Only 30% of sources were obtained from the protocol defined at the outset of the study (that is, from the database and hand searches). Fifty one per cent were identified by \"snowballing\" (such as pursuing references of references), and 24% by personal knowledge or personal contacts.\n Systematic reviews of complex evidence cannot rely solely on protocol-driven search strategies." ]

[ "17027531", "9788086", "15044414", "9346020", "11928967", "17852999" ]

[ "Effectiveness of community-based injury prevention. Long-term injury rate levels, changes, and trends for 14 Swedish WHO-designated Safe Communities.", "Harstad injury prevention study: prevention of burns in young children by community based intervention.", "Impact of social standing on injury prevention in a World Health Organization Safe Community--intervention outcome by household employment contract.", "The Lidköping Accident Prevention Programme--a community approach to preventing childhood injuries in Sweden.", "Controlled evaluation of a community based injury prevention program in Australia.", "Differences in child injury hospitalizations in Sweden: the use of time-trend analysis to compare various community injury-prevention approaches." ]

[ "This study investigates the injury rate levels, changes, and trends between 1987 and 2002 for the 14 Swedish municipalities designated as WHO Safe Communities. The injury rate was defined as the number of injured patients discharged from hospital per 1000 persons. Injury rates were age standardised. Each municipality was compared with its respective municipality group, according to a classification of Sweden's 288 municipalities into nine groups based on numerous structural parameters. The average injury rate levels for the 14 WHO-designated Safe Community municipalities ranged from 11.54 to 19.09 per 1000 population during the study period, which was defined as the time period during which a municipality's injury prevention program has been operational. Eleven of 14 municipalities had higher levels than their corresponding municipality groups. Five of the 14 municipalities \"outperformed\" their respective municipality groups and achieved a greater relative injury rate decrease during the study period. The trends for the 14 municipalities in relation to their municipality groups showed an inconsistent pattern, with only four municipalities exhibiting overall favourable trends for the study period.", "To describe the long term effectiveness of a community based program targeting prevention of burns in young children.\n Quasiexperimental.\n The Norwegian city of Harstad (main intervention), six surrounding municipalities (intervention diffusion), and Trondheim (reference).\n Children under age 5 years in the three study populations.\n Outpatient and inpatient hospital data were coded according to the Nordic system, and collected as part of a national injury surveillance system. Burn data collection started in May 1985. The first 19.5 months of the study provided baseline data, while the last 10 years involved community based intervention, using a mix of passive and active interventions.\n The mean burn injury rate decreased by 51.5% after the implementation of the intervention in Harstad (p < 0.05) and by 40.1% in the six municipalities (not significant). Rates in the reference city, Trondheim, increased 18.1% (not significant). In Harstad and the six surrounding municipalities there was a considerable reduction in hospital admissions, operations, and bed days. Interventions with passive strategies were more effective, stove and tap water burns being eliminated in the last four years, while active strategies were less effective.\n A program targeting burns in children can be effective and sustainable. Local injury data provided the stimulus for community action.", "Although social inequality in health has been an argument for community-based injury prevention programmes, intervention outcomes with regard to differences in social standing have not been analysed. The objective of this study was to investigate rates of injuries treated in health-care among members of households at different levels of labour market integration before and after the implementation of a WHO Safe Community programme.\n A quasi-experimental design was used with pre- and post-implementation data collection covering the total populations <65 years of age during one year in the programme implementation municipality (population 41 000) and in a control municipality (population 26 000). Changes in injury rates were studied using prospective registration of all acute care episodes with regard to social standing in both areas during the study periods.\n Male members of households categorized as not vocationally active displayed the highest pre-intervention injury rates. Also after the intervention, males in households classified as not vocationally active displayed notably elevated injury rates in both the control and study areas. Households in the study area in which the significant member was employed showed a post-intervention decrease in injury rate among both men (P < 0.001) and women (P < 0.01). No statistically significant change was observed in households in which the significant member was self-employed or not vocationally active. In the control area, only an aggregate-level decrease (P < 0.05) among members of households in which the significant member was employed was observed.\n The study displayed areas for improvement in the civic network-based WHO Safe Community model. Even though members of non-vocationally active households, in particular men, were at higher pre-intervention injury risk, they were not affected by the interventions. This fact has to be addressed when planning future community-based injury prevention programmes.", "In Sweden about 100 children 0-14 years die from accidental injuries every year, roughly 40 girls and 60 boys. To reduce this burden the Safe Community concept was developed in Falköping, Sweden in 1975. Several years later a second programme was initiated in Lidköping. The objectives of this paper are to describe the programme in Lidköping and to relate it to changes in injury occurrence.\n The Lidköping Accident Prevention Programme (LAPP) was compared with four bordering municipalities and to the whole of Skaraborg County.\n The programme included five elements: surveillance, provision of information, training, supervision, and environmental improvements. Process evaluation was based mainly on notes and reports made by the health planners, combined with newspaper clippings and interviews with key people. Outcome evaluation was based on information from the hospital discharge registry.\n In Lidköping there was an on average annual decrease in injuries leading to hospital admissions from 1983 to 1991 of 2.4% for boys and 2.1% for girls compared with a smaller decline in one comparison area and an increase in the other.\n Because the yearly injury numbers are small there is a great variation from year to year. However, comparisons over the nine year study period with the four border municipalities and the whole of Skaraborg County strengthen the impression that the programme has had a positive effect. The findings support the proposition that the decrease in the incidence of childhood injuries after 1984 could be attributed to the intervention of the LAPP. Nevertheless, several difficulties in drawing firm conclusions from community based studies are acknowledged and discussed.", "To evaluate the effects of a community based, all age, all injury prevention program, the Safe Living Program, on injury risk and injury rates.\n A quasiexperimental population based evaluation using an intervention and comparison community design.\n The intervention community (Shire of Bulla, n = 37,257) is an outer metropolitan area of Melbourne, Australia. The demographically matched comparison community (Shire of Melton, n=33,592) is located nearby.\n The Safe Living Program in the Shire of Bulla targeted injury reduction in all settings with a focus on high risk groups. Strategies included program publicity, education and training, injury hazard reduction, and environmental change. Baseline and follow up measures of program reach, risk factors, and injury rates in both communities were used to evaluate program process, impact, and outcome.\n Increase in program awareness was moderate and similar to other community based programs. The program achieved injury hazard reduction on the road, in schools, and, to a more limited extent, in the home. Other changes in injury risk factors could not necessarily be attributed to the program as similar changes were observed in the comparison community. No significant changes were found in rates of injury deaths, hospitalisations, or emergency department presentations in the Shire of Bulla after six years. Self reported household injuries, mostly minor, were reduced in the intervention community, but had been higher at program launch than in the comparison community.\n The Safe Living Program was unable to replicate the significant reductions in injuries reported in other community based interventions. Replication of apparently successful community based injury prevention programs in different settings and populations requires evidence based interventions, sustained and effective program penetration, reliable data systems to measure change, at least one control community, and sufficient budget and time for effects to be observable.", "Sweden's child injury fatality rates are among the lowest in the world. The country has engaged in a number of community injury-prevention programmes. The purpose of this study was to compare child injury hospitalization rates from the Skaraborg District with the rest of Sweden. Our study hypothesis was that municipalities that offered comprehensive child injury-prevention programmes would see significant decreases in their child injury hospitalization rates, compared with other areas.\n The study areas comprised three groups, consisting of municipalities in Skaraborg that had adapted the Safe Communities approach to injury prevention programmes, other municipalities in the District, and the rest of Sweden. The aim of the analysis was twofold: (1) to fit time trends for children's injuries in various areas in an integrated manner; and (2) to compare time trends across locations between community safety-promotion programmes as well as with the control areas. Panel data models and parametric splines were used.\n There were differences between incidence rates in the study areas and with regard to gender. There was a steep decrease in injury rates in one of the Safe Communities study areas for both genders.\n The methods applied in this analysis reveal more detailed and sophisticated time trends than the usual simple linear regression approach. The model provided a clearer view of the interactions of gender, area, and time as they impacted on children's injuries, and allowed for better insight into the impact of safety programmes." ]

[ "1732771", "8605126", "9442174", "1396258", "12623473", "15960212", "3688070", "14744822", "10901564", "7643880", "21054896", "9322630" ]

[ "A controlled trial of a program for the active management of labor.", "A randomised controlled trial of early versus delayed use of amniotomy and oxytocin infusion in nulliparous labour.", "Dysfunctional labour: a randomised trial.", "Evaluation of different policies for the management of labour.", "Active management of labour in a district hospital setting.", "Reducing cesarean delivery rates: an active management labor program in a setting with limited resources.", "A prospective randomized study of the aggressive management of early labor.", "Randomised controlled trial of labouring in water compared with standard of augmentation for management of dystocia in first stage of labour.", "A randomised controlled trial and meta-analysis of active management of labour.", "A clinical trial of active management of labor.", "Comparison between amniotomy, oxytocin or both for augmentation of labor in prolonged latent phase: a randomized controlled trial.", "Active management of labor: does it make a difference?" ]

[ "Over the past two decades, the rate of cesarean section in the United States has risen from 5 percent to 25 percent of deliveries, primarily because of the increased frequency of dystocia (arrest of labor). One strategy that has been proposed for increasing the rate of vaginal delivery is a program of active management of labor that encourages early amniotomy, early diagnosis of slow progress in labor, and the use of higher than usual doses of oxytocin; the efficacy and safety of this approach are uncertain, however.\n We conducted a randomized trial in which nulliparous women in spontaneous labor at term were randomly assigned to either active management of labor or traditional management. With active management, amniotomy was performed within one hour of the diagnosis of labor, and when the rate of cervical dilation was less than 1 cm per hour, oxytocin was infused at an initial rate of 6 mU per minute. The dose was increased by 6 mU per minute every 15 minutes (to a maximum of 36 mU per minute) until there were seven contractions every 15 minutes.\n For the women assigned to active management (n = 351), the cesarean-section rate was 10.5 percent, as compared with 14.1 percent for those assigned to traditional management (n = 354, P = 0.18). The 26 percent reduction in the cesarean-section rate was due primarily to a decrease in dystocia. After we controlled for potential confounding variables, the reduction in the rate of delivery by cesarean section was statistically significant (odds ratio for women given active as compared with traditional management, 0.57; 95 percent confidence interval, 0.36 to 0.95). With active management, the average length of labor was shortened by 1.66 hours, principally because of earlier amniotomy and earlier use of oxytocin. There was no increase in maternal or neonatal morbidity, and there were significantly fewer infectious complications in the mothers.\n The program we studied for the active management of labor reduces the incidence of dystocia and increases the rate of vaginal delivery without increasing maternal or neonatal morbidity.", "To compare routine amniotomy and early intravenous oxytocin (active management of labour) with a more selective use of amniotomy and oxytocin in women in true labour who received comparable continuous supportive midwifery care.\n Randomised controlled trial of nulliparous clinic patients in spontaneous labour at term.\n Labour and delivery ward of a university teaching hospital.\n Three hundred and six parturients: 152 received active management of labour; 154 were more selectively managed.\n 1. Active management: early amniotomy, early use of oxytocin. 2. Selective intervention management: no routine amniotomy and more selective use of oxytocin.\n Use of oxytocin and amniotomy. Labour duration, mode of delivery.\n Maternal characteristics were comparable in both groups. Amniotomy was more often performed (91% versus 57%, P <0.01) and oxytocin more often used (53% versus 27%, P < 0.01) in the active management group. The first stage of labour, however, was only shortened by half an hour in the active management group (254 min versus 283 min, P = 0.087). Caesarean section rate (3.9% versus 2.6%), spontaneous vaginal delivery rate (78% versus 79%) and neonatal outcome were not significantly different between groups.\n Within a set-up of strict labour diagnosis and supportive midwifery care, routine amniotomy and early use of oxytocin offered no advantage over a more selective use of amniotomy and oxytocin in terms of mode of delivery and labour duration.", "Sixty-one women making slow progress in the active phase of spontaneous labour with intact membranes were randomised to oxytocin and amniotomy, amniotomy only or expectant management. The data show that oxytocin significantly increases the rate of cervical dilatation and shortens prolonged labour, when compared with amniotomy alone and expectant management (P = 0.0144 and 0.0006, respectively). The impact on the operative delivery rate and neonatal outcome is difficult to assess due to the small number of relevant adverse outcomes. Women reported higher satisfaction score in the two groups where intervention followed the diagnosis of dysfunctional labour.", "Various policies of management of prolonged labour have been proposed to prevent its two main consequences--caesarean section and fetal distress. Two randomised controlled trials were organised; the first to assess the value of amniotomy with oxytocin compared to a more conservative approach. The second trial compared the effect of continuous professional support during labour with the intermittent presence of a member of staff. These were multicentre studies in several countries of Europe. Preliminary results of early amniotomy suggested no difference in the rate of operative delivery. Continuous professional support was associated with a significant reduction in operative deliveries.", "The aim of this randomised trial was to determine the effect of the policy of active management of labour in all its components on the rate of caesarean section in a Nigerian district hospital setting. Two hundred and twenty-one nulliparous women fulfilling selected inclusion criteria were randomised to receive active management of labour, and 227 control women received routine labour management. Labour was significantly shortened by over 2 hours with active management of labour, and caesarean section reduced (9% vs. 16%, RR 0.57, 95% CI 0.34-0.95). There were no significant differences in maternal infectious morbidity, uterine hyperstimulation syndromes, ruptured uterus or neonatal Apgar scores between the two groups. We conclude that active management of labour shortens primigravid labour and reduces caesarean risk.", "To determine the effect of an active management of a labor program on the rate of cesarean section and labor outcomes in low-risk nulliparous pregnancies in a setting with limited resources.\n Nine hundred and seventy-five low risk nulliparous pregnant women were randomized to receive either active management of a labor program (n = 325) or conventional management (n = 650). The rate of cesarean section and labor outcomes were compared between the two groups using Chi-square and t-tests.\n The subjects in the active management program had significantly shortened first stage of labor and total duration of labor compared with the conventional group (538.0 +/- 242.9 min vs 589.4 +/- 263.8 min, p < 0.05, 539.3 +/- 261.4 min vs 610.3 +/- 264.4 min, p < 0.001, respectively). There was no statistical difference found in the rate of cesarean section and other labor outcomes.\n The active management program shortened the first stage and duration of labor in low-risk nulliparous pregnant women.", "The aggressive management of early labor has been suggested as a means to lower the cesarean section rate for dystocia. The aim of our study was to prospectively evaluate a protocol of early intervention in primigravid women with infrequent uterine contractions during early labor in relation to the course of labor, the cesarean section rate, and the perinatal morbidity. In our population the active management of labor did not alter the mode of delivery or the perinatal outcome. Furthermore, the course and duration of labor were not significantly different between the management and control groups.", "To evaluate the impact of labouring in water during first stage of labour on rates of epidural analgesia and operative delivery in nulliparous women with dystocia.\n Randomised controlled trial.\n University teaching hospital in southern England.\n 99 nulliparous women with dystocia (cervical dilation rate < 1 cm/hour in active labour) at low risk of complications. Interventions Immersion in water in birth pool or standard augmentation for dystocia (amniotomy and intravenous oxytocin).\n Primary: epidural analgesia and operative delivery rates. Secondary: augmentation rates with amniotomy and oxytocin, length of labour, maternal and neonatal morbidity including infections, maternal pain score, and maternal satisfaction with care.\n Women randomised to immersion in water had a lower rate of epidural analgesia than women allocated to augmentation (47% v 66%, relative risk 0.71 (95% confidence interval 0.49 to 1.01), number needed to treat for benefit (NNT) 5). They showed no difference in rates of operative delivery (49% v 50%, 0.98 (0.65 to 1.47), NNT 98), but significantly fewer received augmentation (71% v 96%, 0.74 (0.59 to 0.88), NNT 4) or any form of obstetric intervention (amniotomy, oxytocin, epidural, or operative delivery) (80% v 98%, 0.81 (0.67 to 0.92), NNT 5). More neonates of women in the water group were admitted to the neonatal unit (6 v 0, P = 0.013), but there was no difference in Apgar score, infection rates, or umbilical cord pH.\n Labouring in water under midwifery care may be an option for slow progress in labour, reducing the need for obstetric intervention, and offering an alternative pain management strategy.", "To test whether a policy of active management of nulliparous labour would reduce the rate of caesarean section and prolonged labour without influencing maternal satisfaction.\n Randomised controlled trial.\n Tertiary referral obstetric unit, Auckland, New Zealand.\n Nulliparous women in spontaneous labour at term with singleton pregnancy and cephalic presentation and without fetal distress.\n After the onset of active labour, previously consented women were randomly assigned to active management (n = 320) or to routine care (n = 331). Active labour was defined as regular painful contractions, occurring at least once in five minutes, lasting at least 40 seconds, accompanied by either spontaneous rupture of the membranes, or full cervical effacement and dilatation of at least two centimetres. Active management included early amniotomy, two-hourly vaginal assessments, and early use of high dose oxytocin for slow progress in labour. Routine care was not prespecified. Prolonged labour was > 12 hours duration. Maternal satisfaction with labour care was assessed by postal questionnaire at six weeks postpartum.\n Mode of delivery, duration of labour, and maternal satisfaction.\n Active management of labour did not reduce the rate of caesarean section 30/320 (9.4%), compared with 32/331 (9.7%) for routine care, but did shorten the length of first stage of labour (median 240 min vs 290 min; P = 0.02), and reduce the relative risk of prolonged labour (RR 0.39; 95% CI 0.22, 0.71). There were no differences between groups in the rates of newborn nursery admission, neonatal acidosis, low Apgar scores, or postpartum haemorrhage. Satisfaction with labour care was high (77%) and did not differ between groups.\n Active management of labour reduced the duration of the first stage of labour without affecting the rate of caesarean section, maternal satisfaction, or other maternal or newborn morbidity.", "Active management of labor is a multifaceted program that, as implemented at the National Maternity Hospital in Dublin, is associated with a lower rate of cesarean delivery than the rate usually found in the United States. We conducted a randomized trial to evaluate the efficacy of this approach in lowering the rate of cesarean section among women delivering their first babies.\n We randomly assigned 1934 nulliparous women at low risk of complications of pregnancy, before 30 weeks' gestation, to active management of labor or to a usual-care group. The components of active management were customized childbirth classes; strict criteria for the diagnosis of labor; standardized management of labor, including early amniotomy and treatment with high-dose oxytocin; and one-to-one nursing. A low-risk subgroup was defined as including women with full-term, uncomplicated pregnancies who spontaneously went into labor (the protocol-eligible subgroup). Women meeting these criteria who had been randomly assigned to the active-management group were admitted to a separate unit where their labor was managed by trained, certified nurse-midwives.\n There was no difference between groups in the rate of cesarean section either among all women (active management, 19.5 percent; usual care, 19.4 percent) or in the protocol-eligible subgroup (active management, 10.9 percent; usual care, 11.5 percent). In the protocol-eligible subgroup, the median duration of labor was shortened by 2.7 hours by active management (from 8.9 to 6.2 hours), and the rate of maternal fever was lower (7 percent vs. 11 percent, P = 0.007). The percentage of women in whom labor lasted longer than 12 hours was three times higher in the usual-care group than in the active-management group (26 percent vs. 9 percent, P < 0.001).\n Active management of labor did not reduce the rate of cesarean section in nulliparous women but was associated with a somewhat shorter duration of labor and less maternal fever.", "A prolonged latent phase is independently associated with an increased incidence of subsequent labor abnormalities. We aimed to compare between oxytocin augmentation, amniotomy and a combination of both on the duration of labor among women with a prolonged latent phase.\n Women with a singleton fetus in cephalic presentation who have a prolonged latent phase, were randomly allocated to amniotomy (group 1), oxytocin (group 2) or both (group 3). A group of women who progressed spontaneously without intervention composed the control group (group 4). The primary outcome was the duration of time from initiation of augmentation until delivery.\n A total of 213 women were consented and randomized to group 1 (70 women), group 2 (72 women) and group 3 (71 women). Group 4 was composed from additional 70 women. A mean reduction of 120 minutes in labor duration was observed among group 3 compared to group 1 (p = 0.08) and 180 minutes compared to group 2 and 4 (p = 0.001). Women in group 3 had a shorter length of time from augmentation until the beginning of the active phase and a shorter first stage of labor than group 1 (p = 0.03), group 2 (p = 0.001) and group 4 (p = 0.001). Satisfaction was greater among group 3 and 4. Mode of delivery and neonatal outcome were comparable between the groups.\n Labor augmentation by combined amniotomy and oxytocin among women with a prolonged latent phase at term seems superior compared to either of them alone.", "Our goal was to evaluate whether active management of labor lowers cesarean section rates, shortens the length of labor, and overcomes any negative effects of epidural analgesia on nulliparous labor.\n We randomly assigned 405 low-risk term nulliparous patients to either an active management of labor (n = 200) or our usual care control protocol (n = 205). Patients who were undergoing active management of labor were diagnosed as being in labor on the basis of having painful palpable contractions accompanied by 80% cervical effacement, underwent early amniotomy, and were treated with high-dose oxytocin for failure to progress adequately in labor.\n The cesarean section rate in the active management of labor group was lower than that of controls but not significantly so (active management, 7.5%; controls, 11.7%; p = 0.36). The length of labor in the active management group was shortened by 1.7 hours (from 11.4 to 9.7 hours, p = 0.001). Fifty-five percent of patients received epidural analgesics; a reduction in length of labor persisted despite the use of epidural analgesics (active management 11.2 hours vs control 13.3 hours, p = 0.001). A significantly greater proportion of active management patients were delivered by 12 hours compared with controls (75% vs 58%, p = 0.01); this difference also persisted despite the use of epidural analgesics (66% vs 51%, p = 0.03).\n Patients undergoing active management had shortened labors and were more likely to be delivered within 12 hours, differences that persisted despite the use of epidural analgesics. There was a trend toward a reduced rate of cesarean section." ]

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[ "[Acamprosate--a stabilizing factor in long-term withdrawal of alcoholic patients].", "Acamprosate and relapse prevention in the treatment of alcohol dependence: a placebo-controlled study.", "Effect of oral acamprosate on abstinence in patients with alcohol dependence in a double-blind, placebo-controlled trial: the role of patient motivation.", "Ability of calcium bis acetyl homotaurine, a GABA agonist, to prevent relapse in weaned alcoholics.", "Acamprosate appears to decrease alcohol intake in weaned alcoholics.", "Naltrexone versus acamprosate in the treatment of alcohol dependence: A multi-centre, randomized, double-blind, placebo-controlled trial.", "Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial.", "Relapse prevention by acamprosate. Results from a placebo-controlled study on alcohol dependence.", "Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind, placebo-controlled study.", "Combined efficacy of acamprosate and disulfiram in the treatment of alcoholism: a controlled study.", "Acamprosate in Korean alcohol-dependent patients: a multi-centre, randomized, double-blind, placebo-controlled study.", "United Kingdom Multicentre Acamprosate Study (UKMAS): a 6-month prospective study of acamprosate versus placebo in preventing relapse after withdrawal from alcohol.", "Acamprosate and its efficacy in treating alcohol dependent adolescents.", "Acamprosate treatment in a long-term community-based alcohol rehabilitation programme.", "Double-blind randomized multicentre trial of acamprosate in maintaining abstinence from alcohol.", "Comparison of acamprosate and placebo in long-term treatment of alcohol dependence.", "Efficacy and safety of acamprosate in the treatment of detoxified alcohol-dependent patients. A 90-day placebo-controlled dose-finding study.", "[Does acamprosate diminish the appetite for alcohol in weaned alcoholics?].", "Acamprosate during and after acute alcohol withdrawal: a double-blind placebo-controlled study in Spain.", "Acamprosate in alcohol dependence: a randomized controlled efficacy study in a standard clinical setting." ]

[ "In a one-year double-blind-treatment study with acamprosat (six months with and six months without substance) the efficiency of this new medicament could be proved. The number of relapses in the treatment group was significantly lower during the first 30 days with a trend to further 150 days. The substance caused very few side effects.", "The objective of this study was to compare acamprosate with placebo in the treatment of alcohol-dependent patients during a 6-month post-detoxification treatment and a 3-month medication-free follow-up. Patients (n = 330) were detoxified and randomized to treatment with acamprosate (1998 mg/day) or placebo within an out-patient programme including medical counselling, psychotherapy and self-help groups. The main outcome criterion was drinking behaviour as assessed by: abstinence/relapse ratio, cumulative abstinence duration (CAD) and the period of continued abstinence. Anxiety, depression and craving were also monitored. Intention to treat (ITT) statistical principles were followed. Twenty-five per cent of patients dropped out over the first 6 months. At the end of the treatment period, the abstinence rate was 57.9% for acamprosate and 45.2% for placebo (P = 0.03). The CAD was 110+/-77 days for acamprosate and 89+/-77 days for placebo (P = 0.016). Patients on acamprosate had a higher continuous abstinence rate and experienced less severe relapses. No differential effect was noted for anxiety, depression or craving. Treatment remained positive, but not significant, 3 months after termination of study medication. No significant difference in adverse events was noted between treatment groups. Acamprosate treatment over 180 days was consistently more effective than placebo to maintain abstinence and to diminish relapse severity.", "This is the first US study to evaluate the clinical efficacy of acamprosate (Campral), a newly FDA-approved medication for maintaining abstinence in patients with alcohol dependence following alcohol withdrawal. We compared effects of the standard 2 g dose (n=258) and an exploratory 3 g dose of acamprosate (n=83) versus placebo (n=260), and evaluated drug safety in a double-blind, placebo-controlled 6-month trial conducted in 21 outpatient clinics across the US. Participants were 601 volunteers with current alcohol dependence recruited primarily by advertisement. All patients concomitantly received eight sessions of brief manual-guided counseling (www.alcoholfree.info). The main outcome measure was the percentage of alcohol-free days over the 6-month study. Self-report was validated by breath alcohol concentration, gamma-glutamyltransferase (GGT) and collateral informant interviews. The percentage of abstinent days did not differ significantly across groups in a priori analysis (54.3% for placebo, 56.1% for 2 g, 60.7% for 3 g). Post-hoc analysis controlling for baseline variables and treatment exposure found acamprosate was associated with a significantly higher percentage of abstinent days than placebo (52.3% for placebo, 58.2% for 2 g, 62.7% for 3 g; P=0.01), with an even greater effect in the subgroup of 241 patients having a baseline goal of abstinence (58.1% for placebo, 70.0% for 2 g, 72.5% for 3 g; P=0.02). There were no deaths or serious drug-related adverse events. The US study findings suggest that acamprosate is safe and well tolerated in a broadly inclusive sample of alcoholics and appears effective in populations of patients motivated to have a treatment goal of abstinence.", "After they had been weaned off alcohol in hospital 85 severe alcoholics (above 200 g alcohol/day) were included in a double-blind study of calcium bis acetyl homotaurine (Ca AOTA, 25 mg/kg/day), a new gamma-aminobutyric acid agonist, versus placebo. Patients were treated as outpatients during the 3-month study. The only other treatment that patients received was meprobamate, 800 to 1200 mg/day, in the first month. The criterion for success was abstinence at 3 months (with normal gamma-glutamyl transpeptidase being one of the criteria). Of the 70 patients who completed the study, 33 received Ca AOTA and 37 placebo. 20 patients on Ca AOTA did not relapse, compared with 12 on placebo (p less than 0.02 by X2 test). Side-effects were noted by 7 patients on Ca AOTA and 2 on placebo. The results suggest that Ca AOTA may be useful in helping severe alcoholics who have been weaned off alcohol not to relapse.", "Five hundred and sixty-nine alcoholics were included in a double-blind placebo-controlled randomized multicenter study of the effects of Acamprosate (calcium acetylhomotaurinate (CA), 1.3 g/day) on indicators of alcoholic relapse after withdrawal. One hundred and eighty-one patients in the CA group versus 175 in the placebo group completed the three-month study. The major efficacy criterion was plasma gamma-glutamyl transpeptidase (GGT), as an indicator of recent alcohol ingestion. This analysis was completed by criteria concordance analysis on a number of indicators of alcohol intake. Patients in both groups were similar initially. After 3 months of treatment, the patients in the CA group had significantly lower GGT (1.4 +/- 1.56 versus 2.0 +/- 3.19 times normal, P = 0.016). All significant differences (P less than 0.05) or trends (0.10 greater than P greater than 0.05) were in favor of a superior effect of CA over placebo. The major side-effect of CA was diarrhea (present in 13% of CA patients versus 7% of placebo, P = 0.04). CA proved superior to placebo on the evolution of markers of alcohol ingestion at three months, in this large-scale multicenter study. It could be a new modality in the drug therapy of alcoholism, not involving an antabuse effect, an antidepressant action, or conditioning.", "To compare the efficacy of acamprosate and naltrexone in the treatment of alcohol dependence.\n A double-blind, placebo-controlled trial.\n Three treatment centres in Australia.\n A total of 169 alcohol dependent subjects were given naltrexone (50 mg/day), acamprosate (1998 mg/day) or placebo for 12 weeks.\n All subjects were offered manualized compliance therapy, a brief intervention that targets problems that may affect treatment compliance such as ambivalence and misperceptions about medication.\n Time to the first drink, time to first relapse, drinks per drinking day and cumulative abstinence.\n In intention-to-treat analyses, there were no differences between groups on outcome measures of drinking, craving or biochemical markers. Similarly, analyses of the 94 subjects that completed the study in full and demonstrated 80% compliance, revealed no significant treatment effects. Differential treatment effects were identified after stratification according to scores on the Alcohol Dependence Scale (ADS) and Depression Anxiety and Stress Scale (DASS). A significant beneficial treatment effect on time to first relapse was revealed for subjects with 'no depression' allocated to naltrexone (n = 56; P < 0.01). In addition, a significant beneficial treatment effect was revealed in subjects with 'low dependence' allocated to naltrexone (n = 34; P < 0.05).\n The results of this study support the efficacy of naltrexone in the relapse prevention of alcoholism amongst those with low levels of clinical depression and alcohol dependence severity. No effect of acamprosate was found in our sample.", "Alcohol dependence treatment may include medications, behavioral therapies, or both. It is unknown how combining these treatments may impact their effectiveness, especially in the context of primary care and other nonspecialty settings.\n To evaluate the efficacy of medication, behavioral therapies, and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome.\n Randomized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers (median age, 44 years) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnoses of primary alcohol dependence.\n Eight groups of patients received medical management with 16 weeks of naltrexone (100 mg/d) or acamprosate (3 g/d), both, and/or both placebos, with or without a combined behavioral intervention (CBI). A ninth group received CBI only (no pills). Patients were also evaluated for up to 1 year after treatment.\n Percent days abstinent from alcohol and time to first heavy drinking day.\n All groups showed substantial reduction in drinking. During treatment, patients receiving naltrexone plus medical management (n = 302), CBI plus medical management and placebos (n = 305), or both naltrexone and CBI plus medical management (n = 309) had higher percent days abstinent (80.6, 79.2, and 77.1, respectively) than the 75.1 in those receiving placebos and medical management only (n = 305), a significant naltrexone x behavioral intervention interaction (P = .009). Naltrexone also reduced risk of a heavy drinking day (hazard ratio, 0.72; 97.5% CI, 0.53-0.98; P = .02) over time, most evident in those receiving medical management but not CBI. Acamprosate showed no significant effect on drinking vs placebo, either by itself or with any combination of naltrexone, CBI, or both. During treatment, those receiving CBI without pills or medical management (n = 157) had lower percent days abstinent (66.6) than those receiving placebo plus medical management alone (n = 153) or placebo plus medical management and CBI (n = 156) (73.8 and 79.8, respectively; P<.001). One year after treatment, these between-group effects were similar but no longer significant.\n Patients receiving medical management with naltrexone, CBI, or both fared better on drinking outcomes, whereas acamprosate showed no evidence of efficacy, with or without CBI. No combination produced better efficacy than naltrexone or CBI alone in the presence of medical management. Placebo pills and meeting with a health care professional had a positive effect above that of CBI during treatment. Naltrexone with medical management could be delivered in health care settings, thus serving alcohol-dependent patients who might otherwise not receive treatment.\n clinicaltrials.gov Identifier: NCT00006206.", "The effectiveness of acamprosate (calcium bisacetylhomotaurinate) as a treatment to maintain abstinence in alcohol-dependent patients was assessed for 1 year.\n After short-term detoxification, 272 patients participated in a randomized, double-blind, placebo-controlled study. Patients received routine counseling and either the study medication or placebo for 48 weeks; they were followed up for another 48 weeks without medication. Statistical analysis was performed according to the intention-to-treat principle.\n Patients who were receiving acamprosate showed a significantly higher continuous abstinence rate within the first 60 days of treatment compared with patients who were assigned to placebo treatment (67% vs 50%) until completion of the treatment period (43% vs 21%, log rank P = .005), and they had a significantly longer mean abstinence duration of 224 vs 163 days, or 62% vs 45% days abstinent (P < .001); however, there was no difference in psychiatric symptoms. Of the patients who were receiving acamprosate, 41% had dropped out, whereas 60% of the placebo-treated patients dropped out of the study. Few side effects (mainly diarrhea and headache) were recorded. At the end of a further 48 weeks without receiving study medication, 39% and 17% of the acamprosate- and placebo-treated patients, respectively, had remained abstinent (P = .003).\n Acamprosate proved to be a safe and effective aid in treating alcohol-dependent patients and in maintaining the abstinence of patients during 2 years.", "Naltrexone and acamprosate have been shown to be effective in relapse prevention of alcoholism via different pharmacologic mechanisms. Since it remains uncertain whether both substances are equally efficient and whether a combination of both drugs potentiates the efficacy, we conducted the first published controlled study comparing and combining both compounds.\n After detoxification, 160 patients with alcoholism participated in a randomized, double-blind, placebo-controlled protocol. Patients received naltrexone, acamprosate, naltrexone plus acamprosate, or placebo for 12 weeks. Patients were assessed weekly by interview, self-report, questionnaires, and laboratory screening. Time to first drink, time to relapse, and the cumulative abstinence time were the primary outcome measures.\n Naltrexone, acamprosate, and the combined medication were significantly more effective than placebo. Comparing the course of nonrelapse rates between naltrexone and acamprosate, the naltrexone group showed a tendency for a better outcome regarding time to first drink and time to relapse. The combined medication was most effective with significantly lower relapse rates than placebo and acamprosate but not naltrexone.\n The results of this study support the efficacy of pharmacotherapeutic strategies in the relapse prevention of alcoholism. Naltrexone and acamprosate, especially in combination, considerably enhance the potential of relapse prevention.", "This study presents the results of a multicenter investigation of the efficacy of acamprosate in the treatment of patients with chronic or episodic alcohol dependence. One hundred eighteen patients were randomly assigned to either placebo or acamprosate, and both groups were stratified for concomitant voluntary use of disulfiram. Treatment lasted for 360 days, with an additional 360-day follow-up period. The primary efficacy parameters evaluated were: relapse rate and cumulative abstinence duration (CAD). Results were analyzed according to Intention-To-Treat principles using chi2, t, and multiple regression analyses where appropriate. After 30 days on study medication, 40 of 55 (73%) acamprosate-treated patients were abstinent, compared with 26 of 55 (43%) placebo-treated patients (p = 0.019). The treatment advantage remained throughout the study medication period and was statistically significant until day 270 (p = 0.028). Twenty-seven percent of patients on acamprosate and 53% of patients on placebo had a first drink within the first 30 days of the study. The mean CAD was 137 days (40% abstinent days) for the patients treated with acamprosate and 75 days (21% abstinent days) for the placebo group (p = 0.013). No adverse interaction between acamprosate and disulfiram occurred, and the subgroup who received both medications had a better outcome on CAD than the those on only one or no medication. Acamprosate was well tolerated. Diarrhea was the only significant treatment-induced effect. It was concluded that acamprosate was a useful and safe pharmacotherapy in the long-term treatment of alcoholism. Concomitant administration of disulfiram improved the effectiveness of acamprosate.", "A multi-centre, randomized, double-blind, placebo-controlled trial was conducted to evaluate the efficacy and the safety of acamprosate over 8 weeks in Korean alcohol-dependent patients.\n One hundred and forty-two alcohol-dependent patients in 12 centres were randomized to 8 weeks treatment with either acamprosate (n = 72) or a placebo (n = 70) in combination with out-patient psychosocial intervention. They were predominantly male (95.8%), with a mean age of 44.3 +/- 8.3 years; 76.1% were married; 59.9% were employed; 58.5% had received previous alcoholism treatment (previous mean number of admissions in alcoholism in-patient programmes 4.6 +/- 6.9). At visits to the clinic (weekly for 4 weeks, then biweekly for 4 weeks), a record was made of alcohol use (Time-Line Follow-Back), alcohol craving using a Korean version of the Obsessive Compulsive Drinking Scale and a visual analogue scale, and adverse events. Serum aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase (GGT), blood urea nitrogen and creatinine levels were measured on weeks 0, 2, 4 and 8.\n In the acamprosate group (A), 71.4% had had alcohol within the 2 days prior to starting medication, against 65.2% of patients in the placebo group (P); (P > 0.05). One hundred and one subjects (71.1%) completed 8-weeks of treatment (A, 73.6%; P, 68.6%; P > 0.05). During the 8-week treatment period, 37, (A) (n = 72) and 32% (P) (n = 70) achieved continuous abstinence (P > 0.05), and 40, (A) and 39% (P) remained without relapse (P > 0.05) (defined as a day when a man consumed five or more drinks or a woman four or more drinks). The percentage of days abstinent during the 8-week treatment period was 81.2, (A) and 78.5% (P) (P > 0.05), and the percentage of days without heavy drinking 86.1 (A) and 84.9% (P) (P > 0.05). The mean amount drunk per drinking occasion was 7.2, (A) and 8.6 standard drinks (P) (P > 0.05). No statistically significant differences in changes in the serum GGT level or craving scores from baseline to the end-point of treatment were found between the two groups. Recency of drinking prior to commencing study drug predicted percentage of days abstinent in the first 2 weeks on treatment; however, when ANOVAs were conducted using treatment outcomes as a dependent variable, medication condition as an independent variable and the period of abstinence prior to treatment as a covariate, a significant effect of medication condition was still not seen.\n Acamprosate was ineffective in reducing drinking in this Korean sample. The result differs from that of most European acamprosate trials. This might be explained by our sample's relatively severe alcohol dependence, and low social support, or the fact that many patients were still drinking near to their first medication. The variability of the psychosocial support, ethnicity (which might also affect acamprosate pharmacokinetics) and the Korean drinking style, which differs from that of Europeans, might have contributed to our negative result.", "A 6-month randomized controlled study of acamprosate versus placebo in preventing relapse following withdrawal from alcohol was undertaken in 20 centres throughout the UK. Patients diagnosed as alcohol-dependent and detoxified within the preceding 5 weeks were randomly assigned to treatment with either acamprosate (A) 666 mg three times/day or identical placebo (P). A total of 664 patients were screened; 581 were entered into the treatment phase. One-third were episodic drinkers, 84% were male, 44% were unmarried and 48% were unemployed. Medication was first taken on average 24 days after the start of detoxification; 32% of patients had already relapsed by this time. The 6-month study period was completed by 35% of patients; adverse events led to withdrawal of a further 14% (A) and 9% (P) respectively. Compliance was poor in that, by the end of the second week, only 57% of patients were judged to be taking at least 90% of their tablets. The mean total of abstinent days achieved was 77 (A) and 81 (P). Complete abstinence for 6 months was achieved by 12% (A) and 11% (P); drinking remained within controlled limits in a further 3% (A) and 6% (P). An effect of acamprosate on consumption was not seen when subgroups, including those defined by the Lesch typology, were analysed separately. However, the mean percentage reduction in craving for alcohol measured on a visual analogue scale was greater in the acamprosate, than placebo, patients at week 2 and week 4 (P<0.001) and the mean decrease in the Hamilton Anxiety score at the 4th week was greater in the acamprosate than placebo patients (P = 0.017). In comparison with other published trials of acamprosate, patients started study medication after a longer time following detoxification, had more often recommenced drinking before medication was started and had a higher drop-out rate, and this might have contributed to the lack of a treatment effect in this study.", "About 50 % of adult alcoholic patients relapse within 3 months of treatment. Previous studies have suggested that acamprosate may help to prevent such relapse. The aim of our study was to assess the efficacy and safety of long-term acamprosate treatment in alcohol dependence of adolescents.\n In this, double-blind, placebo-controlled study, we recruited 26 patients, aged 16-19 years, with chronic or episodic alcohol dependence. Patients were randomly allocated treatment with acamprosate (1332 mg daily) or placebo for 90 days. Patients were assessed on the day treatment started and on days 30, and 90 by interview, self report, questionnaire, and laboratory screening.\n 13 acamprosate-treated and 13 placebo-treated patients completed the treatment phase: of those withdrawn, 11 (1 vs 6) relapsed, 5 (3 vs 2) refused to continue treatment, 3 (1 vs 2) had concurrent illness, and 2 (1 vs 1) had adverse side-effects. At the end of treatment, 7 acamprosate treated and 2 placebo-treated patients had been continuously abstinent (p = 0.0076). Mean cumulative abstinence duration was significantly greater in the acamprosate group than in the placebo group (79.8 [SD 37.5] vs 32.8 [19.0] days; p = 0.012).\n Acamprosate is an effective and well-tolerated pharmacological adjunct to psychosocial treatment programmes.", "To evaluate the efficacy of acamprosate in maintaining abstinence in weaned alcohol-dependent patients.\n A multicentre, double-blind, randomized control trial. Patients were individually randomly allocated to active or placebo conditions. Abstinence was assessed during a 6-month treatment period and after a 6-month follow-up period.\n A community-based, outpatient alcohol rehabilitation programme.\n Two hundred and forty-six alcohol-dependent patients between the ages of 18 and 65 years were recruited immediately following acute, inpatient withdrawal treatment.\n The primary outcome measure was self-reported abstinence from alcohol since the previous sessions at 3, 6, 9 and 12 months following the start of treatment, with treatment taking place for a period of 6 months.\n A significantly higher proportion of patients in the acamprosate group were abstinent after 3 months and 6 months of treatment. The percentage of patients with continuous abstinence at the end of the treatment period was almost double for the acamprosate group than for the placebo group (40.7% vs. 20.8%, respectively). Acamprosate significantly increased the retention of patients in the treatment programme. Six months after drug treatment ceased, the criterion of abstinence since the previous visit was reached by significantly more patients from the acamprosate group (43.4%) than from the placebo group (29.8%), but this difference was not statistically significant at the 3-month point after cessation of study medication.\n Acamprosate may be a useful pharmacological compound for the long-term treatment of alcohol-dependence when applied in a community-based rehabilitation programme.", "A prospective placebo-controlled, randomized double-blind study of Acamprosate at two dose levels in alcohol-dependent patients followed up for 12 months was performed. After detoxification, each of the 538 patients included was randomly assigned to one of three groups: 177 patients received placebo, 188 received Acamprosate at 1.3 g/day (low dose group) and 173 received 2.0 g/day (high dose group) for 12 months. This was followed by a single blind 6 month period on placebo. The patients' mean age was 43.2 +/- 8.6 years. Their mean daily alcohol intake was high (nearly 200 g/day) and of long duration (9.5 +/- 7.1 years). Abstinence figures followed the order high dose > low dose > placebo. The difference was significant at 6 months (P < or = 0.02) but not at 12 months (P = 0.096). The number of days of continuous abstinence after detoxification was 153 +/- 197 for the high-dose group versus 102 +/- 165 for the placebo group (P = 0.005), with the lose-dose group reporting 135 +/- 189 days. Clinic attendance was significantly better in the Acamprosate groups than in the placebo group at 6 months (P = 0.002) and 12 months (P = 0.005). During the 6-month post-treatment period, no increased relapse rate or residual drug effect was observed. The side effect profile for Acamprosate was good compared with controls with only diarrhoea being reported more frequently (P < 0.01). This study confirms the pharmacological efficacy of Acamprosate and its good acceptability. As an adjunct to psychotherapy, this study supports the inclusion of Acamprosate in a strategy for treating alcoholism.", "About 50% of alcoholic patients relapse within 3 months of treatment. Previous studies have suggested that acamprosate may help to prevent such relapse. The aim of our study was to assess the efficacy and safety of long-term acamprosate treatment in alcohol dependence.\n In this multicentre, double-blind, placebo-controlled study, we recruited 455 patients, aged 18-65 years, with chronic or episodic alcohol dependence. Patients were randomly allocated treatment with acamprosate (1998 mg daily for bodyweight > 60 kg; 1332 mg daily for < or = kg) or placebo for 360 days. Patients were assessed on the day treatment started and on days 30, 90, 180, 270, and 360 by interview, self-report, questionnaire, and laboratory screening. Patients were classified as abstinent, relapsing, or non-attending. Time to first treatment failure (relapse or non-attendance) was the primary outcome measure.\n Seven patients were excluded from the intention-to-treat analysis because they did not attend on the first treatment day and therefore received no medication. The acamprosate (n = 224) and placebo (n = 224) groups were well matched in terms of baseline demographic and alcohol-related variables. 94 acamprosate-treated and 85 placebo-treated patients completed the treatment phase: of those withdrawn, 104 (52 in each group) relapsed, 69 (33 vs 36, respectively) were lost to follow-up, 63 (31 vs 32) refused to continue treatment, 16 (15 vs 11) had concurrent illness, three (two vs one) died, ten (six vs four) had adverse side-effects, one (acamprosate treated) received the wrong medication, and three (placebo treated) were non-compliant. The proportion without treatment failure was higher in the acamprosate than in the placebo group throughout the treatment period (p < 0.001, Mantel-Cox). At the end of treatment, 41 (18.3%) acamprosate-treated and 16 (7.1%) placebo-treated patients had been continuously abstinent (p = 0.007). Mean cumulative abstinence duration was significantly greater in the acamprosate group than in the placebo group (138.8 [SD 137.5] vs 103.8 [119.0] days; p = 0.012). 148 patients (79 acamprosate, 69 placebo) completed 27 months follow-up: 27 (11.9%) acamprosate-treated and 11 (4.9%) placebo-treated patients remained continuously abstinent, and the mean cumulative abstinence duration was 230.8 days (259.1) and 183.0 days (235.2), respectively. Apart from occasional diarrhoea, there was no difference in side-effects between groups.\n Acamprosate is an effective and well-tolerated pharmacological adjunct to psychosocial and behavioural treatment programmes for treatment of alcohol-dependent patients.", "Acamprosate is a newly registered drug that appears to reduce alcohol-drinking in both animal models and clinical conditions.\n In order to assess the efficacy and safety of the drug in the treatment of detoxified alcoholics, we performed a 90-day double-blind trial comparing two dosages of acamprosate (1332 mg/day and 1998 mg/day).\n For all efficacy parameters, acamprosate appeared to be significantly superior to placebo, with a trend towards a better effect at the higher dosage. Furthermore, acamprosate appeared to be extremely safe.\n This study confirms that acamprosate could be an interesting adjuvant for maintaining abstinence in detoxified alcoholics.", "A population of 127 alcoholics of both sexes, hospitalized and weaned (DSM III diagnose: Alcohol Abuse and Alcohol Dependence) received Acamprosate (n = 63) or placebo (n = 64) in a double blind randomized therapeutic trail. The patients were followed during three months and anamnestic as well as biological data were recorded. It appeared no significant differences between the two groups of patients. This negative result could perhaps be explained by the heaviness of the pathology of this hospitalized alcoholic population.", "To test acamprosate's role as an aid in preventing relapse after detoxification, 296 alcohol-dependent patients entered a prospective, multicentre, randomized, double-blind, parallel comparison of acamprosate treatment consisting of two 333 mg tablets given three times daily for 180 days with matching placebo treatment. Unlike previous studies, acamprosate was prescribed from the start of alcohol withdrawal, rather than after the detoxification process. During the treatment period, 110 patients dropped out. The two treatment groups were balanced with regard to baseline values and reasons for discontinuation. There was no difference between the groups in the severity of withdrawal symptoms as measured by the CIWA-Ar (Clinical Institute Withdrawal Assessment for Alcohol scale). Acamprosate given during withdrawal did not cause unwanted effects. The cumulative abstinence duration (CAD, main end-point) was 19 days longer in the acamprosate treatment group than the placebo treatment group (analysis of variance on ranks, P = 0.0006) and the stable recovery duration, defined as the number of abstinent days between the last relapse into any drinking and the end of the trial, was 16 days longer in the acamprosate treatment group (P = 0.021). Continuous abstinence, estimated by survival analysis on time to first relapse, was achieved by 35% of acamprosate-treated patients and 26% of placebo-treated patients (log rank P = 0.068). The geometric mean of the ratio final/baseline values for serum carbohydrate-deficient transferrin was 0.802 (placebo) and 0.733 (acamprosate) (P = 0.059). The geometric mean of the ratio final/baseline values for serum gamma-glutamyltransferase was 0.496 (placebo) and 0.415 (acamprosate) (P = 0.024) which corroborated the greater abstinence reported by the acamprosate group.", "This study was undertaken to evaluate the efficacy and safety of acamprosate in the treatment of alcohol dependence.\n The investigation was a double-blind, placebo-controlled, 24-week study carried out at the University of São Paulo, Brazil. The sample comprised 75 patients, 18-60 years of age, with an International Classification of Diseases (ICD-10) diagnosis of alcohol dependence. After a 1-week detoxification period the patients were randomly divided into two groups: the first received acamprosate (1.998 mg/day) and the second received placebo. After the first 12 weeks, the patients continued follow-up for a similar length of time without medication. The main outcome measures were relapse rates, side effects and time to first relapse.\n On an intention-to-treat basis, the Kaplan-Meier survival curve showed an advantage in relapse rates for acamprosate over placebo (log-rank test, p = .02), and acamprosate was well tolerated.\n Acamprosate seems to be an effective treatment for alcohol dependence in a Brazilian population." ]

[ "19374691" ]

[ "The impact of pressure ulcer risk assessment on patient outcomes among hospitalised patients." ]

[ "To determine whether use of a risk assessment scale reduces nosocomial pressure ulcers.\n There is contradictory evidence concerning the validity of risk assessment scales. The interaction of education, clinical judgement and use of risk assessment scales has not been fully explored. It is not known which of these is most important, nor whether combining them results in better patient care.\n Pretest-posttest comparison.\n A risk assessment scale namely the Braden was implemented in a group of wards after appropriate education and training of staff in addition to mandatory wound care study days. Another group of staff received the same education programme but did not implement the risk assessment scale and a third group carried on with mandatory study days only.\n Nosocomial Pressure Ulcer was reduced in all three groups, but the group that implemented the risk assessment scale showed no significant additional improvement. Allowing for age, gender, medical speciality, level of risk and other factors did not explain this lack of improvement. Clinical judgement seemed to be used by nurses to identify patients at high risk to implement appropriate risk reduction strategies such as use of pressure relieving beds. Clinical judgement was not significantly different from the risk assessment scale score in terms of risk evaluation.\n It is questioned whether the routine use of a risk assessment scale is useful in reducing nosocomial pressure ulcer. It is suggested clinical judgement is as effective as a risk assessment scale in terms of assessing risk (though neither show good sensitivity and specificity) and determining appropriate care.\n Clinical judgement may be as effective as employing a risk assessment scale to assess the risk of pressure ulcers. If this were true it would be simpler and release nursing time for other tasks." ]

[ "14638353", "15842582", "14676594", "12974918", "10994156" ]

[ "Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis.", "A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease.", "Vitamin E treatment in pediatric obesity-related liver disease: a randomized study.", "N-acetylcysteine in the treatment of non-alcoholic steatohepatitis.", "Efficacy and safety of oral betaine glucuronate in non-alcoholic steatohepatitis. A double-blind, randomized, parallel-group, placebo-controlled prospective clinical study." ]

[ "Nonalcoholic steatohepatitis (NASH) is a common cause of liver disease. Although usually indolent, this disease can progress to cirrhosis in some patients. There is currently no proven medical therapy for the treatment of NASH. The aim of our study was to evaluate the efficacy of combination alpha-tocopherol (vitamin E) and vitamin C in reducing histologic inflammation and fibrosis.\n This was a prospective, double-blind, randomized, placebo-controlled trial with a total enrollment of 49 patients; 45 patients completed the study. All patients were randomized to receive either vitamins E and C (1000 IU and 1000 mg, respectively) or placebo daily for 6 months, based on their initial histologic diagnosis of NASH. Additionally, all patients were given standard weight-loss counseling and encouraged to follow a low fat diet (<30 fat g/day). The pre- and posttreatment liver biopsies were reviewed by a single pathologist, who was blinded to the patient's medication. Biopsies were scored based on a modification of the scoring system published by Brunt et al. (Am J Gastroenterol 1999;94:2467-74). A score of 0-4 was possible for fibrosis, and a score of 0-6 was possible for inflammation and hepatocyte degeneration and necrosis. In addition, body mass index, glycohemoglobin, lipids, and liver enzymes were followed throughout the study.\n Forty-five patients completed 6 months of therapy without significant side effects. Vitamin treatment resulted in a statistically significant improvement in fibrosis score (p=0.002). No changes were noted in inflammation with treatment. Vitamin E and vitamin C, in the doses used in this study, were well tolerated and were effective in improving fibrosis scores in NASH patients. No improvement in necroinflammatory activity or ALT was seen with this combination of drug therapy. A larger, multicenter, longer-term trial with vitamin E and vitamin C seems to be warranted.", "Metformin proved useful in the treatment of nonalcoholic fatty liver disease (NAFLD), but its superiority over nutritional treatment and antioxidants has never been demonstrated. We aimed to compare the usefulness of metformin versus prescriptive diet or vitamin E.\n In an open label, randomized trial, nondiabetic NAFLD patients were given metformin (2 g/day; n = 55) for 12 months. The control cases were given either vitamin E (800 IU/day; n = 28) or were treated by a prescriptive, weight-reducing diet (n = 27). Outcome measures were liver enzymes, insulin resistance (homeostasis model assessment), parameters of the metabolic syndrome, and histology.\n Aminotransferase levels improved in all groups, in association with weight loss. The effects in the metformin arm were larger (p < 0.0001), and alanine aminotransferase normalized in 56% of cases (odds ratio (OR) versus. controls, 3.11; 95% confidence interval (CI), 1.56-6.20; p= 0.0013). In multivariate analysis, metformin treatment was associated with higher rates of aminotransferase normalization, after correction for age, gender, basal aminotransferases, and change in body mass index (OR, 5.98; 95% CI, 2.05-17.45). Differences were maintained when the two control groups were separately analyzed. The distribution of positive criteria for the metabolic syndrome was reduced only in the metformin arm (p= 0.001, signed rank test). A control biopsy in 17 metformin-treated cases (14 nonresponders) showed a significant decrease in liver fat (p= 0.0004), necroinflammation, and fibrosis (p= 0.012 for both). No side effects were observed during metformin treatment.\n Metformin treatment is better than a prescriptive diet or vitamin E in the therapy of NAFLD patients receiving nutritional counseling. Limited histological data support an association between improved aminotransferases and biopsy findings, which require confirmation in a double-blind trial with appropriate statistical power based on liver histology.", "A beneficial role of antioxidants in hepatopathic obese individuals has hitherto been inferred only from uncontrolled pilot studies. The authors compared the effect of vitamin E and weight loss on transaminase values and on ultrasonographic bright liver in a controlled group of children with obesity-related liver dysfunction.\n Twenty-eight children with obesity-related hypertransaminasemia and bright liver were randomly allocated to two single-blind groups: group 1 (n = 14) treated with a low-calorie diet associated with oral placebo for 5 months, and group 2 (n = 14) treated with a low-calorie diet associated with oral vitamin E (400 mg/d x 2 months, 100 mg/d x 3 months). Transaminase values and ultrasonographic liver brightness along with weight loss and vitamin E levels were monitored.\n Variations in transaminase levels and percentage of patients with normalized transaminase values were comparable in the two groups. The disappearance of bright liver was observed only in patients who lost weight and was twice as common in patients from group 1. Two subgroups of patients with complete normalization of transaminase values emerged as a consequence of controlled adherence to diet alone (n = 6; significant decrease of percent overweight: P = 0.0019 ) and to vitamin E alone (n = 7; unmodified percent overweight and significant increase of vitamin E/cholesterol ratio: P < 0.0001). Changes in treatment-induced alanine aminotransferase levels in these two subgroups were comparable at month 2, whereas values at month 5 were significantly lower in the subgroup adherent to diet alone (P = 0.04). In the subgroup adherent to vitamin E alone, after 2 months washout, transaminase remained stable in 5 patients and increased in 2; bright liver persisted in all.\n Oral vitamin E warrants consideration in obesity-related liver dysfunction for children unable to adhere to low-calorie diets.", "nan", "In a prospective, randomized, double-blind therapeutic trial, 191 patients with non-alcoholic steatohepatitis were treated for 8 weeks daily b.i.d. orally either with betaine glucuronate combined with diethanolamine glucuronate and nicotinamide ascorbate (Ietepar) (96 patients) or with undistinguishable placebo capsules (95 patients). The verum treatment effectively reduced by 25% hepatic steatosis (p < 0.01) and by 6% hepatomegaly (p < 0.05), while placebo did not significantly reduce the disorders. Verum was also more effective than placebo on discomfort in abdominal upper right quadrant. The global efficacy of treatment was rated by the doctor \"very good\" or \"good\" in 48% of verum treated patients and only in 17% after placcbo (P of difference = 9 x 10(-6)). 52% of patients self-rated efficacy as \"very good\" or \"good\" after verum and only 34% after placebo (P of difference = 0.017). The verum treatment provoked a significant reduction of the increased liver transaminases (ALT, AST and gamma-GT) while placebo was ineffective. Adverse events were recorded in 10% of verum-treated patients and in 7% under placebo (no significant difference). In both groups the adverse events were mild and transient, did not require treatment discontinuation and were undistinguishable from common symptoms of liver disorders. In conclusion, the 8-week treatment with betaine glucuronate combined with diethanolamine glucuronate and nicotinamide ascorbate was found effective in non-alcoholic steatohepatitis, a disorder for which the hitherto pharmacological interventions were poorly and inconsistently effective." ]

[ "6476030", "6849350" ]

[ "Antepartum fetal heart rate testing. XI. Stimulation with orange juice.", "The effect of maternal glucose administration on the specificity of the nonstress test." ]

[ "nan", "To determine whether maternal glucose administration can decrease the incidence of false positive nonstress tests, 296 nonstress tests were performed on 235 high-risk obstetric patients in a prospective controlled study. Patients were alternately given a 50 gm oral glucose drink or an equal volume of water 30 minutes prior to the commencement of each test. Among \"fed\" patients (last meal within 2 hour of the nonstress test) whether receiving glucose or water, and \"fasted\" patients who received glucose, there was no significant difference in the percentage of reactive tests at either 20 minutes (65.2%) or 40 minutes (87.3%) of testing. However, patients fasting and receiving water had a significantly decreased percentage of reactive tests, both at 20 minutes (48.3%, P less than 0.01) and at 40 minutes (76.7%, P less than 0.05). Glucose administered to fasted patients resulted in an increase in the incidence of reactive tests, although this was not statistically significant. Glucose administration had no effect on the nonstress test results when administered to fed patients." ]

[ "19323939", "20668835", "19793927", "20734043", "20434660", "19794165", "19557391", "19509412", "18237696", "20934698", "21610263", "18208432", "15174545", "17560476", "18193194", "21316972" ]

[ "Clinical evaluation of double-bundle anterior cruciate ligament reconstruction procedure using hamstring tendon grafts: a prospective, randomized and controlled study.", "Single-bundle patellar tendon versus non-anatomical double-bundle hamstrings ACL reconstruction: a prospective randomized study at 8-year minimum follow-up.", "Comparison between single-and double-bundle anterior cruciate ligament reconstruction: a prospective, randomized, single-blinded clinical trial.", "A prospective randomised study of anatomical single-bundle versus double-bundle anterior cruciate ligament reconstruction: quantitative evaluation using an electromagnetic measurement system.", "Outcome of arthroscopic single-bundle versus double-bundle reconstruction of the anterior cruciate ligament: a preliminary 2-year prospective study.", "Anterior cruciate ligament reconstruction using autologous hamstring double bundle graft compared with single bundle procedures.", "Double-bundle versus single-bundle ACL reconstruction using the horizontal femoral position: a prospective, randomized study.", "Prospective comparative study of anterior cruciate ligament reconstruction using the double-bundle and single-bundle techniques.", "Prospective randomized comparison of double-bundle versus single-bundle anterior cruciate ligament reconstruction.", "ACL reconstruction in sports active people: transtibial DB technique with ST/G vs. transtibial SB technique with BPTB: preliminary results.", "Double-bundle versus single-bundle anterior cruciate ligament reconstruction: randomized clinical and magnetic resonance imaging study with 2-year follow-up.", "ST/G ACL reconstruction: double strand plus extra-articular sling vs double bundle, randomized study at 3-year follow-up.", "Reconstruction of the anterior cruciate ligament. Single- versus double-bundle multistranded hamstring tendons.", "A prospective randomized study of 4-strand semitendinosus tendon anterior cruciate ligament reconstruction comparing single-bundle and double-bundle techniques.", "Reconstruction of the ACL with a semitendinosus tendon graft: a prospective randomized single blinded comparison of double-bundle versus single-bundle technique in male athletes.", "Evaluation of tibial rotational stability of single-bundle vs. anatomical double-bundle anterior cruciate ligament reconstruction during a high-demand activity - a quasi-randomized trial." ]

[ "In clinical studies there is still a lot of controversy about the increased anterior and rotational stability between double-bundle (DB) and single-bundle (SB) anterior cruciate ligament (ACL) reconstruction. The aim of this study was to evaluate the clinical results of four-tunnel DB ACL reconstruction.\n Sixty-four consecutive patients with ACL ruptures from May 2005 to May 2006 were randomly assigned into two groups: 32 cases for SB ACL reconstruction and 32 cases for DB ACL reconstruction. Clinical data, including KT 2000, Biodex test, Lysholm score, Tegner score and IKDC score, were prospectively collected until at least 10 months post-operative.\n The average values of KT 2000 were (1.47 +/- 1.17) mm and (1.68 +/- 1.14) mm for the SB and DB ACL reconstruction groups at 30 degrees of knee flexion (P > 0.05), and were (1.04 +/- 0.98) mm and (1.13 +/- 0.98) mm at 90 degrees of knee flexion (P > 0.05). There were also no significant differences in Lysholm score, Tegner score, IKDC score and Biodex test scores between the two groups (P > 0.05). The operation time of DB ACL reconstruction was 20 minutes longer than the SB ACL reconstruction (P < 0.05).\n Double bundle ACL reconstructions have no obvious clinical advantages over single bundle ACL reconstructions.", "The purpose of this study was to compare subjective, objective and radiographic outcome of the lateralized single-bundle bone-patellar tendon-bone autograft with a non-anatomical double-bundle hamstring tendons autograft anterior cruciate ligament (ACL) reconstruction technique at long-term follow-up.\n Seventy-nine non-consecutive randomized patients (42 men; 37 women) with unilateral ACL insufficiency were prospectively evaluated, before and after ACL reconstruction by means of the above-mentioned techniques, with a minimum follow-up of 8 years (range 8-10 years; mean 8.6 years). In the double-bundle hamstrings technique, we used one tibial and one femoral tunnel combined with one \"over-the-top\" passage, cortical staple's fixation and we left intact hamstrings' tibial insertion. Patients were evaluated subjectively and objectively, using IKDC score, Tegner level, manual maximum displacement test with KT-2000™ arthrometer. Radiographic evaluation was performed according to IKDC grading system, and re-intervention rate for meniscal lesions was also recorded.\n The subjective and objective IKDC were similar in both groups while double-bundle hamstrings group showed significantly higher Tegner level (P = 0.0007), higher passive range of motion recovery (P = 0.0014), faster sport resumption (P = 0.0052), lower glide pivot-shift phenomenon (P = 0.0302) and lower re-intervention rate (P = 0.0116) compared with patellar tendon group. Radiographic evaluation showed significant lower objective degenerative changes in double-bundle hamstrings group at final follow-up (P = 0.0056).\n Although both techniques provide satisfactory results, double-bundle ACL reconstruction shows better functional results, with a faster return to sport activity, a lower re-operation rate and lower degenerative knee changes.", "Double-bundle ACL reconstruction popularity is increasing with the aim to reproduce native ACL anatomy and improve ACL reconstruction outcome. However, to date, only a few randomized clinical studies have been published.\n The aim of this study was to prospectively compare the clinical results of single- and double-bundle ACL reconstruction.\n Randomized controlled clinical trial; Level of evidence, 1.\n Seventy patients with a chronic unilateral ACL rupture who underwent arthroscopically assisted ACL reconstruction using a hamstring graft were randomized to receive a single- (SB) or double-bundle (DB) reconstruction. Both groups were comparable with regard to preoperative data. A double-incision surgical technique was adopted in both groups. The graft was fixed by looping the hamstring tendons around a bony (DB) or a metallic (SB) bridge on the tibial side and with interference screws reinforced with a staple on the femur. The same rehabilitation protocol was adopted. Outcome assessment was performed by a blinded, independent observer using the visual analog scale (VAS) score, the new International Knee Documentation Committee (IKDC) form, the Knee Injury and Osteoarthritis Outcome Score (KOOS), and KT-1000 arthrometer evaluation.\n All the patients reached a minimum follow-up of 2 years. No differences between the 2 groups were observed in terms of KOOS and IKDC subjective score. A statistically significant difference in favor of the DB group was found with the VAS (P < .03). The objective IKDC final scores showed statistically significantly more \"normal knees\" in the DB group than in the SB group (P = .03). There was 1 stability failure in the DB group and 3 in the SB group. The KT-1000 arthrometer data showed a statistically significant decrease in the average anterior tibial translation in the DB group (1.2 mm DB vs 2.1 mm SB; P < .03). The incidence of a residual pivot-shift glide was 14% in DB and 26% in SB (P = .08).\n In the 2-year minimum follow-up, DB ACL reconstructions showed better VAS, anterior knee laxity, and final objective IKDC scores than SB. However, longer follow-up and accurate instrumented in vivo rotational stability assessment are needed.", "We conducted a prospective randomised study of anatomical single-bundle (A-SB group) versus double-bundle (A-DB group) anterior cruciate ligament (ACL) reconstruction using the hamstrings tendons. Twenty patients with unilateral ACL deficiency were randomised into two groups. We created the bone tunnels at the position of the original insertion of the anteromedial bundle footprint and posterolateral bundle footprint in the A-DB group and at the central position between these two bundles in the A-SB group. All of the patients were tested before ACL reconstruction and one year after surgery. The KT-1000 measurements, isokinetic muscle peak torque and heel-height difference were evaluated and the general knee condition was assessed by Lysholm score. For pre- and postoperative stability assessment, we used the six-degrees-of-freedom of knee kinematic measurement system using an electromagnetic device (the EMS) for quantitative assessment during the Lachman test and the pivot shift test. There were no significant differences in the KT-1000 measurements, isokinetic muscle peak torque, heel-height difference, and Lysholm score at one-year follow-up between these two groups. The EMS data showed there were significant differences in the acceleration of the pivot shift test between the operated knee and the contralateral normal knees in the A-SB group. In conclusion, clinical outcomes were equally good in both groups. However, the EMS data showed the anatomical double-bundle ACL reconstruction tended to be biomechanically superior to the single-bundle reconstruction.", "The purpose of this study was to compare the clinical results of arthroscopic single-bundle and double-bundle anterior cruciate ligament (ACL) reconstruction.\n We designed a prospective study that included patients with an isolated ACL injury. From April 2004 to February 2007, of 147 patients who underwent ACL reconstruction, 113 were included in this study. We serially obtained clinical and radiologic data preoperatively and postoperatively. We compared preoperative data and data at 2 years postoperatively in patients who had undergone single-bundle ACL reconstruction versus patients who had undergone double-bundle ACL reconstruction. There were 50 single-bundle reconstructions and 63 double-bundle reconstructions. Anteroposterior stability was assessed objectively by anterior stress radiographs with the telos device (telos, Marburg, Germany) and the maximal manual test with the KT-2000 arthrometer (MEDmetric, San Diego, CA). Rotational stability was determined by lateral pivot-shift test. The clinical results were assessed by International Knee Documentation Committee and Orthopadische Arbeitsgruppe Knie scores and Tegner activity scale. In addition, we evaluated postoperative thigh circumference and range of motion.\n Residual anteroposterior laxity determined at 2 years postoperatively by telos and KT-2000 was 1.74mm +/- 1.67mm and 1.79mm +/- 1.56mm, respectively, in the single-bundle reconstruction group and 1.63mm +/- 1.50mm and 1.61mm +/- 1.22mm, respectively, in the double-bundle reconstruction group. There were no statistically significant differences. For the lateral pivot-shift test done at 2 years postoperatively, there was no statistically significant difference. In addition, clinical results such as International Knee Documentation Committee score, Orthopadische Arbeitsgruppe Knie score, Tegner activity scale, thigh circumference, and range of motion showed no significant differences between the 2 groups.\n Double-bundle reconstruction of the ACL by a method using 2 femoral tunnel and 2 tibial tunnels showed no differences in stability results or any other clinical aspects or in terms of patient satisfaction.\n Level II, prospective comparative study.", "A total of 218 patients with unilateral anterior cruciate ligament deficiency were randomly assigned to one of four groups. In group A an anatomical double bundle anterior cruciate ligament reconstruction was performed; group B were treated by a single bundle using an Endobutton for femoral fixation; in group C by a single bundle using RigidFix cross pins for femoral fixation; and in group D by a single bundle using a bioabsorbable TransFix II screw for femoral fixation. For tibial fixation a bioabsorbable Intrafix interference screw was used for all the groups and the graft was fashioned from the semitendinosus and gracilis tendons in all patients. In all, 18 patients were lost to follow-up. The remaining 200 were subjected to a clinical evaluation, with assessment of the anterior drawer, Lachman's and the pivot-shift tests, and KT-1000 arthrometer measurement. They also completed the International Knee Documentation Committee, Lysholm knee and Tegner activity scores. At a mean of 29 months (25 to 38) follow-up there were no significant differences concerning time between injury and range of movement and Lysholm knee scores among the four groups. However, the double bundle method showed significantly better results for the pivot-shift test (p = 0.002). The KT 1000 measurements showed a mean difference between the reconstructed knee and the patients' normal knee of 1.4 mm in the double bundle group and 2.4 mm in the single bundle group; which was statistically significant. The Lachman and anterior drawer tests also showed superior results for the double bundle method. The International Knee Documentation Committee scale showed no significant difference among the groups (p < 0.001). On clinical evaluation the double bundle group showed less laxity than the single bundle groups. However, regardless of the technique, all knees were improved by anterior cruciate ligament reconstruction compared with their pre-operative status.", "The aim of this study was to evaluate whether anterior cruciate ligament (ACL) reconstruction using the double bundle technique (DB) improves stability in the knee compared with the single bundle technique (SB) with the femoral tunnel in a more horizontal position (2 or 10 o'clock). We conducted a randomized, prospective study. Forty patients were randomized to the DB group (20 patients) and the SB group (20 patients). Four-stranded semitendinosus and gracilis autologous grafts were used in the SB group and in the DB group the conventional four tunnel technique was carried out using the same tendons. The IKDC complete form was used for the preoperative evaluation, and in the follow-up the IKDC subjective knee evaluation form, IKDC current health assessment form and IKDC knee examination form were used. Anteroposterior (AP) laxity was evaluated by standardised and forced radiology in all patients. No significant preoperative between-group differences were found. During the follow-up, no differences were found between groups, except for significant between-group differences (P < 0.05) between the preoperative and postoperative evaluations. The IKDC index also showed significant differences in the 2-year follow-up. Median scores increased from 48 (range 41-54) to 81 (range 75-87) (P = 0.01) in the SB group and from 52 (range 46-58) to 80 (range 72-88) (P = 0.02) in the DB group. There were no significant differences between the groups in terms of functional scores. In conclusion, the 2 and 10 o'clock placements showed no significant differences between SB and DB techniques in the pivot-shift test, manual and radiological anterior posterior laxity and IKDC scores. However, significant between-group differences were found between the preoperative and postoperative evaluations.", "The intent of double-bundle anterior cruciate ligament reconstruction is to reproduce the normal anterior cruciate ligament anatomy and improve knee joint rotational stability. However, no consensus has been reached on the advantages of this technique over the single-bundle technique.\n We hypothesized that double-bundle anterior cruciate ligament reconstruction could provide better intraoperative stability and clinical outcome than single-bundle reconstruction.\n Cohort study; Level of evidence, 2.\n Forty patients with anterior cruciate ligament injury in one knee were recruited; 20 were allocated to a double-bundle anterior cruciate ligament reconstruction group and 20 to a single-bundle anterior cruciate ligament reconstruction group. Intraoperative stabilities at 30 degrees of knee flexion were compared between the 2 groups using a navigation system. Clinical outcomes including Lysholm knee scores, Tegner activity scores, Lachman and pivot-shift test results, and radiographic stabilities were also compared between the 2 groups after a minimum of 2 years of follow-up.\n Intraoperative anterior and rotational stabilities after anterior cruciate ligament reconstruction in the double-bundle group were significantly better than those in single-bundle group (P = .020 and P < .001, respectively). Nineteen patients (95%) in each group were available at a minimum 2-year follow-up. Clinical outcomes including Lysholm knee and Tegner activity scores were similar in the 2 groups at 2-year follow-up (P > .05). Furthermore, stability results of the Lachman and pivot-shift tests, and radiologic findings at 2-year follow-up failed to reveal any significant intergroup differences (P > .05).\n Although double-bundle anterior cruciate ligament reconstruction produces better intraoperative stabilities than single-bundle anterior cruciate ligament reconstruction, the 2 modalities were found to be similar in terms of clinical outcomes and postoperative stabilities after a minimum of 2 years of follow-up.", "Biomechanical studies show increased anterior and rotational stability with double-bundle (DB) compared to single-bundle (SB) anterior cruciate ligament (ACL) reconstruction. The aim of this study was to evaluate the clinical results of four-tunnel DB ACL reconstruction.\n Seventy patients undergoing arthroscopic hamstring ACL reconstruction were prospectively randomized to DB (n = 35) or SB (n = 35) groups. Each bundle fixation was by means of a femoral EndoButton CL and a tibial biodegradable interference screw. Demographic data were comparable between groups, and the average age of all patients was 29 years. The average follow-up was 19 months for both groups and included a history, clinical evaluation with knee scores, and radiographs.\n The subjective results were similar in groups. The subjective International Knee Documentation Committee (IKDC) 2000 score was 88 P for DB versus 90 P for SB; the Lysholm score was 90 P for DB versus 93 P for SB; and the Cincinnati knee score was 91 P for DB versus 92 P for SB. The objective IKDC was significantly higher for DB: 78% \"A\" (P < .000) and 19% \"B\" compared to 24% \"A\" and 68% \"B\" for SB. The average KT-1000 side-to-side difference was 1.0 mm for DB and 1.6 mm for SB (P = .054) and the pivot shift test was negative in 97% for DB (P = .01) and 71% for SB. The range of motion was comparable for both groups.\n Our study shows a significant advantage in anterior and rotational stability as well as objective IKDC for four-tunnel DB ACL reconstruction compared to SB ACL reconstruction. The subjective Cincinnati knee score, the Lysholm score, and the subjective IKDC 2000 did not show any statistical difference for one or the other technique.\n Level I, randomized controlled trial.", "The single-bundle ACL reconstruction ensures good outcomes and it is a well-established and widespread technique. Nevertheless, some patients still present residual pain and instability. Recent studies have showed that the double-bundle technique restores better natural ACL-fitting kinematics. Long-term clinical studies comparing the two surgical techniques are not frequent and there is no instrument to evaluate function and kinematics during the knee rotation in vivo. In this randomised prospective study performed on sportive people, we compare the BPTB single-bundle ACL reconstruction technique, which is the most common surgical technique performed on these patients' category, with the ACL double-bundle reconstruction technique (DB), in order to evaluate possible differences between the groups. Comparing the two groups, no statistically significant difference regarding the post-operative Lysholm score (p=0.368) the Tegner activity scale (p=0.519) and the arthrometric evaluation with KT-1000 (p=0.74) have been observed. On the contrary, the IKDC evaluation showed a statistically significant difference (p=0.004) better results of the DB group. Moreover, as assessed by the Tegner activity scale, only patients of the DB group were able to return to sports at a pre-injury level. Our data suggest that the double bundle ST/G ACL reconstruction technique results into slightly better outcome than the traditional technique of single-bundle BPTB. The verification and quantification of the advantages of this technique is anticipated with future studies focusing to the accurate measurement of knee rotation during different activities.\n Copyright © 2010 Elsevier Ltd. All rights reserved.", "One aspect of the debate over the reconstruction of the anterior cruciate ligament is whether it should be carried out with the single-bundle or double-bundle technique.\n The double-bundle technique results in fewer graft failures than the single-bundle technique in anterior cruciate ligament reconstruction.\n Randomized controlled trial; Level of evidence, 1.\n A total of 153 patients were prospectively randomized into 2 groups of anterior cruciate ligament reconstruction with hamstring autografts using aperture interference screw fixation: single-bundle technique (SB group, n = 78) and double-bundle technique (DB group, n = 75). The evaluation methods were clinical examination, KT-1000 arthrometric measurement, the International Knee Documentation Committee (IKDC) and the Lysholm knee scores, and magnetic resonance imaging (MRI) evaluation. All of the operations were performed by 1 experienced orthopaedic surgeon, and all clinical assessments were made by 2 blinded and independent examiners. A musculoskeletal radiologist blinded to the clinical data made the MRI interpretation.\n There were no differences between the study groups preoperatively. Ninety percent of patients (n = 138) were available at a minimum 2-year follow-up (range, 24-37 months). Eight patients (7 in the SB group and 1 in the DB group) had graft failure during the follow-up and had anterior cruciate ligament revision surgery (P = .04). In addition, 7 patients (5 in the SB group and 2 in the DB group) had an invisible graft on the MRI assessment at the 2-year follow-up. Also, the anteromedial bundle was partially invisible in 2 patients and the posterolateral bundle in 9 patients. Together, the total number of failures and invisible grafts were significantly higher in the SB group (12 patients, 15%) than the DB group (3 patients, 4%) (P = .024). No significant group differences were found in the knee scores or stability evaluations at the follow-up.\n This 2-year randomized trial showed that the revision rate of the anterior cruciate ligament reconstruction was significantly lower with the double-bundle technique than that with the single-bundle technique. However, additional years of follow-up are needed to reveal the long-term results.", "Several investigators have reported the presence of biomechanical, kinematic, anatomic, fiber orientation patterns and biological differences between the anteromedial bundle and the posterolateral bundle of ACL. The purpose of this prospective randomized study was to compare the clinical, instrumental and X-ray outcome of two ACL reconstruction techniques with hamstring tendons: one with a single intra-articular bundle associated to an extra-articular sling, the second with a more anatomic double-bundle technique that reproduces better the native ACL function. From an initial group of 100 patients who underwent ACL reconstruction, 72 patients (35 single bundle plus lateral plasty and 37 double bundle) were evaluated with IKDC, Tegner score, KT2000 arthrometer, Activity Rating Scale, Psychovitality Questionnaire and Ahlback radiographic score at a mean 3 years follow-up. Double-bundle group showed significantly better results regarding IKDC, ROM, Activity Rating Scale and time to return to sport. Also KT 2000 showed significant differences in objective stability. The double-bundle technique for ACL reconstruction described in this paper has demonstrated significantly better subjective, objective and functional results compared with a double-stranded hamstrings plus extra-articular sling at a minimum 3-year follow-up.", "A total of 108 patients with unilateral instability of the knee, associated with rupture of the anterior cruciate ligament, was prospectively randomised for arthroscopic single- or double-bundle reconstruction of the ligament using hamstring tendons. The same post-operative rehabilitation protocol was used for all. The patients were followed up for a mean of 32 months (24 to 36). We measured the anterior laxity and joint position sense at different angles of flexion of the knee to determine whether both bundles in the double-bundle reconstruction contributed to the stability of the joint and proprioception. No significant difference was found between the two groups with regard to anterior laxity measured by the KT-2000 arthrometer with the knee at 20 degrees or 70 degrees flexion nor with regard to proprioception. A notchplasty was required less often in the double- compared with the single-bundle reconstruction. We did not find any advantage in a double-bundle as opposed to a single-bundle reconstruction in terms of stability or proprioception.", "A randomized clinical study was conducted to compare the outcome between double-bundle (DB) and single-bundle (SB) anterior cruciate ligament (ACL) reconstructions with 4-strand semitendinosus tendon (ST).\n We divided 68 patients with unilateral ACL injury into 2 groups according to their birth date, and they were followed up in person for a mean of 25 months (range, 18 to 41 months). Each group of 34 patients underwent either DB or SB ACL reconstruction using 4-strand ST with EndoButton femoral fixation (Smith & Nephew Endoscopy, Andover, MA) and anchor staple tibial fixation. There was no difference between the 2 groups with regard to age at surgery, sex, follow-up period, period before surgery, combined meniscus injuries, and athletic activity level. All patients followed the same postoperative program. They were evaluated using manual knee laxity tests, instrumented anterior laxity measurements (KT-1000 arthrometer [MEDmetric, San Diego, CA]), knee extension and flexion strength testing, and so on. General knee condition was evaluated by use of the Lysholm knee score and subjective rating scale.\n There were no significant differences between the 2 groups with regard to range of motion, thigh girth, muscle strength, and Lysholm score. Manual knee laxity testing revealed that negative Lachman and pivot-shift test results were found in more patients in the DB group than in the SB group. KT measurements averaged 2.4 mm in the SB group and 1.4 mm in the DB group, which was statistically significantly different. Statistical analysis showed no significant difference regarding all of the modified International Knee Documentation Committee-categorized data between the 2 groups.\n This randomized controlled trial indicated that DB ACL reconstruction via 4-strand ST is superior to the SB technique with regard to anterior and rotational stability; however, it fails to show any subjective difference.\n Level I, prospective randomized controlled clinical study.", "Anterior cruciate ligament (ACL) reconstruction in double-bundle technique is advocated to more closely restore the anatomy and function of the native ligament than conventional single-bundle technique. But up to now there are only a few clinical investigations comparing both techniques in a prospective manner. We hypothesized that double-bundle ACL reconstruction reveals superior clinical and subjective results compared to single-bundle technique in a high-demand collective. A total of 50 male patients (mean age 29.4 years) were prospectively randomized consecutively into one of the two reconstruction techniques. Group 1 (SB) underwent a 4-stranded single-bundle reconstruction with a ST graft in femoral position at 10:00 and 02:00 o'clock, respectively. In group 2 (DB), reconstruction was performed by using a 2-stranded ST graft with double-bundle, four tunnel technique. Before surgery and at a 2 year follow-up (range 23-25 months) patients were evaluated by the same blinded observer. There was no significant difference in the side-to-side anterior laxity-measurement with the KT-1000 between both groups. As evaluated by the pivot shift, no significant correlation could be noted (Fisher exact test P = 0.098) between rotational stability and any of the both reconstruction techniques. However, the anterior and rotational stability improved significantly at 2-year follow-up compared to preoperatively (P = 0.003) in both groups. The statistical analysis showed a significant increase for the IKDC (subjective, objective) and the Lysholm Score at final follow-up among each single technique, while we found no significant difference between the two reconstruction methods. On the basis of our investigation, we conclude that reconstruction of the ACL by a double-bundle ST graft with an extracortical anchorage can achieve excellent clinical results. But in contrast to our initial hypothesis, we could not quote any significant advantages by creating two independent bundles. Reconstruction of the anterior cruciate ligament in conventional single-bundle technique with a more horizontal femoral tunnel placement obtains comparable clinical results in the present high-demand collective.", "The purpose of this study was to compare the tibial rotational stability of anatomical double-bundle anterior cruciate ligament reconstructed knees with single-bundle anterior cruciate ligament reconstructed knees during a high-demand activity. Total of 66 subjects, (22 with double-bundle anterior cruciate ligament reconstruction, 22 with single-bundle anterior cruciate ligament reconstruction, and 22 healthy control individuals) were examined in this study. Using a 9-camera motion analysis system, motion subjects were recorded performing during a drop landing and cutting. Using the point cluster technique, the internal-external tibial rotation of both knees was calculated. The mean maximum range of motion for each knee was evaluated for 3 groups (double-bundle group, single-bundle group, and control group). Clinical assessment, including Tegner score, Lysholm score, and knee arthrometric measurement, revealed restoration of the reconstructed knee stability with no differences between the two anterior cruciate ligament reconstruction groups. The results showed that both groups resulted in tibial rotation values that were significantly smaller than those in the intact legs and those in the healthy controls. There were no significant differences in tibial rotation between the DB group and the SB group. Therefore anatomical double-bundle reconstruction restores normal tibial rotation no more than single-bundle reconstruction during this high-demand dynamic activity. These results suggest a trend towards dynamic overcorrection after the ACL reconstruction.\n Copyright © 2010 Elsevier B.V. All rights reserved." ]

[ "16478899", "16291982", "15836887" ]

[ "Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial.", "Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia.", "Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study." ]

[ "Rimonabant, a selective cannabinoid-1 receptor blocker, may reduce body weight and improve cardiometabolic risk factors in patients who are overweight or obese.\n To compare the efficacy and safety of rimonabant with placebo each in conjunction with diet and exercise for sustained changes in weight and cardiometabolic risk factors over 2 years.\n Randomized, double-blind, placebo-controlled trial of 3045 obese (body mass index > or =30) or overweight (body mass index >27 and treated or untreated hypertension or dyslipidemia) adult patients at 64 US and 8 Canadian clinical research centers from August 2001 to April 2004.\n After a 4-week single-blind placebo plus diet (600 kcal/d deficit) run-in period, patients were randomized to receive placebo, 5 mg/d of rimonabant, or 20 mg/d of rimonabant for 1 year. Rimonabant-treated patients were rerandomized to receive placebo or continued to receive the same rimonabant dose while the placebo group continued to receive placebo during year 2.\n Body weight change over year 1 and prevention of weight regain during year 2. Additional efficacy measures included changes in waist circumference, plasma lipid levels, and other cardiometabolic risk factors.\n At year 1, the completion rate was 309 (51%) patients in the placebo group, 620 (51%) patients in the 5 mg of rimonabant group, and 673 (55%) patients in the 20 mg of rimonabant group. Compared with the placebo group, the 20 mg of rimonabant group produced greater mean (SEM) reductions in weight (-6.3 [0.2] kg vs -1.6 [0.2] kg; P<.001), waist circumference (-6.1 [0.2] cm vs -2.5 [0.3] cm; P<.001), and level of triglycerides (percentage change, -5.3 [1.2] vs 7.9 [2.0]; P<.001) and a greater increase in level of high-density lipoprotein cholesterol (percentage change, 12.6 [0.5] vs 5.4 [0.7]; P<.001). Patients who were switched from the 20 mg of rimonabant group to the placebo group during year 2 experienced weight regain while those who continued to receive 20 mg of rimonabant maintained their weight loss and favorable changes in cardiometabolic risk factors. Use of different imputation methods to account for the high rate of dropouts in all 3 groups yielded similar results. Rimonabant was generally well tolerated; the most common drug-related adverse event was nausea (11.2% for the 20 mg of rimonabant group vs 5.8% for the placebo group).\n In this multicenter trial, treatment with 20 mg/d of rimonabant plus diet for 2 years promoted modest but sustained reductions in weight and waist circumference and favorable changes in cardiometabolic risk factors. However, the trial was limited by a high drop-out rate and longer-term effects of the drug require further study. Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00029861.", "Rimonabant, a selective cannabinoid-1 receptor (CB1) blocker, has been shown to reduce body weight and improve cardiovascular risk factors in obese patients. The Rimonabant in Obesity-Lipids (RIO-Lipids) study examined the effects of rimonabant on metabolic risk factors, including adiponectin levels, in high-risk patients who are overweight or obese and have dyslipidemia.\n We randomly assigned 1036 overweight or obese patients (body-mass index [the weight in kilograms divided by the square of the height in meters], 27 to 40) with untreated dyslipidemia (triglyceride levels >1.69 to 7.90 mmol per liter, or a ratio of cholesterol to high-density lipoprotein [HDL] cholesterol of >4.5 among women and >5 among men) to double-blinded therapy with either placebo or rimonabant at a dose of 5 mg or 20 mg daily for 12 months in addition to a hypocaloric diet.\n The rates of completion of the study were 62.6 percent, 60.3 percent, and 63.9 percent in the placebo group, the group receiving 5 mg of rimonabant, and the group receiving 20 mg of rimonabant, respectively. The most frequent adverse events resulting in discontinuation of the drug were depression, anxiety, and nausea. As compared with placebo, rimonabant at a dose of 20 mg was associated with a significant (P<0.001) mean weight loss (repeated-measures method, -6.7+/-0.5 kg, and last-observation-carried-forward analyses, -5.4+/-0.4 kg), reduction in waist circumference (repeated-measures method, -5.8+/-0.5 cm, and last-observation-carried-forward analyses, -4.7+/-0.5 cm), increase in HDL cholesterol (repeated-measures method, +10.0+/-1.6 percent, and last-observation-carried-forward analyses, +8.1+/-1.5 percent), and reduction in triglycerides (repeated-measures method, -13.0+/-3.5 percent, and last-observation-carried-forward analyses, -12.4+/-3.2 percent). Rimonabant at a dose of 20 mg also resulted in an increase in plasma adiponectin levels (repeated-measures method, 57.7 percent, and last-observation-carried-forward analyses, 46.2 percent; P<0.001), for a change that was partly independent of weight loss alone.\n Selective CB1-receptor blockade with rimonabant significantly reduces body weight and waist circumference and improves the profile of several metabolic risk factors in high-risk patients who are overweight or obese and have an atherogenic dyslipidemia.\n Copyright 2005 Massachusetts Medical Society.", "In animal models, cannabinoid-1 receptor (CB1) blockade produces a lean phenotype, with resistance to diet-induced obesity and associated dyslipidaemia. We assessed the effect of rimonabant, a selective CB1 blocker, on bodyweight and cardiovascular risk factors in overweight or obese patients.\n patients with body-mass index 30 kg/m2 or greater, or body-mass index greater than 27 kg/m2 with treated or untreated dyslipidaemia, hypertension, or both, were randomised to receive double-blind treatment with placebo, 5 mg rimonabant, or 20 mg rimonabant once daily in addition to a mild hypocaloric diet (600 kcal/day deficit). The primary efficacy endpoint was weight change from baseline after 1 year of treatment in the intention-to-treat population.\n Weight loss at 1 year was significantly greater in patients treated with rimonabant 5 mg (mean -3.4 kg [SD 5.7]; p=0.002 vs placebo) and 20 mg (-6.6 kg [7.2]; p<0.001 vs placebo) compared with placebo (-1.8 kg [6.4]). Significantly more patients treated with rimonabant 20 mg than placebo achieved weight loss of 5% or greater (p<0.001) and 10% or greater (p<0.001). Rimonabant 20 mg produced significantly greater improvements than placebo in waist circumference, HDL-cholesterol, triglycerides, and insulin resistance, and prevalence of the metabolic syndrome. The effects of rimonabant 5 mg were of less clinical significance. Rimonabant was generally well tolerated with mild and transient side effects.\n CB1 blockade with rimonabant 20 mg, combined with a hypocaloric diet over 1 year, promoted significant decrease of bodyweight and waist circumference, and improvement in cardiovascular risk factors." ]

[ "15798461", "15325681" ]

[ "Glutamine supplementation of parenteral nutrition does not improve intestinal permeability, nitrogen balance, or outcome in newborns and infants undergoing digestive-tract surgery: results from a double-blind, randomized, controlled trial.", "Glutamine supplementation in infants with gastrointestinal disease: a randomized, placebo-controlled pilot trial." ]

[ "To assess the effect of isocaloric isonitrogenous parenteral glutamine supplementation on intestinal permeability and nitrogen loss in newborns and infants after major digestive-tract surgery.\n Glutamine supplementation in critically ill and surgical adults may normalize intestinal permeability, attenuate nitrogen loss, improve survival, and lower the incidence of nosocomial infections. Previous studies in critically ill children were limited to very-low-birthweight infants and had equivocal results.\n Eighty newborns and infants were included in a double-blind, randomized trial comparing standard parenteral nutrition (sPN; n = 39) to glutamine-supplemented parenteral nutrition (GlnPN; glutamine target intake, 0.4 g kg day; n = 41), starting on day 2 after major digestive-tract surgery. Primary endpoints were intestinal permeability, as assessed by the urinary excretion ratio of lactulose and rhamnose (weeks 1 through 4); nitrogen balance (days 4 through 6), and urinary 3-methylhistidine excretion (day 5). Secondary endpoints were mortality, length of stay in the ICU and the hospital, number of septic episodes, and usage of antibiotics and ICU resources.\n Glutamine intake plateaued at 90% of the target on day 4. No differences were found between patients assigned sPN and patients assigned GlnPN regarding any of the endpoints. Glutamine supplementation was not associated with adverse effects.\n In newborns and infants after major digestive-tract surgery, we did not identify beneficial effects of isonitrogenous, isocaloric glutamine supplementation of parenteral nutrition. Glutamine supplementation in these patients therefore is not warranted until further research proves otherwise.", "Glutamine (Gln) is a non-essential amino acid that plays an important role in energy metabolism for gastrointestinal epithelia and other cells with rapid turnover. We evaluated the effects of enteral supplementation with Gln in infants undergoing surgery for congenital or acquired gastrointestinal disease.\n This was a randomized, double-masked, controlled clinical trial.\n Twenty infants were randomly assigned to receive Gln (n = 9) or placebo amino acid (n = 11), with a goal of supplemental amino acid intake of 0.4 g.kg(-1).d(-1). Infants were weaned from parenteral nutrition, and enteral feeds were started according to a standardized feeding protocol. Median (interquartile range) durations of parenteral nutrition were 39 d (12 to 99) in the Gln group and 21 d (6 to 59) in the control group (P = 0.201). Median (interquartile range) durations needed to reach 80% of the US recommended dietary allowance for energy with enteral nutrition were 24 d (8 to 55) in the Gln group and 12.5 d (5 to 32) in the control group (P = 0.313). There were no differences in the occurrence of infections between groups. Among all infants enrolled, significant correlations were found between duration of parenteral nutrition and residual small bowel length, peak concentrations of direct bilirubin, and alanine aminotransferase. Peak direct bilirubin was associated with longer duration of parenteral nutrition, shorter gestation, older age before feeds were started, shorter bowel length, and larger amounts of parenteral energy and protein intake.\n In this pilot trial, enteral Gln supplementation was well tolerated among infants with surgical gastrointestinal disease. There was no effect observed on the duration of parenteral nutrition, tolerance of enteral feeds, or intestinal absorptive or barrier function. Larger, multicenter trials in infants with surgical gastrointestinal disease are needed due to the variability in important outcome measurements." ]

[ "16186525", "10873185", "19477503", "7072559" ]

[ "Prevention of venous thrombosis in patients with acute intracerebral hemorrhage.", "Randomized trial of graded compression stockings for prevention of deep-vein thrombosis after acute stroke.", "Effectiveness of thigh-length graduated compression stockings to reduce the risk of deep vein thrombosis after stroke (CLOTS trial 1): a multicentre, randomised controlled trial.", "Incidence of deep vein thrombosis and the effect of pneumatic compression of the calf in elderly hemiplegics." ]

[ "To assess intermittent pneumatic compression (IPC) in the prevention of venous thromboembolism (VTE).\n The authors randomly allocated patients with a documented intracerebral hemorrhage (ICH) to elastic stockings (ES) alone or combined with IPC. The primary outcome was a combined criteria assessed at day 10: a symptomatic and well-documented VTE, or a death arising before day 10 and related to pulmonary embolism (PE), or an asymptomatic deep vein thrombosis (DVT) of the lower limbs detected by compression ultrasonography (CUS). Outcome assessment was blinded.\n One hundred fifty-one patients were randomized; 133 (88%) patients were evaluated at day 10. No clinical suspicion of VTE arose before day 10. Fourteen patients died before having a CUS but no death was definitely related to PE. Fourteen asymptomatic DVT were detected by CUS: three (4.7%) in the ES + IPC group (all distal) and 11 (15.9%) in the ES group (three proximal and eight distal). ES combined with IPC is associated with a reduced risk of asymptomatic DVT compared to ES alone: relative risk, 0.29 (95% CI 0.08 to 1.00).\n Asymptomatic deep vein thrombosis (DVT) was detected at day 10 in 15.9% of patients wearing elastic stockings alone. Intermittent pneumatic compression significantly decreased the occurrence of asymptomatic DVT for patients with intracerebral hemorrhage.", "Graded compression stockings are commonly used to prevent deep-vein thrombosis (DVT) after stroke, but their efficacy in this setting has not been evaluated. Extrapolation of effectiveness from trials in patients undergoing elective surgery may be inappropriate. We undertook a randomized, controlled trial, with blinded data review, in a University hospital Acute Stroke Unit. Patients were allocated to graded compression stockings or to standard care alone. DVT incidence was determined at baseline and at day 7+/-2 by colour-flow Doppler ultrasound. Ninety-eight patients with acute, immobilizing stroke were randomized; 97 had full outcome data. One patient had clinically manifest DVT, and no patient had pulmonary thromboembolism. DVT was detected in 7/65 patients allocated stockings, and 7/32 controls (odds ratio 0.43, 95% CI 0.14-1.36); DVT involving femoral veins was detected in 3/65 and 2/32. In the first week after stroke, radiologically-detected DVT remains common, but is usually clinically silent. Proximal DVT is less common. Graded compression stockings produced a reduction in DVT incidence comparable to that in other patient groups, but the reduction was not statistically significant, and the magnitude of effect size requires confirmation. There is greater doubt over efficacy in early prevention of proximal DVT.", "Deep vein thrombosis (DVT) and pulmonary embolism are common after stroke. In small trials of patients undergoing surgery, graduated compression stockings (GCS) reduce the risk of DVT. National stroke guidelines extrapolating from these trials recommend their use in patients with stroke despite insufficient evidence. We assessed the effectiveness of thigh-length GCS to reduce DVT after stroke.\n In this outcome-blinded, randomised controlled trial, 2518 patients who were admitted to hospital within 1 week of an acute stroke and who were immobile were enrolled from 64 centres in the UK, Italy, and Australia. Patients were allocated via a central randomisation system to routine care plus thigh-length GCS (n=1256) or to routine care plus avoidance of GCS (n=1262). A technician who was blinded to treatment allocation undertook compression Doppler ultrasound of both legs at about 7-10 days and, when practical, again at 25-30 days after enrolment. The primary outcome was the occurrence of symptomatic or asymptomatic DVT in the popliteal or femoral veins. Analyses were by intention to treat. This study is registered, number ISRCTN28163533.\n All patients were included in the analyses. The primary outcome occurred in 126 (10.0%) patients allocated to thigh-length GCS and in 133 (10.5%) allocated to avoid GCS, resulting in a non-significant absolute reduction in risk of 0.5% (95% CI -1.9% to 2.9%). Skin breaks, ulcers, blisters, and skin necrosis were significantly more common in patients allocated to GCS than in those allocated to avoid their use (64 [5%] vs 16 [1%]; odds ratio 4.18, 95% CI 2.40-7.27).\n These data do not lend support to the use of thigh-length GCS in patients admitted to hospital with acute stroke. National guidelines for stroke might need to be revised on the basis of these results.\n Medical Research Council (UK), Chief Scientist Office of Scottish Government, Chest Heart and Stroke Scotland, Tyco Healthcare (Covidien) USA, and UK Stroke Research Network.", "nan" ]

[ "15043519", "19285598", "2691239", "10798755", "17234504", "22027191", "9393270", "3142949", "8748357", "10553972", "20698232", "3092894", "1909085", "9073135", "7969324", "8455312", "11023085", "2119446", "1727754", "20005375", "3082733", "20602497", "12679945", "3307390", "20887332", "3932509", "2105256" ]

[ "Long-term oral branched chain amino acids in patients undergoing chemoembolization for hepatocellular carcinoma: a randomized trial.", "A snack enriched with oral branched-chain amino acids prevents a fall in albumin in patients with liver cirrhosis undergoing chemoembolization for hepatocellular carcinoma.", "Nutritional support in hospitalized patients with alcoholic liver disease.", "A prospective randomized study of preoperative nutritional supplementation in patients awaiting elective orthotopic liver transplantation.", "BCAA-enriched snack improves nutritional state of cirrhosis.", "Effect of preoperative immunonutrition in patients undergoing hepatectomy; a randomized controlled trial.", "Long-term oral administration of branched chain amino acids after curative resection of hepatocellular carcinoma: a prospective randomized trial. The San-in Group of Liver Surgery.", "A randomized controlled study of peripheral parenteral nutrition in moderate and severe alcoholic hepatitis.", "Early enteral nutrition support in patients undergoing liver transplantation.", "Prospective randomized control study on the effect of branched-chain amino acids in patients with liver resection for hepatocellular carcinoma.", "Prospective randomized controlled study of short-term perioperative oral nutrition with branched chain amino acids in patients undergoing liver surgery.", "Hyperalimentation of jaundiced patients on percutaneous transhepatic biliary drainage.", "A randomized, controlled trial of treatment of alcoholic hepatitis with parenteral nutrition and oxandrolone. I. Short-term effects on liver function.", "Early feeding or enteral nutrition in patients with cirrhosis after bleeding from esophageal varices? A randomized controlled study.", "Perioperative nutritional support in patients undergoing hepatectomy for hepatocellular carcinoma.", "Controlled trial on nutrition supplementation in outpatients with symptomatic alcoholic cirrhosis.", "Short-term effects of branched-chain amino acids on liver function tests in cirrhotic patients.", "Nutritional support after liver transplantation: a randomized prospective study.", "Accelerated improvement of alcoholic liver disease with enteral nutrition.", "Nutrition support with glutamine dipeptide in patients undergoing liver transplantation.", "A randomized clinical trial of supplementary parenteral nutrition in jaundiced alcoholic cirrhotic patients.", "Randomized clinical trial of laxatives and oral nutritional supplements within an enhanced recovery after surgery protocol following liver resection.", "The influence of Enteral Nutrition in postoperative patients with poor liver function.", "A prospective randomized clinical trial of peripheral amino acid-glucose supplementation in acute alcoholic hepatitis.", "Effect of an oral branched chain amino acid-enriched snack in cirrhotic patients with sleep disturbance.", "Controlled trial of nutritional supplementation, with and without branched chain amino acid enrichment, in treatment of acute alcoholic hepatitis.", "Effect of total enteral nutrition on the short-term outcome of severely malnourished cirrhotics. A randomized controlled trial." ]

[ "Patients undergoing transarterial chemoembolization for hepatocellular carcinoma have advanced tumour or severe cirrhosis and frequently have associated protein-calorie malnutrition. The role of nutritional supplements for such patients is unclear.\n To investigate, in a randomized controlled trial, any benefit of the long-term administration of branched chain amino acids in patients undergoing chemoembolization for hepatocellular carcinoma.\n Forty-one patients received oral branched chain amino acids for up to four courses of chemoembolization and 43 patients did not receive any nutritional supplement. Morbidity, liver function, nutritional status, quality of life and long-term survival were compared between the two groups.\n The administration of branched chain amino acids resulted in a lower morbidity rate compared with the control group (17.1% vs. 37.2%, P = 0.039). In particular, the group given branched chain amino acids showed a significantly lower rate of ascites (7.3% vs. 23.2%, P = 0.043) and peripheral oedema (9.8% vs. 27.9%, P = 0.034). Significantly higher serum albumin, lower bilirubin and a better quality of life were observed after chemoembolization in the group given branched chain amino acids. However, there was no significant difference in survival between the two groups.\n Nutritional supplementation with oral branched chain amino acids is beneficial in increasing the serum albumin level, reducing the morbidity and improving the quality of life in patients undergoing chemoembolization for inoperable hepatocellular carcinoma.", "Nutritional support may play an important role in management of liver cirrhosis (LC) associated with unresectable hepatocellular carcinoma (HCC). Total protein and albumin deteriorate in patients with LC undergoing trans-arterial chemoembolization (TACE). Therefore, in this study, we examined the hypothesis that short-term administration of branched-chain amino acids (BCAA) will prevent a fall in total protein and albumin in the perioperative period. The subjects were 56 patients who underwent TACE for HCC between 2004 and 2005 at Nagasaki University Hospital. The patients were randomly placed in the BCAA group (n = 28) or a control group (n = 28). The patients in the BCAA group consumed a snack containing 50 g of BCAA once a day at 10:00 pm starting 1 day before TACE and continuing until 2 weeks after TACE. A comparison of baseline and end point data showed greater decreases in the concentrations of total protein, albumin, cholinesterase, and total cholesterol and in the red blood cell count in the control group compared to the BCAA group. Ammonia levels decreased in the BCAA group and increased in the control group. Our findings indicate that a BCAA supplement taken orally as a late evening snack prevents suppression of liver function by TACE in patients with LC complicated with HCC during the 2-week period after TACE.", "The effects of a nutritional support in hospitalized patients with alcoholic cirrhosis and liver failure were studied in a controlled protocol. Thirty-six patients were included, 17 were randomly assigned to an experimental group and the rest to a control group. Experimentals received a diet aiming at 50 kcal (209 kJ)/kg bodyweight/d and 1.5 g protein/kg bodyweight/d (as proteins of high biological value). Controls received the standard diet prescribed by the attending physician. The severity of liver failure and the nutritional status on admission were similar in both groups. The measured energy intake in controls was 1813 +/- 121 kcal/d (7589 +/- 506 kJ/d) and 2707 +/- 71 kcal/d (1131 +/- 297 kJ/d) in experimentals (P less than 0.001). The protein intake in controls was 47 +/- 3.8 g/d and in experimentals 80 +/- 3 g/d (P less than 0.001). There were seven deaths during the study period (two experimentals and five controls). No differences were observed in the evolution of liver failure, hepatic encephalopathy or nutritional status between both study groups. It is concluded that a higher energy and protein intake in these patients does not have adverse effects and is associated with a non-significant reduction in mortality.", "Poor nutritional status is common among patients awaiting orthotopic liver transplantation and is associated with poor outcome.\n This prospective randomized controlled trial examined the effect of pretransplant nutritional supplementation on the outcome of patients undergoing liver transplantation. Of 82 consecutive patients with mid-arm muscle circumference <25th percentile, 42 received enteral supplementation, and the remainder acted as the control group. The supplemented group received a calorie-dense enteral feed taken daily (in addition to diet) until transplantation. Nutritional status was monitored by upper arm anthropometric measurements and handgrip strength. Dietary intake was calculated from 5-day food diaries.\n Supplementation improved mid-arm circumference, mid-arm muscle circumference, and grip strength. Pretransplant nutritional status was not associated with posttransplant sepsis or major complications. Preoperative grip strength of <85% of normal values was predictive of increased incidence of posttransplant major complications. Supplementation did not affect outcome, although there were more deaths in the control group (seven deaths before and two deaths after transplant) than there were in the supplemented group (two deaths before and three deaths after transplant). There was no difference in overall survival (P = 0.075).\n Enteral supplementation improved some parameters of nutritional status pretransplant. Dietary intake of patients in the two groups was similar at transplant. Nutritional supplementation has not increased nutritional intake, although this may reflect the importance of regular dietetic input and support, rather than suggesting that nutritional supplementation is ineffective. Supplementation had no effect on outcome of liver transplantation.", "A late evening snack improves the catabolic state in patients with advanced liver cirrhosis. We tested whether long-term (3 mo) late evening snacking that included a branched-chain amino acid (BCAA)-enriched nutrient mixture produces a better nutritional state and better quality of life than ordinary food in patients with hepatitis C virus-positive liver cirrhosis.\n In a multicenter, randomized study, 48 patients with liver cirrhosis received late-evening supplementation with the BCAA-enriched nutrient mixture or ordinary food, such as a rice ball or bread, for 3 mo. During the study period, each patient was instructed on energy and protein intake. Blood biochemical data, nitrogen balance, respiratory quotient, and health-related quality of life (Short Form 36 questionnaire) were evaluated at baseline and at the end of the study.\n Total and late-evening energy intakes were similar in the two groups at 3 mo. Serum albumin level, nitrogen balance, and respiratory quotient were significantly improved by the BCAA mixture but not by ordinary food. The parameters of the Short Form 36 did not statistically significantly improve over 3 mo in either group.\n Long-term oral supplementation with a BCAA mixture is better than ordinary food in a late evening snack at improving the serum albumin level and the energy metabolism in patients with cirrhosis.", "No consensus has been reached concerning the effects of preoperative immunonutrition in patients undergoing hepatectomy. We evaluated the effects of immunonutrition before hepatectomy on perioperative management. This study was performed as a randomized controlled trial. Patients expected to undergo segmentectomy or more extensive hepatectomy for liver tumors were randomized to immunonutrition (IM) and control (C) groups each consisting of 13 patients. The IM group was given 750 ml of IMPACT in addition to half-size hospital meals orally from 5 days before to the day before surgery, and the C group was given conventional hospital meals. The blood level of eicosapentaenoic acid was elevated preoperatively in all patients of the IM group. The white blood cell count and interleukin 6 levels, which are indices of postoperative inflammation, were significantly lower in the IM group. As regards liver function, postoperative increases in the aspartate aminotransferase and alanine aminotransaminase levels were slightly suppressed in the IM group. No significant difference was noted in postoperative complications or duration of postoperative hospital stay. In patients undergoing hepatectomy, preoperative immunonutrition reduced inflammation and protected against liver dysfunction.", "Live cirrhosis is a state of protein calorie malnutrition which may induce various complications. This study aimed to elucidate if long-term nutritional support with branched chain amino acids (BCAAs) is effective after hepatic resection for hepatocellular carcinoma (HCC).\n Between 2 and 3 weeks after operation, 75 patients were randomized to receive oral BCAAs (Aminoleban EN) 100 g per day for 1 year, and another 75 patients were assigned to a control group. Mean follow-up times were 35.8 months and 36.0 months respectively.\n Flapping tremor was less common, body-weight was greater and performance status was better in the BCAA-treated group throughout the 1-year period. BCAA treatment significantly increased red blood cell and serum albumin level in patients with Child grade B and C disease. Substantially similar effects were observed in those with major hepatic resection. Higher Fischer molar ratios were maintained in the treated group. However, there were no differences in cumulative tumour recurrence and survival rates.\n Long-term oral nutritional support with BCAAs after resection of HCC is beneficial in improving clinical features and laboratory data without increasing the rate of tumour recurrence, particularly in patients with advanced cirrhosis or after major hepatic resection.", "We performed a controlled trial of peripheral hyperalimentation in moderate and severe alcoholic hepatitis to determine whether improvement in survival and liver function could be obtained. Twelve patients with moderate and 22 with severe alcoholic hepatitis were randomized to 28 days of peripheral parenteral nutrition (PPN) or standard therapy (ST). In the moderate group, six were treated with each therapy. In the severe group, 10 were treated with PPN and 12 with ST. Routine liver tests, hepatocyte function (galactose elimination capacity), estimated hepatic blood flow (galactose clearance) and assessment of ascites and encephalopathy were performed at randomization and at 28 days. Groups were equally matched at randomization. In the moderate group PPN produced no improvement in morbidity (liver tests) and mortality (no deaths). In the severe group there were seven deaths (4 PPN, 3 ST). PPN produced greater improvement than ST in serum bilirubin and transferrin concentrations and a trend toward greater improvement in prothrombin time, serum albumin and galactose elimination capacity. PPN had no deleterious effect on encephalopathy or ascites as only ST patients developed ascites or encephalopathy after randomization. We conclude that PPN compared to ST (1) provides no benefit in moderate alcoholic hepatitis, but (2) did more rapidly improve morbidity (liver tests) and probably liver function in severe alcoholic hepatitis; (3) PPN did not improve early mortality, and (4) it had no deleterious effect on encephalopathy or ascites.", "The purpose of this study was to determine the effects of early postoperative tube feeding on outcomes of liver transplant recipients.\n Fifty transplant patients were randomized prospectively to receive enteral formula via nasointestinal feeding tubes (tube-feeding [TF] group) or maintenance i.v. fluid until oral diets were initiated (control group). Thirty-one patients completed the study. Resting energy expenditure, nitrogen balance, and grip strength were measured on days 2, 4, 7, and 12 after liver transplantation. Calorie and protein intakes were calculated for 12 days posttransplant.\n Tube feeding was tolerated in the TF group (n = 14). The TF patients had greater cumulative 12-day nutrient intakes (22,464 +/- 3554 kcal, 927 +/- 122 g protein) than did the control patients (15,474 +/- 5265 kcal, 637 +/- 248 g protein) (p < .002). Nitrogen balance was better in the TF group on posttransplant day 4 than in the control group (p < .03). There was a rise in the overall mean resting energy expenditure in the first two posttransplant weeks from 1487 +/- 338 to 1990 +/- 367 kcal (p = .0002). Viral infections occurred in 17.7% of control patients compared with 0% of TF patients (p = .05). Although other infections tended to occur more frequently in the control group vs the TF group (bacterial, 29.4% vs 14.3%; overall infections, 47.1% vs 21.4%), these differences were not statistically significant. Early posttransplant tube feeding did not influence hospitalization costs, hours on the ventilator, lengths of stay in the intensive care unit and hospital, rehospitalizations, or rejection during the first 21 posttransplant days.\n Early posttransplant tube feeding was tolerated and promoted improvements in some outcomes and should be considered for all liver transplant patients.", "Aminoleban EN contains branched-chain amino acids (BCAA) and is known to be beneficial for the protein-energy malnutrition in cirrhotic patients. Patients suffering from hepatocellular carcinoma often have background cirrhosis, and the present study investigates the effect of Aminoleban EN on these patients after hepatic resection for the primary disease.\n A prospective randomized controlled clinical trial, to which 50 patients were recruited, was carried out. The study group received Aminoleban EN in addition to normal diet for 12 weeks and the control group received an isonitrogenous and isocaloric diet only.\n After exclusions, there were 21 patients in the study group and 23 patients in the control. The study group had a shorter hospital stay, and had a significantly higher haemoglobin level, higher sodium level, higher albumin level and lower bilirubin during the postoperative course. There was no significant difference in terms of neuropsychiatric symptoms or Karnofsky performance score. There was no difference in gastrointestinal symptoms or other signs. No adverse reaction was associated with the administration of Aminoleban, and there was no significant difference in terms of morbidity and mortality between the two groups of patients.\n Aminoleban EN is safe to administer and does not have significant adverse effects. It contributes to a shorter hospital stay and quicker improvement of liver function in the early postoperative period. These beneficial results require only a 12-week period of administration of BCAA after operation.", "Early prospective randomized clinical trials demonstrated that perioperative parenteral nutrition (PN) with branched chain amino acids (BCAA) is beneficial in cirrhotic patients with hepatocellular carcinoma who undergo hepatectomy. However, PN support is expensive and requires a long hospital stay. Moreover, PN support has not been evaluated in patients with a normal liver who undergo hepatectomy. It was studied the benefits of perioperative oral nutrition (ON) with BCAA in patients who underwent hepatectomy, including those with a non-hepatitis liver.\n In this prospective, randomized, controlled trial, 38 patients were assessed for eligibility. Fourteen patients were excluded because they had received intraoperative blood transfusions or incomplete resections. The 24 eligible patients (20 with malignant liver tumors and 4 with benign liver tumors) were randomly assigned to receive perioperative ON with BCAA (11 patients, BCAA group) or a usual diet (13 patients, control group). The BCAA group received a BCAA supplement twice daily plus a usual diet for 14 days before operation and on days 1 to 7 after operation. The control group received a usual diet alone. The primary end point was the improvement in postoperative biochemical measurements.\n Two of the 11 patients in the BCAA group developed postoperative complications, as compared with 3 of the 13 patients in the control group (18.2% vs. 23.1%, p = 0.7686). Serum levels of alanine aminotransferase, aspartate aminotransferase, and ammonia did not differ significantly between the BCAA group and control group; however, peak values were lower in the BCAA group. There was no difference between the groups in serum hemoglobin levels after operation. Among patients with hepatitis, serum erythropoietin (EPO) levels on POD 3, 5, and 7 were slightly but not significantly higher in the BCAA group than in the control group. Among patients with non-hepatitis, serum EPO levels on POD 3, 5, and 7 were significantly higher in the BCAA group than in the control group (p = 0.0174, p = 0.0141, and p = 0.0328, respectively).\n Short-term ON support with BCAA was associated with higher serum EPO levels than was a normal diet in patients with non-hepatitis who underwent curative hepatic resection. Higher EPO levels might be beneficial in protecting liver cells from ischemic injury and preventing intraoperative hemorrhage associated with lower perioperative levels of alanine aminotransferase and aspartate aminotransferase in serum. This is the first study to demonstrate an effect of EN support with BCAA in patients with non-hepatitis, as well as those with hepatitis.", "Although percutaneous transhepatic biliary drainage (PTBD) restores hepatic and renal function in patients with obstructive jaundice, it is not certain whether it reduces the rate of complications and death after biliopancreatic surgery. We studied the possibility that the operative risks of jaundiced patients are related to malnutrition and the usefulness of hyperalimentation with PTBD to reduce the incidence of complications. Sixty-four patients with obstructive jaundice and serum bilirubin greater than 200 mumol/l were randomized into two treatment groups (n = 32) with PTBD or PTBD + hyperalimentation. Four patients were withdrawn from the latter group, two for metastatic cancer and two for complications of PTBD. Before starting hyperalimentation, the incidence of malnutrition was assessed by biochemical, immunological and anthropometric tests: malnutrition was found in 70 per cent of the patients. All the patients had good recovery of hepatic function but patients treated with PTBD alone still had high mortality (12.5 per cent) and morbidity (46.8 per cent) after biliopancreatic surgery. When hyperalimentation was provided to patients on PTBD for a period of 20 days before the operation, the incidence of complications fell to 17.8 per cent and mortality to 3.5 per cent. These results suggest that the combined use of PTBD and hyperalimentation, improving both hepatic function tests and the nutritional status of jaundiced patients, can reduce the rate of complications after biliary and pancreatic surgery.", "The present studies were designed to provide careful measures of effects of oxandrolone, an anabolic steroid, intravenous nutritional supplementation, and the combination of these two treatments on liver functions, metabolic balances, nitrogen metabolism, and nutritional status in patients with moderate to severe alcoholic hepatitis. Of 43 patients originally recruited, 39 (19 men, 20 women) with typical clinical and laboratory features of alcoholic hepatitis (11 Child's-Pugh class B; 28 class C) were admitted to a metabolic unit and completed a 35-day three-phase protocol. Phase I was a 10-day baseline period of observation, during which routine and special quantitative tests of liver function (galactose and antipyrine metabolism), a 7-day elemental balance study, and a 15N, 13C-leucine metabolism study were done. Phase II was a 21-day treatment period during which patients were randomly assigned to receive one of four regimens: 1) standard therapy, consisting of abstinence, a balanced, nutritionally adequate diet, and multivitamins; 2) oxandrolone (20 mg orally four times a day) plus standard therapy; 3) nutritional supplementation, consisting of 2 L daily of 3.5% crystalline amino acids (in 5% dextrose), given by peripheral vein; or 4) a combination of oxandrolone and nutritional supplementation, along with standard therapy. Metabolic balances were repeated during phase II. Phase III was 2 or 3 days posttreatment, during which special studies of liver functions and volumes and leucine metabolism were repeated. All patients who completed phase I of study and were randomly allocated to one of the four treatment groups completed the subsequent two phases. Overall, with time, patients showed highly significant improvements in most clinical and laboratory features. For most standard laboratory tests (e.g., serum albumin, transferrin, prothrombin time) improvements were more marked in patients treated with nutritional supplementation and/or oxandrolone than in those given standard therapy alone. Liver volumes fell in all treatment groups, with greater improvement in those treated with nutritional supplementation. Improvements in galactose and antipyrine metabolism rates were significant only in those treated with nutritional supplementation or oxandrolone. Effects of treatments on metabolic balances, nitrogen metabolism, and measures of nutrition are described in this issue in a companion paper. We conclude that the addition of nutritional supplementation and oxandrolone to standard therapy of moderately severe or severe alcoholic hepatitis is well tolerated, and leads to more rapid improvement in the laboratory parameters measured.", "The aim of this randomized controlled study was to assess the nutritional and clinical effects of early enteral nutrition (EN) in cirrhotic patients with bleeding from esophageal varices. From August 1994 through August 1995, all patients admitted for acute variceal bleeding underwent emergency sclerotherapy or banding ligation and continuous infusion of octreotide and were randomized in two groups. In group A, patients received from day 1 discontinuous polymeric EN (1665 kcal/day, through nasogastric tube) and in group B, patients were nil by mouth. On day 4, all patients received oral diet. Nutritional status, liver function, and rebleeding were evaluated on days 4, 7, and 35. Twenty-two patients (17 men, 5 women, mean age 56 years) were included. On day 0, patients in group A (N = 12) and group B (N = 10) were comparable. On day 4, nitrogen balance was 0.7 +/- 2.5 g/day in group A and -11.2 +/- 6.7 g/day in group B (P = 0.01, Mann-Whitney test). On days 4, 7, and 35, no significant differences between the two groups were observed for nutritional status and liver function. Four (33%) group A patients rebled compared with one (10%) group B patient (NS). Hospital stay (14.5 +/- 4.1 days vs 12.9 +/- 5.3 days) and mortality (3 vs 2 patients), were comparable between the two groups. In conclusion, our study failed to demonstrate any favorable effect of short-term EN on nutritional status and liver function in cirrhotic patients hospitalized for variceal bleeding.", "Resection of hepatocellular carcinoma is associated with high rates of morbidity and mortality. Since intensive nutritional support can reduce the catabolic response and improve protein synthesis and liver regeneration, we performed a prospective study to investigate whether perioperative nutritional support could improve outcome in patients undergoing hepatectomy for hepatocellular carcinoma.\n We studied 124 patients undergoing resection of hepatocellular carcinoma. Sixty-four patients (39 with cirrhosis, 18 with chronic active hepatitis, and 7 with no associated liver disease) were randomly assigned to receive perioperative intravenous nutritional support in addition to their oral diet, and 60 patients (33 with cirrhosis, 12 with chronic active hepatitis, and 15 with no associated liver disease) were randomly assigned to a control group. The perioperative nutritional therapy consisted of a solution enriched with 35 percent branched-chain amino acids, dextrose, and lipid emulsion (50 percent medium-chain triglycerides) given intravenously for 14 days perioperatively.\n There was a reduction in the overall postoperative morbidity rate in the perioperative-nutrition group as compared with the control group (34 percent vs. 55 percent; relative risk, 0.66; 95 percent confidence interval, 0.45 to 0.96), predominantly because of fewer septic complications (17 percent vs. 37 percent; relative risk, 0.57; 95 percent confidence interval, 0.34 to 0.96). There were also a reduction in the requirement for diuretic agents to control ascites (25 percent vs. 50 percent; relative risk, 0.57; 95 percent confidence interval, 0.37 to 0.87), less weight loss after hepatectomy (median loss, 0 kg vs. 1.4 kg, P = 0.01), and less deterioration of liver function as measured by the change in the rate of clearance of indocyanine green (-2.8 percent vs. -4.8 percent at 20 minutes, P = 0.05). These benefits were seen predominantly in the patients with underlying cirrhosis who underwent major hepatectomy. There were five deaths during hospitalization in the perioperative-nutrition group, and nine in the control group (P not significant).\n Perioperative nutritional support can reduce complications after major hepatectomy for hepatocellular carcinoma associated with cirrhosis.", "A controlled trial on nutrition supplementation in ambulatory patients with decompensated alcoholic liver disease was carried out during 1 year. Fifty-one patients were studied; 26 were assigned to an experimental group receiving a daily supplement of 1000 kcal and 34 g of proteins given as a casein-based enteral nutrition product and 25 to a control group receiving one placebo capsule. Patients were examined in a special clinic once a month or more if required. Sixty-eight percent of patients admitted to alcohol ingestion or had alcohol in urine samples on at least one occasion. Dietary recalls showed a significantly higher protein and caloric intake in case patients subjects (p < .0001). Nine patients died during the study, three case patients and six control patients (p = NS). The frequency of hospitalizations was significantly less in the experimental group. This difference was attributed to a reduction in severe infections. Mid-arm circumference, serum albumin concentration, and hand grip strength improved earlier in case patients, although both groups had a significant improvement in these parameters. Bilirubin and aspartate aminotransferase decreased and prothrombin time increased significantly in both groups during the study period, without differences between groups. It is concluded that nutrition support decreases nutrition-associated complications in patients with alcoholic liver disease.", "A randomized study was conducted in 29 ambulatory cirrhotic patients to determine the short-term effects of branched-chain amino acids (BCAA) on nutritional status, biochemical liver function tests and caffeine clearance. Each patient received a 4-week period of isonitrogenous and isocaloric regimens, either a standardized diet contained 40 g protein with supplementation of BCAA 150 g daily (group I) or only a standardized diet contained 80 g protein daily (group II). At the end of treatment, only group I showed significant improvements in transaminase levels as well as the caffeine clearance test compared with those of the pre-treatment levels. Nonetheless, significant improvements in nutritional parameters and additional liver function tests were not yet detected. We conclude that the short-term nutritional supplementation of BCAA is well tolerated and leads to improvement in hepatic metabolic capacity assessed by the caffeine clearance test.", "Nutritional support in patients with advanced cirrhosis is difficult due to protein, fluid and salt restrictions. Successful liver transplantation should improve nutrient tolerance. We randomly assigned 28 hypoalbuminemic cirrhotic patients to receive, immediately after liver transplantation, one of three regimens: group 1, no nutritional support (n = 10); group 2, total parenteral nutrition (TPN) (35 kcal/kg/day) with standard amino acids (1.5 g/kg/day) (n = 8); or group 3, isocaloric isonitrogenous TPN with added branched-chain amino acids (n = 10). Therapy was continued for 7 days posttransplant. Jaundice resolution was unaffected by nutritional support. Nitrogen balance favored both TPN groups. Branched-chain amino acid (BCAA) aromatic amino acid ratios were highest in group 3. Coma scores and serum ammonia levels were similar in all groups. Both TPN groups achieved respirator independence earlier; this difference was not statistically significant. Group 1 patients stayed longest in ICU; the difference was statistically significant. TPN with either standard or BCAA- enriched amino acids is tolerated well immediately after successful liver transplant. Positive nitrogen balance is achieved; large protein loads do not worsen encephalopathy. Nutritional support may improve respiratory muscle function, allowing earlier weaning from ventilatory support. A shortened length of ICU stay justifies the expense of TPN.", "This prospective study compared the effects of tube-fed nutrition with those of a regular diet in alcoholic liver disease. The high prevalence of malnutrition in patients with alcoholic liver disease requires clarification of the benefits of aggressive nutritional support. Patients were randomly assigned a regular diet without or with tube-fed supplementation, delivering 1.5 g/kg protein and 167 kJ/kg daily. Comparisons of encephalopathy, antipyrine clearance, metabolic rate, and biochemical parameters were performed weekly for 4 weeks. Sixteen patients receiving enteral supplementation had antipyrine half-life (50% vs. 3% reduction), serum bilirubin (25% vs. 0% reduction), and median encephalopathy scores that improved more rapidly than those of controls. Initially, 15 controls did not consume adequate calories to meet measured resting energy expenditure. Aggressive nutritional intervention accelerated improvement in alcoholic liver disease. Adverse effects did not offset the demonstrated benefits of a 2-cal/mL, casein-based tube-fed supplement. These findings support the use of standard, casein-based solutions in the treatment of alcoholic liver disease and as the control condition for future studies.", "The effect of total parenteral nutrition (TPN) support supplemented with alanyl-glutamine (Ala-Gln) dipeptide was investigated in a randomized, controlled clinical trial.\n Sixty-five patients with the diagnosis of end-stage liver disease or hepatic cellular carcinoma admitted for orthotopic liver transplantation were randomly divided into 3 groups: diet group (n = 21), TPN group (n = 22), and Gln group (n = 22). Patients in the TPN and Gln groups received isocaloric and isonitrogenous TPN for 7 days. Venous heparin blood samples were obtained for assay on days 2 and 9 after surgery; we performed routine pathologic tests.\n Compared with the results on day 9 in the TPN group, there was a significant increase in the prognostic nutrition index and in prealbumin among the Gln group. Aspartate aminotransferase improved significantly by Gln treatment compared with traditional TPN support (P < .05). The pathologic results also showed Gln supplementation to reduce hepatic cell injury. A significant decrease in postoperative hospital stay was observed in the Gln group.\n Posttransplant TPN support greatly improved protein metabolism and nutritional state of patients. TPN with Ala-Gln helped to improve synthetic function and to reduce the injury to a transplanted liver.", "Between March 1982 and September 1983, 40 inpatients (25 men and 15 women, mean age 53 years) with alcoholic cirrhosis and total serum bilirubin greater than or equal to 5 mg per dl were studied. Those with hepatocellular carcinoma, renal failure, hyponatremia, septicemia, spontaneous bacterial peritonitis, gastrointestinal bleeding, and hepatic coma were excluded. Patients were studied for 28 days. The two groups were offered an oral diet containing 40 kcal per kg per day. Patients in the supplementary parenteral nutrition group received 40 kcal per kg per day and 200 mg nitrogen per kg per day using a central catheter. The major endpoint was total serum bilirubin on Day 28. On admission, serum bilirubin was not significantly different in the two groups: oral group, 12.5 +/- 6.6 mg per dl; supplementary parenteral nutrition group, 12.3 +/- 8.5 mg per dl. On Day 28, serum bilirubin was lower in the supplementary parenteral nutrition group (2.5 +/- 1.4 mg per dl) than in the oral group (4.1 +/- 2.2 mg per dl) (p less than 0.02). Serum bilirubin was also lower in the supplementary parenteral nutrition group than in the oral group on Days 7, 14 and 21 (p less than 0.05). Analysis of covariance, considering serum bilirubin on admission and at randomization and time between admission and randomization, confirmed these results. On Day 28, anthropometric parameters, serum transferrin, prealbumin and retinol-binding protein were higher in the supplementary parenteral nutrition group, but the differences were not significant. Serum albumin was significantly lower in the supplementary parenteral nutrition group. The incidence of encephalopathy and sepsis was not significantly different between the two groups.", "Routine laxatives may expedite gastrointestinal recovery and early tolerance of food within an enhanced recovery after surgery (ERAS) programme. Combined with carbohydrate loading and oral nutritional supplements (ONS), it may further enhance recovery of gastrointestinal function and promote earlier overall recovery.\n Seventy-four patients undergoing liver resection were randomized in a two-by-two factorial design to receive either postoperative magnesium hydroxide as a laxative, preoperative carbohydrate loading and postoperative ONS, their combination or a control group. Patients were managed within an ERAS programme of care. The primary outcome measure was time to first passage of stool. Secondary outcome measures were gastric emptying, postoperative oral calorie intake, time to functional recovery and length of hospital stay.\n Sixty-eight patients completed the trial. The laxative group had a significantly reduced time to passage of stool: median (interquartile range) 4 (3-5) versus 5 (4-6) days (P = 0.034). The ONS group showed a trend towards a shorter time to passage of stool (P = 0.076) but there was no evidence of interaction in patients randomized to the combination regimen. Median length of hospital stay was 6 (4-7) days. There were no differences in secondary outcomes between groups.\n Within an ERAS protocol for patients undergoing liver resection, routine postoperative laxatives result in an earlier first passage of stool but the overall rate of recovery is unaltered.\n Copyright (c) 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.", "To investigate the safety, rationality and the practicality of enteral nutritional (EN) support in the postoperative patients with damaged liver function and the protective effect of EN on the gut barrier.\n 135 patients with liver function of Child B or C grade were randomly allocated to enteral nutrition group (EN, 65 cases), total parenteral nutrition group (TPN, 40 cases) and control group (CON, 30 cases). Nutritional parameters, hepatic and kidney function indexes were measured at the day before operation, 5th and 10th day after the operation respectively. Comparison was made to evaluate the efficacy of different nutritional support. Urinary concentrations of lactulose(L) and mannitol(M) were measured by pulsed electrochemical detection(HPLC-PED) and the L/M ratio calculated to evaluate their effectiveness on protection of gut barrier.\n No significant damages in hepatic and kidney function were observed in both EN and TPN groups between pre- and postoperatively. EN group was the earliest one reaching the positive nitrogen balance after operation and with the lowest loss of body weight and there was no change in L/M ratio after the operation (0.026+/-0.004) at the day 1 before operation, 0.030+/-0.004 at the day 5 postoperative and 0.027+/-0.005 at the day 10 postoperative), but the change in TPN group was significant at the day 5 postoperative (0.027+/-0.003 vs 0.038+/-0.009,P<0.01).\n EN is a rational and effective method in patients with hepatic dysfunction after operation and has significant protection effect on the gut barrier.", "Twenty-eight patients with biopsy or clinical acute alcoholic hepatitis were prospectively randomized to 21 days of conventional therapy (14 control patients) or, in addition, to 2 L/day of a peripheral iv infusion of a 900 mosmol amino acid-glucose solution (14 patients). Cirrhosis was present in 64% of controls and in 54% of infused patients. There were three deaths in controls and one in the infused group. There were no significant intergroup differences in mortality, clinical findings, liver tests, or functional mass by the galactose elimination capacity either at entry or after completion of the study. In controls, there was intragroup improvement in serum bilirubin (p = 0.033) and AST (p = 0.008) but not in other \"liver tests\" or in functional hepatic mass by galactose elimination capacity. In infused patients there was improvement in bilirubin (p = 0.001), AST (p = 0.008), and serum albumin (p = 0.016). Improvement in functional mass by galactose elimination capacity was significant at the p = 0.052 level. Hyaline was initially present in six of eight pairs of biopsies in both groups. After treatment, five of six pairs in controls but only one of six pairs in the infused group still had hyaline (p = 0.03). This latter finding, if confirmed in larger groups, may be of considerable clinical importance. It is suggested that 3- to 4-wk trials of such protocols may require a longer duration of follow-up in greater numbers of patients to detect important advantages of amino acid-glucose infusions which are only implicit in these findings.", "Aim:  Sleep is closely related to physical and mental health. Sleep disturbance is reported in patients without encephalopathy. We examined the relationship among cirrhotic symptoms, laboratory data and sleep disturbances. Next, we examined the influence of a branched chain amino acid (BCAA) supplement on sleep disturbance in cirrhotic patients. Methods:  We investigated a total of 21 patients at Nagasaki University Hospital from January to June 2009. We constructed questionnaire items for the evaluation of cirrhotic symptoms. The items, as major symptoms of cirrhotic patients, were as follows: hand tremor, appetite loss, muscle cramp of foot, fatigue, decreased strength, anxiety, abdominal fullness, abdominal pain and a feeling of low energy. We used the Epworth Sleepiness Scale (ESS) for the evaluation of daytime hypersomnolence. Energy supplementation with a BCAA snack was performed as a late evening snack (LES). All patients were assessed at the time of entry into the study, and at 4 and 8 weeks. Results:  It was found that BCAA snack, taken p.o. as an LES, improved the ESS for cirrhotic patients without encephalopathy. This beneficial result was recognized in the short term, 4 weeks after beginning of treatment. This study demonstrated the utility of BCAA supplementation for cirrhotic patients with sleep disturbance. However, the cirrhotic symptom-related score was positively relation with the Child-Pugh score at the time of patient entry, and we were unable to identify the item that related to ESS. Conclusion:  A BCAA snack is a useful drug for cirrhotic patients who do not have any overt encephalopathy, but who suffered from sleep disturbance.\n © 2010 The Japan Society of Hepatology.", "Sixty-four patients admitted with acute alcoholic hepatitis, with or without underlying cirrhosis, were randomized regardless of encephalopathy to receive a controlled diet either alone, or supplemented orally, nasogastrically, or intravenously as necessary, with 2000 kCal and 10 g nitrogen daily. Whether this came from a conventional protein source or a branched chain amino acid enriched formulation was also randomly determined. In the absence of renal failure, nitrogen intakes of 10 g or more daily were invariably associated with positive nitrogen balance, but complications of liver dysfunction prevented the attainment of significantly more positive balance in the supplemented groups than in controls. Neither in the series as a whole, nor in any identifiable subgroup of patients, was mortality affected by treatment. Changes in prothrombin time and in measured nutritional parameters during the study did not differ between supplemented and control groups, and the observed changes in midarm muscle circumference appeared to reflect changes in degree of fluid retention. Neither enteral nor parenteral branched chain amino acids showed any consistent effect upon encephalopathy.", "Thirty-five severely malnourished cirrhotic patients were randomized to receive either enteral-tube feeding as the sole nutritional support (n = 16) or an isocaloric, isonitrogenous, low-sodium standard oral diet (n = 19). Both groups were homogeneous regarding age, sex distribution, etiology of liver cirrhosis, history of previous complications, clinical status, liver and renal function, modified Child's score, and nutritional status at admission. The enteral formula diet was energy dense, containing 40 mmol Na/day, whole protein plus branched-chain amino acids, medium- and long-chain triglycerides, and maltodextrin. It supplied 2115 kcal/day. The amount of vitamins and trace elements was at the upper limit of the recommended dietary allowances. The orally fed patients were encouraged to eat all meals served. Total enteral nutrition was well tolerated without major complications. Serum albumin and Child's score improved in the enterally fed patients but not in controls. Mortality rate while in the hospital was lower in patients on enteral feeding than in controls (12% vs 47%). These results show that total enteral nutrition is safe and effective in improving the short-term clinical outcome in severely malnourished cirrhotics." ]

[ "12243210", "15450054", "23075176", "10448776", "21845596", "19138567", "9322135", "14744180" ]

[ "A randomized, placebo-controlled trial of the discontinuation of long-term antipsychotics in dementia.", "Effect of antipsychotic withdrawal on behavior and sleep/wake activity in nursing home residents with dementia: a randomized, placebo-controlled, double-blinded study. The Bergen District Nursing Home Study.", "Relapse risk after discontinuation of risperidone in Alzheimer's disease.", "Withdrawal of haloperidol, thioridazine, and lorazepam in the nursing home: a controlled, double-blind study.", "A 6-month, randomized, double-blind, placebo-controlled pilot discontinuation trial following response to haloperidol treatment of psychosis and agitation in Alzheimer's disease.", "The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial.", "Withdrawal of neuroleptic medications from institutionalized dementia patients: results of a double-blind, baseline-treatment-controlled pilot study.", "A 3-month, randomized, placebo-controlled, neuroleptic discontinuation study in 100 people with dementia: the neuropsychiatric inventory median cutoff is a predictor of clinical outcome." ]

[ "The objectives of this randomized clinical trial were to investigate the impact of the discontinuation of long-term antipsychotics in residents with dementia in chronic care institutions and to identify clinical predictors of safe discontinuation. Subjects included 34 residents with dementia who were on antipsychotics for more than 6 months and whose behavior was currently stable. Subjects were randomized to either continue receiving their regular dosage of antipsychotics or to receive placebo for 6 months. Early withdrawal from the study was not statistically different between the groups (relative risk [RR] = 1.57, 95% confidence interval [CI] 0.76-3.26), and though not significantly different, subjects in the placebo group were more likely to be withdrawn from the study because of worsening behavior (RR = 1.25, 95% Cl 0.33-4.76). Three subjects in the placebo group were withdrawn from the study due to worsening of extrapyramidal symptoms. The active treatment group had more behavioral problems (e.g., physical aggression towards others, p < .05) compared to the placebo group. The placebo group developed more apathy, but balancing this outcome was a relative improvement in cognitive functioning. Baseline antipsychotic dose was predictive of behavioral worsening upon discontinuation of long-term antipsychotic drugs. The primary limitation of the study was the small sample size. In conclusion, a trial of discontinuation of antipsychotics should be considered in this population.", "To explore the effect on sleep/wake activity and on behavioral and psychological symptoms of the withdrawal of antipsychotic medications from nursing home (NH) patients with dementia.\n Randomized, placebo-controlled, double-blind trial.\n NHs in Bergen, Norway.\n Thirty patients (mean age 83.5) taking haloperidol, risperidone, or olanzapine for nonpsychotic symptoms. Intervention: Study participants were randomly assigned to withdrawal (intervention group) or continued treatment with antipsychotic medications (reference group) for 4 consecutive weeks.\n Behavioral rating using the Neuropsychiatric Inventory Questionnaire (NPI-Q) and actigraphy.\n After antipsychotic withdrawal, behavioral scores remained stable or improved in 11 of 15 patients, whereas four had worsening scores. Actigraphy revealed decreased sleep efficiency after drug discontinuation and increased 24-hour and night activity in both groups. Actigraphy records of nighttime and daytime activity indicated sleep problems and restlessness, in terms of the NPI-Q. One patient was restarted on antipsychotics.\n Antipsychotic drug withdrawal affected activity and sleep efficiency over the short term. Increases in total activity and impaired sleep quality after drug discontinuation should be monitored, because the long-term effect of these changes is not known. The NPI-Q and actigraphy are feasible tools that disclose relevant changes occurring during antipsychotic withdrawal in NH patients with dementia. Their use in clinical practice should be substantiated by larger studies.", "Among patients with Alzheimer's disease who have had a response to antipsychotic medication for psychosis or agitation-aggression, the risk of a recurrence of symptoms after discontinuation of the medication has not been established.\n Patients with Alzheimer's disease and psychosis or agitation-aggression received open-label treatment with risperidone for 16 weeks. Those who had a response to risperidone therapy were then randomly assigned, in a double-blind fashion, to one of three regimens: continued risperidone therapy for 32 weeks (group 1), risperidone therapy for 16 weeks followed by placebo for 16 weeks (group 2), or placebo for 32 weeks (group 3). The primary outcome was the time to relapse of psychosis or agitation.\n A total of 180 patients received open-label risperidone (mean dose, 0.97 mg daily). The severity of psychosis and agitation were reduced, although there was a mild increase in extrapyramidal signs; 112 patients met the criteria for response to treatment, of whom 110 underwent randomization. In the first 16 weeks after randomization, the rate of relapse was higher in the group that received placebo than in the groups that received risperidone (60% [24 of 40 patients in group 3] vs. 33% [23 of 70 in groups 1 and 2]; P=0.004; hazard ratio with placebo, 1.94; 95% confidence interval [CI], 1.09 to 3.45; P=0.02). During the next 16 weeks, the rate of relapse was higher in the group that was switched from risperidone to placebo than in the group that continued to receive risperidone (48% [13 of 27 patients in group 2] vs. 15% [2 of 13 in group 1]; P=0.02; hazard ratio, 4.88; 95% CI, 1.08 to 21.98; P=0.02). The rates of adverse events and death after randomization did not differ significantly among the groups, although comparisons were based on small numbers of patients, especially during the final 16 weeks.\n In patients with Alzheimer's disease who had psychosis or agitation that had responded to risperidone therapy for 4 to 8 months, discontinuation of risperidone was associated with an increased risk of relapse. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00417482.).", "Ongoing regimens of haloperidol, thioridazine, and lorazepam are commonly administered to manage behavior problems in nursing home residents. Nevertheless, there is controversy over whether periodic drug withdrawal should be attempted when those medications are prescribed. This study addressed that issue by examining the effects of discontinuing treatment with haloperidol, thioridazine, and lorazepam among residents of a large suburban nursing home.\n In a double-blind, crossover study, half of 58 nursing home residents (43 women and 15 men with a mean age of 86 years) continued to take the psychotropic medication they had been prescribed, whereas the other half were tapered to placebo. After 6 weeks of taking placebo or original drug, patients were tapered to the reverse schedule and remained on it for 6 weeks. Assessments included informant ratings by the nursing staff who completed the Brief Psychiatric Rating Scale and the Cohen-Mansfield Agitation Inventory.\n Analyses comparing residents taking placebo to those taking medication after completion of the first phase showed no impact of drug therapy discontinuation on their behavior. Similarly, using the crossover design to compare residents' behaviors while taking placebo vs. taking drugs, withdrawal of medication had no impact on Cohen-Mansfield Agitation Inventory or Brief Psychiatric Rating Scale scores.\n Results of this work suggest that longterm use of haloperidol, thioridazine, and lorazepam in nursing homes to manage agitation should be closely monitored for their efficacy. Furthermore, routine attempts at drug withdrawal should be considered for most residents taking psychotropic medication.", "In patients with Alzheimer's disease (AD) with psychosis or agitation that respond to haloperidol treatment, to evaluate the risk of relapse following discontinuation.\n In outpatients with AD with symptoms of psychosis or agitation, responders to 20 weeks of haloperidol (0.5-5 mg daily) were randomized to a 24-week, double-blind pilot trial of discontinuation on placebo versus continuation haloperidol. Phase A response criteria were minimum 50% reduction in three target symptoms, and improvement on the Clinical Global Impression-Change (CGI-C) score for psychosis/agitation. Phase B relapse criteria required 50% worsening in target symptoms and on the CGI-C. α = 0.1 was the significance criterion in this pilot study.\n Of 44 patients, 22 patients responded in Phase A. The sum score of target symptoms, and Brief Psychiatric Rating Scale (BPRS) psychosis and hostile suspiciousness factor scores, decreased in Phase A (p's < 0.001). Extrapyramidal signs increased in Phase A (p < 0.01). Of 22 responders, 21 patients entered Phase B, and 20 had at least one follow-up visit. Four of 10 patients (40%) on continuation haloperidol relapsed compared to eight of 10 patients on placebo (80%, χ(2)  = 3.3, p = 0.07). In survival analyses, time to relapse was shorter on placebo than haloperidol (χ(2)  = 4.1, p = 0.04).\n Haloperidol open treatment was efficacious, and relapse was greater on placebo than with haloperidol continuation. In patients with AD who have psychosis or agitation and respond to antipsychotic medication, the increased risk of relapse after discontinuation needs to be weighed against the side effects associated with continuing the medication.\n Copyright © 2010 John Wiley & Sons, Ltd.", "Data from 12-week placebo-controlled trials have led to mounting concerns about increased mortality in patients with Alzheimer's disease (AD) who are prescribed antipsychotics; however, there are no mortality data from long-term placebo-controlled trials. We aimed to assess whether continued treatment with antipsychotics in people with AD is associated with an increased risk of mortality.\n Between October, 2001, and December, 2004, patients with AD who resided in care facilities in the UK were enrolled into a randomised, placebo-controlled, parallel, two-group treatment discontinuation trial. Participants were randomly assigned to continue with their antipsychotic treatment (thioridazine, chlorpromazine, haloperidol, trifluoperazine, or risperidone) for 12 months or to switch their medication to an oral placebo. The primary outcome was mortality at 12 months. An additional follow-up telephone assessment was done to establish whether each participant was still alive 24 months after the enrollment of the last participant (range 24-54 months). Causes of death were obtained from death certificates. Analysis was by intention to treat (ITT) and modified intention to treat (mITT). This trial is registered with the Cochrane Central Registry of Controlled Trials/National Research Register, number ISRCTN33368770.\n 165 patients were randomised (83 to continue antipsychotic treatment and 82 to placebo), of whom 128 (78%) started treatment (64 continued with their treatment and 64 received placebo). There was a reduction in survival in the patients who continued to receive antipsychotics compared with those who received placebo. Cumulative probability of survival during the 12 months was 70% (95% CI 58-80%) in the continue treatment group versus 77% (64-85%) in the placebo group for the mITT population. Kaplan-Meier estimates of mortality for the whole study period showed a significantly increased risk of mortality for patients who were allocated to continue antipsychotic treatment compared with those allocated to placebo (mITT log rank p=0.03; ITT p=0.02). The hazard ratio for the mITT group was 0.58 (95% CI 0.35 to 0.95) and 0.58 (0.36 to 0.92) for the ITT population. The more pronounced differences between groups during periods of follow up longer than 12 months were evident at specific timepoints (24-month survival 46%vs 71%; 36-month survival 30%vs 59%).\n There is an increased long-term risk of mortality in patients with AD who are prescribed antipsychotic medication; these results further highlight the need to seek less harmful alternatives for the long-term treatment of neuropsychiatric symptoms in these patients.\n UK Alzheimer's Research Trust.", "Among dementia patients in long-term care facilities, neuroleptics (NL) are frequently prescribed for the treatment of agitation. Although good clinical practice and federal law mandate attempts at withdrawal of these medications, empiric data regarding the cessation of NL treatment are limited in this population. The objective of the present study was to assess through direct observation the effects of short-term NL withdrawal on physically aggressive behavior and other aspects of agitation. We carried out a randomized, double-blind, baseline NL-controlled 4-week trial of the effects of NL withdrawal in 36 institutionalized patients with possible or probable Alzheimer's disease. Patients were directly observed for four 2-hour sessions during baseline, a prerandomization week, and during weeks 1, 2, and 4 of the double-blind portion of the study. Completion of the 4 weeks of double-blind medication and number of observed episodes of physically aggressive behavior (PAB) were the two primary outcome measures. Of the 22 patients who were withdrawn from NL, 20 (91%) completed the 4-week double-blinded withdrawal. Two patients were discontinued from the study due to unacceptable levels of agitation at the request of their nursing staff. Of the 14 patients not withdrawn, all completed the 4-week trial. The chi-square test for the difference between groups was not significant (P > .05). Based on the observed instances of PAB, there was no significant difference (P > .05) between withdrawn and not-withdrawn subjects. Half of the withdrawn patients remained off NLs for an extended period of time after the end of the study, even after the blind was broken. Withdrawing institutionalized dementia patients from NLs was successful in most but not all study patients. Generalization of these results is limited by the highly selected nature of the participants. Unmasking of unmanageable agitation and physical aggressiveness in a small minority must be weighed against the benefits of removing unnecessary medication in the majority of dementia patients in whom NL withdrawal is attempted. PAB itself should not drive continuing NL use without regard to objective assessment of efficacy of the NL treatment.", "Although few placebo-controlled neuroleptic discontinuation studies have been conducted in people with dementia, such studies are essential to inform key clinical decisions.\n A 3-month, double-blind, placebo-controlled, neuroleptic discontinuation study (June 2000 to June 2002) was completed in 100 care-facility residents with probable or possible Alzheimer's disease (according to National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria) who had no severe behavioral disturbances and had been taking neuroleptics for longer than 3 months. The Neuropsychiatric Inventory (NPI) was used to measure changes in behavioral and psychiatric symptoms. Quality of life was evaluated using Dementia Care Mapping.\n Eighty-two patients completed the 1-month assessment (36 placebo, 46 active). The number of participants withdrawing overall (N = 14 [30%] placebo, N = 14 [26%] active treatment) and because of exacerbation of behavioral symptoms (N = 6 [13%] placebo, N = 5 [9%] active treatment) was similar in the neuroleptic- and placebo-treated patients. As hypothesized, patients with baseline NPI scores at or below the median (< or = 14) had a particularly good outcome, with a significantly greater reduction of agitation in the patients receiving placebo (Mann-Whitney U test, z = 2.4, p =.018), while patients with higher baseline NPI scores were significantly more likely to develop marked behavioral problems if discontinued from neuroleptics (chi(2) = 6.8, p =.009). There was no overall difference in the change of quality of life parameters between groups.\n A standardized evaluation with an instrument such as the NPI may be a clinical indicator of which people with dementia are likely to benefit from discontinuation of neuroleptic treatment." ]

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[ "Effectiveness of MF59-adjuvanted subunit influenza vaccine in preventing hospitalisations for cardiovascular disease, cerebrovascular disease and pneumonia in the elderly.", "Guillain-Barre syndrome following vaccination in the National Influenza Immunization Program, United States, 1976--1977.", "Different protection rates in various groups of volunteers given subunit influenza virus vaccine in 1976.", "Impact of influenza A in a nursing home.", "Study of the effectiveness of influenza vaccination in the elderly in the epidemic of 1989-90 using a general practice database.", "Effectiveness of influenza vaccination in preventing influenza-like illness among community-dwelling elderly: population-based cohort study in Japan.", "Two outbreaks of influenza A (H3N2) in a Japanese nursing home in the winter of 1996-1997, with differing vaccine efficacy.", "[Effectiveness of an anti-influenza vaccination program in 4 primary care centers].", "The effectiveness of influenza vaccine against influenza a (H3N2) virus infections in nursing homes in Niigata, Japan, during the 1998-1999 and 1999-2000 seasons.", "Influenza A/Philippines/2/82 outbreak in a nursing home: limitations of influenza vaccination in the aged.", "Influenza outbreaks in nursing homes: how effective is influenza vaccine in the institutionalized elderly?", "The roles of vaccination and amantadine prophylaxis in controlling an outbreak of influenza A (H3N2) in a nursing home.", "[Efficacy of influenza vaccination: results in a community controlled for 2 years].", "Influenza vaccination in community-dwelling elderly: impact on mortality and influenza-associated morbidity.", "A prospective, Internet-based study of the effectiveness and safety of influenza vaccination in the 2001-2002 influenza season.", "Influenza vaccine effectiveness in preventing hospitalization for pneumonia in the elderly.", "Additive preventive effect of influenza and pneumococcal vaccines in elderly persons.", "Guillain-Barré syndrome in the United States, 1979-1980 and 1980-1981. Lack of an association with influenza vaccination.", "Failure of inactivated influenza vaccine to protect an aged population.", "A case-control study of elderly patients with acute respiratory illness: effect of influenza vaccination on admission to hospital in winter 2003-2004.", "Influenza vaccine effectiveness in preventing hospitalization among the elderly during influenza type A and type B seasons.", "Influenza vaccination programs for elderly persons: cost-effectiveness in a health maintenance organization.", "Is influenza vaccination cost effective for healthy people between ages 65 and 74 years? A randomised controlled trial.", "An outbreak of influenza A (H3N2) in a well immunized nursing home population.", "Effectiveness of inactivated influenza vaccine among nursing home residents during an influenza type A (H3N2) epidemic.", "A cohort study of the effectiveness of influenza vaccine in older people, performed using the United Kingdom general practice research database.", "Efficacy of influenza vaccine in nursing homes. Reduction in illness and complications during an influenza A (H3N2) epidemic.", "Benefits of influenza vaccination for low-, intermediate-, and high-risk senior citizens.", "Immunogenicity and efficacy of Russian live attenuated and US inactivated influenza vaccines used alone and in combination in nursing home residents.", "Influenza in a partially immunized aged population. Effectiveness of killed Hong Kong vaccine against infection with the England strain.", "Age-related responses to influenza vaccination in the Newcastle region during 1983 and 1984.", "Influenza in the elderly: report of an outbreak and a review of vaccine effectiveness reports.", "Reduction in hospital admissions for pneumonia in non-institutionalised elderly people as a result of influenza vaccination: a case-control study in Spain.", "Influenza A among community-dwelling elderly persons in Leicestershire during winter 1993-4; cigarette smoking as a risk factor and the efficacy of influenza vaccination.", "Influenza vaccine and pneumonia mortality in a nursing home population.", "Effectiveness of influenza vaccine in reducing hospital admissions during the 1989-90 epidemic.", "Reduction in mortality associated with influenza vaccine during 1989-90 epidemic.", "Increasing doses of purified influenza virus hemagglutinin and subvirion vaccines enhance antibody responses in the elderly.", "Evaluation of monovalent influenza vaccine in a retirement community during the epidemic of 1965-66.", "Evaluation of cold-adapted, reassortant influenza B virus vaccines in elderly and chronically ill adults.", "Adverse reactions to influenza vaccine in elderly people: randomised double blind placebo controlled trial.", "The efficacy of influenza vaccination in elderly individuals. A randomized double-blind placebo-controlled trial.", "Efficacy of the antiinfluenza A vaccination during epidemics due to A/VIC/3/75 and A/Texas/1/77 viruses.", "[Analysis of an influenza vaccination campaign in rural environment].", "Influenza vaccination, hospitalizations, and costs among members of a Medicare managed care plan.", "Outbreak of influenza A in an Ontario nursing home--January 1997.", "Frequency of adverse reactions to influenza vaccine in the elderly. A randomized, placebo-controlled trial.", "Influence of high-risk medical conditions on the effectiveness of influenza vaccination among elderly members of 3 large managed-care organizations.", "Influenza vaccination: reduction in hospitalizations and death rates among members of \"Maccabi Healthcare Services\" during the 2000-2001 influenza season.", "Association of influenza immunization with reduction in mortality in an elderly population. A prospective study.", "Influenza vaccine effectiveness in preventing hospitalizations and deaths in persons 65 years or older in Minnesota, New York, and Oregon: data from 3 health plans.", "The Guillain-Barré syndrome and the 1992-1993 and 1993-1994 influenza vaccines.", "Effects of a large-scale intervention with influenza and 23-valent pneumococcal vaccines in adults aged 65 years or older: a prospective study.", "Lessons from a nursing home outbreak of influenza A.", "Unusual outbreak of influenza A in a Wyoming nursing home.", "Clinical effectiveness of influenza vaccination in Manitoba.", "Spread of influenza: a study of risk factors in homes for the elderly in Wales.", "Influenza vaccine efficacy in a Maryland nursing home.", "Nursing home outbreak of influenza A (H3N2): evaluation of vaccine efficacy and influenza case definitions.", "Influenza vaccine effectiveness among elderly nursing home residents: a cohort study.", "The efficacy and cost effectiveness of vaccination against influenza among elderly persons living in the community.", "Effectiveness of the MF59-adjuvanted influenza vaccine in preventing emergency admissions for pneumonia in the elderly over 64 years of age.", "[Effectiveness of anti-flu vaccine in the elderly].", "Effectiveness of influenza vaccination in the elderly in a community in Italy.", "Efficacy of Influenza Vaccine in Elderly Persons in Welfare Nursing Homes: Reduction in Risks of Mortality and Morbidity During an Influenza A (H3N2) Epidemic.", "A comparison of subcutaneous, nasal, and combined influenza vaccination. II. Protection against natural challenge.", "Influenza vaccination and reduction in hospitalizations for cardiac disease and stroke among the elderly.", "An outbreak of influenza A in a nursing home.", "Influenza vaccination and mortality from bronchopneumonia in the elderly." ]

[ "Annual circulation of influenza virus coincides with a peak in cardiovascular and pneumonia mortality/morbidity. This study aimed to determine the effectiveness of MF59-adjuvanted subunit influenza vaccine in preventing hospitalisation due to acute coronary syndrome (ACS), cerebrovascular accident (CVA) and pneumonia in the elderly. Three case-control studies were performed during the 2004-2005 influenza season in three health districts in Valencia, Spain (total elderly [>64 years of age] population: n=105,454). Controls were patients admitted for an acute surgical process or trauma within 10 days of case admission. In total, 159 patients were hospitalised for ACS, 148 for CVA and 242 for pneumonia. The risk of hospitalisation after the start of the influenza season was significantly lower in vaccinated patients compared with non-vaccinated patients (adjusted odds ratios: 0.13 [P=0.013] for ACS; 0.07 [P=0.007] for CVA; 0.31 [P=0.005] for pneumonia). During peak virus circulation, vaccination with MF59-adjuvanted subunit influenza vaccine was associated with an 87% relative risk reduction in hospitalisation for ACS, 93% for CVA, and 69% for pneumonia.", "Because of an increase in the number of reports of Guillian-Barre syndrome (GBS) following A/New Jersey influenza vaccination, the National Influenza Immunization Program was suspended December 16, 1976 and nationwide surveillance for GBS was begun. This surveillance uncovered a total of 1098 patients with onset of GBS from October 1, 1976, to January 31, 1977, from all 50 states, District of Columbia, and Puerto Rico. A total of 532 patients had recently received an A/New Jersey influenza vaccination prior to their onset of GBS (vaccinated cases), and 15 patients received a vaccination after their onset of GBS. Five hundred forty-three patients had not been recently vaccinated with A/New Jersey influenza vaccine and the vaccination status for 8 was unknown. Epidemiologic evidence indicated that many cases of GBS were related to vaccination. When compared to the unvaccinated population, the vaccinated population had a significantly elevated attack rate in every adult age group. The estimated attributable risk of vaccine-related GBS in the adult population was just under one case per 100,000 vaccinations. The period of increased risk was concentrated primarily within the 5-week period after vaccination, although it lasted for approximately 9 or 10 weeks.", "Different rates of protection were observed in various groups of volunteers given trivalent subunit influenza virus vaccine during an epidemic caused by A/Victoria/3/75 strains of influenza virus in Melbourne, Victoria, Australia, in 1976. The degree of protection varied from 80% protection from infection in one group to a moderation in the severity of clinical illness in a geriatric group. The response to immunization may depend on the previous experience of the vaccinees, and it may be necessary to use different dose schedules in different groups for optimal protection.", "Outbreaks of influenza A in the institutionalized elderly have been reported only rarely. Such an outbreak occurred in a nursing home in the period Dec 12, 1980, through Jan 21, 1981. Thirty (25%) of the 120 residents had onset of influenza-like illness during the outbreak. Influenza A/Bangkok/79-like (H3N2) virus was isolated from throat swab specimens from five of eight acutely ill patients. Thirteen persons were hospitalized; nine persons died (case-fatality ratio, 30%). This outbreak documents that mortality associated with an influenza outbreak can be substantial in a closed population of the elderly. Because nursing home residents are an easily accessible high-risk population, control and prevention of influenza should be a high priority in nursing homes.", "The effectiveness of influenza vaccination in preventing serious illness and death was determined in an elderly population during the influenza epidemic of was determined in an elderly population during the influenza epidemic of was determined in an elderly population during the influenza epidemic of 1989-90. A retrospective cohort study was carried out using computerized general practitioner records on nearly 10,000 patients aged 55 years and over. After adjustment for potential confounding factors, recent immunization was found to have a protective effect of 75% (95% confidence intervals: 21-92%) against death. Protection did not appear to vary with either age or the presence of underlying chronic disease. As the complications of influenza are most common in those with underlying chronic disease, the study findings are consistent with the recommended policy for the use of influenza vaccine in the UK. Further work is necessary to determine the cost-effectiveness of extending immunization to other groups.", "A population-based cohort study was conducted during the 2003-2004 season to examine the effectiveness of influenza vaccine among community-dwelling elderly. The subjects consisted of 4787 elderly, ranging from 65 to 79 years. We either interviewed the elderly directly or their families regarding acute febrile illness, hospital visits, hospitalization and death by telephone every month. The vaccination status and physician-diagnosed clinical influenza (hereinafter referred as clinical influenza) were determined based on data obtained from the city office and hospitals, respectively. Influenza-like illness (ILI) was defined as an acute febrile illness (> or = 38.5 degrees C) during the epidemic period. After adjusting for confounders, vaccination decreased ILI significantly (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.17-0.85), but not clinical influenza (OR, 0.76; 95% CI, 0.28-2.06). The results were inconclusive for preventing hospitalization for influenza or pneumonia (OR, 0.37; 95% CI, 0.09-1.47) and death (OR, 3.68; 95% CI, 0.75-18.12), due to the inadequate sample size. In conclusion, the influenza vaccination was thus found to be associated with a decreased ILI during the epidemic period in community-dwelling elderly.", "Sixty of 128 (46.9%) residents of a nursing home were immunized with two doses of the trivalent split influenza vaccine. They developed 7.4-11.5-fold antibody increases, with a 69-82% protection rate, presenting good immune response rates to the influenza vaccine. Two outbreaks of influenza A (H3N2) occurred. There were no significant antigenic differences among the vaccine strain and the strains isolated from both outbreaks in haemagglutination-inhibition tests, suggesting that the second might have been a reoccurrence. There were no residents who were infected in both outbreaks. The vaccine efficacy against clinical illness in the first outbreak of typical influenza-like-illness (ILI) was 51% (relative risk: 0.49), and the febrile period was reduced significantly by vaccination. In the second outbreak, however, in which all patients had atypical ILI with a high fever but not respiratory symptoms, vaccine efficacy was not apparent for unknown reason.", "A influenza immunization programme held in 4 health centres is evaluated, by testing the hypothesis that programme compliance lowers their hospital admissions and mortality. A cohort of 4,558 people over 65 belonging to 4 \"Baix Llobregat\" health centres was followed-up during 7 months. The population covered by immunization programme (43.8%) showed a hospital admission rate (6.2%) lower than the non immunized one (4.3%). Nevertheless, the cardiorespiratory disease admission rate in the whole sample (2.0% in immunized and 1.3% in non immunized), and in females (1.3% in immunized and 1.2 in non immunized) didn't show differences between covered and non covered by the programme. Mortality is lower in compliant (0.8% in immunized, and 1.9% in non immunized), but it's due to a higher death rate in the counted unimmunized, non demanding, and non hospital admitted population. If we interpret these data as the immunization covered population is more health services consumer, we can consider that at least in women, the programme has a contention effect for cardiorespiratory disease hospital admission. The mortality drop can not be attributed to immunization but it will be due to the health centers incapacity for reaching the high risk population of the assigned community. On the basis of these results, health centers should reconsider the need for continuing carry out these immunizations programmes. Primary Health care teams should establish programmes that would allow them to cover the assigned community health needs, even for non demanded services.", "To evaluate the effectiveness of influenza vaccines against influenza-like illness (ILI) among nursing home residents.\n Prospective, nonrandomized, cohort study.\n Nine nursing homes during the 1998-1999 influenza season and 11 nursing homes during the 1999-2000 influenza season in Niigata Prefecture, Japan.\n Six hundred ninety-nine residents and 440 healthcare workers (HCWs) during the first season, and 930 residents and 517 HCWs during the second season, with vaccination rates ranging from 0% to 97.7%.\n Overall, ILI decreased from 24.3% during the 1998-1999 season to 8.8% during the 1999-2000 season. Multivariate analysis adjusted for several factors, including gender, age, underlying diseases, and resident and HCW vaccination rates, failed to demonstrate clear individual protection of residents (relative risk [RR], 1.42; P = .2 for the first season; RR, 0.95; P = .9 for the second season). However, vaccination rates of 60% or greater for residents and HCWs reduced the risk of ILI, and also could prevent outbreaks during the 2 seasons. Highly impaired activities of daily living and chronic respiratory diseases were significantly associated with increased ILI.\n A high vaccination rate for both residents and HCWs may reduce the risk of ILI and institutional outbreaks in nursing homes.", "The failure of the 1982-1983 influenza vaccine to protect elderly NHCU residents from clinical infection with influenza A/Philippines/2/82 resulted primarily from antigenic drift of the epidemic strain, inasmuch as the attack rates in the vaccinated and nonvaccinated patients were not significantly different. This experience supports the decision to replace A/Bangkok/1/79 with A/Philippines/2/82 virus antigen in the 1983-1984 influenza vaccine.", "During the 1984-1985 influenza season, outbreaks of influenza A (H3N2) occurred in three Connecticut nursing homes. Influenza vaccination rates were 67% (96 out of 144), 35% (30 out of 85) and 69% (332 out of 483), respectively. The relative risk of illness for vaccinated compared to unvaccinated residents was 1.8 (95% confidence interval, 0.6, 5.9), 1.6 (95% confidence interval, 0.8, 3.0) and 1.1 (95% confidence interval, 0.8, 1.7) for each of the three nursing homes, respectively. In the third outbreak, 22 vaccinated residents without clinical illness had a geometric mean titer of hemagglutination-inhibition (HI) antibody of 20. Although low, this titer was significantly higher than that of nine unvaccinated residents without clinical illness (12, p less than .05); only three (14%) vaccinated residents had HI titers of greater than or equal to 40. These results suggest that levels of HI antibody in vaccinated residents were not protective at the time of the third outbreak, four to five months after vaccination. In general, the study of vaccine effectiveness in nursing homes is limited by sample size and statistical power. Despite these limits, the retrospective investigation of influenza outbreaks in nursing homes is often the only practical way to evaluate influenza vaccine effectiveness in the elderly on a yearly basis.", "An outbreak caused by influenza A/Philippines/2/82 (H3N2)-like viruses occurred in a partially vaccinated nursing home population in January 1985. During the first six days of the outbreak, 14 (25%) of 55 residents developed influenzalike illness. The risk of illness was most strongly associated with undetectable levels of antibody against the epidemic strain, with unvaccinated case-patients having more severe illnesses and a higher rate of hospitalization than vaccinated case-patients (5/8 vs 0/6). During the period of amantadine hydrochloride prophylaxis (100 mg/d) from days 7 to 35, only two (5%) of the remaining 41 residents became ill, even though 11 (27%) had no detectable antibody. Serum amantadine levels obtained on day 35 ranged from 117 to 737 ng/mL (mean 309 ng/mL), similar to therapeutic levels documented in younger adults who have taken the standard regimen of 200 mg/d; there were few clinically significant side effects. These findings illustrate the benefits of influenza vaccination and support the use of amantadine hydrochloride at a dosage of 100 mg daily for outbreak control among elderly persons.", "The effectiveness of influenza vaccination has been studied in an old age colony during the winters 1977-78 and 1978-79. The subjects, vaccinated and non-vaccinated, were submitted to continuous clinical and virological controls for about 6 months during the cold season. Three blood samples were obtained from the vaccinated subjects: 2 in November (before and after vaccination) and 1 in May of the following year. From the non-vaccinated 2 blood samples were obtained in November and May, respectively. The hemagglutino-inhibition test (HAI) permitted studying the serological response after vaccination, and verifying changes of the antibody titer to be related to influenza virus infections, contracted during the winter, which had escaped the clinico-virological detection. The serological response to the bivalent vaccine employed in November 1977 (A/Victoria/3/75 - 600 I.U.; B/Hong Kong/8/73 - 300 I.U.) was good for type A virus, and fair for B type. The low circulation of influenza virus, both among the 61 non-vaccinated and the 126 vaccinated subjects, during the following winter 1977-78 did not allow to arrive at any information on the vaccine protective efficacy. In autumn 1978 a trivalent vaccine had been employed, containing 300 I.U. of A/Texas/1/77, A/USSR/90/77, B/Hong Kong/8/73 viruses, respectively. During the following winter 1978-79, cases of infection, caused by type B/Hong Kong/5/72 - like influenza viruses were detected. The morbidity turned out significantly lower (P less than 0.05) in the vaccinated subjects (4 out of 140 cases) versus the non-vaccinated (7 out of 56 cases). The protection index supplied by the vaccine on such occasion was 77%.", "Influenza-related morbidity and mortality have been extensively studied with hospital and reimbursement data. However, little is known about the effectiveness of the annual vaccination programs in generally healthy community-dwelling elderly. The objective of our study was to investigate the effectiveness of influenza vaccination in community-dwelling elderly during the 1996 to 1997 influenza epidemic.\n We performed a population-based cohort study using the computerized Integrated Primary Care Information database in the Netherlands. Subjects who were 65 years and older in 1996 with a permanent status in a practice in the source population were considered eligible for study participation. Two cohorts were defined on the basis of vaccination status. We estimated and compared all-cause mortality, pneumonia, and clinical influenza infection rates between the cohorts.\n Influenza vaccination was associated with a significant reduction of morbidity and mortality in vaccinated elderly (relative risk [RR], 0.72; 95% confidence interval [CI], 0.60-0.87). Influenza infections decreased significantly in the vaccinated population (RR, 0.48; 95% CI, 0.26-0.91). Mortality was reduced significantly in elderly with comorbidity (RR, 0.67; 95% CI, 0.48-0.94). The risk reduction for pneumonia was nonsignificant (RR, 0.77; 95% CI, 0.55-1.07) but was temporally related to the peak influenza activity.\n In this study, influenza vaccination was associated with decreased mortality and influenza infections in community-dwelling elderly. Our results indicate that, in a season of mild influenza activity and good antigenic match between vaccine strains and circulating strains, influenza vaccination reduced mortality in the vaccinated population. Our data support an annual vaccination strategy for all community-dwelling elderly.", "The effectiveness of the influenza vaccine used in the 2001-2002 influenza season in Japan was investigated in a large-scale, geographically widely distributed, Internet-based study. Data were collected from 8841 of 9902 subjects registered by 38 clinics prior to the start of influenza season. Subjects were categorized into three groups by vaccination regimen: unvaccinated, vaccinated once, and vaccinated twice. Efficacy was also analyzed for three age groups: 0-15, 16-64, and 65-104 years. Influenza-like illness (ILI) was diagnosed according to Ministry of Health (MWH, Labor and Welfare in Japan) criteria. Laboratory-confirmed influenza cases were analyzed separately. The respective vaccine efficacy in the 0-15 years group for the one- and two-dose regimens was 67.6 and 84.5% for ILI and 54.0 and 79.8% for laboratory-confirmed influenza. Influenza vaccination was also shown to be effective in subjects 16-64 years. Vaccine effectiveness was not able to be determined for the over 65 years group, probably due to an insufficient number of infected patients. These results suggest that influenza vaccination is effective for children and adults and that a two-dose regimen is superior to a single dose in children 0-15 years.", "During the winter of 1989-1990, influenza type A(H3N2) circulated widely, causing excess morbidity and mortality nationwide. From November through April, 1989-1990, hospitalized cases of pneumonia and influenza occurring among noninstitutionalized individuals 65 or more years of age were identified by 20 acute care hospitals in southern lower Michigan. These cases were group matched on age, sex, race, and zip code to randomly sampled, community-based controls from a comprehensive listing of Medicare beneficiaries residing in the study area. Self-reported data were collected from cases and controls on influenza vaccine status for the 1989-1990 season and on a number of other factors which could have influenced vaccination status or outcome. Questionnaires were completed by 1,907 individuals, 449 of whom were cases, resulting in an overall response rate of 76%. A community-based influenza surveillance system was implemented to determine the timing and intensity of viral activity and influenza-like illness. Vaccine effectiveness in preventing overall pneumonia and influenza hospitalizations was estimated by logistic regression. During the 3-month period of surveillance-confirmed peak influenza type A(H3N2) circulation, vaccine effectiveness was 45% (95% confidence interval 14-64, p = 0.009). However, during the 3-month period of low or absent virus activity, identical methodology and model specification resulted in an effectiveness estimate of 21% that was not statistically different from zero (p = 0.36). The effectiveness determined during the peak period of virus circulation is felt to be a conservative estimate, since agents other than influenza are responsible for pneumonia and influenza hospitalizations, even during times of peak influenza activity.", "In 1999, all individuals > or = 65 yrs of age (n=258,754) in Stockholm County, Sweden, were offered influenza and pneumococcal vaccination in a prospective study on the effectiveness of these vaccines in reducing the need for hospital treatment and death due to influenza, pneumonia and invasive pneumococcal disease (IPD). Data on hospitalisation and mortality during 1 yr were obtained from the administrative database in Stockholm County Council. Vaccination was performed in 124,702 (48%) subjects; 72,107 had both vaccines, 29,346 only had the influenza vaccine and 23,249 only had the pneumococcal vaccine. Compared with the unvaccinated cohort, a lower incidence of hospitalisation for all endpoint diagnoses was seen in vaccinated persons. An additive effectiveness of vaccination was seen when both vaccines were given, with a reduction of hospital admissions for influenza (37%), pneumonia (29%) and IPD (44%). In-hospital mortality for pneumonia was significantly lower in those who received both vaccines, than in unvaccinated persons. To conclude, vaccination with influenza and pneumococcal vaccines together was effective in reducing the need for hospital admission for influenza and pneumonia. There was a strong indication that pneumococcal vaccination alone, was effective not only in the prevention of invasive pneumococcal disease, but also of pneumonia overall, although to a low degree.", "An ongoing surveillance program was intensified during the 1979-1980 and the 1980-1981 influenza seasons to determine whether an increased risk of acquiring Guillain-Barré syndrome (GBS) within eight weeks after influenza vaccination existed for adults in the United States who received influenza vaccine, when compared with adult who had not been vaccinated recently. Five hundred twenty-eight cases of GBS with onset between Sept 1 and March 31, including seven following recent vaccination, were reported by participating neurologists in 1979-1980; 459 cases, including 12 following recent vaccination, were reported in 1980-1981. The relative risk of acquiring GBS following influenza vaccination--0.6 in 1979-1980 and 1.4 in 1980-1981--was not significantly different from 1.0 in either season. These results suggest that there was no increased risk of acquiring GBS associated with the influenza vaccines administered during these seasons and that the causative \"trigger agent\" in the A/New Jersey (swine) influenza vaccine administered in 1976 has not been present in subsequent influenza vaccine preparations.", "nan", "Every winter, hospitals face a large increase in emergency respiratory admissions in elderly people. A case-control study was undertaken to assess the effect of routine influenza vaccine in preventing such admissions among a cohort of UK elderly presenting with acute respiratory illness during winter 2003-2004. 157 hospitalised cases and 639 controls (matched for age, sex and week of consultation) were interviewed. In a winter typical of levels of circulating influenza in recent years, influenza vaccine did not show a protective effect on emergency respiratory admissions overall (adjusted OR 1.2 (95%CI 0.8, 1.9). Policy makers should not rely solely on influenza vaccine routinely having a large effect on winter pressures, and should focus on additional preventive strategies.", "Influenza vaccine effectiveness evaluations were carried out among the elderly, as part of a demonstration established to estimate the value of including influenza vaccination as a covered Medicare benefit.\n Cases hospitalized with pneumonia and influenza-related diagnoses during November through April were identified and group matched to randomly selected community controls. Data were collected from cases and controls on influenza vaccination status and other factors which could have confounded the association between vaccination and hospitalization. A community-based influenza surveillance programme was conducted each year to determine the timing and aetiology of influenza activity. Logistic regression analyses were carried out to evaluate the association of influenza vaccination with the likelihood of hospitalization.\n In 1990-1991, during the peak of the influenza type B outbreak, influenza vaccination was estimated to be 31% (95% CI: 4-51%) effective in reducing the likelihood of hospitalization. In 1991-1992, during the peak of the influenza type A(H3N2) epidemic, a nearly identical point estimate for vaccine effectiveness was demonstrated (32%, 95% CI: 7-50%). Identical analyses carried out each year during the periods of low or absent influenza activity failed to demonstrate a significant effect for vaccination in preventing hospitalization.\n Results indicated that a significant benefit for vaccination could be expected during both type A and type B influenza seasons.", "To estimate the cost-effectiveness and net medical care costs of programs for annual influenza vaccinations for the elderly in a health maintenance organization (HMO).\n Population-based, case-control study.\n The Northwest Region of Kaiser Permanente, a prepaid group practice HMO in Portland, Oregon.\n Kaiser Permanente members 65 years of age and older who had at least 1 month of HMO eligibility during any of nine influenza seasons in the 1980s.\n The HMO's costs for providing medical care and conducting vaccination programs were estimated using accounting data.\n 32% of high-risk elderly persons and 22% of non-high-risk elderly persons received influenza vaccinations. Aggregate vaccine effectiveness in preventing pneumonia and influenza hospitalizations was 30% (95% CI, 17% to 42%) for high-risk and 40% (CI, 1% to 64%) for non-high-risk elderly persons. The net savings to the HMO per vaccination was $6.11 for high-risk elderly persons and $1.10 for all elderly persons. The HMO incurred a net cost of $4.82 per vaccination for non-high-risk elderly persons.\n Influenza vaccination rates in this HMO were relatively low for high-risk elderly persons. The medical care costs saved by preventing pneumonia and influenza through vaccination of high-risk elderly persons provide a compelling rationale to increase compliance with recommendations for annual influenza vaccination. Indirect benefits, such as prevention of suffering, incapacity, and lost wages, are likely to compensate for the small net cost of vaccinating non-high-risk elderly persons.", "The aim of this study was to determine the cost effectiveness of influenza vaccination for healthy people aged 65-74 years living in the UK. People without risk factors for influenza (chronic heart, lung or renal disease, diabetic, immunosuppressed or those living in an institution) were identified from 20 general practitioner (GP) practices in Liverpool in September 1999. 729/5875 (12.4%) eligible individuals were recruited and randomised to receive either influenza vaccine or placebo (ratio 3:1), with all participants receiving 23-valent-pneumococcal polysaccharide vaccine unless already administered. The primary analysis was the frequency of influenza as recorded by a GP diagnosis of pneumonia or influenza like illness. In 2000, the UK vaccination policy was changed with influenza vaccine becoming available for all people aged 65 years and over irrespective of risk. As a consequence of this policy change, the study had to be fundamentally restructured and only results obtained over a one rather than the originally planned two-year randomised controlled trial framework were used. Results from 1999/2000 demonstrated no significant difference between groups for the primary outcome (relative risk 0.8, 95% CI 0.16-4.1). In addition, there were no deaths or hospitalisations for influenza associated respiratory illness in either group. The subsequent analysis, using both national and local sources of evidence, estimated the following cost effectiveness indicators: (1) incremental NHS cost per GP consultation avoided = 2000 pound sterling; (2) incremental NHS cost per hospital admission avoided = 61,000 pound sterling; (3) incremental NHS cost per death avoided = 1,900,000 pound sterling and (4) incremental NHS cost per QALY gained = 304,000 pound sterling. The analysis suggested that influenza vaccination in this population would not be cost effective.", "To describe the epidemiologic features of an outbreak of influenza A that occurred in a skilled nursing home although over 90 percent of the resident population had previously received influenza vaccine.\n Retrospective cohort study.\n Skilled nursing home facility in western New York State.\n Nursing home residents and patient-care staff.\n Incidence of influenza-like illness among vaccinated versus unvaccinated nursing home residents and staff.\n Thirty-seven of 124 residents (attack rate = 30%) and 18 of 146 staff (attack rate = 12%) had an influenza-like illness. Staff illness began 16 days prior to onset among residents. Six cases of pneumonia and three influenza-related deaths occurred, all among the vaccinated residents. Ninety percent of the nursing home residents and 10% of the staff received the influenza vaccine prior to the outbreak. The calculated vaccine efficacies were minus 21% and plus 45% for residents and staff, respectively.\n While antigenic drift of the circulating influenza virus was the major factor in the apparent vaccine failure, the observed poor staff immunization rate (10%) and absence of surveillance which precluded the use of amantadine chemoprophylaxis suggest that the use of these strategies may be of importance in controlling influenza outbreaks in nursing homes.", "To evaluate the use of influenza vaccine in nursing homes and its effectiveness in reducing the likelihood of influenza-like illness.\n A retrospective case-control study with active identification of influenza infection.\n All nursing homes in a seven-county study area in southern lower Michigan were eligible for participation. Analyses were based on data collected from 23 homes with documented influenza transmission.\n Persons aged 65 years or older who were residents of the nursing homes under study during the influenza type A(H3N2) outbreak in 1989-1990.\n Residents were identified as cases or controls based on occurrence of febrile respiratory illness meeting a case definition. Demographic and underlying illness information were gathered as were data on the use of influenza vaccine, antibiotics, and antivirals. Characteristics of the nursing homes were also recorded. Logistic regression analyses were carried out to determine vaccine effectiveness.\n Determinants of vaccine use were different from those observed in a parallel community-based study. In a multivariate model that considered the effects of resident and nursing home characteristics, vaccinated residents were significantly less likely than those who were not vaccinated to have an influenza-like illness (OR = .58 (95% CI, .43-.78), P < .001, imputed vaccine effectiveness estimate of 42%). Vaccination was more effective in younger residents (those aged 65 to 84) then in older residents (those older than 84 years).\n Influenza vaccination was effective in reducing the likelihood of influenza-like illness in nursing home residents. Effectiveness appeared to be related to age, which may function as a surrogate for related immunologic factors. Older nursing home residents should be targeted for newer vaccines and/or potential prophylactic use of antivirals.", "The effectiveness of influenza vaccination against hospitalization and death can only ethically be assessed in observational studies. A concern is that individuals who are vaccinated are healthier than individuals who are not vaccinated, potentially biasing estimates of effectiveness upward.\n We conducted a historical cohort study of individuals >64 years of age, for whom there were data available in the General Practice Research Database for 1989 to 1999 in England and Wales. Rates of admissions for acute respiratory diseases and rates of death due to respiratory disease were compared over 692,819 person-years in vaccine recipients and 1,534,280 person-years in vaccine nonrecipients.\n The pooled effectiveness of vaccine against hospitalizations for acute respiratory disease was 21% (95% confidence interval [CI], 17%-26%). The rate reduction attributable to vaccination was 4.15 hospitalizations/100,000 person-weeks in the influenza season. Among vaccine recipients, no important reduction in the number of admissions to the hospital was seen outside influenza seasons. The pooled effectiveness of vaccine against deaths due to respiratory disease was 12% (95% CI, 8%-16%). A greater proportionate reduction was seen among people without medical disorders, but absolute rate reduction was higher in individuals with medical disorders, compared with individuals without such disorders (6.14 deaths due to respiratory disease/100,000 person-weeks vs. 3.12 deaths due to respiratory disease/100,000 person-weeks). Clear protection against death due to all causes was not seen.\n Influenza vaccination reduces the number of hospitalizations and deaths due to respiratory disease, after correction for confounding in individuals >64 years of age who had a high risk or a low risk for influenza. For elderly people, untargeted influenza vaccination is of confirmed benefit against serious outcomes.", "From December 10, 1982, to March 4, 1983, when influenza A (H3N2) viruses circulated in Michigan, outbreaks of influenza-like illness were identified in seven nursing homes in Genesee County; 272 (27%) of 1,018 residents were affected. Unvaccinated residents were more likely than vaccinated residents to become ill (risk ratio [RR], 2.6; 95% confidence interval [Cl], 1.8-3.6) and were subsequently more likely to be hospitalized (RR, 2.4; 95% Cl, 1.2-4.8), develop roentgenographically proven pneumonia (RR, 2.9; 95% Cl, 1.6-5.3), or die (RR, 5.6; 95% Cl, 1.2-9.1). Similar observations were made during investigations in six of the eight remaining nursing homes in Genesee County, in which 57 (12%) of 458 residents became ill sporadically. These findings suggest that influenza vaccine can reduce the incidence and severity of influenza virus infections among the elderly and chronically ill and underscore the importance of vaccination programs for those in nursing homes and in the general community.", "Vaccination rates for healthy senior citizens are lower than those for senior citizens with underlying medical conditions such as chronic heart or lung disease. Uncertainty about the benefits of influenza vaccination for healthy senior citizens may contribute to lower rates of utilization in this group.\n To clarify the benefits of influenza vaccination among low-risk senior citizens while concurrently assessing the benefits for intermediate- and high-risk senior citizens.\n All elderly members of a large health maintenance organization were included in each of 6 consecutive study cohorts. Subjects were grouped according to risk status: high risk (having heart or lung disease), intermediate risk (having diabetes, renal disease, stroke and/or dementia, or rheumatologic disease), and low risk. Outcomes were compared between vaccinated and unvaccinated subjects after controlling for baseline demographic and health characteristics.\n There were more than 20000 subjects in each of the 6 cohorts who provided 147551 person-periods of observation. The pooled vaccination rate was 60%. There were 101 619 person-periods of observation for low-risk subjects, 15 482 for intermediate-risk, and 30 450 for high-risk subjects. Vaccination over the 6 seasons was associated with an overall reduction of 39% for pneumonia hospitalizations (P<.001), a 32% decrease in hospitalizations for all respiratory conditions (P<.001), and a 27% decrease in hospitalizations for congestive heart failure (P<.001). Immunization was also associated with a 50% reduction in all-cause mortality (P<.001). Within the risk subgroups, vaccine effectiveness was 29%, 32%, and 49% for high-, intermediate-, and low-risk senior citizens for reducing hospitalizations for pneumonia and influenza (for high and low risk, P< or =.002; for intermediate risk, P = .11). Effectiveness was 19%, 39%, and 33% (for each, P< or =.008), respectively, for reducing hospitalizations for all respiratory conditions and 49%, 64%, and 55% for reducing deaths from all causes (for each, P<.001). Vaccination was also associated with direct medical care cost savings of $73 per individual vaccinated for all subjects combined (P = .002). Estimates of cost savings within each risk group suggest that vaccination would be cost saving for each subgroup (range of cost savings of $171 per individual vaccinated for high risk to $7 for low risk), although within the subgroups these findings did not reach statistical significance (for each, P> or =.05).\n This study confirms that healthy senior citizens as well as senior citizens with underlying medical conditions are at risk for the serious complications of influenza and benefit from vaccination. All individuals 65 years or older should be immunized with this vaccine.", "The immunogenicity and efficacy of Russian live attenuated and US inactivated trivalent influenza vaccines administered alone or in three different combinations were evaluated in a randomized, placebo-controlled, double-blinded study of 614 elderly or chronically ill nursing home residents in St. Petersburg, Russia during the 1996-97 influenza season. Postvaccination serum antibody responses were more frequent among individuals administered the combination vaccines than among those vaccinated with live or inactivated vaccine alone. Only individuals who received live vaccine, alone or in combination with inactivated vaccine, achieved significant postvaccination increases in virus-specific nasal IgA. Efficacy in preventing laboratory-confirmed influenza in vaccinated versus nonvaccinated individuals was 67% (95%CI, 36-81%) for recipients of a combination of the vaccines compared with 51% (95%CI, -17-79%) for recipients of live vaccine alone and 50% (95%CI, -26-80%) for recipients of inactivated vaccine alone. These results suggest that administration of a combination of influenza vaccines may provide a strategy for improved influenza vaccination of elderly people.", "nan", "A study was carried out in Newcastle to assess responses to influenza vaccines in elderly nursing home patients and in younger adults during 1983 and 1984. The decision to vaccinate the elderly subjects was made by their general practitioners. A concurrent randomized placebo-controlled trial of the same vaccine was performed in young adult volunteers. Elderly subjects generally possessed higher levels of pre-existing antibody to the influenzal haemagglutinins that were present in the vaccines than did younger subjects. The highest levels were observed in the 52-63 years' age group. Younger subjects showed significantly greater responses to vaccines compared with elderly subjects (P less than 0.05). Peak responses were noted in the 16-24 years' age group. Of a total of 326 elderly subjects (70% of whom had been vaccinated), six participants, two of whom had been vaccinated, contracted laboratory-proven influenza during 1983. Only one unvaccinated subject of a total of 365 subjects (50% of whom had been vaccinated) contracted influenza during 1984. In both years illness was produced by strain A/Philippines/2/82.", "An outbreak of influenza A in nursing home residents is reported and other studies of influenza vaccine effectiveness in elderly populations are reviewed. The outbreak occurred in a Los Angeles nursing home between February and March 1983. Of the 87 residents, 46 (53%) were affected with influenza-like illness. Attack rates were similar between immunized and unimmunized residents (52% versus 58%), and yielded a vaccine effectiveness estimate of 10%. No additional protection could be demonstrated in residents who received vaccine for two consecutive years. Seven persons died (mortality rate of 8.1%); the mortality rate was greater in the unimmunized (15.8%) than in the immunized (6.2%). Because this study and other field studies of influenza vaccine are limited in precision and power, a statistical summary of the various studies was constructed. Summarizing the studies of institutionalized elderly (in hospitals and nursing and retirement homes) yielded an estimate of 74% for the average vaccine effectiveness in mortality reduction, and an estimate of 33% for the average effectiveness in preventing clinical illness. For the non-institutionalized elderly, the corresponding estimates were 47% for mortality, and 5% for clinical illness. Despite the obvious limitations of such summaries, it seems reasonable to conclude that influenza vaccines have on the average been of clear benefit in the institutionalized elderly, while the benefits in the non-institutionalized elderly have been less dramatic and may warrant further investigation.", "To estimate the effectiveness of influenza vaccine in preventing hospital admission for pneumonia in non-institutionalised elderly people.\n This was a case-control study.\n All three public hospitals in the Castellón area of Spain.\n Cases were people aged 65 or more not living in an institution who were admitted to hospital for pneumonia between November 15, 1994 and March 31, 1995. Each case was matched with two sex matched control subjects aged 65 years or older admitted to hospital in the same week for acute abdominal surgical conditions or trauma. The sampling of incident cases was consecutive. Eighty three cases and 166 controls were identified and included in the study.\n Trained interviewers completed a questionnaire for each subject on the vaccination status, smoking habits, previous diseases, health care use, social contacts, family background, the vaccination status of the family carer, home characteristics, and socioeconomic status.\n The adjusted odds ratio of the influenza vaccination preventing admission to hospital for pneumonia was 0.21 (95% confidence interval 0.09, 0.55). The variables which best explained the risk of being a case were age, intensity of social contacts, health care use, previous diseases, and the existence of a vaccinated family carer.\n Influenza vaccination reduced significantly hospital admissions for pneumonia in non-institutionalised elderly people.", "In a prospective study of community-dwelling people 60-90 years of age, we examined the coverage of influenza vaccine during 1992-3 and 1993-4, the efficacy of vaccination in reducing serologically-confirmed clinical episodes of influenza A during 1993, and the effect of cigarette smoking. During 1992 and 1993, influenza vaccine was given to 106/215 (49%) and 120/204 (59%) people with risk conditions, and 84/225 (37%) and 103/235 (44%) without risk conditions. Influenza vaccination and general practitioner consultations during 1992 were independent predictors of vaccination in 1993, but current smoking was a negative predictor. Of 209 unimmunized people, 8/35 (23%) smokers had clinical influenza as compared with 11/174 (6%) non-smokers (OR 4.4, 95% CI 1.6 to 11.9). Of 371 non-smokers, 1/197 (0.5%) vaccinees had influenza as compared with 11/174 (6%) non-vaccinees (OR 0.075, 95% CI 0.587 to 0.009). No cases of influenza occurred among 21 current smokers who were vaccinated.", "The effectiveness of immunization against influenza in elderly persons is uncertain. A retrospective cohort study in a New York City nursing home examined the occurrence of pneumonia and its related mortality over three consecutive influenza seasons (Nov 1 through April 30, 1979 to 1980, 1980 to 1981, and 1981 to 1982). Nearly one half of approximately 450 residents (mean age, 84 years) accepted immunization each year. The vaccinated and unvaccinated groups were similar. The attack rate of pneumonia did not differ significantly between the vaccinated and unvaccinated groups in any of the three influenza seasons. When influenza was occurring in the community (1979 to 1980 and 1980 to 1981), however, the risk of death from pneumonia in the unvaccinated group was three-fold higher than in the vaccinated group (60% vs 18% and 73% vs 25%, respectively). In a year when influenza was specifically sought and not found in the facility (1981 to 1982), however, vaccination did not affect pneumonia-related mortality. This study also suggests that estimates of mortality due to pneumonia should include deaths that occur up to 60 days after onset of pneumonia; shorter follow-up may overestimate the protective effect of vaccination.", "The effectiveness of influenza vaccine in reducing hospital admissions for pneumonia, influenza, bronchitis, or emphysema was assessed by a case-control study of people aged 16 years and older who were admitted to 10 Leicestershire hospitals between 1 December 1989 and 31 January 1990. Hospital and general practitioners' records for 156 admissions (the cases) and 289 controls matched for age and sex were reviewed. Information was collected on demography, the usual place of residence (institutional or non-institutional), the existence of chronic illness, and vaccination during the 5 years before admission. The odds ratio for hospital admission among vaccinees was 0.67 (95% CI 0.39-1.12) giving an estimate of vaccine effectiveness in this setting of 33% (95% CI 0-61). However, multivariate logistic regression, adjusting for the effects of institutional care and chronic illness, revealed that influenza vaccination reduced hospital admissions by 63% (95% CI 17-84%). There was a strong trend towards improved vaccine effectiveness when used in institutional settings. Influenza vaccine is effective in reducing hospital admissions for influenza, pneumonia, bronchitis and emphysema, and effectiveness is comparable to that observed for influenza and pneumonia admissions in North America.", "Influenza epidemics are associated with excess winter mortality. Risk factors for influenza complications and death include chronic illness and living in residential care. In the UK uptake of influenza vaccine among high-risk groups is only 10-40%, partly because of scepticism about vaccine efficacy. We have assessed the efficacy of influenza vaccine in reducing mortality from certified influenza by a case-control study of subjects aged 16 years or older who died between Nov 4, 1989, and Feb 23, 1990, in 36 district health authorities in England. We reviewed general practitioners' records for 315 patients who died of influenza and 777 controls, matched for age, sex, and area of residence, who died a year after the epidemic. Information was collected on demography, the usual place of residence (institutional or noninstitutional), and the existence of chronic illness. Conditional logistic regression analysis for matched case-control studies showed that influenza vaccination reduced mortality by 41% (95% CI 13-60) for all subjects. Further adjustments showed that among subjects who received the vaccine for the first time in 1989, vaccination reduced mortality by 9% (0-59); however, among those who had also been vaccinated previously, mortality was reduced by 75% (31-91). We detected no significant differences in the effect of vaccine between subjects who lived in institutions and in the community (p = 0.16), or between subjects with high-risk medical conditions and those without (p = 0.76). Influenza vaccine is effective in reducing mortality from influenza, and efficacy seems to be greater after repeated annual vaccination than after first administration.", "The reactogenicities and immunogenicities of two influenza virus vaccines were compared in a placebo-controlled clinical trial among healthy ambulatory persons > or = 65 years old (mean age, 72 years). Volunteers were assigned randomly to receive 15-, 45-, or 135-micrograms doses of monovalent influenza A/Taiwan (H1N1) hemagglutinin (HA) or subvirion (SV) vaccine intramuscularly or a placebo. Increasing doses of SV vaccine were associated with a higher rate of injection site discomfort (P < 0.05; chi-square test for linear trend), but all doses of both vaccines were well tolerated. Increasing the dose of the HA or the SV vaccine resulted in increasingly higher postimmunization levels of serum hemagglutination inhibition and neutralizing antibody levels (P < 0.001; multiple linear regression). Mean serum antibody titers at 1 month increased two- to threefold with a ninefold increase in dose; the frequencies of fourfold or greater rises in titer likewise increased. An increase in the dose of the HA or the SV vaccine also resulted in increased frequencies of rises in immunoglobulin A or G antibody titers in nasal wash specimens. The frequencies increased approximately twofold for each vaccine with a ninefold increase in the dose. These data suggest that increasing the HA vaccine dose is a promising approach to the development of improved influenza virus vaccines for use in elderly people.", "nan", "The safety and immunogenicity of two recent cold-adapted reassortant influenza B viruses were evaluated in persons at high risk for influenza-related morbidity and mortality. Ambulatory adults > 65 years old or with chronic high-risk conditions were randomly assigned to receive parenteral trivalent inactivated influenza vaccine containing either influenza B/Ann Arbor/86 or B/Yamagata/88 hemagglutinin antigens, cold-adapted reassortant influenza B/Ann Arbor/1/86 or B/Yamagata/16/88 viruses (10(7.2) TCID50), or placebo in double-blind fashion. Cold-adapted vaccine viruses were well tolerated, with similar rates of respiratory symptoms in all groups. There were no changes in spirometry or oxygen saturation following vaccination. Immune responses to both types of vaccine were modest, with serum antibody responses occurring significantly more frequently and with higher magnitude in those receiving inactivated than in those receiving cold-adapted vaccine. Cold-adapted, reassortant influenza B vaccines are safe in the elderly and those with chronic illness but are not optimally immunogenic in this group.", "To assess the frequency and type of side effects after influenza vaccination in elderly people.\n Randomised double blind placebo controlled study.\n 15 general practices in the southern Netherlands.\n 1806 patients aged 60 or older, of whom 904 received influenza vaccine and 902 placebo.\n Adverse reactions reported on postal questionnaire completed four weeks after vaccination.\n 210 (23%) patients given vaccine reported one or more adverse reactions compared with 127 (14%) given placebo. The frequency of local adverse reactions were 17.5% in the vaccine group and 7.3% in the placebo group (p < 0.001). There was no difference in systemic adverse reactions (11% v 9.4%; p = 0.34). In general, men reported fewer side effects than women.\n Only local side effects were more common in vaccinated patients and all side effects were mild.", "To determine the efficacy of influenza vaccination in elderly people.\n Randomized double-blind placebo-controlled trial.\n Fifteen family practices in the Netherlands during influenza season 1991-1992.\n A total of 1838 subjects aged 60 years or older, not known as belonging to those high-risk groups in which vaccination was previously given.\n Purified split-virion vaccine containing A/Singapore/6/86(H1N1), A/Beijing/353/89(H3N2), B/Beijing/1/87, and B/Panama/45/90 (n = 927) or intramuscular placebo containing physiological saline solution (n = 911).\n Patients presenting with influenzalike illness up to 5 months after vaccination; self-reported influenza in postal questionnaires 10 weeks and 5 months after vaccination; serological influenza (fourfold increase of antibody titer between 3 weeks and 5 months after vaccination).\n The incidence of serological influenza was 4% in the vaccine group and 9% in the placebo group (relative risk [RR], 0.50; 95% confidence interval [CI], 0.35 to 0.61). The incidences of clinical influenza were 2% and 3%, respectively (RR, 0.53; 95% CI, 0.39 to 0.73). The effect was strongest for the combination of serological and clinical influenza (RR, 0.42; 95% CI, 0.23 to 0.74). The effect was less pronounced for self-reported influenza.\n In the elderly, influenza vaccination may halve the incidence of serological and clinical influenza (in periods of antigenic drift).", "nan", "nan", "To evaluate the effectiveness and possible cost savings of influenza vaccination.\n Members age 65 and older in a Medicare managed care plan during the 1994-1995, 1995-1996, and 1996-1997 influenza seasons.\n The study examined administrative data on influenza vaccination and subsequent hospitalizations. Outcomes included hospitalization with pneumonia or influenza, with any respiratory condition, and with congestive heart failure (CHF).\n Vaccinated subjects experienced fewer hospitalizations with respiratory conditions or CHF than had unvaccinated subjects (OR=0.8 (95% CI, 0.7, 0.9) in analyses adjusted for age, sex, pneumococcal vaccination, health utilization, and morbidity). Analyses adjusted in addition for ethnicity obtained similar results among the subgroup of members whose ethnicity was known. Subjects without major disease in the previous 12 months had lower odds ratios for vaccination than subjects with major disease (OR values of 0.5 [95% CI, 0.4, 0.7] and 0.9 [95% CI, 0.8, 1.1], respectively). Subjects ages 65 to 79 had lower odds ratios for vaccination than subjects ages 80 and older (OR values of 0.7 [95% CI, 0.6, 0.9] and 0.9 [95% CI, 0.8, 1.1], respectively). Estimated cost savings averaged about $80 per vaccinated subject.\n Subjects ages 65 to 79 who had received influenza vaccination experienced fewer hospitalizations and had lower costs than had unvaccinated subjects. Associations were weaker for subjects age 80 and older. The results, consistent with recommendations for the use of influenza vaccine, suggest that people ages 65 to 79 should be heavily targeted for vaccination.", "nan", "Concern about side effects constitutes a major deterrent to patient compliance with influenza vaccination, yet there is a paucity of data about the occurrence of adverse reactions in the population targeted for immunization. We conducted a randomized, double-blind, crossover trial to compare the frequency of adverse reactions following administration of 1988-1989 trivalent split-antigen influenza vaccine and saline placebo. Outpatient veterans 65 years of age or over (n = 336) were recruited by mail and were randomly assigned to receive vaccine followed 2 weeks later by placebo injection or placebo followed 2 weeks later by vaccine. There was no significant difference between influenza vaccine and placebo with respect ot the proportion of subjects reporting disability or systemic symptoms.", "This serial cohort study assessed the risk of hospitalization or death associated with influenza and the effectiveness of influenza vaccination among subgroups of elderly members of 3 managed-care organizations in the United States. Data on baseline characteristics and outcomes were obtained from computerized databases. A total of 122,974 (1996-1997 season) and 158,454 (1997-1998 season) persons were included in the cohorts. Among unvaccinated persons, hospitalizations for pneumonia/influenza or death occurred in 8.2 of 1000 healthy and 38.4 of 1000 high-risk persons in year 1, and in 8.2 of 1000 healthy and 29.3 of 1000 high-risk persons in year 2. After adjustments, vaccination was associated with a 48% reduction in the incidence of hospitalization or death (95% confidence interval [CI], 42-52) in year 1 and 31% (95% CI, 26-37) in year 2. Effectiveness estimates were statistically significant and generally consistent across the healthy and high-risk subgroups. The absolute risk reduction, however, was 2.4- to 4.7-fold higher among high-risk than among healthy elderly persons. All elderly individuals may substantially benefit from vaccination. However, the impact of influenza is greater in persons with high-risk medical conditions.", "Upper respiratory tract illnesses have been associated with an increased risk of morbidity and mortality.\n To assess the influence of vaccination against influenza on the risk of hospitalization in internal medicine and geriatric wards, and the risk of death from all causes during the 2000-2001 influenza season.\n A historical cohort study was conducted using computerized general practitioner records on patients aged 65 years and above, members of \"Maccabi Healthcare Services\"--the second largest health maintenance organization in Israel with 1.6 million members. The patients were divided into high and low risk groups corresponding to coexisting conditions, and were studied. Administrative and clinical data were used to evaluate outcomes.\n Of the 84,613 subjects in the cohort 42.8% were immunized. At baseline, vaccinated subjects were sicker and had higher rates of coexisting conditions than unvaccinated subjects. Vaccination against influenza was associated with a 30% reduction in hospitalization rates and 70% in mortality rates in the high risk group. The NNT (number needed to treat) measured to prevent one hospitalization was 53.2 (28.2 in the high risk group and 100.4 in the low risk group). When referring to length of hospitalization, one vaccine was needed to prevent 1 day of hospitalization among the high risk group. Analyses according to age and the presence or absence of major medical conditions at baseline revealed similar findings across all subgroups.\n In the elderly, vaccination against influenza is associated with a reduction in both the total risk of hospitalization and in the risk of death from all causes during the influenza season. These findings compel the rationale to increase compliance with recommendations for annual influenza vaccination among the elderly.", "We prospectively studied the efficacy of influenza vaccine during an influenza A/Arizona/80 (H3N2) outbreak at the Jewish Home and Hospital for the Aged in New York in the winter season of 1982 to 1983. All patients had been offered influenza vaccine before the outbreak; 181 chose to be vaccinated and 124 refused vaccination but agreed to participate in the study. Among those with serologic evidence of influenza infection, respiratory illness was significantly more common in the unvaccinated group (six of 14 vs one of 22). The overall mortality was 13 (7.2%) of 181 in the vaccinated group and 22 (17.7%) of 124 in the control group. The vaccinated and the control groups were examined for comparability. A logistic regression analysis, which controlled for differences in sex and level of nursing care, indicated that the difference in mortality was still significant, with a summary odds ratio of 2.7. The relative risk of death in the unvaccinated group was comparable at 2.18. Influenza vaccine reduced the mortality by 59% in the vaccinated group compared with the control group.", "This study developed methods and determined the impact of influenza vaccination on elderly persons in 3 large health plans: Kaiser Permanente Northwest, HealthPartners, and Oxford Health Plans. Data for the 1996-1997 and 1997-1998 seasons were extracted from administrative databases. Subjects were health plan members > or = 65 years old. Comorbid conditions collected from the preceding year were used for risk adjustment with logistic regression. The virus-vaccine match was excellent for year 1 and fair for year 2. Both years, during peak and total periods, vaccination reduced all causes of death and hospitalization for pneumonia and influenza: hospitalizations were reduced by 19%-20% and 18%-24% for years 1 and 2, respectively, and deaths were reduced by 60%-61% and 35%-39% for the same periods. These results show that all elderly persons should be immunized annually for influenza. The methods used in this study are an efficient cost-effective way to study vaccine impact and similar questions.", "The number of reports of influenza-vaccine-associated Guillain-Barré syndrome to the national Vaccine Adverse Event Reporting System increased from 37 in 1992-1993 to 74 in 1993-1994, arousing concern about a possible increase in vaccine-associated risk.\n Patients given a diagnosis of the Guillain-Barré syndrome in the 1992-1993 and 1993-1994 influenza-vaccination seasons were identified in the hospital-discharge data bases of four states. Vaccination histories were obtained by telephone interviews during 1995-1996 and were confirmed by the vaccine providers. Disease with an onset within six weeks after vaccination was defined as vaccine-associated. Vaccine coverage in the population was measured through a random-digit-dialing telephone survey.\n We interviewed 180 of 273 adults with the Guillain-Barré syndrome; 15 declined to participate, and the remaining 78 could not be contacted. The vaccine providers confirmed influenza vaccination in the six weeks before the onset of Guillain-Barré syndrome for 19 patients. The relative risk of the Guillain-Barré syndrome associated with vaccination, adjusted for age, sex, and vaccine season, was 1.7 (95 percent confidence interval, 1.0 to 2.8; P=0.04). The adjusted relative risks were 2.0 for the 1992-1993 season (95 percent confidence interval, 1.0 to 4.3) and 1.5 for the 1993-1994 season (95 percent confidence interval, 0.8 to 2.9). In 9 of the 19 vaccine-associated cases, the onset was in the second week after vaccination, all between day 9 and day 12.\n There was no increase in the risk of vaccine-associated Guillain-Barré syndrome from 1992-1993 to 1993-1994. For the two seasons combined, the adjusted relative risk of 1.7 suggests slightly more than one additional case of Guillain-Barré syndrome per million persons vaccinated against influenza.", "The effectiveness of influenza and pneumococcal vaccination in the prevention of hospital admissions and death has not been assessed prospectively. We have therefore examined the effects of influenza and pneumococcal vaccination in individuals aged 65 years and older in a 3-year prospective study, between Dec 1, 1998 and May 31, 1999.\n All individuals in Stockholm County aged 65 years or older (259,627) were invited to take part in a vaccination campaign against influenza and pneumococcal infection. We recorded for all vaccine recipients (100,242) name, and date of birth, and whether they had been given both or one of the vaccines. All individuals (> or = 65 years) admitted to hospital in Stockholm County with influenza and pneumonia related diagnoses were identified between Dec 1, 1998, and May 31, 1999.\n The incidence (per 100,000 inhabitants per year) of hospital treatment was lower in the vaccinated than in the unvaccinated cohort for all diagnoses: 263 versus 484 (-46% [95% CI 34-56]) for influenza; 2199 versus 3097 (-29% [24-34)) for pneumonia; 64 versus 100 (-36% [3-58]) for pneumococcal pneumonia; and 20 versus 40 (-52% [1-77]) for invasive pneumococcal disease. The total mortality was 57% (55-60) lower in vaccinated than in unvaccinated individuals (15.1 vs 34.7 deaths per 1000 inhabitants).\n These findings show that general vaccination leads to substantial health benefits and to a reduction of mortality from all causes in this age group.", "To characterize risk factors for outbreak-associated influenza illness and death in a nursing home.\n Outbreak investigation with predetermined and concurrently determined risk information.\n A nursing home service in a multiward chronic care hospital, Honolulu, Oahu, 1989 to 1990.\n Elderly nursing home patients receiving long-term care.\n Influenza vaccination, amantadine administration, and infection control measures.\n Neither routine infection control measures nor vaccination prevented illness, complications, or death in a nursing home outbreak of influenza A. The 55% case-fatality rate resulted from severe pneumonia. Influenza transmission may have been mediated by staff via either contaminated hands or fomites.\n Data from this and other outbreaks suggest that recommendations for preventing nosocomial influenza in the nation's 1.5 million nursing home residents should be reconsidered.", "An explosive outbreak of Influenza A (H3N2) occurred during early February 1985 among the 55 residents of a nursing home in Douglas, Wyoming. Thirty of the 55 (55%) had febrile respiratory illnesses. Thirty-six (65%) had received influenza vaccine. The attack rate was 84% in unvaccinated and 39% in vaccinated persons. Vaccine efficacy was estimated to be 54%. There were eight cases of pneumonia in unvaccinated and four in vaccinated persons, three deaths in unvaccinated and one death in vaccinated persons. Complement fixation and hemagglutination inhibition tests on sera from 47 residents confirmed the diagnosis of Influenza A in the great majority of individuals, and furthermore showed very low levels of antibody for the Influenza A H1N1 and Influenza B components of the vaccine.", "To assess the clinical effectiveness of influenza vaccination in preventing influenza-associated hospitalization and death.\n Case-control study.\n Noninstitutionalized persons aged 45 years or older living in Manitoba, on December 1, 1982, and December 1, 1985.\n Linked records of the Manitoba population registry, hospital-discharge abstracts, physician claims for ambulatory-patient visits and influenza vaccination, and vital statistics were used. A matched-set analysis estimated the clinical effectiveness of influenza vaccination in preventing hospital admissions and deaths from influenza-associated conditions during influenza A (H3N2) outbreak periods in 1982 to 1983 (12 weeks) and 1985 to 1986 (10 weeks). The analysis adjusted for hospital discharge and ambulatory care for high-risk conditions within the previous 15 months and 3 months, respectively.\n Influenza vaccination prevented 32% to 39% of hospital admissions with pneumonia and influenza and 15% to 34% of admissions with all respiratory conditions. Vaccination was 43% to 65% effective in preventing hospital deaths with these conditions (all listed diagnoses) and 27% to 30% effective in preventing deaths from all causes.\n Influenza vaccination has substantial clinical effectiveness in preventing hospital admission and death from influenza-associated conditions in noninstitutionalized individuals.", "nan", "nan", "Describe an outbreak of influenza A (H3N2); provide an analysis of vaccine efficacy; measure the sensitivity, specificity, and positive predictive value of 3 clinical case definitions of influenza.\n A nursing home in Washington County, Maryland. The outbreak involved 52 residents (attack rate = 47.7%) and at least 10 of 140 employees (minimum attack rate = 7.1%).\n Twenty-five residents exhibited a 4-fold or greater increase in titer to influenza A/Sichuan/2/87. Vaccine efficacy was measured at -7.1%, suggesting that the influenza vaccine in 1988/1989 did not offer optimal protection against influenza A infection for the institutionalized elderly.\n The outbreak was a clear indicator of the need for rapid diagnosis. With the use of rapid diagnostic tests, influenza A could have been detected in time to use amantadine.", "Outbreaks of influenza in nursing homes still occur, even when a large portion of residents have been inoculated with inactivated vaccine. Data were collected in 1991--1992 from 83 eligible skilled nursing homes located in southern Lower Michigan to determine the effectiveness of inactivated influenza vaccine in preventing influenza-like illness and influenza-associated pneumonia. Surveillance was conducted to identify the occurrence of influenza in the homes and, at the end of the season, specific data were gathered on all residents of homes with influenza activity. Age- and sex-adjusted estimates of vaccine effectiveness were calculated using Cox proportional hazards models for each nursing home. Estimates were pooled using precision-based weights calculated from data for each home. Vaccine was found to be 33% effective in preventing total respiratory illness (influenza-like illness and clinically diagnosed pneumonia). In prevention of pneumonia alone, vaccine was 43% effective. The estimate for prevention of pneumonia rose to 55% if the period under consideration was limited to the time of peak influenza activity. Given the number of eligible homes and the cohort methodology used, the results support continuation of current policy, encouraging use of vaccine in all nursing home residents.", "Despite recommendations for annual vaccination against influenza, more than half of elderly Americans do not receive this vaccine. In a serial cohort study, we assessed the efficacy and cost effectiveness of influenza vaccine administered to older persons living in the community.\n Using administrative data bases, we studied men and women over 64 years of age who were enrolled in a large health maintenance organization in the Minneapolis-St. Paul area. We examined the rate of vaccination and the occurrence of influenza and its complications in each of three seasons: 1990-1991, 1991-1992, and 1992-1993. Outcomes were adjusted for age, sex, diagnoses indicating a high risk, use of medications, and previous use of health care services.\n Each cohort included more than 25,000 persons 65 years of age or older. Immunization rates ranged from 45 percent to 58 percent. Although the vaccine recipients had more coexisting illnesses at base line than those who did not receive the vaccine, during each influenza season vaccination was associated with a reduction in the rate of hospitalization for pneumonia and influenza (by 48 to 57 percent, P < or = 0.002) and for all acute and chronic respiratory conditions (by 27 to 39 percent, P < or = 0.01). Vaccination was also associated with a 37 percent reduction (P = 0.04) in the rate of hospitalization for congestive heart failure during the 1991-1992 season, when influenza A was epidemic. The costs of hospitalization for all types of illness studied were lower in the vaccinated group during 1991-1992 (range of reduction, 47 to 66 percent; P < 0.005) and for acute and chronic respiratory conditions and congestive heart failure in 1990-1991 (reductions of 37 percent and 43 percent, respectively; P < or = 0.05). Direct savings per year averaged $117 per person vaccinated (range, $21 to $235), with cumulative savings of nearly $5 million. Vaccination was also associated with reductions of 39 to 54 percent in mortality from all causes during the three influenza seasons (P < 0.001).\n For elderly citizens living in the community, vaccination against influenza is associated with reductions in the rate of hospitalization and in deaths from influenza and its complications, as compared with the rates in unvaccinated elderly persons, and vaccination produces direct dollar savings.", "Case-control study designed to determine the effectiveness of an MF59-adjuvanted influenza vaccine in the population aged 65 years and older living in the community. Detailed health histories were obtained on both cases and controls that included a functional measure of co-morbidity (Barthel Index). Subjects were all eligible persons admitted to various hospitals with a diagnosis of pneumonia during the winter months and were matched by sex, hospital and admission week to controls admitted for non-medical reasons. The influenza vaccination programme using the MF59-adjuvanted influenza vaccine significantly reduced the probability of being hospitalised for pneumonia in the elderly over 64 years of age, even in a season with a low influenza activity, during which the predominant circulating strains were types B and A (H1N1).", "To evaluate the effectiveness of anti-flu vaccination on elderly people not in institutions, by measuring its effect on the reduction of deaths and hospital admissions due to Cardio-respiratory failure.\n A retrospective cohort.\n La Chana Health Centre, Granada.\n 1,965 elderly people who were seen at the Health Centre over the previous three years.\n 779 elderly people (39.6%) were vaccinated. 35 were admitted to hospital with Cardio-respiratory failure and 59 died. Of these two groups, 13 and 23 respectively had been given the anti-flu vaccination that year. After checking for variables which could lead to confusion, the vaccine was shown to be effective both in reducing admissions (advantage ratio 1,330) and deaths (advantage ratio 1,221).\n Given the effectiveness of anti-flu vaccinations, active efforts to encourage non-institutionalised elderly people to be vaccinated should be increased.", "Assess the effectiveness of influenza vaccination in reducing hospitalization due to pneumonia and influenza among elderly subjects in a community in central Italy. Estimate the hospitalization fraction preventable by extending the vaccination program.\n Case-control study. Cases were subjects aged 65+ at hospital admission (1 December 1994-31 March 1995). For each case two population controls were randomly chosen, matched by sex, age and residence. Variables of interest were recorded through a postal questionnaire and telephone interview. A matched-set analysis was carried out adjusting for concomitant chronic diseases, education, type of home heating, and smoking habits. The preventable fraction of hospitalization was computed through the application of the attributable risk estimate. The setting was 33 municipalities in central Italy including 169,370 residents aged 65 years or more.\n Two hundred and seventy-five cases 550 controls were analyzed. Influenza vaccination was effective in preventing 33% of hospitalization due to pneumonia/influenza. The fraction of hospital admissions preventable by extending the vaccination was 17%. When the analysis was limited to self-respondents to the questionnaire (excluding next-of-kin) and to pneumonia/influenza as primary discharge diagnosis, protection from hospitalization by vaccination almost reached 50%, a better result in comparison with most case-control studies.\n Influenza vaccination was shown to be successful in reducing hospital admissions due to pneumonia and influenza. A large number of hospitalizations could be reduced extending the vaccination campaign.", "The effect of influenza vaccination on the occurrence and severity of influenza virus infection in a population residing in nursing homes was studied through a program by the Osaka Prefectural Government, which is the first and official support for influenza vaccination of the elderly population during an influenza A (H3N2) epidemic in JAPAN:\n A cohort study located in the Osaka Prefecture, Japan, followed the outcomes of elderly nursing home residents who received influenza vaccinations (n = 10,739) in comparison with control subjects who did not receive influenza vaccinations (n = 11,723) and monitored clinically the onset of serious morbidity and mortality of influenza illness. Subjects were 22,462 persons older than 65 years who resided in 301 welfare nursing homes in the Osaka Prefecture, Japan during an influenza A (H3N2) epidemic in 1998 to 1999.\n Of 22,462 individuals living in 301 nursing homes, 10,739 received either one dose (2027 subjects) or two doses (8712 subjects) of inactivated, subunit trivalent influenza vaccine. Through the period from November 1998 to March 1999, there were 950 cases of influenza infection diagnosed clinically with cases by virus isolation and/or serology. There were statistically significantly fewer clinical cases of influenza, hospital admissions due to severe infection, and deaths due to influenza in the vaccinated cohort (256 cases, 32 hospital admissions, and one death) compared with the unvaccinated controls (694 cases, 150 hospital admissions, and five deaths). Vaccination was equally effective in those who received one dose of vaccine as in those who received two doses. No serious adverse reactions to vaccination were recorded. Thus, influenza vaccination is safe and effective in this population and should be an integral part of the routine care of persons aged 65 years and older residing in nursing homes.\n This study provides an analysis of the clinical efficacy of influenza vaccination in a large cohort of nursing home residents in JAPAN: Annual influenza vaccine administration requires the attention of all nursing home attendants, physicians, and public health organizations.", "nan", "Upper respiratory tract illnesses have been associated with an increased risk of ischemic heart disease and stroke. During two influenza seasons, we assessed the influence of vaccination against influenza on the risk of hospitalization for heart disease and stroke, hospitalization for pneumonia and influenza, and death from all causes.\n Cohorts of community-dwelling members of three large managed-care organizations who were at least 65 years old were studied during the 1998-1999 and 1999-2000 influenza seasons. Administrative and clinical data were used to evaluate outcomes, with multivariable logistic regression to control for base-line demographic and health characteristics of the subjects.\n There were 140,055 subjects in the 1998-1999 cohort and 146,328 in the 1999-2000 cohort, of which 55.5 percent and 59.7 percent, respectively, were immunized. At base line, vaccinated subjects were on average sicker, having higher rates of most coexisting conditions, outpatient care, and prior hospitalization for pneumonia than unvaccinated subjects. Unvaccinated subjects, however, were more likely to have been given a prior diagnosis of dementia or stroke. Vaccination against influenza was associated with a reduction in the risk of hospitalization for cardiac disease (reduction of 19 percent during both seasons [P<0.001]), cerebrovascular disease (reduction of 16 percent during the 1998-1999 season [P<0.018] and 23 percent during the 1999-2000 season [P<0.001]), and pneumonia or influenza (reduction of 32 percent during the 1998-1999 season [P<0.001] and 29 percent during the 1999-2000 season [P<0.001]) and a reduction in the risk of death from all causes (reduction of 48 percent during the 1998-1999 season [P<0.001] and 50 percent during the 1999-2000 season [P<0.001]). In analyses according to age, the presence or absence of major medical conditions at base line, and study site, the findings were consistent across all subgroups.\n In the elderly, vaccination against influenza is associated with reductions in the risk of hospitalization for heart disease, cerebrovascular disease, and pneumonia or influenza as well as the risk of death from all causes during influenza seasons. These findings highlight the benefits of vaccination and support efforts to increase the rates of vaccination among the elderly.\n Copyright 2003 Massachusetts Medical Society", "An outbreak of influenza A occurred in an elderly population in a Maryland nursing home between December 8, 1980 and January 13, 1981 and involved 76 of the 170 residents. Throat swabs from two of 10 acutely ill residents yielded influenza A virus similar to the A/Taiwan/1/79 strain. Fourfold or greater increases in the titer of complement-fixing (CF) or hemagglutination-inhibiting (HI) antibodies were detected in paired sera from four of five ill residents and from none of four well residents. One hundred (62.9 per cent) of 159 residents with known vaccination histories had been vaccinated with trivalent influenza virus vaccine in October and November 1980. Crude illness attack rates and mortality rates were similar in vaccinees and nonvaccinees. Various risk factors and hypotheses were examined in an attempt to explain the apparent lack of vaccine efficacy.", "In a three-year influenza vaccination programme carried out among elderly patients these were found to have a lower haemagglutination-inhibiting antibody level and a poorer serological response to vaccination than younger persons in the same city. Although there was little difference in overall respiratory illness between the vaccinated and unvaccinated groups until the third year of observation, those who received vaccine showed a substantially smaller incidence of bronchopneumonia and a significantly lower mortality than those not so protected. The observations are believed to justify the giving of influenza vaccine in this age-group." ]

[ "9609364", "10326334" ]

[ "Conservative surgical approach versus non-surgical management for diabetic neuropathic foot ulcers: a randomized trial.", "Diabetic foot ulcerations. A controlled, randomized comparison of two moist wound healing protocols: Carrasyn Hydrogel Wound dressing and wet-to-moist saline gauze." ]

[ "To test the efficacy of surgical treatment of non-infected neuropathic foot ulcers compared to conventional non-surgical management, a group of diabetic outpatients attending our diabetic foot clinic were studied. All patients who came to the clinic for the first time from January to December 1995 inclusive with an uncomplicated neuropathic ulcer were randomized into two groups. Group A received conservative treatment, consisting of relief of weight-bearing, regular dressings; group B underwent surgical excision, eventual debridement or removal of bone segments underlying the lesion and surgical closure. Healing rate, healing time, prevalence of infection, relapse during a 6-month period following intervention and subjective discomfort were assessed. Twenty-four ulcers in 21 patients were treated in group A (17 Type 2 DM/3 Type 1 DM, age 63.24 +/- 13.46 yr, duration of diabetes 18.2 +/- 8.41 yr, HbA1c 9.5 +/- 3.8%) and 22 ulcers in 21 patients in group B (19 Type 2 DM/2 Type 1 DM, age 65.53 +/- 9.87yr, duration of diabetes 16.84 +/- 10.61 yr; HbA1c 8.9 +/- 2.2%). Healing rate was lower (79.2% = 19/24 ulcers) in group A than in group B (95.5% = 21/22 ulcers; p < 0.05), and healing time was longer (128.9 +/- 86.60 days vs 46.73 +/- 38.94 days; p < 0.001). Infective complications occurred significantly more often in group A patients (3/24, 12.5% vs 1/22, 4.5%; p < 0.05), as did relapses of ulcerations (8 vs 3; p < 0.01). There were only two minor perioperative complications in group B patients. Patients reported a higher degree of satisfaction in group B (p < 0.01) as well as lower discomfort (p < 0.05) and restrictions (p < 0.05). Thus surgical treatment of neuropathic foot ulcers in diabetic patients proved to be an effective approach compared to conventional treatment in terms of healing time, complications, and relapses, and can be safely performed in an outpatient setting.", "nan" ]

[ "15796635", "16322140", "19091806", "20686425", "11289465", "20216531", "22353006", "9640900", "16819378", "18411833", "20061311", "16456392", "17327320", "15382974", "20167185", "16822102", "22108765", "12712059", "8201068", "15944167", "19091804", "18540868", "21890828", "21522034", "9303253", "373642", "16078340", "16861397", "19695776", "10907154", "16093516" ]

[ "Using problem-solving skills training to reduce negative affectivity in mothers of children with newly diagnosed cancer: report of a multisite randomized trial.", "The effects of multisystemic therapy on diabetes stress among adolescents with chronically poorly controlled type 1 diabetes: findings from a randomized, controlled trial.", "Conducting a randomized clinical trial of an psychological intervention for parents/caregivers of children with cancer shortly after diagnosis.", "A family-based randomized controlled trial of pain intervention for adolescents with sickle cell disease.", "Behavior therapy for families of adolescents with diabetes: maintenance of treatment effects.", "Cognitive-behavioral therapy for children with functional abdominal pain and their parents decreases pain and other symptoms.", "Home-based family intervention for low-income children with asthma: a randomized controlled pilot study.", "Brief report: an intervention program for parents of pediatric cancer patients: a randomized controlled trial.", "Treatment of nonorganic recurrent abdominal pain: cognitive-behavioral family intervention.", "Incorporating family therapy into asthma group intervention: a randomized waitlist-controlled trial.", "Problem-solving skills training for vulnerable families of children with persistent asthma: report of a randomized trial on health-related quality of life outcomes.", "Putting the pieces together: preliminary efficacy of a family problem-solving intervention for children with traumatic brain injury.", "Randomized trial of behavioral family systems therapy for diabetes: maintenance of effects on diabetes outcomes in adolescents.", "Treatment of posttraumatic stress symptoms in adolescent survivors of childhood cancer and their families: a randomized clinical trial.", "Telehealth behavior therapy for the management of type 1 diabetes in adolescents.", "An online family intervention to reduce parental distress following pediatric brain injury.", "Cognitive behavioral therapy for the treatment of juvenile fibromyalgia: a multisite, single-blind, randomized, controlled clinical trial.", "Impact of ambulatory, family-focused teamwork intervention on glycemic control in youth with type 1 diabetes.", "The treatment of recurrent abdominal pain in children: a controlled comparison of cognitive-behavioral family intervention and standard pediatric care.", "A randomized controlled trial of a cognitive-behavioral family intervention for pediatric recurrent abdominal pain.", "Report from a multi-institutional randomized clinical trial examining computer-assisted problem-solving skills training for English- and Spanish-speaking mothers of children with newly diagnosed cancer.", "Short-term effects of coping skills training in school-age children with type 1 diabetes.", "Effect on behavior problems of teen online problem-solving for adolescent traumatic brain injury.", "Coping skills training for parents of children with type 1 diabetes: 12-month outcomes.", "Brief cognitive-behavioral group treatment for children's headache.", "Childhood asthma. A controlled trial of family psychotherapy.", "Efficacy of cognitive-behavioral intervention for juvenile primary fibromyalgia syndrome.", "Headstrong: a pilot study of a CD-ROM intervention for recurrent pediatric headache.", "Randomized controlled trial of an Internet-delivered family cognitive-behavioral therapy intervention for children and adolescents with chronic pain.", "[Direct versus video-aided parent education in atopic eczema in childhood as a supplement to specialty physician treatment. A controlled pilot study].", "Online psychological treatment for pediatric recurrent pain: a randomized evaluation." ]

[ "Mothers of children with cancer experience significant distress associated with their children's diagnosis and treatment. The efficacy of problem-solving skills training (PSST), a cognitive-behavioral intervention based on problem-solving therapy, was assessed among 430 English- and Spanish-speaking mothers of recently diagnosed patients. Participants were randomized to usual psychosocial care (UPC; n=213) or UPC plus 8 sessions of PSST (PSST; n=217). Compared with UPC mothers, PSST mothers reported significantly enhanced problem-solving skills and significantly decreased negative affectivity. Although effects were largest immediately after PSST, several differences in problem-solving skills and distress levels persisted to the 3-month follow-up. In general, efficacy for Spanish-speaking mothers exceeded that for English-speaking mothers. Findings also suggest young, single mothers profit most from PSST.\n Copyright (c) 2005 APA, all rights reserved", "The goal of this study was to determine whether multisystemic therapy (MST), an intensive, home-based psychotherapy, could decrease diabetes-related stress among adolescents with chronically poorly controlled type 1 diabetes. Stress was also evaluated as a mediator of the effect of MST on adherence and metabolic control.\n A randomized, controlled trial was conducted with 127 adolescents with type 1 diabetes mellitus and chronically poor metabolic control (hemoglobin A1c levels of > or =8% at study enrollment and for the past 1 year) who received their diabetes care in a children's hospital located in a major Midwestern city. Participants assigned randomly to MST received treatment for approximately 6 months. Data were collected at baseline and at a 7-month posttest (ie, treatment termination). Changes in diabetes-related stress, as measured with a self-report questionnaire, were assessed. Structural equation models were used to test the degree to which changes in stress levels mediated the ability of the MST intervention to improve adherence and metabolic control.\n In intent-to-treat analyses, participation in MST was associated with significant reductions in diabetes-related stress. Tests for moderation found no significant effects of age, gender, or ethnicity, which suggests that the intervention was equally effective in reducing diabetes stress for all participants. However, structural equation modeling did not provide support for diabetes stress as the mechanism through which MST improved health outcomes. Rather, the final model suggested that MST improved metabolic control through increased regimen adherence.\n Intensive, home-based psychotherapy reduces diabetes-related stress among adolescents with chronically poorly controlled type 1 diabetes. Such stress reductions are important for the psychological wellbeing of a subset of youths with diabetes who are at high risk for future health complications.", "To report acceptability, feasibility, and outcome data from a randomized clinical trial (RCT) of a brief intervention for caregivers of children newly diagnosed with cancer.\n Eighty-one families were randomly assigned following collection of baseline data to Intervention or Treatment as Usual (TAU). Recruitment and retention rates and progression through the protocol were tracked. Measures of state anxiety and posttraumatic stress symptoms served as outcomes.\n Difficulties enrolling participants included a high percentage of newly diagnosed families failing to meet inclusion criteria (40%) and an unexpectedly low participation rate (23%). However, movement through the protocol was generally completed in a timely manner and those completing the intervention provided positive feedback. Outcome data showed no significant differences between the arms of the RCT.\n There are many challenges inherent in conducting a RCT shortly after cancer diagnosis. Consideration of alternative research designs and optimal timing for interventions are essential next steps.", "The study had 2 aims---to determine the efficacy of a family-based cognitive-behavioral pain management intervention for adolescents with sickle cell disease (SCD) in (1) reducing pain and improving health-related variables and (2) improving psychosocial outcomes. Each adolescent and a family support person were randomly assigned to receive a brief pain intervention (PAIN) (n=27) or a disease education attention control intervention (DISEASE ED) (n=26) delivered at home. Assessment of primary pain and health-related variables (health service use, pain coping, pain-related hindrance of goals) and secondary psychosocial outcomes (disease knowledge, disease self-efficacy, and family communication) occurred at baseline (before randomization), postintervention, and 1-year follow-up. Change on outcomes did not differ significantly by group at either time point. When groups were combined in exploratory analyses, there was evidence of small to medium effects of intervention on health-related and psychosocial variables. Efforts to address barriers to participation and improve feasibility of psychosocial interventions for pediatric SCD are critical to advancing development of effective treatments for pain. Sample size was insufficient to adequately test efficacy, and analyses did not support this focused cognitive-behavioral pain management intervention in this sample of adolescents with SCD. Exploratory analyses suggest that comprehensive interventions, that address a broad range of skills related to disease management and adolescent health concerns, may be more effective in supporting teens during healthcare transition.", "This study reports 6- and 12-month follow-up for the families of adolescents with diabetes who participated in a trial of Behavioral-Family Systems Therapy (BFST).\n A total of 119 families of adolescents with type 1 diabetes were randomized to 3 months of treatment with either BFST, an education and support (ES) group, or current therapy (CT). Family relationships, adjustment to diabetes, treatment adherence, and diabetic control were assessed at baseline, after 3 months of treatment, and 6 and 12 months later. This report focuses on the latter two evaluations.\n Compared with CT and ES, BFST yielded lasting improvements in parent-adolescent relationships and diabetes-specific conflict. Delayed effects on treatment adherence emerged at 6- and 12-month follow-ups. There were no immediate or delayed effects on adolescents' adjustment to diabetes or diabetic control.\n BFST yielded lasting improvement in parent-adolescent relationships and delayed improvement in treatment adherence, but it had no effect on adjustment to diabetes or diabetic control. A variety of adaptations to BFST could enhance its impact on diabetes outcomes.", "Unexplained abdominal pain in children has been shown to be related to parental responses to symptoms. This randomized controlled trial tested the efficacy of an intervention designed to improve outcomes in idiopathic childhood abdominal pain by altering parental responses to pain and children's ways of coping and thinking about their symptoms.\n Two hundred children with persistent functional abdominal pain and their parents were randomly assigned to one of two conditions-a three-session intervention of cognitive-behavioral treatment targeting parents' responses to their children's pain complaints and children's coping responses, or a three-session educational intervention that controlled for time and attention. Parents and children were assessed at pretreatment, and 1 week, 3 months, and 6 months post-treatment. Outcome measures were child and parent reports of child pain levels, function, and adjustment. Process measures included parental protective responses to children's symptom reports and child coping methods.\n Children in the cognitive-behavioral condition showed greater baseline to follow-up decreases in pain and gastrointestinal symptom severity (as reported by parents) than children in the comparison condition (time x treatment interaction, P<0.01). Also, parents in the cognitive-behavioral condition reported greater decreases in solicitous responses to their child's symptoms compared with parents in the comparison condition (time x treatment interaction, P<0.0001).\n An intervention aimed at reducing protective parental responses and increasing child coping skills is effective in reducing children's pain and symptom levels compared with an educational control condition.", "Low-income African American children have disproportionately higher asthma morbidity and mortality. Education alone may not address barriers to asthma management due to psychosocial stress. This study evaluated the efficacy of a home-based family intervention integrating asthma education and strategies to address stress using a community-based participatory research model. Children age 8 to 13 with poorly controlled asthma and their caregivers were recruited from an urban hospital and an asthma camp. Caregivers with elevated scores on a stress measure were enrolled. Forty-three families were randomized to the 4- to 6-session Home Based Family Intervention (HBFI) or the single session of Enhanced Treatment as Usual (ETAU). All families received an asthma action plan and dust mite covers; children performed spirometry and demonstrated MDI/spacer technique at each home visit. The HBFI addressed family-selected goals targeting asthma management and stressors. Asthma management, morbidity, family functioning, and caregiver stress were assessed at baseline, postintervention, and 6 months after the intervention. ED visits and hospitalizations were ascertained by medical record review for a year after intervention completion. Only one child (5%) in HBFI had an asthma-related hospitalization compared to 7 patients (35%) in ETAU in the year following intervention. Participants in both groups demonstrated improved asthma management and family functioning, and reduced ED visits, symptom days, missed school days, and caregiver stress, but there were no differential treatment effects. The results suggest that a home-based intervention addressing medical and psychosocial needs may prevent hospitalizations for children with poorly controlled asthma and caregivers under stress.\n (c) 2012 APA, all rights reserved.", "To evaluate a psychoeducational intervention program for parents of pediatric cancer patients, using cognitive and behavioral techniques.\n Parents were randomly assigned to an intervention (n = 39) and a control condition (n = 42). Baseline assessment took place at diagnosis. Short-term effects were measured immediately after the intervention, long-term effects six months later. Control parents received standard care. Intervention parents received, in addition, a manual-guided program during the first six months following the diagnosis.\n With time all parents became significantly less psychologically distressed. However, no between-group differences were noted in psychological functioning, satisfaction with support, and intensity of emotions immediately postintervention and six months later.\n Although the clinical evaluation of the intervention was positive, it appeared that a structured intervention program as described in this study was not any more effective than standard care.", "We evaluated the efficacy of cognitive-behavioral family intervention in the treatment of crises of pain in children with nonorganic recurrent abdominal pain (RAP) and the thresholds of pain for 17 body surface areas in these children.\n A randomized clinical trial was undertaken with 32 children between the ages of 5.1 and 13.9 years with nonorganic RAP. A group of 15 patients, aged 9.9 +/- 2.2 years (11 girls), received standard pediatric care and cognitive-behavioral family intervention for treatment of pain crises. The control group of 17 children, aged 8.4 +/- 2.0 years (11 girls), received only standard pediatric care. These procedures were undertaken by general pediatricians over 4 monthly sessions. An analog visual scale was used to measure the frequency and intensity of the pain crises per month and a mechanical pressure algometer for the measurement of pain threshold.\n The median frequency of pain crises per month reported by patients at the 3 monthly cognitive-behavioral family intervention sessions was 15, 5, 2 and 2, respectively. In contrast, the median frequency for pain crises per month reported by the control group was 12, 8, 10 and 8, respectively. The difference between the intervention group and the controls was statistically significant for frequency of pain at the second, third and fourth visits. There was no statistical difference for intensity of pain or for measured pain thresholds between the control and the intervention group.\n The cognitive-behavioral family intervention reduced the frequency of pain crises of children with nonorganic RAP. This successful intervention was carried out by the intervention of general pediatricians.", "Asthma psychoeducational programs have been found to be effective in terms of symptom-related outcome. They are mostly illness-focused, and pay minimal attention to systemic/familial factors. This study evaluated a novel asthma psychoeducation program that adopted a parallel group design and incorporated family therapy. A randomized waitlist-controlled crossover clinical trial design was adopted. Children with stable asthma and their parents were recruited from a pediatric chest clinic. Outcome measures included, for the patients: exhaled nitric oxide (eNO), spirometry, and adjustment to asthma; and for the parents: perceived efficacy in asthma management, Hospital Anxiety and Depression Scale anxiety subscale, Body Mind Spirit Well-being Inventory emotion subscale, and Short Form 12 health-related quality of life scale. Forty-six patients participated in the study. Attrition rates were 13.0% and 26.0% for the active and control groups, respectively. Repeated-measures ANOVA revealed a significant decrease in airway inflammation, as indicated by eNO levels, and an increase in patient's adjustment to asthma and parents' perceived efficacy in asthma management. Serial trend analysis revealed that most psychosocial measures continued to progress steadily after intervention. Significant improvements in both symptom-related measures and mental health and relationship measures were observed. The findings supported the value of incorporating family therapy into asthma psychoeducation programs.", "To test the efficacy of problem-solving skill training (PST) in improving health-related quality of life (HRQOL) of children with persistent asthma from predominantly lower socioeconomic status (SES) Spanish-speaking Hispanic families.\n Randomized controlled trial comparing standard care waitlist (SC) control, home-visiting asthma education/care coordination (CC), and combined intervention (CC + PST) at baseline, after intervention, and 6-month follow-up. The primary outcome was parent proxy-report child HRQOL (PedsQL).\n Participants (n = 252) were 83.3% Hispanic and 56.3% monolingual Spanish speakers, and 72.6% of mothers had not graduated high school. We found a significant (P = 0.05) intervention effect for parent proxy-reported child generic (but not asthma-specific) HRQOL, with CC + PST superior to SC [83.8 vs 79.8; adjusted mean difference of 4.05 points (95% confidence interval 0.63-7.4], but no difference between the CC and SC groups.\n In this sample of vulnerable families of children with persistent asthma, a CC + PST intervention was efficacious in improving children's generic HRQOL.", "To describe a family-centered problem-solving intervention (FPS) for pediatric traumatic brain injury (TBI), and to assess the efficacy of the intervention in a randomized clinical trial.\n Families of 32 school-aged children with moderate to severe TBI randomly assigned to FPS or usual care (UC) group.\n Child Behavior Checklist, Brief Symptom Inventory, Conflict Behavior Questionnaire.\n Seven-session problem-solving/skill-building intervention delivered over a 6-month period for the participating families.\n Parents in the FPS group reported significantly greater improvements in their children in internalizing symptoms, anxiety/depression, and withdrawal than did parents in the UC comparison group.\n FPS holds promise for reducing child behavior problems, the most common and persistent sequelae of TBI.", "Studies showing that family communication and conflict resolution are critical to effective management of type 1 diabetes in adolescents have stimulated interest in evaluating psychological treatments targeting these processes. Previous trials have shown that Behavioral Family Systems Therapy (BFST) improved parent-adolescent relationships but not treatment adherence or glycemic control. This study evaluates a revised intervention, BFST for Diabetes (BFST-D), modified to achieve greater impact on diabetes-related family conflict, treatment adherence, and metabolic control.\n A sample of 104 families of adolescents with inadequate control of type 1 diabetes was randomized to either remain in standard care (SC) or to augmentation of that regimen by 12 sessions of either a multifamily educational support (ES) group or 12 sessions of BFST-D over 6 months. Pertinent measures were collected at baseline and at follow-up evaluations at 6, 12, and 18 months.\n BFST-D was significantly superior to both SC and ES in effects on A1C, while effects on treatment adherence and family conflict were equivocal. Improvement in A1C appeared to be mediated by improvement in treatment adherence. A significantly higher percentage of BFST-D youth achieved moderate or greater improvement (>0.5 SD) in treatment adherence compared with the SC group at each follow-up and the ES group at 6 and 18 months. Change in treatment adherence correlated significantly with change in A1C at each follow-up.\n These results support the efficacy of BFST-D in improving A1C, but further research is needed to identify the mechanisms of this effect and to achieve cost-effective dissemination of the intervention.", "Posttraumatic stress symptoms (PTSS), particularly intrusive thoughts, avoidance, and arousal, are among the most common psychological aftereffects of childhood cancer for survivors and their mothers and fathers. We conducted a randomized wait-list control trial of a newly developed 4-session, 1-day intervention aimed at reducing PTSS that integrates cognitive-behavioral and family therapy approaches--the Surviving Cancer Competently Intervention Program (SCCIP). Participants were 150 adolescent survivors and their mothers, fathers, and adolescent siblings. Significant reductions in intrusive thoughts among fathers and in arousal among survivors were found in the treatment group. A multiple imputations approach was used to address nonrandom missing data and indicated that treatment effects would likely have been stronger had more distressed families been retained. The data are supportive of brief interventions to reduce PTSS in this population and provide additional support for the importance of intervention for multiple members of the family.\n Copyright 2004 American Psychological Association", "Poor management of type 1 diabetes mellitus (T1DM) may result in serious medical complications. Psychological intervention may improve adherence to medical regimens; however, access to trained professionals is limited, particularly in rural communities. Telehealth interventions may address this by allowing families to access services at home; however, little is known about the efficacy of such services.\n This study presents results from a pilot trial of a randomized waitlist controlled trial of Telehealth Behavioral Therapy (TBT) for youths with T1DM. Primary outcome measures were adherence to the diabetes regimen, glycemic control, and level of family discord. Thirty-two youths (23 female) with T1DM (aged 9 to 17 years) and one parent or caregiver participated. Telehealth Behavioral Therapy sessions were conducted thrice weekly for 12 weeks by phone and lasted an average of 15 min each.\n Results indicated that youths in treatment decreased their hemoglobin A1c by 0.74 compared to 0.09 in the waitlist, though this was not statistically significant. Youths in treatment reported increased unsupportive and decreased caring parental behaviors.\n Telehealth Behavioral Therapy improves access to knowledgeable providers and results in a clinically significant improvement in glycemic control. Despite some youths experiencing an increase in unsupportive parental behaviors, TBT is a promising method of service delivery that warrants further investigation.\n 2010 Diabetes Technology Society.", "This study examined whether an online problem-solving intervention could improve parental adjustment following pediatric traumatic brain injury (TBI). Families of children with moderate-to-severe TBI were recruited from the trauma registry of a large children's hospital and randomly assigned to receive online family problem solving therapy (FPS; n = 20) or Internet resources (IRC; n = 20) in addition to usual care. The FPS group reported significantly less global distress, depressive symptoms, and anxiety at follow-up than did the IRC group after controlling for baseline symptoms. The FPS group also reported significant improvements in problem-solving skills, although the groups did not differ significantly at follow-up. Findings suggest that an online, skill-building approach can be effective in facilitating parental adaptation after TBI.\n Copyright 2006 APA, all rights reserved.", "Juvenile fibromyalgia syndrome (FMS) is a chronic musculoskeletal pain disorder in children and adolescents for which there are no evidence-based treatments. The objective of this multisite, single-blind, randomized clinical trial was to test whether cognitive-behavioral therapy (CBT) was superior to fibromyalgia (FM) education in reducing functional disability, pain, and symptoms of depression in juvenile FMS.\n Participants were 114 adolescents (ages 11-18 years) with juvenile FMS. After receiving stable medications for 8 weeks, patients were randomized to either CBT or FM education and received 8 weekly individual sessions with a therapist and 2 booster sessions. Assessments were conducted at baseline, immediately following the 8-week treatment phase, and at 6-month followup.\n The majority of patients (87.7%) completed the trial per protocol. Intent-to-treat analyses showed that patients in both groups had significant reductions in functional disability, pain, and symptoms of depression at the end of the study, and CBT was significantly superior to FM education in reducing the primary outcome of functional disability (mean baseline to end-of-treatment difference between groups 5.39 [95% confidence interval 1.57, 9.22]). Reduction in symptoms of depression was clinically significant for both groups, with mean scores in the range of normal/nondepressed by the end of the study. Reduction in pain was not clinically significant for either group (<30% decrease in pain). There were no study-related adverse events.\n In this controlled trial, CBT was found to be a safe and effective treatment for reducing functional disability and symptoms of depression in adolescents with juvenile FMS.\n Copyright © 2012 by the American College of Rheumatology.", "To evaluate an ambulatory, family-focused intervention aimed at optimizing\n Study design We randomly assigned 105 children and adolescents, 8 to 17 years of age, with T1DM for < or =6 years, to a family-focused teamwork (TW) intervention or to standard multidisciplinary diabetes care (SC). Patients in both study groups were seen at 3- to 4-month intervals and were followed prospectively for 1 year. Measures of family involvement in diabetes tasks, DFC, and quality of life were performed at baseline and after 1 year. Hemoglobin A1c was measured at each visit.\n Patients (n = 100) completed follow-up, (50 in TW and 50 in SC). At entry, A1c was 8.4% +/- 1.3% in TW and 8.3% +/- 1.0% in SC. After 1 year, A1c was 8.2% +/- 1.1% in TW compared with 8.7% +/- 1.5% in SC (P <.05). Both groups had similar frequencies of blood glucose monitoring (BGM) and insulin dosing. Families exposed to the TW intervention maintained or increased family involvement significantly more than families exposed to SC (P =.05). In multivariate analysis, the TW intervention and the daily frequency of BGM significantly predicted A1c (R (2) = 0.17, P =.05). Despite increased family involvement, the TW group reported no increase in DFC or decrease in quality of life.\n The ambulatory TW intervention prevented the expected deterioration in glycemic control seen with SC in youths with T1DM of < or =6 years' duration. Successful family involvement may assist in the preservation of health and the prevention of long-term diabetes complications for youth with diabetes.", "This study describes the results of a controlled clinical trial involving 44 7- to 14-year-old children with recurrent abdominal pain who were randomly allocated to either cognitive-behavioral family intervention (CBFI) or standard pediatric care (SPC). Both treatment conditions resulted in significant improvements on measures of pain intensity and pain behavior. However, the children receiving CBFI had a higher rate of complete elimination of pain, lower levels of relapse at 6- and 12-month follow-up, and lower levels of interference with their activities as a result of pain and parents reported a higher level of satisfaction with the treatment than children receiving SPC. After controlling for pretreatment levels of pain, children's active self-coping and mothers' caregiving strategies were significant independent predictors of pain behavior at posttreatment.", "To investigate whether the combination of standard medical care (SMC) and short-term cognitive-behavioral family treatment (CBT) in the treatment of recurrent abdominal pain (RAP) was more effective than SMC alone.\n Children recently diagnosed with RAP via physician examination were randomized into SMC (n = 29) and SMC plus CBT (n = 40) groups. Outcome measures included multiple dimensions of child and parent reported child pain, somatization, and functional disability, and school absences and physician contacts.\n Children and parents participating in the combined SMC + CBT intervention reported significantly less child and parent reported child abdominal pain than children in the SMC intervention immediately following the intervention and up to 1 year following study entry, as well as significantly fewer school absences. Significant differences in functional disability and somatization were not revealed.\n These results, in combination with previous studies, add support to the effectiveness of CBT intervention in reducing the sensory aspects of RAP. Results are discussed with respect to the cost-benefit of integrated medical and short-term psychological services.", "To evaluate the feasibility and efficacy of a handheld personal digital assistant (PDA)-based supplement for maternal Problem-Solving Skills Training (PSST) and to explore Spanish-speaking mothers' experiences with it.\n Mothers (n = 197) of children with newly diagnosed cancer were randomized to traditional PSST or PSST + PDA 8-week programs. Participants completed the Social Problem-Solving Inventory-Revised, Beck Depression Inventory-II, Profile of Mood States, and Impact of Event Scale-Revised pre-, post-treatment, and 3 months after completion of the intervention. Mothers also rated optimism, logic, and confidence in the intervention and technology.\n Both groups demonstrated significant positive change over time on all psychosocial measures. No between-group differences emerged. Despite technological \"glitches,\" mothers expressed moderately high optimism, appreciation for logic, and confidence in both interventions and rated the PDA-based program favorably. Technology appealed to all Spanish-speaking mothers, with younger mothers showing greater proficiency.\n Well-designed, supported technology holds promise for enhancing psychological interventions.", "Little is known about the use of psychosocial interventions in children younger than adolescence with type 1 diabetes (T1D) and their parents. We report preliminary short-term outcomes of a randomized controlled trial of coping skills training (CST) compared with group education (GE) in school-aged children with T1D and their parents.\n One hundred and eleven children (range = 8-12 yr) with T1D for at least 6 months (3.71 +/- 2.91 yr) were randomized to CST (55.6% female (F); 81.5% white (W)) or GE (69.7% F; 90.9% W). Children and parents (n = 87) who completed the intervention, baseline, 1- and 3-month data are included. Children completed measures of self-efficacy, coping, and quality of life; parents completed measures of family functioning (adaptability and cohesion), diabetes-related conflict, parent depression, and parent coping. Metabolic control was assessed with glycosylated hemoglobin A1c. Mixed-model repeated measures anova was used to analyze the data.\n CST and GE group composition was generally comparable. Children had good psychosocial adaptation and metabolic status. CST parents reported significantly more improvement in family adaptability compared with GE parents, and a trend was seen indicating that CST children showed greater improvement in life satisfaction than GE children. Effect sizes for this short-term follow-up period were small, but group participants were receptive to the intervention and reported positive gains.\n In these preliminary results, CST and GE were more similar than different across multiple measure of psychosocial adaptation, although CST showed promising statistical trends for more adaptive family functioning and greater life satisfaction. Longer term follow-up is underway.", "To report the results of a randomized clinical trial of teen online problem-solving (TOPS) meant to improve behavioral outcomes of adolescents with traumatic brain injury (TBI).\n A randomized clinical trial was conducted to compare the efficacy of TOPS with access to Internet resources in teenagers with TBI in improving parent and self-reported behavior problems and parent-teen conflicts. Participants included 41 adolescents aged 11 to 18 years (range: 11.47-17.90 years) who had sustained a moderate-to-severe TBI between 3 and 19 months earlier. Teens in the TOPS group received 10 to 14 online sessions that provided training in problem-solving, communication skills, and self-regulation. Outcomes were assessed before treatment and at a follow-up assessment an average of 8 months later. Groups were compared on follow-up scores after we controlled for pretreatment levels. Injury severity and socioeconomic status were examined as potential moderators of treatment efficacy.\n Forty-one participants provided consent and completed baseline assessments, and follow-up assessments were completed for 35 participants (16 TOPS, 19 Internet resource comparison). The TOPS group reported significantly less parent-teen conflict at follow-up than did the Internet-resource-comparison group. Improvements in teen behavior after TOPS were moderated by injury severity; there were greater improvements in the teens' internalizing symptoms after TOPS among adolescents with severe TBI. Family socioeconomic status also moderated the efficacy of TOPS in improving behavior problems reported by both parents and teens, although the nature of the moderation effects varied.\n Our findings suggest that TOPS contributes to improvements in parent-teen conflict generally and parent and self-reported teen behavior problems for certain subsets of participants.", "Although it is recognized that caring for a child with Type 1 diabetes (T1D) is stressful for parents, few interventions have been developed and tested for this population.\n The aim of this study was to compare a group educational intervention for parents of children with T1D to a coping skills training intervention.\n Parents of children with T1D were randomized to the group educational (n = 106) or coping skills training (n = 75) conditions. Parents completed measures of family conflict, responsibility for treatment, coping, and quality of life at baseline and at 3, 6, and 12 months postintervention. Clinical data (i.e., HbA1c) were collected from children's medical records preintervention and postintervention.\n There were no significant treatment effects 12 months postintervention, but parents in both groups reported improved coping (p < .001), less responsibility for treatment management (p < .001), and improved quality of life (p = .005). While children's metabolic control worsened over time, mean values at 12 months were still within the recommended levels in this well-controlled sample (HbA1c <8%).\n Group-based interventions for parents of children with T1D may lessen the impact of treatment management, improving coping and quality of life.", "Using a randomized design with a waiting list control condition, we assessed the effectiveness of an abbreviated cognitive therapy group program for headaches in children 7 to 12 years of age. In the treatment condition, small groups of five to eight children were taught relaxation, distraction, visualization, and stress management skills in two 90-minute sessions. Parent groups, seen concurrently, reviewed the children's program and addressed parenting strategies. The waiting list control groups were treated 5 weeks later. Thirty-six children meeting inclusion criteria were included in the study; complete data were available for 29 participants (mean age, 9.4 years; 66% female). DEPENDENT MEASURES: We obtained children's ratings of headache frequency, intensity, duration, and five other variables in a diary kept for 3 weeks before and 3 weeks after treatment. Parent measures were collected once before treatment and once at 3-month follow-up.\n CHILD RATINGS: The control condition showed a significant reduction in children's self-rated headache frequency, while the treatment condition did not. On all other self-reported variables, there were no significant differences between the control and treatment conditions. Two participants in each condition achieved a 50% or greater reduction in a self-rating headache index.\n PARENT RATINGS: Follow-up ratings, obtained over the telephone from parents after the children in both conditions had been treated, indicated that the children in both conditions had experienced reduced intensity, frequency, and duration of headaches and that 82% of the children were using the techniques taught in the program. Fourteen children achieved a 50% or greater reduction in a headache index based on parent ratings.\n Although parents were very positive about the effectiveness of the program, the results for children's self-ratings do not support the use of this highly abbreviated treatment method.", "In an attempt to evaluate the effectiveness of family psychotherapy as an adjunct conventional treatment in childhood asthma, children with moderate to severe asthma were randomly allocated to a control group or to an experimental group; the latter group received 6 hours of family treatment during a 4-month period, and both groups had standard medical treatment. While there was no significant difference between the two groups on three parameters, the experimental group were significantly better in day-wheeze score and thoracic gas volume. These results suggest that family treatment in selected cases may have a place in the overall management of childhood asthma, and that more research with larger numbers of children is necessary.", "There are currently no controlled studies of behavioral interventions for juvenile primary fibromyalgia syndrome (JPFM). In this small-sample randomized study, we tested the efficacy of a behavioral intervention, i.e., coping skills training (CST), for the treatment of adolescents with JPFM. Outcomes tested in this study were functional disability, pain intensity, pain-coping efficacy, and depressive symptoms.\n Thirty patients with JPFM were randomly assigned to 8 weeks of either CST or self-monitoring. Adolescents in the CST condition received training in active pain-coping techniques, while those in the self-monitoring condition monitored daily pain intensity and sleep quality with no instructions about behavior change. After posttreatment assessment, subjects were crossed over into the opposite treatment arm for 8 weeks (so that all adolescents eventually received both CST and self-monitoring) and were reassessed at Week 16.\n At Week 8, adolescents in both conditions showed significant decrease in depressive symptoms and functional disability. Those who received CST showed significantly greater ability to cope with pain than those in the self-monitoring condition and a trend toward decreased pain intensity. At Week 16, adolescents had significantly lower levels of disability and depressive symptoms compared to baseline, but those who received self-monitoring followed by CST seemed to receive the most benefit.\n CST can lead to improved functioning among JPFM patients. Although some of the improvement may be due to increased monitoring and attention, CST provides the specific benefit of improving adolescents' ability to cope with pain.", "To empirically evaluate a minimal therapist contact CD-ROM pain management program for recurrent pediatric headache developed as part of this study.\n Participants were 37 children aged 7-12 attending a pediatric neurology clinic for evaluation of recurrent headache. Children who were randomly assigned to the treatment group worked through the CD-ROM program on home computers for 4 weeks following baseline assessment, whereas those assigned to the wait-list group continued following the prescriptions of their neurologist. Data on daily headache activity and headache-related disability were collected at baseline and up to 3 months after treatment.\n Children who received the adjunctive CD-ROM program had significant improvements in headache activity above and beyond those in the control group. Results provide initial support for the utility of adding an adjunctive CD-ROM psychological intervention to standard medical care for recurrent pediatric headache and potentially other chronic pain conditions in children.", "Cognitive-behavioral therapy (CBT) interventions show promise for decreasing chronic pain in youth. However, the availability of CBT is limited by many factors including distance to major treatment centers and expense. This study evaluates a more accessible treatment approach for chronic pediatric pain using an Internet-delivered family CBT intervention. Participants included 48 children, aged 11-17 years, with chronic headache, abdominal, or musculoskeletal pain and associated functional disability, and their parents. Children were randomly assigned to a wait-list control group or an Internet treatment group. Primary treatment outcomes were pain intensity ratings (0-10 NRS) and activity limitations on the Child Activity Limitations Interview, both completed via an online daily diary. In addition to their medical care, the Internet treatment group completed 8 weeks of online modules including relaxation training, cognitive strategies, parent operant techniques, communication strategies, and sleep and activity interventions. Youth randomized to the wait-list control group continued with the current medical care only. Findings demonstrated significantly greater reduction in activity limitations and pain intensity at post-treatment for the Internet treatment group and these effects were maintained at the three-month follow-up. Rate of clinically significant improvement in pain was also greater for the Internet treatment group than for the wait-list control group. There were no significant group differences in parental protectiveness or child depressive symptoms post-treatment. Internet treatment was rated as acceptable by all children and parents. Findings support the efficacy and acceptability of Internet delivery of family CBT for reducing pain and improving function among children and adolescents with chronic pain.", "Psychological problems in children and parents related to children's atopic eczema (AE) may impede the success of treatment. We studied the question, if behavior-based parental education in groups (DPE) or standardized video-education (VPE) could enhance dermatological treatment effects and reduce skin-damaging behaviors in children and stress in their mothers.\n 47 mothers attending the university outpatient-clinic for dermatology and their AE-children (mean age 4 years) participated in the study. 18 mothers underwent the DPE (10 sessions), 15 mothers worked with VPE at home. Dermatological standard treatment (CG; N = 14) served as control for a 16-weeks-evaluation-period.\n AE-symptoms improved overall, but the effectiveness of the treatments differed significantly, improval with parent education and was best with VPE. Psychological problems of mothers were equally reduced with DPE and VPE.\n It is suggested that VPE is a cost effective and less time consuming method for supporting dermatological therapy of AE in children.", "To evaluate the efficacy of a distance treatment delivered through Internet and telephone for pediatric recurrent pain.\n Forty-seven participants (9-16 years of age) were randomly assigned to either an Internet-based treatment or a standard medical care waitlist. Treatment employed a Web-based manual for children and parents with weekly therapist contact by telephone or e-mail. At 1- and 3-month follow-ups, participants were assessed on the outcome variables of pain and quality of life. A 50% reduction in diary pain scores was considered clinically significant.\n Significant between-group differences were found: 71 and 72% of the treatment group achieved clinically significant improvement at the 1- and 3-month follow-ups, respectively, whereas only 19 and 14% of the control group achieved the criterion. No significant differences were found on the quality of life variable.\n Distance methods have considerable potential for making effective treatments more accessible with lower associated costs." ]

[ "11794558", "7362427", "17978323", "10560218", "5658377" ]

[ "Efficacy of inpatient and home treatment in psychiatrically disturbed children and adolescents. Follow-up assessment of the results of a controlled treatment study.", "Home vs hospital care of children with behavior disorders. A controlled investigation.", "Clinical effectiveness of treatments for anorexia nervosa in adolescents: randomised controlled trial.", "Home-based multisystemic therapy as an alternative to the hospitalization of youths in psychiatric crisis: clinical outcomes.", "Avoiding institutionalization of psychotic children." ]

[ "In two German child and adolescent psychiatric treatment and research centers, a controlled treatment study was conducted in which two randomized treatment groups (in-patient treatment and home treatment) were compared. Subjects were children and adolescents with severe psychiatric disorders, for whom normal outpatient treatment was not sufficient (mean age of the patients was 11 years and 9 months at the beginning of treatment). The results showed no differences in therapy outcome between the two treatment modalities. In a further study, the results of which are presented here, a follow-up assessment (average follow-up interval: 3 years and 8 months) of the two treatment groups (follow-up sample of the inpatient treatment group: n = 33; home treatment group: n = 35) was undertaken in order to investigate the course of the psychiatric disturbances and the long-term effects of the treatments. As measurement categories for the outcome \"adaption at school\" and \"number of marked symptoms\" were used in pre-, post- and follow-up assessment. The most important results are 1) The number of marked psychiatric symptoms and the adaptation at school or work exhibit the same type of course over time. Post-treatment scores are much better when compared to pre-treatment scores, but decline slightly upon follow-up, although they remain significantly better than the pre-treatment scores. Thus, the study shows that improvements relating to the psychiatric symptoms are quite stable after several years. 2) There were no relevant differences between the treatment modalities \"inpatient treatment\" and \"home treatment\" in terms of effect-size upon follow-up, and in inferential analysis. Any tendency towards difference was in favor of home treatment. So the results give strong support to the conclusion that at least for a specific group of patients (about 15% of those patients usually treated in an inpatient setting) residential treatment can be replaced by home treatment and that the long-term therapeutic outcome of home treatment is stable and persistent. Thus, in terms of psychiatric care and clinical practice, our results provide empirical support to the idea that home treatment should be used more frequently and much more broadly in the future.", "A controlled investigation was conducted to assess and compare the treatment outcomes of community and hospital care for children with behavior disorders. Findings showed that (1) community care was effective with regard to behavioral control, and (2) both treatments were comparable concerning educational achievement, parent role function, family adjustment, and parent satisfaction with treatment. It was noted that many severely disturbed children who are in dire socioeconomic predicaments can be maintained in the community with special care and intervention.", "Treatment guidelines identify few adequately powered trials to guide recommendations for anorexia nervosa.\n To evaluate the effectiveness of three readily available National Health Service treatments for adolescents (aged 12-18 years) with anorexia nervosa.\n Multicentre randomised controlled trial of 167 young people comparing in-patient, specialist out-patient and general child and adolescent mental health service (CAMHS) treatment.\n Each group made considerable progress at 1 year, with further improvement by 2 years. Full recovery rates were poor (33% at 2 years, 27% still with anorexia nervosa). Adherence to in-patient treatment was only 50%. Neither in-patient nor specialist out-patient therapy demonstrated advantages over general CAMHS treatment by intention to treat, although some CAMHS out-patients were subsequently admitted on clinical grounds. In-patient treatment (randomised or after out-patient transfer) predicted poor outcomes.\n First-line in-patient psychiatric treatment does not provide advantages over out-patient management. Out-patient treatment failures do very poorly on transfer to in-patient facilities.", "The primary purpose of this study was to determine whether multisystemic therapy (MST), modified for use with youths presenting psychiatric emergencies, can serve as a clinically viable alternative to inpatient psychiatric hospitalization.\n One hundred sixteen children and adolescents approved for emergency psychiatric hospitalization were randomly assigned to home-based MST or inpatient hospitalization. Assessments examining symptomatology, antisocial behavior, self-esteem, family relations, peer relations, school attendance, and consumer satisfaction were conducted at 3 times: within 24 hours of recruitment into the project, shortly after the hospitalized youth was released from the hospital (1-2 weeks after recruitment), and at the completion of MST home-based services (average of 4 months postrecruitment).\n MST was more effective than emergency hospitalization at decreasing youths' externalizing symptoms and improving their family functioning and school attendance. Hospitalization was more effective than MST at improving youths' self-esteem. Consumer satisfaction scores were higher in the MST condition.\n The findings support the view that an intensive, well-specified, and empirically supported treatment model, with judicious access to placement, can effectively serve as a family- and community-based alternative to the emergency psychiatric hospitalization of children and adolescents.", "nan" ]

[ "15115831", "20554983", "16420253" ]

[ "Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection.", "Antiretroviral regimens in pregnancy and breast-feeding in Botswana.", "A prospective, 96-week study of the impact of Trizivir, Combivir/nelfinavir, and lamivudine/stavudine/nelfinavir on lipids, metabolic parameters and efficacy in antiretroviral-naive patients: effect of sex and ethnicity." ]

[ "Regimens containing three nucleoside reverse-transcriptase inhibitors offer an alternative to regimens containing nonnucleoside reverse-transcriptase inhibitors or protease inhibitors for the initial treatment of human immunodeficiency virus type 1 (HIV-1) infection, but data from direct comparisons are limited.\n This randomized, double-blind study involved three antiretroviral regimens for the initial treatment of subjects infected with HIV-1: zidovudine-lamivudine-abacavir, zidovudine-lamivudine plus efavirenz, and zidovudine-lamivudine-abacavir plus efavirenz.\n We enrolled a total of 1147 subjects with a mean baseline HIV-1 RNA level of 4.85 log10 (71,434) copies per milliliter and a mean CD4 cell count of 238 per cubic millimeter were enrolled. A scheduled review by the data and safety monitoring board with the use of prespecified stopping boundaries led to a recommendation to stop the triple-nucleoside group and to present the results in the triple-nucleoside group in comparison with pooled data from the efavirenz groups. After a median follow-up of 32 weeks, 82 of 382 subjects in the triple-nucleoside group (21 percent) and 85 of 765 of those in the combined efavirenz groups (11 percent) had virologic failure; the time to virologic failure was significantly shorter in the triple-nucleoside group (P<0.001). This difference was observed regardless of the pretreatment HIV-1 RNA stratum (at least 100,000 copies per milliliter or below this level; P< or =0.001 for both comparisons). Changes in the CD4 cell count and the incidence of grade 3 or grade 4 adverse events did not differ significantly between the groups.\n In this trial of the initial treatment of HIV-1 infection, the triple-nucleoside combination of abacavir, zidovudine, and lamivudine was virologically inferior to a regimen containing efavirenz and two or three nucleosides.\n Copyright 2004 Massachusetts Medical Society", "The most effective highly active antiretroviral therapy (HAART) to prevent mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) in pregnancy and its efficacy during breast-feeding are unknown.\n We randomly assigned 560 HIV-1-infected pregnant women (CD4+ count, > or = 200 cells per cubic millimeter) to receive coformulated abacavir, zidovudine, and lamivudine (the nucleoside reverse-transcriptase inhibitor [NRTI] group) or lopinavir-ritonavir plus zidovudine-lamivudine (the protease-inhibitor group) from 26 to 34 weeks' gestation through planned weaning by 6 months post partum. A total of 170 women with CD4+ counts of less than 200 cells per cubic millimeter received nevirapine plus zidovudine-lamivudine (the observational group). Infants received single-dose nevirapine and 4 weeks of zidovudine.\n The rate of virologic suppression to less than 400 copies per milliliter was high and did not differ significantly among the three groups at delivery (96% in the NRTI group, 93% in the protease-inhibitor group, and 94% in the observational group) or throughout the breast-feeding period (92% in the NRTI group, 93% in the protease-inhibitor group, and 95% in the observational group). By 6 months of age, 8 of 709 live-born infants (1.1%) were infected (95% confidence interval [CI], 0.5 to 2.2): 6 were infected in utero (4 in the NRTI group, 1 in the protease-inhibitor group, and 1 in the observational group), and 2 were infected during the breast-feeding period (in the NRTI group). Treatment-limiting adverse events occurred in 2% of women in the NRTI group, 2% of women in the protease-inhibitor group, and 11% of women in the observational group.\n All regimens of HAART from pregnancy through 6 months post partum resulted in high rates of virologic suppression, with an overall rate of mother-to-child transmission of 1.1%. (ClinicalTrials.gov number, NCT00270296.)\n 2010 Massachusetts Medical Society", "To compare the lipid and metabolic effects, efficacy, and safety of twice-daily regimens of Trizivir (abacavir 300 mg/lamivudine 150 mg/zidovudine 300 mg triple nucleoside tablet; TZV), Combivir (lamivudine 150 mg/zidovudine 300 mg combination tablet; COM)+nelfinavir (NFV), and stavudine (d4 T)+lamivudine (3TC)+NFV.\n An international, phase 4, open-label, parallel-group, 34-centre study was conducted in 254 non-diabetic, antiretroviral-naive, HIV-infected out-patients with an HIV-1 RNA level of >1000 HIV-1 RNA copies/mL and < or =200,000 copies/mL and a CD4 cell count of >50 cells/microL.\n Patients were randomized 1 : 1 : 1 to TZV twice daily (n = 85), COM/NFV 1250 mg twice daily (n = 88), or d4T 40 mg+3TC 150 mg+NFV 1250 mg twice daily (n = 81) for 96 weeks. Treatments were compared using analysis of covariance (ANCOVA) with regard to changes from baseline in fasting lipids in the total population and in sex and ethnic subgroups. The proportions of patients achieving HIV-1 RNA <50 and <400 copies/mL were compared using a 95% confidence interval (CI) on the difference between proportions.\n The study population was diverse (50% female, 40% black and 37% Hispanic). Mean baseline low-density lipoprotein (LDL) cholesterol was 99 mg/dL, HIV-1 RNA was 4.43 log10 copies/mL and CD4 cell count was 355 cells/microL. At week 96, fasting LDL cholesterol changed minimally in the TZV group [least square mean (LSM) change from baseline, -8 mg/dL], but increased with d4T/3TC/NFV and COM/NFV (+29 and +19 mg/dL, respectively; P < 0.001 versus TZV). Week 96 LDL-cholesterol levels were significantly lower in the TZV group than in the other two treatment groups in women and men and lower than in the d4T/3TC/NFV group in Hispanic and black patients. In black patients, the week-96 LSM change from baseline in LDL cholesterol was significantly less with TZV than with d4T/3TC/NFV (+1 vs+39 mg/dL; P = 0.003). Total cholesterol >200 mg/dL occurred in a smaller proportion of patients receiving TZV (30%) compared with COM/NFV (50%) or d4T/3TC/NFV (60%; P = 0.005 vs TZV). High-density lipoprotein (HDL) cholesterol did not change markedly with any treatment. Although triglycerides increased, they changed least in women and Hispanic patients receiving TZV. Virological and CD4 responses to the treatments were similar in the total population and in the subgroups. Diarrhoea was reported more often in the NFV arms and nausea in the ZDV arms.\n Over 96 weeks, TZV twice daily has significantly less effect on LDL cholesterol than COM/NFV or d4T/3TC/NFV twice daily, especially in women and black patients, and is associated with similar virological and CD4 responses." ]

[ "18675970", "1633902", "2723511", "1955546" ]

[ "Ovarian follicular flushing among low-responding patients undergoing assisted reproductive technology.", "A prospective randomized study comparing aspiration only with aspiration and flushing for transvaginal ultrasound-directed oocyte recovery.", "A prospective randomized comparison of single- and double-lumen needles for transvaginal follicular aspiration.", "Is follicular flushing necessary for oocyte retrieval? A randomized trial." ]

[ "A randomized comparison trial was performed to evaluate whether follicular reaspiration with use of a double-lumen retrieval needle improves oocyte recovery when compared with direct follicular aspiration among low-responding patients undergoing ART. There were no differences observed in the number of oocytes retrieved (single lumen: 6.5 +/- 2.2 oocytes, double lumen: 7.2 +/- 2.3 oocytes) whereas follicular reaspiration with the double-lumen retrieval needle resulted in a twofold increase in procedure time.", "To compare aspiration only with aspiration and flushing of ovarian follicles during transvaginal ultrasound (US)-directed oocyte recovery.\n Prospective randomized study.\n One hundred patients who were undergoing an in vitro fertilization (IVF) treatment cycle.\n All patients underwent pituitary desensitization before the administration of gonadotropins. Monitoring of ovarian stimulation and the criteria for the administration of human chorionic gonadotropin were similar in both groups. In patients in whom aspiration alone was used, each follicle was aspirated until it was empty. The US probe was then rotated until every drop of follicular fluid had been aspirated before the next follicle was aspirated and the procedure repeated. For patients who had aspiration and flushing, each follicle was aspirated and then flushed up to a maximum of six times before moving to the next follicle. In both groups, all follicles greater than 10 mm were aspirated.\n The indication for IVF and mean age of the patients were comparable in the two groups. There were no significant differences between the aspiration and the aspiration and flushing groups in terms of the number of oocytes retrieved (11 versus 9), the oocyte recovery rates (77.5% versus 77.0%), the fertilization rates (55.6% versus 60.0%), the number of embryos transferred (2 versus 2), or the number of clinical pregnancies (12 versus 13). The time taken for oocyte recovery was significantly shorter (15 versus 30 minutes, P less than 0.00001), and the dose of pethidine required significantly less (50 mg versus 100 mg, P less than 0.00001) in the aspiration only group.\n Aspiration alone produces comparable oocyte recovery rates as aspiration and flushing while significantly reducing the length of the procedure and the dose of analgesia required. Aspiration alone suffices for virtually all cases during transvaginal US-directed oocyte recovery.", "Patients undergoing ultrasound-directed transvaginal follicular aspiration in a large in vitro fertilization (IVF) program were randomized for retrieval with either a single-lumen needle (SLN; N = 22) or a double-lumen needle (DLN; N = 22) to compare recovery rates and the technical aspects of their use. Two hundred ten and two hundred two follicles were aspirated with each needle, respectively. Follicular diameters were measured ultrasonically at the time of aspiration and recorded. One or more washes were performed when using the DLN and the SLN was withdrawn each time to recover the fluid in the dead space of the needle. The distribution of follicular sizes was the same for both needles. Oocyte recovery rates (SLN = 65.7%; DLN = 63.9%) and the incidence of fractured zonae (SLN = 9.1%; DLN = 6.4%) were the same for both needles (alpha greater than 0.50; beta less than 0.01). Although there were no differences between the two needles in the number of oocytes provided for IVF, there were technical differences. The DLN needle was more flexible and frequently deviated from the projected path as observed by ultrasound. The SLN may be preferable because it is technically easier to use; however, there may remain specific indications for the use of the DLN.", "A prospective randomized trial was performed to evaluate the necessity of follicular flushing during transvaginal, ultrasonically guided oocyte recovery under mild sedation. Patients with tubal damage as the sole cause of their infertility were randomized into one of two groups. Group one had their follicles aspirated only. Follicles of patients in Group 2 were aspirated and flushed with a total of 10 ml of flushing medium. There was no significant difference in the number of oocytes retrieved, fertilization rate or pregnancy rate in each group. There was, however, a significant shortening of operating time in the aspiration only group." ]

[ "11889647", "11889659", "17689192", "19604319", "16570467", "7892015", "8907093", "12455427", "16495014", "7616460", "11523332", "10373091", "19837207", "3607094", "8371179", "20655662" ]

[ "Physical self-regulation training for the management of temporomandibular disorders.", "A randomized clinical trial using research diagnostic criteria for temporomandibular disorders-axis II to target clinic cases for a tailored self-care TMD treatment program.", "Hypnosis in the management of persistent idiopathic orofacial pain--clinical and psychosocial findings.", "Effect of hypnosis on oral function and psychological factors in temporomandibular disorders patients.", "Efficacy of an early intervention for patients with acute temporomandibular disorder-related pain: a one-year outcome study.", "Brief group cognitive-behavioral intervention for temporomandibular disorders.", "Dysfunctional patients with temporomandibular disorders: evaluating the efficacy of a tailored treatment protocol.", "A randomized clinical trial of a tailored comprehensive care treatment program for temporomandibular disorders.", "Short- and long-term efficacy of brief cognitive-behavioral therapy for patients with chronic temporomandibular disorder pain: a randomized, controlled trial.", "Cognitive therapy in the treatment of patients with resistant burning mouth syndrome: a controlled study.", "Long-term efficacy of biobehavioral treatment of temporomandibular disorders.", "Posture correction as part of behavioural therapy in treatment of myofascial pain with limited opening.", "Group psychotherapy: an additional approach to burning mouth syndrome.", "A comparison of treatment modes in the management of myofascial pain dysfunction syndrome.", "Effects of intraoral appliance and biofeedback/stress management alone and in combination in treating pain and depression in patients with temporomandibular disorders.", "Brief cognitive-behavioral treatment for TMD pain: long-term outcomes and moderators of treatment." ]

[ "To evaluate the long-term effectiveness of a brief skills training program for the management of chronic facial muscle pain. This program of physical self-regulation (PSR) involved primarily training in breathing, postural relaxation, and proprioceptive re-education.\n Physical self-regulation training was presented by a dentist during two 50-minute sessions spaced at 3-week intervals and was compared to a standard dental care (SDC) program that included a flat-plane intraoral appliance and self-care instructions provided by a dentist. Participants (n = 44) were initially evaluated by a dentist experienced in the diagnosis and management of orofacial pain and were determined to have myofascial pain (Type 1a and 1b diagnoses per the Research Diagnostic Criteria) prior to random assignment to either the PSR or SDC conditions. Posttreatment evaluations 6 weeks and 26 weeks after treatment had begun were conducted by a dentist who was not aware of which treatment the participants received.\n Initial results indicated that pain severity and life interference from pain were reduced in both groups (P < 0.001), while perception of control was increased (P < 0.001), as was incisal opening without pain (P < 0.05). At the 26-week follow-up, the PSR group reported less pain (P < 0.04) and greater incisal opening, both with (P < 0.04) and without (P < 0.01) pain, than the SDC group. There were also significant decreases (P < 0.05) in affective distress, somatization, obsessive-compulsive symptoms, tender point sensitivity, awareness of tooth contact, and sleep dysfunction for both groups over time.\n The findings support the use of PSR for the short- and long-term management of muscle pain in the facial region. These results are discussed in terms of the potential mechanisms by which self-regulation treatment strategies are effective for the management of these pain disorders.", "To carry out a randomized clinical trial (RCT) contrasting usual conservative treatment of TMD by clinical TMD specialists with a structured self-care intervention, targeted to clinic cases independent of TMD physical diagnosis, who were reporting minimal levels of psychosocial dysfunction; the intervention was delivered by dental hygienists in lieu of usual treatment.\n The Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) was used to target subjects who exhibited minimal TMD-related psychosocial interference. Criteria for study inclusion were: (1) self-report of facial and/or masticatory muscle pain discomfort for which usual care was prescribed by the clinic TMD specialist; (2) RDC/TMD Axis II graded scale of chronic pain (GCP) score of 0, I, or II-Low. (3) Age 18 to 70 years.\n On 1-year follow-up, while both groups showed improvement in all clinical and self-report categories measured, patients in the tailored self-care treatment program compared to usual TMD treatment showed significantly; (a) decreased TMD pain, (b) decreased pain-related interference in activity; (c) reduced number of masticatory muscles painful; (d) fewer additional visits for TMD treatment. Groups were comparable with regard to measures of vertical range of motion. The self-care program was associated with consistent, but non-statistically significant, trends towards lower levels of depression and somatization. Ability to cope with TMD, knowledge concerning TMD and patient satisfaction was significantly enhanced for the self-care group. No participating patients experienced physical or personal adverse effects during the 1-year post-treatment follow-up period.\n Use of RDC/TMD psychosocial assessment criteria can contribute to successful clinical decision-making for the management of TMD.", "This controlled and patient blinded study tested the effect of hypnosis on persistent idiopathic orofacial pain (PIOP) in terms of clinical and psychosocial findings. Forty-one PIOP were randomized to active hypnotic intervention or simple relaxation as control for five individual 1-h sessions. Primary outcome was average pain intensity scored three times daily in a pain diary using visual analogue scale (VAS). Secondary outcome measures were pain quality assessed by McGill pain questionnaire (MPQ), psychological symptoms assessed by symptom check list (SCL), quality of life assessed by SF36, sleep quality, and consumption of analgesic. Data were compared between groups before and after treatment using ANOVA models and paired t-tests. The change in VAS pain scores from baseline to the last treatment (t4) was (33.1+/-7.4%) in the hypnosis group and (3.2+/-5.4%) in the control group (P<0.03). In the hypnosis group, highly hypnotic susceptible patients had greater decreases in VAS pain scores (55.0+/-12.3%) when compared to less susceptible patients (17.9+/-6.7%) (P<0.02). After the last treatment there were also statistically significant differences between groups in perceived pain area (MPQ) and the use of weak analgesics (P<0.03). There were no statistically significant changes in SCL or SF36 scores from baseline to t4. In conclusion, hypnosis seems to offer clinically relevant pain relief in PIOP, particularly in highly susceptible patients. However, stress coping skills and unresolved psychological problems need to be included in a comprehensive management plan in order also to address psychological symptoms and quality of life.", "This study investigated the effect of hypnosis in patients with temporomandibular disorders (TMD) with focus on oral function and psychological outcomes. Forty women (mean age +/- s.d.: 38.6 +/- 10.8 years) suffering from TMD (mean duration 11.9 +/- 9.9 years) were randomized to four individual 1-hour sessions of either hypnotic intervention or a control condition of simple relaxation. Pain intensity was assessed three times daily on a 0-10 Numerical Rating Scale. Additional outcomes were TMD-associated symptoms assessed by the Research Diagnostic Criteria examination form and questionnaire, psychological symptoms (Symptom Check List 60), pain coping strategies (Coping Strategies Questionnaire), sleep difficulties (Pittsburgh Sleep Quality Index) and use of analgesics. Data were analyzed with between-groups within-subjects anovas. The hypnosis group significantly reduced the daily NRS pain scores from 4.5 +/- 2.1 at baseline to 2.9 +/- 2.4 after treatment (P < 0.001) compared to the control group where no significant changes were found (4.2 +/- 1.4 to 3.9 +/- 1.5) (P = 0.733). Number needed to treat for a 50% pain reduction was 4.0. The hypnosis group also increased use of the coping strategy 'reinterpreting pain sensations' from 5.2 +/- 6.9 to 10.3 +/- 6.8 (P < 0.001). Both groups exhibited significant reductions in the number of painful muscle palpation sites and pain on palpation (P < 0.004), in number of awakenings due to pain (P < 0.006), and in somatization, obsessive compulsive symptoms and anxiety (P < 0.004). Hypnosis thus appears to effectively reduce some aspects of complex TMD pain.", "The authors conducted a randomized clinical trial to evaluate the efficacy of a biopsychosocial intervention for patients who were at high risk (HR) of progressing from acute to chronic temporomandibular disorder (TMD)-related pain.\n The authors classified subjects' risk using a predictive algorithm and randomized them into an early-intervention (EI) or a nonintervention (NI) group. The EI included cognitive behavioral skills training and biofeedback. The authors assessed pain and psychosocial measures at intake and at a one-year follow-up. Subjects' self-reported pain levels were measured on an analog scale and as a response to palpation.\n At one year, EI-group subjects had significantly lower levels of self-reported pain and depression. At one year, more NI-group subjects than EI-group subjects had utilized health care for jaw-related pain. NI-group subjects were 12.5 times as likely to have a somatoform disorder, more than seven times as likely to have an anxiety disorder, and 2.7 times more likely to have an affective disorder at one year, compared with EI-group subjects.\n EI-group subjects had reduced pain levels, improved coping abilities and reduced emotional distress at one year.\n The TMD-related pain experience is complex and requires early identification with a biopsychosocial EI to achieve maximal, sustainable results.", "Temporomandibular disorders (TMD) are currently viewed as an interrelated set of clinical conditions presenting with signs and symptoms in masticatory and related muscles of the head and neck, and the soft tissue and bony components of the temporomandibular joint. Epidemiologic and clinical studies of TMD confirm its status as a chronic pain problem. In this report we present results from a randomized clinical trial which compared, at 3- and 12-month follow-ups, the effects of usual TMD treatment on TMD pain and related physical and psychological variables with the effects of a cognitive-behavioral (CB) intervention delivered to small groups of patients before usual TMD treatment began. The purpose of this study was to determine whether a minimal CB intervention followed by dental TMD treatment enhanced the effects of usual clinical dental treatment. A second purpose of the study was to determine whether patients classified as high in somatization and psychosocial dysfunction would respond less favorably to this minimal intervention than would those low in somatization and dysfunction. Patients who participated in the CB intervention followed by usual treatment showed greater long-term decreases in reported pain level and pain interference in daily activities than did patients who received only usual treatment. The benefits of CB intervention were not seen when the CB and UT groups were compared at 3-month follow-up. During the 3-12-month follow-up interval, however, the UT group maintained essentially the same level of improvement in characteristic pain while the CB group continued to improve, as hypothesized. During this same follow-up interval, the CB group also showed a strong trend toward continued improvement in pain interference. Such effects were not observed for depression, somatization, or clinical measures of jaw range of motion. Additionally, as hypothesized, dysfunctional chronic pain patients did not appear to benefit from the brief CB intervention. Intent to treat analyses were also performed to assess generalizability of the results.", "Forty-eight dysfunctional patients (i.e., high levels of pain, interference, and affective distress and low levels of perceived control) with temporomandibular disorders (TMDs) were randomly assigned either to a treatment consisting of an intraoral appliance (IA) and stress management with biofeedback (SM) plus nondirective, supportive counseling (SC) -- IA + SM + SC -- or to a customized treatment that included cognitive therapy (CT) with the IA and SM--IA + SM + CT. Both treatment groups reported statistically significant reductions on a set of physical, psychosocial, and behavioral measures posttreatment and at a 6-month follow-up. However, the intervention that included CT demonstrated significantly greater reductions in pain, depression, and medication use. Only the groups receiving the treatment that included the CT demonstrated continued improvements to the follow-up on pain associated with muscle palpation, self-reported pain severity, depression, and use of medications. These results support the efficacy of the tailored treatment for dysfunctional TMD.", "To test the usefulness of tailoring cognitive-behavioral therapy (CBT) for patients with temporomandibular disorders (TMD) who demonstrated poor psychosocial adaptation to their TMD condition, independent of physical diagnosis.\n A randomized clinical trial compared a 6-session CBT intervention delivered in conjunction with the usual TMD treatment to the usual conservative treatment by TMD specialist dentists. For study inclusion, Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD), Axis II criteria, were used to target patients with elevated levels of TMD pain-related interference with daily activities, independent of physical diagnosis (i.e., Axis I).\n At the post-treatment assessment, about 4 months after the baseline evaluations, the comprehensive care group, when compared to the usual treatment group, showed significantly lower levels of characteristic pain intensity, significantly higher self-reported ability to control their TMD pain, and a strong trend (P = .07) toward lower pain-related interference in daily activities. From post-intervention to 1-year follow-up, all subjects showed improvement. At the 1-year follow-up, the comprehensive care group, while not losing any of its early gains, was not significantly different from the usual care group with regard to reported levels of pain, ability to control pain, and levels of interference in activities. For many of these psychosocially disabled TMD patients, pain and interference 1 year after treatment remained at the same or higher levels than those observed at baseline among a group of patients selected for a separate randomized clinical trial on the basis of better psychosocial adaptation.\n The 6-session CBT intervention for patients with heightened psychologic and psychosocial disability was effective in improving pain-related variables over the course of the CBT in conjunction with usual treatment, but was too brief an intervention to result in further improvement after the sessions ended. Patient ratings of treatment satisfaction and helfulness were high for both groups, but they were significantly higher for the comprehensive care group.", "We evaluated the short- and long-term efficacy of a brief cognitive-behavioral therapy (CBT) for chronic temporomandibular disorder (TMD) pain in a randomized controlled trial. TMD clinic patients were assigned randomly to four sessions of either CBT (n=79) or an education/attention control condition (n=79). Participants completed outcome (pain, activity interference, jaw function, and depression) and process (pain beliefs, catastrophizing, and coping) measures before randomization, and 3 (post-treatment), 6, and 12 months later. As compared with the control group, the CBT group showed significantly greater improvement across the follow-ups on each outcome, belief, and catastrophizing measure (intent-to-treat analyses). The CBT group also showed a greater increase in use of relaxation techniques to cope with pain, but not in use of other coping strategies assessed. On the primary outcome measure, activity interference, the proportion of patients who reported no interference at 12 months was nearly three times higher in the CBT group (35%) than in the control group (13%) (P=0.004). In addition, more CBT than control group patients had clinically meaningful improvement in pain intensity (50% versus 29% showed > or =50% decrease, P=0.01), masticatory jaw function (P<0.001), and depression (P=0.016) at 12 months (intent-to-treat analyses). The two groups improved equivalently on a measure of TMD knowledge. A brief CBT intervention improves one-year clinical outcomes of TMD clinic patients and these effects appear to result from specific ingredients of the CBT.", "The effect of cognitive therapy (CT) on resistant burning mouth syndrome (BMS) was studied. Thirty patients with resistant BMS after odontological and medical treatment were randomly divided into two equal groups; a therapy group (TG) was treated with CT and an attention/placebo group (APG) served as a control group. The intensity of BMS, which was estimated by the use of a visual analogue scale, was significantly reduced in the TG directly after CT was completed and was further reduced in a 6-month follow-up. The APG did not show any decrease in intensity of BMS. The results of this study indicate that, in some cases, resistant BMS probably is of psychological origin.", "This study evaluated the relative long-term efficacy of biofeedback, cognitive-behavioral skills training (CBST), combined biofeedback and CBST (Combined), and no-treatment comparison groups in 108 patients suffering from chronic temporomandibular disorder (TMD). After an initial evaluation, patients were assigned to one of the four treatment conditions. The three biobehavioral treatment interventions consisted of 12 standardized sessions. Patients were reevaluated 1 year after completing treatment. Results demonstrated that patients who received the biobehavioral treatments reported significant improvement in subjective pain, pain-related disability, and mandibular functioning 1 year after receiving treatment. The no-treatment comparison group did not demonstrate such improvements. The combined biofeedback and CBST treatment produced the most comprehensive improvements across all outcome measures. These results again demonstrate the heuristic value of adopting a biopsychosocial perspective to the assessment and treatment of chronic medical/dental disorders such as TMD.", "In this study, we applied cognitive behavioural intervention to subjects who had painful limited mouth opening, with or without posture correction in daily life. The efficacy of non-intervention control was then compared with it in order to study the effectiveness of posture correction as part of a biobehavioural therapy. The visual analogue scale (VAS) value of pain intensity at maximum mouth opening and disturbance in daily life sharply declined in the group which received only cognitive behavioural intervention and those who received it together with posture correction in daily life compared to the non-intervention control group although there was little difference between the intervention groups. Moreover, pain-free unassisted mouth opening was restored earlier in the group which had added posture correction. This suggests that posture correction in daily life has a positive effect in alleviating myofascial pain with limited mouth opening.", "Glossodynia or burning mouth syndrome (BMS) is a common and poorly understood disorder. Its treatment is uncertain. Otherwise, there is some evidence of the importance of psychological factors in the genesis of this disease.\n Verify the usefulness of group psychotherapy as an adjuvant therapeutic method in the treatment of BMS. CASUISTICS AND METHODS: The study group consisted of 64 consecutive patients with a clinical diagnosis of BMS seen at the Stomatology Outpatient Clinic, ENT Department, Sao Paulo University Medical School, between May 2002 and May 2007. All the patients were submitted to physical examination, laboratorial screening tests, psychological assessment (Crown-Crisp Experimental Inventory), and answered a short form of the McGill Pain Questionnaire. Only 44 patients who did not show any abnormality in the protocol exams entered the study. Twenty-four of them underwent group psychotherapy. Twenty patients received placebo. Chi-square test was applied to compare the results of treatment with or without psychotherapy.\n There were 15 men and 29 women in the study group. Tongue burning was the main complaint of the patients. Improvement of symptoms was reported by 17 (70.8%) of the patients undergoing psychotherapy, while among those who did not eight (40%) had improvement of symptoms (P=.04).\n Psychological assessment demonstrated a close correlation between symptoms and psychological factors, suggesting that group psychotherapy is an important alternative to conventional treatment methods.", "This research compares different treatment regimes for the management of chronic facial pain associated with the masticatory musculature. Twenty-one females meeting specific criteria were randomly assigned to one of three treatment conditions: a dental splint and physiotherapy program; a relaxation program utilizing progressive muscle relaxation, biofeedback, and stress management techniques; or a minimal treatment program involving transcutaneous electrical nerve stimulation. Improvement was assessed through a dental examination, self-monitoring of pain, and an assessment of EMG activity during resting and task conditions. Significant changes were obtained in response to all treatment programs. The treatment programs differed only in the relative pattern of treatment effects obtained from the self-report monitoring of pain. The data are consistent with the concept of MPD as a psychological response to stress which maintains chronic pain through increased muscle tension in the jaw.", "To assess the differential efficacy of two commonly used treatments for temporomandibular disorders (TMD), intraoral appliances (IAs) and biofeedback (BF), separately and in combination, two studies were conducted. The first study directly compared IA treatment, a combination of biofeedback and stress management (BF/SM), and a waiting list control group in a sample of 80 TMD patients. Both treatments were determined to be equally credible to patients, ruling out this potential threat to the validity of the results obtained. The results demonstrated that the IA treatment was more effective than the BF/SM treatment in reducing pain after treatment, but at a 6-month follow-up the IA group significantly relapsed, especially in depression, whereas the BF/SM maintained improvements on both pain and depression and continued to improve. The second study examined the combination of IA and BF/SM in a sample of 30 TMD patients. The results of this study demonstrated that the combined treatment approach was more effective than either of the single treatments alone, particularly in pain reduction, at the 6-month follow-up. These results support the importance of using both dental and psychologic treatments to successfully treat TMD patients if treatment gains are to be maintained.", "The purpose of this study was to determine whether a brief (6-8 sessions) cognitive-behavioral treatment for temporomandibular dysfunction-related pain could be efficacious in reducing pain, pain-related interference with lifestyle and depressive symptoms. The patients were 101 men and women with pain in the area of the temporomandibular joint of at least 3 months duration, randomly assigned to either standard treatment (STD; n=49) or standard treatment+cognitive-behavioral skills training (STD+CBT; n=52). Patients were assessed at posttreatment (6 weeks), 12 weeks, 24 weeks, 36 weeks, and 52 weeks. Linear mixed model analyses of reported pain indicated that both treatments yielded significant decreases in pain, with the STD+CBT condition resulting in steeper decreases in pain over time compared to the STD condition. Somatization, self-efficacy and readiness for treatment emerged as significant moderators of outcome, such that those low in somatization, or higher in self-efficacy or readiness, and treated with STD+CBT reported of lower pain over time. Somatization was also a significant moderator of treatment effects on pain-related interference with functioning, with those low on somatization reporting of less pain interference over time when treated in the STD+CBT condition. It was concluded that brief treatments can yield significant reductions in pain, life interference and depressive symptoms in TMD sufferers, and that the addition of cognitive-behavioral coping skills will add to efficacy, especially for those low in somatization, or high in readiness or self-efficacy.\n Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved." ]

[ "8508009" ]

[ "Effects of garlic coated tablets in peripheral arterial occlusive disease." ]

[ "For the first time, a weak clinical efficacy of a 12-week therapy with garlic powder (daily dose, 800 mg) is demonstrated in patients with peripheral arterial occlusive disease stage II. The increase in walking distance in the verum group by 46 m (from 161.0 +/- 65.1 to 207.1 +/- 85.0 m) was significantly higher (P < 0.05) than in the placebo group (by 31 m, from 172.0 +/- 60.9 to 203.1 +/- 72.8). Both groups received physical therapy twice a week. The diastolic blood pressure, spontaneous thrombocyte aggregation, plasma viscosity, and cholesterol concentration also decreased significantly. Body weight was maintained. It is quite interesting that the garlic-specific increase in walking distance did not appear to occur until the 5th week of treatment, connected with a simultaneous decrease in spontaneous thrombocyte aggregation. Therefore, garlic may be an appropriate agent especially for the long-term treatment of an incipient intermittent claudication." ]

[ "18653490", "18319698", "19369895", "16966957", "17984718", "12873245", "17901438", "16319361", "9851475", "19165321", "18519154", "16940340", "16046685", "18089625", "18435394", "17032987", "19684191", "18669427", "16728756", "19398142", "19151105", "18003652", "17482249", "18676987", "18268149", "16528420", "17000911", "11114317", "18047180", "16754947", "19032538", "19208693", "15066887", "17760974", "16230313", "17477965", "17652238", "11988448", "17204724", "17827487", "16380571", "18825478", "18815714", "17827485" ]

[ "Changes in air quality and second-hand smoke exposure in hospitality sector businesses after introduction of the English Smoke-free legislation.", "Reduction incidence of myocardial infarction associated with a national legislative ban on smoking.", "Impact of an indoor smoking ban on bar workers' exposure to secondhand smoke.", "Effects of a smoke-free law on hair nicotine and respiratory symptoms of restaurant and bar workers.", "The effects on smokers of Boston's smoke-free bar ordinance: a longitudinal analysis of changes in compliance, patronage, policy support, and smoking at home.", "Four-year follow-up of smoke exposure, attitudes and smoking behaviour following enactment of Finland's national smoke-free work-place law.", "Declines in hospital admissions for acute myocardial infarction in New York state after implementation of a comprehensive smoking ban.", "Secondhand smoke exposure and risk following the Irish smoking ban: an assessment of salivary cotinine concentrations in hotel workers and air nicotine levels in bars.", "Bartenders' respiratory health after establishment of smoke-free bars and taverns.", "Impact of the Spanish smoking law on exposure to second-hand smoke and respiratory health in hospitality workers: a cohort study.", "Smoke-free laws and adult smoking prevalence.", "Short-term effects of Italian smoking regulation on rates of hospital admission for acute myocardial infarction.", "Changes in hospitality workers' exposure to secondhand smoke following the implementation of New York's smoke-free law.", "Changes in smoking among restaurant and bar employees following Norway's comprehensive smoking ban.", "Implications of a public smoking ban.", "Respiratory symptoms, pulmonary function, and markers of inflammation among bar workers before and after a legislative ban on smoking in public places.", "Secondhand smoke exposure and survival following acute coronary syndrome: prospective cohort study of 1261 consecutive admissions among never-smokers.", "Smoke-free legislation and hospitalizations for acute coronary syndrome.", "Decline in respiratory symptoms in service workers five months after a public smoking ban.", "Does the workplace-smoking ban eliminate differences in risk for environmental tobacco smoke exposure at work?", "The impact of smokefree legislation in Scotland: results from the Scottish ITC: Scotland/UK longitudinal surveys.", "Did the Tobacco Control Act Amendment in 1995 affect daily smoking in Finland? Effects of a restrictive workplace smoking policy.", "The impact of a smoking ban on hospital admissions for coronary heart disease.", "Study of the impact of laws regulating tobacco consumption on the prevalence of passive smoking in Spain.", "Effect of the Italian smoking ban on population rates of acute coronary events.", "Airborne exposure and biological monitoring of bar and restaurant workers before and after the introduction of a smoking ban.", "Reduction in the incidence of acute myocardial infarction associated with a citywide smoking ordinance.", "Association of the California Tobacco Control Program with declines in cigarette consumption and mortality from heart disease.", "Reduced admissions for acute myocardial infarction associated with a public smoking ban: matched controlled study.", "Reductions in tobacco smoke pollution and increases in support for smoke-free public places following the implementation of comprehensive smoke-free workplace legislation in the Republic of Ireland: findings from the ITC Ireland/UK Survey.", "Scottish smoke-free legislation and trends in smoking cessation.", "Bar workers' health and environmental tobacco smoke exposure (BHETSE): symptomatic improvement in bar staff following smoke-free legislation in Scotland.", "Reduced incidence of admissions for myocardial infarction associated with public smoking ban: before and after study.", "Impact of the \"Tobacco control law\" on exposure to environmental tobacco smoke in Spain.", "Legislation for smoke-free workplaces and health of bar workers in Ireland: before and after study.", "Smoking in Italy 2005-2006: effects of a comprehensive National Tobacco Regulation.", "Legislation reduces exposure to second-hand tobacco smoke in New Zealand bars by about 90%.", "Clean indoor air: advances in California, 1990-1999.", "Effects of the Irish smoking ban on respiratory health of bar workers and air quality in Dublin pubs.", "Changes in child exposure to environmental tobacco smoke (CHETS) study after implementation of smoke-free legislation in Scotland: national cross sectional survey.", "Early evidence on the effectiveness of clean indoor air legislation in New York State.", "Prevalence of smoking among bar workers prior to the Republic of Ireland smokefree workplace legislation.", "Exposure to environmental tobacco smoke and health effects among hospitality workers in Sweden--before and after the implementation of a smoke-free law.", "Changes in exposure of adult non-smokers to secondhand smoke after implementation of smoke-free legislation in Scotland: national cross sectional survey." ]

[ "To monitor and disseminate the short-term effects of the English Smoke-free legislation on air quality and employee exposure in businesses of the hospitality industry.\n Indoor particle concentrations and salivary cotinine levels were measured in businesses in the hospitality sector and non-smoking employees one month before and after the implementation of the legislation. Results were immediately released to the media to announce the improvements in air quality and employee exposure to the wider public.\n Measurements were collected in 49 businesses and from 75 non-smoking individuals. Indoor PM(2.5) concentrations decreased by 95% from 217 microg/m(3) at baseline to 11 microg/m(3) at follow-up (P < 0.001). Salivary cotinine in employees was reduced by 75%, from 3.6 ng/ml at baseline to 0.9 ng/ml at follow-up (P < 0.001). The findings were presented to the public through press releases and interviews and were cited in over 20 media articles.\n The project demonstrates the positive effects of the English Smoke-free legislation on air quality and second-hand smoke exposure in the hospitality industry sector. We believe that quick and positive feedback to the public on the effects of smoking restrictions is essential when introducing public health legislation such as the Smoke-free legislation.", "The aim of the present study was to assess change in admissions for acute myocardial infarction (AMI) in the period immediately subsequent to the coming into force of law no. 3/2003 ''Protection of the health of non-smokers''.\n Four Italian regions (Piedmont, Friuli Venezia Giulia, Lazio and Campania) took part in the study. Data regarding admissions for AMI were taken from the daily discharge papers of patients aged between 40 and 64 (cod. ICD9-CM 410.), in the period 10 January-10 March 2001-2005. Repeated admissions were excluded. Admission rates standardised by age and overall total, and specifically by region, age and gender were calculated. The hypothesis of a significant reduction between 2005 and 2004 was also checked.\n The results showed a decrease in the number of cases and in the standardised rates between 2004 and 2005. The number of admissions estimated with a linear regression model for 2005 was significantly higher than that really observed (+13%). The decrease between the 2005 and 2004 rates was noteworthy for all four regions. Analysis by gender shows that the effect is observed only in male patients and in the age classes 45-49 and 50-54.\n This study shows that there has been an appreciable reduction in the incidence of heart attacks in the period immediately subsequent to the coming into force of the non-smoking Law in the populations surveyed, and that this reduction mainly regards men of working age. The reduction reverses a trend that has been evident for a number of years, namely that of a decidedly upward trend in the number of admissions for AMI.", "To evaluate the impact of an indoor smoke-free bylaw in Toronto, Ontario, implemented June 2004.\n We used a pre-post comparison design to assess secondhand smoke (SHS) exposure among 79 eligible bar workers in Toronto, Ontario (bylaw enacted), and 49 eligible bar workers in a control community, Windsor, Ontario (no bylaw change), at four times: preban, and 1, 2, and 9 months postban.\n SHS exposure time and urinary cotinine level were substantially reduced in Toronto bar workers immediately after the ban by 94% (from 7.8 to 0.5 hours) and 68% (from 24.2 to 7.8 ng/mL), respectively. The reduction was sustained throughout follow-up. There was no change among Windsor bar workers before and after the ban.\n Compliance with the ban was high, and the ban led to a substantial reduction in SHS exposure.", "Bar and restaurant workers' exposure to secondhand smoke (SHS) was compared before and 3 and 6 months after implementation of a smoke-free ordinance.\n Hair nicotine, self-reported exposure to SHS, and respiratory symptoms were assessed on 105 smoking and nonsmoking workers from randomly selected establishments in Lexington, Kentucky. Thirty-eight percent were current smokers with more than half smoking 10 or fewer cigarettes per day. Workers provided a hair sample at baseline and at the 3-month interview.\n There was a significant decline in hair nicotine 3 months postlaw when controlling for cigarettes smoked per day. Bar workers showed a significantly larger decline in hair nicotine compared with restaurant workers. The only significant decline in SHS exposure was in the workplace and other public places. Regardless of smoking status, respiratory symptoms declined significantly postlaw.\n Hospitality workers demonstrated significant declines in hair nicotine and respiratory symptoms after the law. Comprehensive smoke-free laws can provide the greatest protection to bar workers who are the most vulnerable to SHS exposure at work.", "We prospectively examined effects of the implementation of a smoking ban in bars on Boston, Massachusetts, smokers.\n A representative sample of Massachusetts smokers was interviewed before and after the smoking ban was implemented in Boston. Participants were adult smokers living in Boston (n = 83) and in 203 other Massachusetts cities and towns that did not adopt smoking bans in bars prior to July 2004 (n = 903). The outcome measures were changes in reports of smoking in bars, frequency of bar patronage, support for smoke-free bars, smoking at home, and exposure to secondhand smoke at home based on town of residence.\n Compared to changes over the same time period among smokers in towns where smoking in bars was permitted, smokers in Boston were significantly less likely to observe smoking and less likely to decrease their bar patronage after the smoking ban was implemented. Changes in support for smoke-free bars, smoking patterns at home, and exposure to secondhand smoke at home did not differ between the groups. Conclusion: Expectations about noncompliance, declines in patronage, and displacement of smoking to the home as a consequence of extending smoking restrictions to bars are not supported by the data.", "This study evaluated the possible impact of national smoke-free work-place legislation on employee exposure to environmental tobacco smoke (ETS), employee smoking habits and attitudes on work-place smoking regulations.\n Repeated cross-sectional questionnaire surveys and indoor air nicotine measurements were carried out before, and 1 and 3 years after the law had come into effect.\n Industrial, service sector and office work-places from the Helsinki metropolitan area, Finland.\n A total of 880, 940 and 659 employees (response rates 70%, 75% and 75%) in eight work-places selected from a register kept by the Uusimaa Regional Institute of Occupational Health to represent various sectors of public and private work-places.\n Reported exposure to ETS, smoking habits, attitudes on smoking at work and measurements of indoor air nicotine concentration.\n Employee exposure to ETS for at least 1 hour daily decreased steadily during the 4-year follow-up, from 51% in 1994 to 17% in 1995 and 12% in 1998. Respondents' daily smoking prevalence and tobacco consumption diminished 1 year after the enforcement of legislation from 30% to 25%, and remained at 25% in the last survey 3 years later. Long-term reduction in smoking was confined to men. Both smokers' and non-smokers' attitudes shifted gradually towards favouring a total ban on smoking at work. Median indoor airborne nicotine concentrations decreased from 0.9 micro g/m3 in 1994-95 to 0.1 micro g/m3 in 1995-96 and 1998.\n This is the first follow-up study on a nationally implemented smoke-free work-place law. We found that such legislation is associated with steadily reducing ETS exposure at work, particularly at work-places, where the voluntary smoking regulations have failed to reduce exposure. The implementation of the law also seemed to encourage smokers to accept a non-smoking work-place as the norm.", "Reductions in exposure to environmental tobacco smoke have been shown to attenuate the risk of cardiovascular disease. We examined whether the 2003 implementation of a comprehensive smoking ban in New York State was associated with reduced hospital admissions for acute myocardial infarction and stroke, beyond the effect of moderate, local and statewide smoking restrictions, and independent of secular trends.\n We analyzed trends in county-level, age-adjusted, monthly hospital admission rates for acute myocardial infarction and stroke from 1995 to 2004 to identify any association between admission rates and implementation of the smoking ban. We used regression models to adjust for the effects of pre-existing smoking restrictions, seasonal trends in admissions, differences across counties, and secular trends.\n In 2004, there were 3813 fewer hospital admissions for acute myocardial infarction than would have been expected in the absence of the comprehensive smoking ban. Direct health care cost savings of $56 million were realized in 2004. There was no reduction in the number of admissions for stroke.\n Hospital admission rates for acute myocardial infarction were reduced by 8% as a result of a comprehensive smoking ban in New York State after we controlled for other relevant factors. Comprehensive smoking bans constitute a simple, effective intervention to substantially improve the public's health.", "To investigate whether the Irish smoking ban has had an impact on secondhand smoke (SHS) exposures for hospitality workers.\n Before and after the smoking ban a cohort of workers (n = 35) from a sample of city hotels (n = 15) were tested for saliva cotinine concentrations and completed questionnaires. Additionally, a random sample (n = 20) of city centre bars stratified by size (range 400-5000 square feet), were tested for air nicotine concentrations using passive samplers before and after the ban.\n Salivary cotinine concentrations (ng/ml), duration of self reported exposures to secondhand smoke, air nicotine (microg/cubic metre).\n Cotinine concentrations reduced by 69%, from 1.6 ng/ml to 0.5 ng/ml median (SD 1.29; p < 0.005). Overall 74% of subjects experienced decreases (range 16-99%), with 60% showing a halving of exposure levels at follow up. Self reported exposure to SHS at work showed a significant reduction from a median 30 hours a week to zero (p < 0.001). There was an 83% reduction in air nicotine concentrations from median 35.5 microg/m3 to 5.95 microg/m3 (p < 0.001). At baseline, three bars (16%) were below the 6.8 microg/m3 air nicotine significant risk level for lung cancer alone; at follow up this increased to 10 (53%).\n Passive smoking and associated risks were significantly reduced but not totally eliminated. Exposure to SHS is still possible for those working where smoking is still allowed and those working where smoke may migrate from outdoor areas. Further research is required to assess the true extent and magnitude of these exposures.", "The association between environmental tobacco smoke (ETS) exposure and respiratory symptoms has not been well established in adults.\n To study the respiratory health of bartenders before and after legislative prohibition of smoking in all bars and taverns by the state of California.\n Cohort of bartenders interviewed before and after smoking prohibition.\n Bartenders at a random sample of bars and taverns in San Francisco.\n Interviews assessed respiratory symptoms, sensory irritation symptoms, ETS exposure, personal smoking, and recent upper respiratory tract infections. Spirometric assessment included forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) measurements.\n Fifty-three of 67 eligible bartenders were interviewed. At baseline, all 53 bartenders reported workplace ETS exposure. After the smoking ban, self-reported ETS exposure at work declined from a median of 28 to 2 hours per week (P<.001). Thirty-nine bartenders (74%) initially reported respiratory symptoms. Of those symptomatic at baseline, 23 (59%) no longer had symptoms at follow-up (P<.001). Forty-one bartenders (77%) initially reported sensory irritation symptoms. At follow-up, 32 (78%) of these subjects had resolution of symptoms (P<.001). After prohibition of workplace smoking, we observed improvement in mean FVC (0.189 L; 95% confidence interval [CI], 0.082-0.296 L; 4.2% change) and, to a lesser extent, mean FEV1 (0.039 L; 95% CI, -0.030 to 0.107 L; 1.2% change). Complete cessation of workplace ETS exposure (compared with continued exposure) was associated with improved mean FVC (0.287 L; 95% CI, 0.088-0.486; 6.8% change) and mean FEV1 (0.142 L; 95% CI, 0.020-0.264 L; 4.5% change), after controlling for personal smoking and recent upper respiratory tract infections.\n Establishment of smoke-free bars and taverns was associated with a rapid improvement of respiratory health.", "A smoke-free law came into effect in Spain on 1st January 2006, affecting all enclosed workplaces except hospitality venues, whose proprietors can choose among totally a smoke-free policy, a partial restriction with designated smoking areas, or no restriction on smoking on the premises. We aimed to evaluate the impact of the law among hospitality workers by assessing second-hand smoke (SHS) exposure and the frequency of respiratory symptoms before and one year after the ban.\n We formed a baseline cohort of 431 hospitality workers in Spain and 45 workers in Portugal and Andorra. Of them, 318 (66.8%) were successfully followed up 12 months after the ban, and 137 nonsmokers were included in this analysis. We obtained self-reported exposure to SHS and the presence of respiratory symptoms, and collected saliva samples for cotinine measurement. Salivary cotinine decreased by 55.6% after the ban among nonsmoker workers in venues where smoking was totally prohibited (from median of 1.6 ng/ml before to 0.5 ng/ml, p<0.01). Cotinine concentration decreased by 27.6% (p = 0.068) among workers in venues with designated smoking areas, and by 10.7% (p = 0.475) among workers in venues where smoking was allowed. In Portugal and Andorra, no differences between cotinine concentration were found before (1.2 ng/ml) and after the ban (1.2 ng/ml). In Spain, reported respiratory symptom declined significantly (by 71.9%; p<0.05) among workers in venues that became smoke-free. After adjustment for potential confounders, salivary cotinine and respiratory symptoms decreased significantly among workers in Spanish hospitality venues where smoking was totally banned.\n Among nonsmoker hospitality workers in bars and restaurants where smoking was allowed, exposure to SHS after the ban remained similar to pre-law levels. The partial restrictions on smoking in Spanish hospitality venues do not sufficiently protect hospitality workers against SHS or its consequences for respiratory health.", "To evaluate whether the adult smoking rate changed in Lexington-Fayette County, Kentucky, following the enactment of a smoke-free public places ordinance.\n Behavioral Risk Factor Surveillance System (BRFSS) data from 2001-2005 were used to test whether smoking rates changed in Fayette County from the pre- to post-law period, relative to the change in 30 Kentucky counties with similar demographics. The sample consisted of 10,413 BRFSS respondents: 7139 pre-law (40 months) and 3274 post-law (20 months).\n There was a 31.9% decline in adult smoking in Fayette County (25.7% pre-law to 17.5% post-law). In the group of 30 Control counties, the rate was 28.4% pre-law and 27.6% post-law. Controlling for seasonality, time trend, age, gender, ethnicity, education, marital status, and income, there was a significant Time (pre- vs. post-law) by Group (Fayette vs. Controls) interaction. There were an estimated 16,500 fewer smokers in Fayette County during post-law compared to pre-law.\n There was a significant effect of smoke-free legislation on adult smoking rates.", "We used the hospital discharge records of Piedmont region (northern Italy) to evaluate whether a national law banning smoking in public resulted in a short-term reduction in hospital admissions for acute myocardial infarction (AMI).\n Rates of admission for AMI before the ban (October-December 2004) and during the ban (February-June 2005) were analysed. Each period was compared with the corresponding period 12 months before. Among persons aged under 60, the number of admissions for AMI decreased significantly after the introduction of the ban: from 922 cases in February-June 2004 to 832 cases in February-June 2005 (sex- and age-adjusted rate ratio, 0.89; 95% confidence interval, 0.81-0.98). No decrease was seen before the ban. No effect was found among persons aged at least 60. We estimated that the observed reduction in active smoking after the introduction of the ban could account for a 0.7% decrease in admissions for AMI during the study period, suggesting that most of the observed effect (11%) might be due to the reduction of passive smoking.\n Our study, based on a population of about 4 million inhabitants, suggests that smoke-free policies may result in a short-term reduction in admissions for AMI.", "To assess the impact on hospitality workers' exposure to secondhand smoke of New York's smoke-free law that prohibits smoking in all places of employment, including restaurants, bars, and bowling facilities.\n Pre-post longitudinal follow up design.Settings: Restaurants, bars, and bowling facilities in New York State.\n At baseline, 104 non-smoking workers in restaurants, bars, and bowling facilities were recruited with newspaper ads, flyers, and radio announcements. Of these, 68 completed a telephone survey and provided at least one saliva cotinine specimen at baseline. At three, six, and 12 month follow up studies, 47, 38, and 32 workers from the baseline sample of 68 completed a telephone survey and provided at least one saliva cotinine specimen.\n The smoke-free law went into effect 24 July 2003.\n Self reported sensory and respiratory symptoms and exposure to secondhand smoke; self administered saliva cotinine specimens. Analyses were limited to subjects in all four study periods who completed a telephone survey and provided at least one saliva cotinine specimen.\n All analyses were limited to participants who completed both an interview and a saliva specimen for all waves of data collection (n = 30) and who had cotinine concentrations < or = 15 ng/ml (n = 24). Hours of exposure to secondhand smoke in hospitality jobs decreased from 12.1 hours (95% confidence interval (CI) 8.0 to 16.3 hours) to 0.2 hours (95% CI -0.1 to 0.5 hours) (p < 0.01) and saliva cotinine concentration decreased from 3.6 ng/ml (95% CI 2.6 to 4.7 ng/ml) to 0.8 ng/ml (95% CI 0.4 to 1.2 ng/ml) (p < 0.01) from baseline to the 12 month follow up. The prevalence of workers reporting sensory symptoms declined from 88% (95% CI 66% to 96%) to 38% (95% CI 20% to 59%) (p < 0.01); there was no change in the overall prevalence of upper respiratory symptoms (p < 0.16).\n New York's smoke-free law had its intended effect of protecting hospitality workers from exposure to secondhand smoke within three months of implementation. One year after implementation, the results suggest continued compliance with the law.", "Norway implemented a nationwide ban on indoor smoking in June 2004. This study documents the smoking patterns of Norway's restaurant and bar workers before and after the ban, to determine changes in smoking prevalence and explore which individual and environmental characteristics were related to cessation. A national sample of food service workers was surveyed by telephone or Internet immediately before the ban and at 4 and 11 months post-implementation. Results showed that between baseline measurement and 4 months post-implementation, there were significant declines in prevalence of daily smoking (-3.6% points, p < 0.005), daily smoking at work (-6.2% points, p < 0.001), number of cigarettes smoked by continuing smokers (-1.55, p < 0.001) and number of cigarettes smoked at work by continuing smokers (-1.63, p < 0.001). No significant changes occurred in any of these variables between 4 and 11 months post-implementation. Logistic regression analysis revealed that only smokers' intentions at baseline to quit within 30 days predicted cessation at both follow-up time points. In addition, cessation at 4 months was predicted by lower daily cigarette consumption at baseline, whereas cessation at 11 months was predicted by baseline attitude toward ETS and exposure to ETS as measured at follow-up. In sum, Norway's smoking ban was accompanied by a reduction in smoking in the period immediately following the ban, and the reduction was maintained almost a year later. The finding that smoking cessation was consistently associated with smokers' intentions to quit within 30 days suggests that motivational and support programs could play a significant role in boosting cessation rates. It is recommended that targeted interventions be used to supplement the benefits of a comprehensive ban to achieve tobacco control objectives.", "Legislation to ban smoking in public places is currently a major area of interest across Canada. The main objectives of the study were to 1) determine the effect of the smoking ban on incidence of acute myocardial infarction, 2) determine if the new legislation altered population-based smoking prevalence, and 3) measure public support for the public smoking ban.\n The city of Saskatoon initiated a public smoking ban on July 1, 2004. We retrospectively reviewed all hospital discharges for acute MI from July 2000 to June 2005. We reviewed CCHS survey information on smoking prevalence for Saskatoon, Saskatchewan and Canada from 2003 to 2005. We prospectively contacted 1,255 Saskatoon residents by telephone to determine support for the public smoking ban.\n The age-standardized incidence rate of acute MI fell from 176.1 (95% CI 165.3-186.8) cases per 100,000 population (July 1, 2000 to June 30, 2004) to 152.4 (95% CI 135.3-169.3) cases per 100,000 population (July 1, 2004 to June 30, 2005). Smoking prevalence in Saskatoon fell from 24.1% in 2003 (95% CI 20.4-27.7) to 18.2% in 2005 (95% CI 15.7-20.9) while smoking prevalence in Saskatchewan remained unchanged at 23.8% (95% CI 22.6-25.3) and Canada reduced from 22.9% (95% CI 22.5-23.3) to 21.3% (95% CI 20.8-21.8). Seventy-nine percent of Saskatoon residents believed the smoking ban was a good idea.\n The public smoking ban in Saskatoon, Canada, is associated with reduced incidence rates of acute MI, lower smoking prevalence and high levels of public support.", "Scotland prohibited smoking in confined public places on March 26, 2006.\n To investigate the association of smoke-free legislation with symptoms, pulmonary function, and markers of inflammation of bar workers.\n This prospective observational study was conducted in Tayside, Scotland from February-June 2006. One hundred five nonasthmatic and asthmatic nonsmoking bar workers were initially enrolled, of whom 77 completed the study per protocol.\n Respiratory and sensory symptoms, spirometry measurements, serum cotinine levels, peripheral inflammatory cell count, asthma quality-of-life scores, and exhaled nitric oxide levels were evaluated before and after introduction of the smoking ban.\n For the per-protocol analysis, the percentage of bar workers with respiratory and sensory symptoms decreased from 79.2% (n = 61) before the smoke-free policy to 53.2% (n = 41) (total change, -26%; 95% confidence interval [CI], -13.8% to -38.1%; P<.001) and 46.8% (n = 38) (-32.5%; 95% CI, -19.8% to -45.2%; P<.001) 1 and 2 months afterward. Forced expiratory volume in the first second increased from 96.6% predicted to 104.8% (change, 8.2%; 95% CI, 3.9% to 12.4%; P<.001) and then 101.7% (change, 5.1%; 95% CI, 2.1% to 8.0%; P = .002), and serum cotinine levels decreased from 5.15 ng/mL to 3.22 ng/mL (change, -1.93 ng/mL; 95% CI, -2.83 to -1.03 ng/mL; P<.001) and then 2.93 ng/mL (-2.22 ng/mL; 95% CI, -3.10 to -1.34 ng/mL; P<.001). The total white blood cell and neutrophil count was reduced from 7610 to 6980 cells/microL at 2 months (-630 cells/muL; 95% CI, -1010 to -260 cells/microL; P = .002) and from 4440 to 4030 cells/microL (-410 cells/microL; 95% CI, -740 to -90 cells/microL; P = .03), respectively. Asthmatic bar workers also had less airway inflammation, with a reduction in exhaled nitric oxide from 34.3 parts per billion (ppb) to 27.4 ppb 1 month after the ban (0.8-fold change; 95% CI, 0.67 to 0.96 ppb; P = .04), and Juniper quality-of-life scores increased from 80.2 to 87.5 points (7.3 points; 95% CI, 0.1 to 14.6 points; P = .049).\n Smoke-free legislation was associated with significant early improvements in symptoms, spirometry measurements, and systemic inflammation of bar workers. Asthmatic bar workers also had reduced airway inflammation and improved quality of life.", "To determine whether exposure to secondhand smoke is associated with early prognosis following acute coronary syndrome.\n We interviewed consecutive patients admitted to nine Scottish hospitals over 23 months. Information was obtained, via questionnaire, on age, sex, smoking status, postcode of residence and admission serum cotinine concentration was measured. Follow-up data were obtained from routine hospital admission and death databases.\n Of the 5815 participants, 1261 were never-smokers. Within 30 days, 50 (4%) had died and 35 (3%) had a non-fatal myocardial infarction. All-cause deaths increased from 10 (2.1%) in those with cotinine < or =0.1 ng/ml to 22 (7.5%) in those with cotinine >0.9 ng/ml (chi(2) test for trend p<0.001). This persisted after adjustment for potential confounders (cotinine >0.9 ng/ml: adjusted OR 4.80, 95% CI 1.95 to 11.83, p = 0.003). The same dose response was observed for cardiovascular deaths and death or myocardial infarction.\n Secondhand smoke exposure is associated with worse early prognosis following acute coronary syndrome. Non-smokers need to be protected from the harmful effects of secondhand smoke.", "Previous studies have suggested a reduction in the total number of hospital admissions for acute coronary syndrome after the enactment of legislation banning smoking in public places. However, it is unknown whether the reduction in admissions involved nonsmokers, smokers, or both.\n Since the end of March 2006, smoking has been prohibited by law in all enclosed public places throughout Scotland. We collected information prospectively on smoking status and exposure to secondhand smoke based on questionnaires and biochemical findings from all patients admitted with acute coronary syndrome to nine Scottish hospitals during the 10-month period preceding the passage of the legislation and during the same period the next year. These hospitals accounted for 64% of admissions for acute coronary syndrome in Scotland, which has a population of 5.1 million.\n Overall, the number of admissions for acute coronary syndrome decreased from 3235 to 2684--a 17% reduction (95% confidence interval, 16 to 18)--as compared with a 4% reduction in England (which has no such legislation) during the same period and a mean annual decrease of 3% (maximum decrease, 9%) in Scotland during the decade preceding the study. The reduction in the number of admissions was not due to an increase in the number of deaths of patients with acute coronary syndrome who were not admitted to the hospital; this latter number decreased by 6%. There was a 14% reduction in the number of admissions for acute coronary syndrome among smokers, a 19% reduction among former smokers, and a 21% reduction among persons who had never smoked. Persons who had never smoked reported a decrease in the weekly duration of exposure to secondhand smoke (P<0.001 by the chi-square test for trend) that was confirmed by a decrease in their geometric mean concentration of serum cotinine from 0.68 to 0.56 ng per milliliter (P<0.001 by the t-test).\n The number of admissions for acute coronary syndrome decreased after the implementation of smoke-free legislation. A total of 67% of the decrease involved nonsmokers. However, fewer admissions among smokers also contributed to the overall reduction.\n 2008 Massachusetts Medical Society", "To evaluate the effect of a total ban on smoking indoors in restaurants and other hospitality business premises in Norway, on respiratory symptoms among workers in the industry.\n Phone interviews with 1525 employees in the hospitality business were conducted immediately before the enacting of the law. In a follow-up study five months later, 906 of the workers from the baseline sample participated. Questions were asked on demographic variables, passive smoking exposure, personal smoking, attitudes towards the law, and five respiratory symptoms. Change in symptom prevalence was analysed with McNemar's test and with analysis of variance (ANOVA) for repeated measures.\n The prevalence of all five symptoms declined after the ban; for morning cough from 20.6% to 16.2% (p < 0.01); for daytime cough from 23.2% to 20.9%; for phlegm cough from 15.3% to 11.8% (p < 0.05); for dyspnoea from 19.2% to 13.0% (p < 0.01); and for wheezing from 9.0% to 7.8%. ANOVA showed that the largest decline in symptom prevalence was seen among workers who themselves gave up smoking, and subjects with a positive attitude towards the law before it took effect.\n A significant decrease in respiratory symptoms among service industry workers was found five months after the enacting of a public smoking ban.", "A workplace-smoking ban in the Netherlands was introduced on January 1, 2004. Before the ban male and low educated employees were at higher risk for exposure to environmental tobacco smoke (ETS). Effective implementation of the ban should result not only in an overall decline of exposure, but also in the disappearance of systematic differences in exposure between subgroups of employees.\n Data from a Dutch continuous Internet survey were used. From July 2003 through June 2005, 200 respondents were randomly selected each week. The sample consisted of 11,291 non-smoking, working respondents, aged 16-65 years.\n ETS exposure decreased among all employees and among subgroups at higher risk before the ban. However, also after the ban, males and low educated employees were still most likely to be exposed to ETS.\n The workplace-smoking ban was effective in reducing ETS exposure among employees. However, after the ban still 52.2% of non-smoking workers reported to be exposed. We did not find the expected stronger effect among employees who were at higher risk. Both before and after implementation of the ban, males and lower educated employees were about two times more likely to be exposed to ETS.", "To evaluate how Scotland's smokefree law impacted self-reported secondhand smoke (SHS) exposure in hospitality venues, workplaces and in people's homes. In addition, we examine changes in support for the law, pub and restaurant patronage, smoking cessation indicators and whether any observed changes varied by socioeconomic status.\n A quasi-experimental longitudinal telephone survey of nationally representative samples of smokers and non-smokers interviewed before the Scottish law (February to March 2006) and 1 year later after the law (March 2007) in Scotland (n = 705 smokers and n = 417 non-smokers) and the rest of the UK (n = 1027 smokers and n = 447 non-smokers) where smoking in public places was not regulated at the time.\n Dramatic declines in the observance of smoking in pubs, restaurants and workplaces were found in Scotland relative to the rest of the UK. The change in the percent of smokers reporting a smokefree home and number of cigarettes smoked inside the home in the evening was comparable in Scotland and the rest of the UK. Support for smokefree policies increased to a greater extent in Scotland than in the rest of the UK. Self-reported frequency of going to pubs and restaurants was generally comparable between Scotland and the rest of the UK; however, non-smokers in Scotland were more likely to frequent pubs more often. No differences in smoking cessation indicators were observed between countries.\n The Scottish smokefree law has been successful in decreasing secondhand smoke exposure while causing none of the hypothesized negative outcomes.", "This study examined changes in adult daily smoking in 1981-2005 in Finland, in order to evaluate the impact of the 1995 Tobacco Control Act Amendment (TCAA) and accompanying measures on the proportion of daily smokers. The main focus of the TCAA was to prohibit smoking at workplaces (designated rooms excluded) in order to protect workers from environmental tobacco smoke.\n The study was based on data from annual postal surveys among 15- to 64-year-olds in 1981-2005 (average response rate 73%). The data set for this study comprised men and women aged 25-64 years (n = 73 471). Logistic models were used to test the effect of the 1995 TCAA across employment status while controlling for the effect of changes in the real price of tobacco and in gross domestic product per capita, and adjusting for age, education, secular trend and prevalence of ever-smokers in each birth cohort.\n Controlling for confounding factors, the odds ratio (OR) for daily smoking after 1995 among employed men was 0.83 (95% CI 0.73-0.94) compared with the OR (1.0) for the period ending 1994. The corresponding figure for employed women was 0.78 (95% CI 0.68-0.91). The results can be interpreted as a positive effect of the 1995 TCAA on employees' daily smoking. Moreover, a similar decrease in daily smoking was not seen among those not targeted by the TCAA (including farmers, students, housewives, pensioners and the unemployed).\n Smoking behaviour was and can be influenced by national tobacco policy measures.", "In March 2002, the city of Bowling Green, Ohio, implemented a clean indoor air ordinance banning smoking in workplaces and public places. This study evaluates the effect of this ordinance on hospital admissions for smoking-related diseases.\n A quasi-experimental design with interrupted time-series was used including a matched control city (Kent, Ohio) with no clean indoor air ordinance. Data on hospital admissions during the period of January 1999 to June 2005 were analyzed using Autoregressive Integrated Moving Average (ARIMA) models.\n A reduction in admission rates for smoking-related diseases was achieved in Bowling Green compared to the control city. The largest reduction was for coronary heart disease, where rates were decreased significantly by 39% after 1 year and by 47% after 3 years following the implementation of the ordinance. ARIMA models revealed a statistically significant downward trend in monthly admission rates for coronary heart disease (Bowling Green, omega=-1.69, p=0.036 vs. Kent, omega=-1.14, p=0.183) and support the hypothesis that the ordinance had a significant impact on admission rates for coronary heart disease.\n The findings of this study suggest that clean indoor air ordinances lead to a reduction in hospital admissions for coronary heart disease, thus reducing health care costs.", "In 2005, the Spanish parliament passed the Spanish anti-smoking law. This legislation restricted tobacco smoking in public places, including recreation venues (bars and restaurants), but smoking was not completely prohibited in bars and restaurants. The law was enforced in January 2006. With the objective of analysing the impact that this law has had on the general Spanish population, the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) designed and implemented a survey of a representative sample of the general Spanish population on two separate occasions: in 2005 and in 2007 (12 months after the ban came into effect).\n Two epidemiological, observational and cross-sectional surveys were performed among a random and representative sample of the general Spanish population, using the Computer-Assisted Telephone Interview system.\n In the first survey, a total of 6533 subjects were interviewed, of whom 3907 (59.8%) were non-smokers and in the second, a total of 3289 subjects were interviewed, of whom 2174 (65.9%) were non-smokers. The overall prevalence of exposure to environmental tobacco smoke (ETS) decreased from 49.5% in 2005 to 37.9% in 2007 (22% reduction). The greatest reduction in prevalence of ETS exposure was in workplaces (from 25.8% to 11%, a decrease of 58.8%). Smaller reductions occurred in the home (from 29.5% to 21.4%, a decrease of 27%) and in recreation venues (from 37.4% to 31.8%, a decrease of 8%).\n Implementation of the smoking ban resulted in a significant decrease in exposure to ETS.", "Several countries in the world have not yet prohibited smoking in public places. Few studies have been conducted on the effects of smoking bans on cardiac health. We evaluated changes in the frequency of acute coronary events in Rome, Italy, after the introduction of legislation that banned smoking in all indoor public places in January 2005.\n We analyzed acute coronary events (out-of-hospital deaths and hospital admissions) between 2000 and 2005 in city residents 35 to 84 years of age. We computed annual standardized rates and estimated rate ratios by comparing the data from prelegislation (2000-2004) and postlegislation (2005) periods. We took into account several time-related potential confounders, including particulate matter (PM10) air pollution, temperature, influenza epidemics, time trends, and total hospitalization rates. The reduction in acute coronary events was statistically significant in 35- to 64-year-olds (11.2%, 95% CI 6.9% to 15.3%) and in 65- to 74-year-olds (7.9%, 95% CI 3.4% to 12.2%) after the smoking ban. No evidence was found of an effect among the very elderly. The reduction tended to be greater in men and among lower socioeconomic groups.\n We found a statistically significant reduction in acute coronary events in the adult population after the smoking ban. The size of the effect was consistent with the pollution reduction observed in indoor public places and with the known health effects of passive smoking. The results affirm that public interventions that prohibit smoking can have enormous public health implications.", "The aims were to assess the impact of a total smoking ban on the level of airborne contaminants and the urinary cotinine levels in the employees in bars and restaurants. In a follow up design, 13 bars and restaurants were visited before and after the implementation of a smoking ban. Ninety-three employees in the establishments were initially included into the study. The arithmetic mean concentration of nicotine and total dust declined from 28.3 microg m(-3) (range, 0.4-88.0) and 262 microg m(-3) (range, 52-662), respectively, to 0.6 microg m(-3) (range, not detected-3.7) and 77 microg m(-3) (range, not detected-261) after the smoking ban. The Pearson correlation coefficient between airborne nicotine and total dust was 0.86 (p < 0.001; n = 48). The post-shift geometric mean urinary cotinine concentration declined from 9.5 microg g(-1) creatinine (cr) (95% CI 6.5-13.7) to 1.4 microg g(-1) cr (95% CI 0.8-2.5) after the ban (p < 0.001) in 25 non-snuffing non-smokers. A reduction from 1444 microg g(-1) cr (95% CI 957-2180) to 688 microg g(-1) cr (95% CI 324-1458) was found (p < 0.05) in 29 non-snuffing smokers. The urinary cotinine levels increased from 11.7 microg g(-1) cr (95% CI 7.0-19.6) post-shift to 21.9 microg g(-1) cr (95% CI 13.3-36.3) (p < 0.01) in the next morning in 24 non-snuffing non-smokers before the smoking ban. A substantial reduction of airborne nicotine and total dust was observed after the introduction of a smoking ban in bars and restaurants. The urinary cotinine levels were reduced in non-smokers. The decline found in smokers may suggest a reduction in the amount of smoking after intervention. In non-smokers cotinine concentrations were higher based on urine sampled the morning after a shift than based on urine sampled immediately post-shift.", "Secondhand smoke exposure increases the risk of acute myocardial infarction (AMI). One study (Helena, Mont) examined the issue and found a decrease in AMI associated with a smoke-free ordinance. We sought to determine the impact of a smoke-free ordinance on AMI admission rates in another geographically isolated community (Pueblo, Colo).\n We assessed AMI hospitalizations in Pueblo during a 3-year period, 1.5 years before and 1.5 years after implementation of a smoke-free ordinance. We compared the AMI hospitalization rates among individuals residing within city limits, the area where the ordinance applied, versus those outside city limits. We also compared AMI rates during this time period with another geographically isolated but proximal community, El Paso County, Colo, that did not have an ordinance. A total of 855 patients were hospitalized with a diagnosis of primary AMI in Pueblo between January 1, 2002, and December 31, 2004. A reduction in AMI hospitalizations was observed in the period after the ordinance among Pueblo city limit residents (relative risk [RR]=0.73, 95% confidence interval [CI] 0.63 to 0.85). No significant changes in AMI rates were observed among residents outside city limits (RR=0.85, 95% CI 0.63 to 1.16) or in El Paso County during the same period (RR=0.97, 95% CI 0.89 to 1.06). The reduction in AMI rate within Pueblo differed significantly from changes in the external control group (El Paso County) even after adjustment for seasonal trends (P<0.001).\n A public ordinance reducing exposure to secondhand smoke was associated with a decrease in AMI hospitalizations in Pueblo, Colo, which supports previous data from a smaller study.", "The California Tobacco Control Program, a large, aggressive antitobacco program implemented in 1989 and funded by a voter-enacted cigarette surtax, accelerated the decline in cigarette consumption and in the prevalence of smoking in California. Since the excess risk of heart disease falls rapidly after the cessation of smoking, we tested the hypothesis that this program was associated with lower rates of death from heart disease.\n Data on per capita cigarette consumption and age-adjusted rates of death from heart disease in California and the United States from 1980 to 1997 were fitted in multiple regression analyses. The regression analyses included the rates in the rest of the United States and variables that allowed for changes in the rates after 1988, when the tobacco-control program was approved, and after 1992, when the program was cut back.\n Between 1989 and 1992, the rates of decline in per capita cigarette consumption and mortality from heart disease in California, relative to the rest of the United States, were significantly greater than the pre-1989 rates, by 2.72 packs per year per year (P = 0.001) and by 2.93 deaths per year per 100,000 population per year (P<0.001). These rates of decline were reduced (by 2.05 packs per year per year, [P=0.04], and by 1.71 deaths per year per 100,000 population per year, [P=0.031) when the program was cut back, beginning in 1992. Despite these problems, the program was associated with 33,300 fewer deaths from heart disease between 1989 and 1997 than the number that would have been expected if the earlier trend in mortality from heart disease in California relative to the rest of the United States had continued. The diminished effectiveness of the program after 1992 was associated with 8300 more deaths than would have been expected had its initial effectiveness been maintained.\n A large and aggressive tobacco-control program is associated with a reduction in deaths from heart disease in the short run.", "There has been no research linking implementation of a public smoking ban and reduced incidence of acute myocardial infarction (AMI) among nonsmoking patients. An ex post facto matched control group study was conducted to determine whether there was a change in hospital admissions for AMI among nonsmoking patients after a public smoking ban was implemented in Monroe County compared with Delaware County, Indiana without such a ban. Poisson analysis was conducted for 44 months of hospital admissions. A significant drop occurred in the number of admissions among nonsmoking patients in Monroe County after the ban whereas a nonsignificant decrease in the number of admissions occurred in Delaware County. The changes in the number of smoking-patient admissions before and after the ban were not significant.", "To evaluate the psychosocial and behavioural impact of the first ever national level comprehensive workplace smoke-free law, implemented in Ireland in March 2004.\n Quasi-experimental prospective cohort survey: parallel cohort telephone surveys of national representative samples of adult smokers in Ireland (n = 769) and the UK (n = 416), surveyed before the law (December 2003 to January 2004) and 8-9 months after the law (December 2004 to January 2005).\n Respondents' reports of smoking in key public venues, support for total bans in those key venues, and behavioural changes due to the law.\n The Irish law led to dramatic declines in reported smoking in all venues, including workplaces (62% to 14%), restaurants (85% to 3%), and bars/pubs (98% to 5%). Support for total bans among Irish smokers increased in all venues, including workplaces (43% to 67%), restaurants (45% to 77%), and bars/pubs (13% to 46%). Overall, 83% of Irish smokers reported that the smoke-free law was a \"good\" or \"very good\" thing. The proportion of Irish homes with smoking bans also increased. Approximately 46% of Irish smokers reported that the law had made them more likely to quit. Among Irish smokers who had quit at post-legislation, 80% reported that the law had helped them quit and 88% reported that the law helped them stay quit.\n The Ireland smoke-free law stands as a positive example of how a population-level policy intervention can achieve its public health goals while achieving a high level of acceptance among smokers. These findings support initiatives in many countries toward implementing smoke-free legislation, particularly those who have ratified the Framework Convention on Tobacco Control, which calls for legislation to reduce tobacco smoke pollution.", "To investigate trends in smoking cessation before and after the introduction of Scottish smoke-free legislation and to assess the perceived influence of the legislation on giving up smoking and perceptions of the legislation in smokers.\n Longitudinal data on smoking cessation were obtained from 1998 to 2007 on a cohort of 3350 Scottish adults aged between 50 and 75 years at baseline. All members of the cohort were participating in a clinical trial of aspirin in people at moderately increased risk of cardiovascular events. A subgroup of 474 participants who had smoked in the year prior to the introduction of legislation in March 2006 also completed a questionnaire on the influence and perceptions of the smoke-free legislation following its introduction.\n Smoking status was recorded yearly, including dates of quitting and restarting. Participants who gave up smoking for at least 3 months were recorded as having quit smoking. The questionnaire included scales on whether the smoke-free legislation had helped/influenced cessation, made the individual think about/prompt them to quit and perceptions of the legislation.\n The odds of smokers quitting annually increased throughout the 7-year period prior to introduction of the smoke-free legislation to 2 years afterwards (odds ratio 1.09, 95% confidence interval 1.05-1.12, P<0.001). During 2006, the pattern of quarterly quitting rates changed, with an increase in quit rates (to 5.1%) in the 3-month period prior to introduction of the legislation (January-March 2006). Socio-economic status was not related to smoking cessation. In the subgroup completing the questionnaire (n=474), 57 quit smoking between June 2005 and May 2007 and 43.9% of these said that the smoke-free legislation had helped them to quit. Most (>70%) smokers were positive about the legislation, especially those from more affluent compared with more deprived communities (P=0.01).\n The Scottish smoke-free legislation was associated with an increase in the rate of smoking cessation in the 3-month period immediately prior to its introduction. Overall quit rates in the year the legislation was introduced and the subsequent year were consistent with a gradual increase in quit rates prior to introduction of the legislation. Socio-economic status was not related to smoking cessation, but individuals from more affluent communities were more positive about the legislation.", "To examine changes in the health of bar workers after smoke-free legislation was introduced.\n Longitudinal study following bar workers from before legislation introduction, at 2 months after introduction and at 1 year to control for seasonal differences.\n Bars across a range of socio-economic settings in Scotland.\n 371 bar workers recruited from 72 bars.\n Introduction of smoke-free legislation prohibiting smoking in enclosed public places, including bars. Main outcomes measures: Change in prevalence of self-reported respiratory and sensory symptoms.\n Of the 191 (51%) workers seen at 1-year follow-up, the percentage reporting any respiratory symptom fell from 69% to 57% (p = 0.02) and for sensory symptoms from 75% to 64% (p = 0.02) following reductions in exposure, effects being greater at 2 months, probably partly due to seasonal effects. Excluding respondents who reported having a cold at either baseline or 1 year, the reduction in respiratory symptoms was similar although greater for \"any\" sensory symptom (69% falling to 54%, p = 0.011). For non-smokers (n = 57) the reductions in reported symptoms were significant for phlegm production (32% to 14%, p = 0.011) and red/irritated eyes (44% to 18%, p = 0.001). Wheeze (48% to 31%, p = 0.006) and breathlessness (42% to 29%, p = 0.038) improved significantly in smokers. There was no relationship between change in salivary cotinine levels and change in symptoms.\n Bar workers in Scotland reported significantly fewer respiratory and sensory symptoms 1 year after their working environment became smoke free. As these improvements, controlled for seasonal variations, were seen in both non-smokers and smokers, smoke-free working environments may have potentially important benefits even for smokers.", "To determine whether there was a change in hospital admissions for acute myocardial infarction while a local law banning smoking in public and in workplaces was in effect.\n Analysis of admissions from December 1997 through November 2003 using Poisson analysis.\n Helena, Montana, a geographically isolated community with one hospital serving a population of 68 140.\n All patients admitted for acute myocardial infarction.\n Number of monthly admissions for acute myocardial infarction for people living in and outside Helena.\n During the six months the law was enforced the number of admissions fell significantly (- 16 admissions, 95% confidence interval - 31.7 to - 0.3), from an average of 40 admissions during the same months in the years before and after the law to a total of 24 admissions during the six months the law was effect. There was a non-significant increase of 5.6 (- 5.2 to 16.4) in the number of admissions from outside Helena during the same period, from 12.4 in the years before and after the law to 18 while the law was in effect.\n Laws to enforce smoke-free workplaces and public places may be associated with an effect on morbidity from heart disease.", "The initial evaluations of the introduction of legislation that regulates smoking in enclosed public places in European countries, describe an important effect in the control of exposure to environmental tobacco smoke. However, the evidence is still limited. The objective of this study is to estimate the short-term effects of the comprehensive \"Tobacco control law\" introduced in Spain on January 2006, which includes a total ban of smoking in workplaces and a partial limitation of smoking in bars and restaurants.\n Cross-sectional, population-based study. The self-reported exposure to environmental tobacco smoke at home, at work, in bars and restaurants of the population aged 18 to 64 years in the Madrid Region during a period prior to the law (October and November 2005; n = 1750) was compared to that of the period immediately after the law came into force (January-July 2006; n = 1252). Adjusted odds ratios (OR) were calculated using logistic regression models.\n Passive exposure to tobacco smoke at home has hardly changed. However, at indoor workplaces there has been a considerable reduction: after the law came into force the OR for daily exposure > 0-3 hours versus non-exposure was 0.11 (95% CI: 0.07 to 0.17) and for more than 3 hours, 0.12 (95% CI: 0.09 to 0.18). For fairly high exposure in bars and restaurants versus non-exposure, the OR in the former was 0.30 (95% CI: 0.20 to 0.44) and in the latter was 0.24 (95% CI: 0.18 to 0.32); for very high exposure versus non-exposure they were 0.16 (95% CI: 0.10 to 0.24) and 0.11 (95% CI: 0.07 to 0.19), respectively. These results were similar for the smoking and non-smoking populations.\n A considerable reduction in exposure to environmental tobacco smoke in the workplace and, to a lesser extent, in bars and restaurants, is related to the implementation of the \"Tobacco control law\". Although only initial figures, these results already demonstrate the effectiveness of strategies that establish control measures to guarantee smoke-free places.", "To compare exposure to secondhand smoke and respiratory health in bar staff in the Republic of Ireland and Northern Ireland before and after the introduction of legislation for smoke-free workplaces in the Republic.\n Comparisons before and after the legislation in intervention and control regions.\n Public houses in three areas in the Republic (intervention) and one area in Northern Ireland (control).\n 329 bar staff enrolled in baseline survey; 249 (76%) followed up one year later. Of these, 158 were non-smokers both at baseline and follow-up.\n Salivary cotinine concentration, self reported exposure to secondhand smoke, and respiratory and sensory irritation symptoms.\n In bar staff in the Republic who did not themselves smoke, salivary cotinine concentrations dropped by 80% after the smoke-free law (from median 29.0 nmol/l (95% confidence interval 18.2 to 43.2 nmol/l)) to 5.1 nmol/l (2.8 to 13.1 nmol/l) in contrast with a 20% decline in Northern Ireland over the same period (from median 25.3 nmol/l (10.4 to 59.2 nmol/l) to 20.4 nmol/l (13.2 to 33.8 nmol/l)). Changes in self reported exposure to secondhand smoke were consistent with the changes in cotinine concentrations. Reporting any respiratory symptom declined significantly in the Republic (down 16.7%, -26.1% to -7.3%) but not in Northern Ireland (0% difference, -32.7% to 32.7%). After adjustment for confounding, respiratory symptoms declined significantly more in the Republic than in Northern Ireland and the decline in cotinine concentration was twice as great.\n The smoke-free law in the Republic of Ireland protects non-smoking bar workers from exposure to secondhand smoke.", "On 10 January 2005 Italy became the first large European country adopting a comprehensive smoke-free legislation. We provide information on smoking prevalence in Italy and evaluate the effects of the 2005 regulations.\n We considered data from three companion surveys on smoking, conducted in 2004, 2005 and 2006 in Italy. Each survey included more than 3000 subjects aged 15 years or over, representative of the general Italian adult population.\n Current smokers declined from 26.2% (30.0% of men, 22.5% of women) in 2004, to 25.6% (29.3% of men, 22.2% of women) in 2005 and to 24.3% (28.6% of men, 20.3% of women) in 2006. Whereas no significant difference was found comparing smoking prevalence in 2003-2004 vs. 2001-2002, the drop in smoking prevalence in 2005-2006 vs. 2003-2004 was significant (p<0.05) in the total population, in men and in subjects aged 15-44 years. Smokers consumed a mean of 15.4 cigarettes per day in 2004, 14.6 in 2005 and 13.9 cigarettes per day in 2006. Italians reported to go more frequently to restaurants and cafes.\n The drop in smoking prevalence and consumption is due, at least in part and particularly for younger generations, to the comprehensive smoke-free legislation adopted in Italy.", "To measure exposure to second-hand smoke (SHS) in New Zealand bars before and after comprehensive smoke-free legislation enacted on 10 December 2004.\n Cotinine is the main specific metabolite of nicotine and a well-established biomarker for SHS exposure. We measured cotinine levels in saliva of non-smoking volunteers before and after a 3 h visit to 30 randomly selected bars in 3 cities across the country. Two measures of cotinine before the smoke-free law change during winter and spring 2004, and two follow-up measurements in the same volunteers and venues during winter and spring 2005, were included.\n Before the smoke-free law change, in all bars and in all volunteers, exposure to SHS was evident with an average increase in saliva cotinine of 0.66 ng/ml (SE 0.03 ng/ml). Increases in cotinine correlated strongly with the volunteers' subjective observation of ventilation, air quality and counts of lit cigarettes. However, even venues that were judged to be \"seemingly smoke free\" with \"good ventilation\" produced discernable levels of SHS exposure. After the law change, there remained some exposure to SHS, but at much lower levels (mean saliva cotinine increase of 0.08 ng/ml, SE 0.01 ng/ml). Smoking indoors in bars was almost totally eliminated: in 2005 only one lit cigarette was observed in 30 visits.\n Comprehensive smoke-free legislation in New Zealand seems to have reduced exposure of bar patrons to SHS by about 90%. Residual exposures to SHS in bars do not result from illicit smoking indoors.", "This study assessed progress in achieving clean indoor air in California.\n Data were from large, cross-sectional population-based surveys (1990-1999).\n Indoor workers reporting smoke-free workplaces increased from 35.0% (95% confidence interval [CI] = 33.7, 36.3) in 1990 to 93.4% (95% CI = 92.6, 94.2) in 1999. Exposure of nonsmoking indoor workers to secondhand tobacco smoke decreased from 29.0% (95% CI = 27.2, 30.8) to 15.6% (95% CI = 14.1, 17.1). Adults with smoke-free homes increased from 37.6 % (95% CI = 35.1, 40.1) in 1992 to 73.7% (95% CI = 73.2, 74.2) in 1999; nearly half of smokers in 1999 had smoke-free homes. In 1999, 82.2% (95% CI = 81.5, 82.9) of children and adolescents (0-17 years) had smoke-free homes, up from 38.0% (95% CI = 35.1, 40.9) in 1992.\n California's advances highlight an important opportunity for tobacco control.", "Environmental tobacco smoke (ETS) causes disease in nonsmokers. Workplace bans on smoking are interventions to reduce exposure to ETS to try to prevent harmful health effects. On March 29, 2004, the Irish government introduced the first national comprehensive legislation banning smoking in all workplaces, including bars and restaurants. This study examines the impact of this legislation on air quality in pubs and on respiratory health effects in bar workers in Dublin.\n Exposure study. Concentrations of particulate matter 2.5 microm or smaller (PM(2.5)) and particulate matter 10 microm or smaller (PM(10)) in 42 pubs were measured and compared before and after the ban. Benzene concentrations were also measured in 26 of the pubs. Health effects study. Eighty-one barmen volunteered to have full pulmonary function studies, exhaled breath carbon monoxide, and salivary cotinine levels performed before the ban and repeated 1 year after the ban. They also completed questionnaires on exposure to ETS and respiratory symptoms on both occasions.\n Exposure study. There was an 83% reduction in PM(2.5) and an 80.2% reduction in benzene concentration in the bars. Health effects study. There was a 79% reduction in exhaled breath carbon monoxide and an 81% reduction in salivary cotinine. There were statistically significant improvements in measured pulmonary function tests and significant reductions in self-reported symptoms and exposure levels in nonsmoking barmen volunteers after the ban.\n A total workplace smoking ban results in a significant reduction in air pollution in pubs and an improvement in respiratory health in barmen.", "To detect any change in exposure to secondhand smoke among primary schoolchildren after implementation of smoke-free legislation in Scotland in March 2006.\n Comparison of nationally representative, cross sectional, class based surveys carried out in the same schools before and after legislation.\n Scotland.\n 2559 primary schoolchildren (primary 7; mean age 11.4 years) surveyed in January 2006 (before smoke-free legislation) and 2424 in January 2007 (after legislation).\n Salivary cotinine concentrations, reports of parental smoking, and exposure to tobacco smoke in public and private places before and after legislation.\n The geometric mean salivary cotinine concentration in non-smoking children fell from 0.36 (95% confidence interval 0.32 to 0.40) ng/ml to 0.22 (0.19 to 0.25) ng/ml after the introduction of smoke-free legislation in Scotland-a 39% reduction. The extent of the fall in cotinine concentration varied according to the number of parent figures in the home who smoked but was statistically significant only among pupils living in households in which neither parent figure smoked (51% fall, from 0.14 (0.13 to 0.16) ng/ml to 0.07 (0.06 to 0.08) ng/ml) and among pupils living in households in which only the father figure smoked (44% fall, from 0.57 (0.47 to 0.70) ng/ml to 0.32 (0.25 to 0.42) ng/ml). Little change occurred in reported exposure to secondhand smoke in pupils' own homes or in cars, but a small decrease in exposure in other people's homes was reported. Pupils reported lower exposure in cafes and restaurants and in public transport after legislation.\n The Scottish smoke-free legislation has reduced exposure to secondhand smoke among young people in Scotland, particularly among groups with lower exposure in the home. We found no evidence of increased secondhand smoke exposure in young people associated with displacement of parental smoking into the home. The Scottish smoke-free legislation has thus had a positive short term impact on young people's health, but further efforts are needed to promote both smoke-free homes and smoking cessation.", "In July 2003, New York State implemented the Clean Indoor Air Act (CIAA) to reduce exposure to environmental tobacco smoke (ETS). In this cross-sectional study, workers (n=168) completed an interview assessing ETS exposure and provided urine for cotinine analysis. Hospitality workers recruited after implementation of the CIAA had significant reductions in ETS exposure and urine cotinine, compared with those recruited before implementation. The New York State CIAA yielded measurable reductions in ETS exposure for hospitality workers.", "This study establishes baseline prevalence of smoking and cigarette consumption among Cork bar workers prior to the Republic of Ireland's (ROI) smokefree workplace legislation and compares gender- and age-specific smoking rates and estimates the adjusted odds of being a smoker for Cork bar workers relative to the general population.\n Cross-sectional random sample of bar workers in Cork city and cross-sectional random telephone survey of the general population were conducted prior to the smokefree legislation.\n Self reported smoking prevalence among Cork bar workers (n = 129) was 54% (58% using cotinine-validated measures), with particularly high rates in women (70%) and 18-28 years old (72%). Within the ROI (n = 1,240) sub-sample rates were substantially lower at 28%. Bar workers were twice as likely to be smokers as the general population sub-sample (OR = 2.15).\n Cork bar workers constitute an occupational group with an extremely high smoking prevalence.", "This study attempted to identify changes in exposure to environmental tobacco smoke, as well as symptoms and attitudes among hospitality workers after the introduction of extended smoke-free workplace legislation.\n A total of 37 volunteers working in bingo halls and casinos (gaming workers) and 54 bars and restaurant employees (other workers) in nine Swedish communities participated in the study. Altogether 71 of 91 persons (14 daily smokers and 57 nonsmokers) participated in both the pre-ban baseline survey and the follow-up 12 months after the ban. Exposure to environmental tobacco smoke, smoking habits, respiratory and sensory symptoms, and attitudes towards the ban were recorded, and spirometry was carried out.\n The frequency of reported respiratory and sensory symptoms was approximately halved among the nonsmokers in both occupational groups after the introduction of the ban. Initially 87% had exposure to environmental tobacco smoke that was over the nicotine cut-off level chosen to identify possible health risk ( <0.5 microg/m3) while, after the ban, it was only 22%, a relative risk of 0.25 (95% confidence interval 0.15-0.41). The risk decreased in both occupational groups, but gaming workers experienced the highest pre-ban exposure levels. Attitudes towards the legislation were largely positive, particularly after the ban. However, there was no notable change in lung function, and there was no notable reduction in the number of cigarettes consumed by smokers.\n The introduction of smoke-free legislation was associated with a substantial reduction in respiratory and sensory symptoms, as well as reduced exposure to environmental tobacco smoke at work, particularly among gaming workers.", "To measure change in adult non-smokers' exposure to secondhand smoke in public and private places after smoke-free legislation was implemented in Scotland.\n Repeat cross sectional survey.\n Scotland.\n Scottish adults, aged 18 to 74 years, recruited and interviewed in their homes.\n Comprehensive smoke-free legislation that prohibits smoking in virtually all enclosed public places and workplaces, including bars, restaurants, and cafes.\n Salivary cotinine, self reported exposure to smoke in public and private places, and self reported smoking restriction in homes and in cars.\n Overall, geometric mean cotinine concentrations in adult non-smokers fell by 39% (95% confidence interval 29% to 47%), from 0.43 ng/ml at baseline to 0.26 ng/ml after legislation (P<0.001). In non-smokers from non-smoking households, geometric mean cotinine concentrations fell by 49% (40% to 56%), from 0.35 ng/ml to 0.18 ng/ml (P<0.001). The 16% fall in cotinine concentrations in non-smokers from smoking households was not statistically significant. Reduction in exposure to secondhand smoke was associated with a reduction after legislation in reported exposure to secondhand smoke in public places (pubs, other workplaces, and public transport) but not in homes and cars. We found no evidence of displacement of smoking from public places into the home.\n Implementation of Scotland's smoke-free legislation has been accompanied within one year by a large reduction in exposure to secondhand smoke, which has been greatest in non-smokers living in non-smoking households. Non-smokers living in smoking households continue to have high levels of exposure to secondhand smoke." ]

[ "15103233", "12179676", "11641669" ]

[ "A double-blinded, randomized controlled trial of oxytocin at the beginning versus the end of the third stage of labor for prevention of postpartum hemorrhage.", "A randomized controlled trial of oxytocin administered at the end of the second stage of labor versus oxytocin administered at the end of the third stage of labor in the prevention of postpartum hemorrhage.", "A randomized controlled trial comparing oxytocin administration before and after placental delivery in the prevention of postpartum hemorrhage." ]

[ "The objective of this study was to compare the administration of oxytocin at the beginning and end of the third stage of labor for the prevention of postpartum hemorrhage.\n Patients with documented singleton pregnancies were randomly assigned to two groups. The first received 10 units of oxytocin intramuscularly at delivery of the anterior shoulder of the fetus and an identical appearing placebo injection following delivery of the placenta. The second received the opposite medication sequence. The study was double blinded. Blood loss was measured by weighing all fluids collected, visual estimation, and serial blood counts.\n 27 women received oxytocin at the delivery of the fetal shoulder and 24 after the placenta. Oxytocin given after placenta delivery resulted in lower blood loss (345 vs. 400 ml, p = 0.28), lower collection bag weight (763 vs. 833 g, p = 0.55), lower change in HgB (-1.26 vs. -1.32 g, p = 0.86), lower DeltaHCT (-3.43 vs. -3.64%, p = 0.85), and a shorter third stage of labor duration (8.6 vs. 9.2 min, p = 0.75). The incidence of postpartum hemorrhage, defined as estimated blood loss >500 ml (0 vs. 14.8%) was significantly lowered with oxytocin following placental delivery (p = 0.049).\n In our study, postpartum hemorrhage was less frequent when oxytocin administration was delayed until after placenta delivery.\n Copyright 2004 S. Karger AG, Basel", "The general objective was to determine the incidence of postpartum hemorrhage when oxytocin was administered at the end of the second stage of labor compared to when oxytocin was administered at the end of the third stage. The specific objectives were to determine the mean amount of blood loss, duration of the third stage of labor, need for additional uterotonics and blood transfusion, incidence of hypotension and retained placenta, and mean difference in hemoglobin levels. A randomized controlled trial was conducted in a tertiary care training hospital. 130 women with term, singleton, live pregnancies in cephalic presentation who delivered vaginally were included. Patients were randomly allocated to receive oxytocin after the second stage or after the third stage of labor. Oxytocin was administered as a continuous intravenous infusion. The placenta was delivered by controlled cord traction after placental separation. Blood loss was measured by weight, and the corresponding volume was computed. Relative risk was calculated. Incidence of postpartum hemorrhage, volume of blood loss, duration of the third stage of labor, need for additional uterotonics and blood transfusion, incidence of hypotension and retained placenta, and difference in hemoglobin levels were the main outcome measures. There was a decreased incidence of postpartum hemorrhage (39.66% vs. 48.61%, relative risk [RR] = 0.82, 95% confidence interval [CI] = 0.55-1.21) and less amount of blood loss (557.93 ml vs. 636.84 ml, p = 0.352) when oxytocin was administered at the end of the second stage of labor. There was less need for additional uterotonics (12.07% vs. 13.89%, RR = 0.87, 95% CI = 0.35-2.14), and blood transfusion (5.17% vs. 5.56%, RR = 0.87, 95% CI = 0.22-3.99). There was a smaller mean difference in hemoglobin (16.20 g/dl vs. 20.29 g/dl, p = 0.145). Mean duration of the third stage of labor were comparable (7.93 minutes vs. 7.96 minutes, p = 0.863). However, more patients developed hypotension (3.45% vs. 1.39%, RR = 2.48, 95% CI = 0.23-26.70). All results were not statistically significant. There was no incidence of retained placenta. There is a trend towards a reduction of the risk of postpartum hemorrhage when oxytocin is administered at the end of the second stage of labor. This is not accompanied by an increased risk for any morbidity.", "To determine if the timing of the administration of prophylactic oxytocin influences the incidence of postpartum hemorrhage caused by uterine atony, retained placenta, and third-stage duration.\n Parturients who presented for vaginal delivery were randomized in a double-blinded fashion to receive oxytocin, 20 units in a 500-mL crystalloid intravenous bolus, beginning upon delivery of either the fetal anterior shoulder or placenta. For all patients, the third stage of labor was managed with controlled cord traction until placental expulsion, followed by at least 15 seconds of fundal massage. Patients were excluded if they had a previous cesarean section, multiple gestation, antepartum hemorrhage, or bleeding disorder.\n A total of 1486 patients were enrolled: 745 in the before-placenta group and 741 in the after-placenta group. The groups were similar with respect to gestational age, fetal weight, labor duration, maternal age, parity, and ethnicity. The incidence of postpartum hemorrhage did not differ significantly between the two groups (5.4% vs 5.8%; crude OR, 0.92; 95% CI, 0.59 to 1.43). There were no significant differences between the two groups with respect to incidence of retained placenta (2.4% vs 1.6%; OR, 1.49; 95% CI, 0.72 to 3.08), or third-stage duration (7.7 minutes vs 8.1 minutes; P =.23).\n The administration of prophylactic oxytocin before placental delivery does not reduce the incidence of postpartum hemorrhage or third-stage duration, when compared with giving oxytocin after placental delivery. Early administration, however, does not increase the incidence of retained placenta." ]

[ "2915004", "8905861", "8951003", "11480593" ]

[ "Abductor function after total hip replacement. An electromyographic and clinical review.", "Early outcome of total hip arthroplasty using the direct lateral vs the posterior surgical approach.", "Nerve injury after posterior and direct lateral approaches for hip replacement. A clinical and electrophysiological study.", "Hip abductor strength following total hip arthroplasty: a prospective comparison of the posterior and lateral approach in 100 patients." ]

[ "Electromyographic and clinical studies were performed on patients undergoing total hip replacement by the modified direct lateral (29 hips), the direct lateral (29 hips) and the posterior approaches (21 hips). Assessments were made three months after operation. The Trendelenburg test was positive (Grade II) in eight cases operated upon by the direct lateral route, but in only one of each of the other two groups. Denervation occurred in only five of the 28 hips with abductor weakness without statistical difference between the groups. In the modified direct lateral group, radiological evidence of union of the trochanteric sliver was associated with significantly better abductor function than in those with malunion or non-union.", "A consecutive series of 49 patients who had a primary total hip arthroplasty (THA) for osteoarthritis is reviewed to determine the difference in clinical outcome between the direct lateral and the posterior surgical approaches to the hip. Group 1 comprised 28 patients off had THA by the same surgeon using a posterolateral approach. Group 2 comprised 21 patients who had THA using the direct lateral approach, modified from Hardinge. The improvement in the limp, abductor strength, Trendelenburg test, and range of motion over time was similar in the two groups. The average Harris hip score at 1 year was 90 for Group 1 (posterior approach) and Group 2 (lateral approach). At 2-year minimum follow up, the Harris hip score was 94 for both groups. Radiographic review showed that the incidence and severity of heterotopic bone was also similar for both groups. The authors conclude that the clinical and radiographic outcome for THA using the posterior and the lateral approaches to the hip yield similar clinical results.", "Nerve injury is a rare complication of total hip replacement which may be related to the exposure used for the operation. The posterior approach is traditionally associated with injury to the sciatic nerve. We have compared the incidence of nerve injury after primary total hip replacement (THR) using either a posterior or a direct lateral approach. We studied 42 consecutive patients undergoing primary total hip replacement. The surgeons used a posterior (22 patients) or direct lateral (20 patients) approach in accordance with their normal practice. The obturator, femoral, posterior tibial and common peroneal nerves were assessed clinically and electrophysiologically by electromyography (EMG) and measurement of the velocity of nerve conduction before operation and at four weeks after. All patients were free from symptoms of nerve injury after operation but five lesions were identified in four patients by the electrophysiological studies; the obturator nerve was involved in two, the femoral in one, the common peroneal in one and the posterior tibial in one. All these injuries occurred using the lateral approach. Clinical assessment alone underestimates the incidence of nerve injury complicating THR. Our study does not confirm the association of nerve injury with the posterior approach which had been described previously.", "We studied the hip abductor strength and Trendelenburg test prospectively in 100 patients undergoing total hip replacement via a lateral or posterior approach. In 49 patients, we used the lateral approach to implant the Charnley total hip replacement, and in 51 patients, the posterior approach to implant the Exeter total hip. Isometric abductor strength was measured with the kinetic communicator device and the Trendelenburg test was recorded preoperatively and at 3 and 12 months postoperatively. Of the original 100 patients, 83 were available for study at 3 months and 73 at 12 months. Hip abductor strength and the Trendelenburg test improved postoperatively in both groups, but we found no difference in hip abductor strength recovery at 3 and 12 months between the lateral approach and the posterior approach. Similarly there was no difference in the Trendelenburg test between the two groups 3 and 12 months following hip replacement." ]

[ "8156307", "8633378", "9059953", "2892989", "7653482", "8049820", "7914635" ]

[ "Intermittent cyclical etidronate in the prevention of corticosteroid-induced bone loss.", "Prevention of bone loss in cardiac transplant recipients. A comparison of biphosphonates and vitamin D.", "Cyclical etidronate in the prevention of bone loss in corticosteroid-treated primary biliary cirrhosis. A prospective, controlled pilot study.", "Prevention of steroid-induced osteoporosis with (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD).", "Cyclical etidronate reverses bone loss of the spine and proximal femur in patients with established corticosteroid-induced osteoporosis.", "Therapy of steroid-induced bone loss in adult asthmatics with calcium, vitamin D, and a diphosphonate.", "Increased bone density in patients on steroids with etidronate." ]

[ "We conducted a prospective study of etidronate's effects on corticosteroid-induced bone loss in postmenopausal women with temporal arteritis for whom high-dose prednisone therapy was indicated. Group A (n = 10) received etidronate (400 mg/day for 2 weeks, then 11 weeks off etidronate; four cycles total) and prednisone: Group B (n = 10) received only prednisone. Vertebral bone mineral density (BMD) was measured blinded by dual X-ray absorptiometry. At 3, 6 and 12 months, vertebral BMD was significantly (P < 0.01) increased in Group A and decreased in Group B, based on mean actual and percent changes in BMD and mean changes in BMD Z-score from baseline. Between-group comparisons were also significant (P < 0.002) at each time point. No adverse events related to etidronate treatment were reported. Our results suggest that corticosteroid-induced bone loss may be prevented by instituting intermittent cyclical etidronate therapy when high-dose prednisone therapy is begun. Further research into bisphosphonate use in corticosteroid-induced bone loss (with larger patient populations, longer follow-up and fracture assessment) is warranted.", "Bone mineral density is already abnormally reduced at the moment of cardiac transplantation and bone loss occurs at an impressive rate in the first postoperative year. The aim of the study was to compare two prophylactic medical regimens as to their efficacy in mitigating bone loss after transplantation. Forty-eight consecutive recipients were randomized to receive either alternating calcium carbonate and disodium etidronate (group A) or a daily supplement of calcium carbonate and alphacalcidol (group B). Bone mineral density measurements were performed immediately before hospital discharge and 6, 12, and 24 months after surgery using dual energy X-ray absorptiometry. Clinical events were recorded and roentgenograms of the spine were performed postoperatively and 1 and 2 years later. In both treatment groups bone loss remained significant at the level of the lumbar spine in the first postoperative year (P<0.005) and at the level of the femoral neck in the first (P<0.005) and the second (P<0.06) year after transplantation. Six months after transplantation, however, patients receiving alphacalcidol had a significant reduction in bone loss at the level of the lumbar spine (P=0.047) and at the level of the femoral neck (P=0.043). At the level of the femoral neck this decrease in bone loss was even more pronounced in the second postoperative year (P<0.001). In the group of patients treated with disodium etidronate, 4 recipients needed additional hospitalizations for treatment of symptomatic fractures at the level of the lumbar spine or the femoral neck. No such events happened in recipients receiving vitamin D supplements. Prophylactic administration of calcium carbonate and alphacalcidol after cardiac transplantation reduces bone loss and seems to decrease osteoporotic complications.", "Recently, promising disease modifying effects of low dose corticosteroid treatment in primary biliary cirrhosis have been reported. However, steroid-induced bone loss constitutes a potential drawback of this treatment option.\n To assess whether etidronate can reduce bone loss during corticosteroid treatment.\n Twelve primary biliary cirrhosis patients (all Child-Pugh Class A), treated with prednisone in the context of a 1-year placebo-controlled pilot study with prednisone (maintenance dose 10 mg daily), and azathioprine (50 mg daily), were randomized to receive either cyclical etidronate (400 mg daily, during 2 weeks) alternated with calcium 500 mg daily during 11 weeks or calcium alone. All patients had been receiving ursodeoxycholic acid during at least 1 year and this treatment was continued. Bone mass was measured in the lumbar spine and the femoral neck by dual energy X-ray absorptiometry before and after 3 and 12 months of treatment. Markers of bone formation (serum osteocalcin, procollagen-I-propeptide) and bone resorption (urinary deoxypyridinoline and calcium) were also monitored.\n The mean lumbar bone mineral density did not significantly change in the patients taking etidronate + calcium, in contrast to patients treated with calcium alone (+0.4 vs. -3.0%; p = 0.01). Changes in femoral bone mineral density and markers of bone turnover did not significantly differ between both groups. No adverse effects of etidronate were noted.\n Cyclical etidronate appears to prevent bone loss associated with prednisone treatment in patients with primary biliary cirrhosis. These preliminary results encourage the further evaluation of long term prednisone treatment and concurrent bisphosphonate therapy in primary biliary cirrhosis.", "In a prospective, randomised, placebo-controlled trial comparing the effect of (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) (150 mg/day) plus calcium (1 g/day) with that of calcium alone on the bone mass of patients receiving long-term glucocorticoid therapy, the mean metacarpal cortical area in patients receiving APD increased by 1.2% between 0 and 6 months (p less than 0.06) and then remained stable between 6 and 12 months. In contrast, this index progressively declined in the placebo group (p less than 0.05 at 12 months). The two groups differed significantly in the changes at both 6 and 12 months (p less than 0.01). Mean vertebral mineral density, as measured by quantitative computed tomography, increased by 19.6% over 12 months in the APD group (p less than 0.02) but showed a non-significant decline of 8.8% in controls. The differences between the changes were again significant (p less than 0.005). Biochemical indices and bone histomorphometry indicated a reduction in bone resorption and bone formation but there was no evidence of osteomalacia. APD may thus prevent bone loss in glucocorticoid-treated patients over a year.", "To compare the bone-mass effects of calcium supplementation and intermittent cyclic etidronate in patients with established corticosteroid-induced osteoporosis.\n Eighteen male and 21 female patients who had established corticosteroid-induced osteoporosis and were receiving chronic prednisone therapy (> or = 10 mg/d) were enrolled in a prospective 12-month, open-label study. In addition to continuing prednisone therapy, patients received continuous calcium supplementation 500 mg/d (n = 20) or four cycles of intermittent cyclic etidronate therapy consisting of etidronate 400 mg/d for 14 days followed by calcium 500 mg/d for 76 days (n = 19). Bone mineral density (BMD) of the spine (L1 through L4) and proximal femur (total hip, femoral neck, trochanter, Ward's triangle) was measured by dual-energy x-ray absorptiometry at baseline, 6 months, and 12 months by staff blinded to the treatment. Serum calcium, phosphorus, and alkaline phosphatase were also measured at these times.\n Treatment with intermittent cyclic etidronate for 12 months resulted in significant increases of 5.7% and 6.8% in BMD of the spine and proximal femur (total hip), respectively (P < 0.02 versus baseline; P < 0.001 versus calcium group). Calcium supplementation alone did not prevent significant losses of 3.4% and 4.1% in BMD at the respective sites (P < 0.02 versus baseline). At the end of the study Z scores reflected significant increases in BMD of the spine and proximal femur (all regions) in the etidronate group (P < 0.01), and significant decreases at the spine, proximal femur, and trochanter in the calcium group (P < 0.01). After 12 months, the difference between the groups was 9.1% (P < 0.01; 95% CI 6.3% to 11.9%) at the spine and 10.9% (P < 0.01; 95% CI 7.8% to 14.1%) at the proximal femur (total hip). Seventeen (89%) of the etidronate-treated patients had increases in BMD of both skeletal sites, whereas only 2 (10%) and 3 (15%) of the calcium-treated patients had positive changes in BMD of the spine and proximal femur (total hip), respectively (P < 0.01). Serum calcium, phosphorus, and alkaline phosphatase levels did not change significantly during the study in either treatment group. Both treatment regimens were well tolerated, with no interactions between prednisone therapy and the study medications. Analyses of response by subgroups (female/male, pulmonary/nonpulmonary indication for prednisone) showed no significant attribute-dependent changes during the 12-month study. At baseline, women had significantly lower BMD of the spine and proximal femur (total hip) (P < 0.01), and patients with pulmonary disease had significantly longer duration of prednisone therapy and cumulative prednisone dose (P < 0.03).\n Intermittent cyclic etidronate reversed the progressive loss of bone mineral density of the spine and proximal femur in female and male patients with established osteoporosis secondary to chronic corticosteroid (prednisone) therapy for pulmonary and nonpulmonary diseases. Calcium supplementation alone did not prevent or attenuate corticosteroid-induced losses.", "In a prospective, controlled, and randomized clinical trial, we examined the effects of treatment with vitamin D (1,000 IU/d), calcium (1 g/d), and ethane-1-hydroxy-1,1-diphosphonate (EHDP; 7.5 mg/kg body weight) on vertebral bone mass in fourteen asthmatics undergoing long-term treatment with systemically applied corticosteroids. The extent of steroid-induced bone loss was judged by vertebral bone density of the lumbar spine measured by dual-photon absorptiometry as well as by vertebral crush fracture incidence examined by conventional X-ray. Results of the measurements before treatment and after six mo were compared with those of an untreated control group of nineteen asthmatics. Bone density increased during the observation period by 5% in the treated group, compared with a decrease of 4.3% in the untreated control group (p < 0.01). Moreover, in the treated group no radiologically visible new fractures occurred; in the control group new fractures were observed in four patients. There were no serious side effects of the applied drugs during the 6-mo period. Therefore, the combination of EHDP, calcium, and vitamin D appears to be a useful regimen for the management of steroid-induced bone loss in adult asthmatics.", "nan" ]

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[ "The effects of family involvement and practitioner home visits on the control of hypertension.", "Improving compliance with therapeutic regimens in hypertensive patients in a community health center.", "Comparing standard care with a physician and pharmacist team approach for uncontrolled hypertension.", "Pharmaceutical care program for patients with uncontrolled hypertension. Report of a double-blind clinical trial with ambulatory blood pressure monitoring.", "Nurse management for hypertension. A systems approach.", "The effects of self-monitoring by patients on the control of hypertension.", "Improving hypertension control: impact of computer feedback and physician education.", "Evaluation of two educative models in a primary care hypertension programme.", "Evaluation of the IMPACT blood pressure program.", "Impact on hypertension control of a patient-held guideline: a randomised controlled trial.", "Self-recording of blood pressure in the management of hypertension.", "Home blood pressure monitoring. Effect on use of medical services and medical care costs.", "Using nurses for preventive activities with computer assisted follow up: a randomised controlled trial.", "Effect of pharmacist intervention and initiation of home blood pressure monitoring in patients with uncontrolled hypertension.", "Home blood pressure monitoring for mild hypertensives.", "Evaluation of a structured treatment and teaching programme on hypertension in general practice.", "Improvement of medication compliance in uncontrolled hypertension.", "Effectiveness of a two-part educational intervention to improve hypertension control: a cluster-randomized trial.", "Nurse-led adherence support in hypertension: a randomized controlled trial.", "Pharmacist involvement in primary care improves hypertensive patient clinical outcomes.", "Home monitoring service improves mean arterial pressure in patients with essential hypertension. A randomized, controlled trial.", "Randomised clinical trial of strategies for improving medication compliance in primary hypertension.", "Evaluation of a nurse-run hypertension clinic in general practice.", "Linking community-based blood pressure measurement to clinical care: a randomized controlled trial of outreach and tracking by community health workers.", "The effect of instruction on control of blood pressure in individuals with essential hypertension.", "Therapeutic control of blood pressure in the Hypertension Detection and Follow-up Program. Hypertension Detection and Follow-up Program Cooperative Group.", "Improving blood pressure control in diabetes: limitations of a clinical reminder in influencing physician behavior.", "A randomized trial to improve follow-up care in severe uncontrolled hypertensives at an inner-city walk-in clinic.", "From screening to seeking care: removing obstacles in hypertension control.", "Comprehensive pharmaceutical care in the chain setting.", "Antihypertensive drug treatment: a comparison of usual care with self blood pressure measurement.", "Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative Group.", "Management of hypertension. Effect of improving patient compliance for follow-up care.", "Improving hypertension control in a private medical practice.", "Effect of nurse-directed hypertension treatment among First Nations people with existing hypertension and diabetes mellitus: the Diabetes Risk Evaluation and Microalbuminuria (DREAM 3) randomized controlled trial.", "Treatment of hypertension by computer and physician-a prospective controlled study.", "Screening, treatment and adherence to treatment for hypertension.", "Effect of nurse counselling on metabolic risk factors in patients with mild hypertension: a randomised controlled trial.", "The effect of treatment on mortality in \"mild\" hypertension: results of the hypertension detection and follow-up program.", "Self-monitoring of blood pressure promotes achievement of blood pressure target in primary health care.", "A multimethod quality improvement intervention to improve preventive cardiovascular care: a cluster randomized trial.", "A telecommunications system for monitoring and counseling patients with hypertension. Impact on medication adherence and blood pressure control.", "A randomized study comparing a patient-directed hypertension management strategy with usual office-based care.", "The impact of a patient education programme in the control of hypertension.", "A controlled trial of health education in the physician's office.", "Does free care improve adults' health? Results from a randomized controlled trial.", "A randomized controlled trial of an information booklet for hypertensive patients in general practice.", "Effects of home telemonitoring and community-based monitoring on blood pressure control in urban African Americans: a pilot study.", "A computer-based monitoring system for follow-up of elevated blood pressure.", "Efficacy of telephone and mail intervention in patient compliance with antihypertensive drugs in hypertension. ETECUM-HTA study.", "Evaluation of computer based clinical decision support system and risk chart for management of hypertension in primary care: randomised controlled trial.", "Electronic monitoring of adherence as a tool to improve blood pressure control. A randomized controlled trial.", "Randomised controlled trial of computer assisted management of hypertension in primary care.", "Pragmatic randomized trial of home visits by a nurse to elderly people with hypertension in Mexico.", "Physicians' management of hypertension: a randomized controlled CME trial.", "Health education for hypertensive patients.", "Influence of self-measurement of blood pressure on the responder rate in hypertensive patients treated with losartan: results of the SVATCH Study. Standard vs Automatic Treatment Control of COSAAR in Hypertension.", "Does a mailed continuing education program improve physician performance? Results of a randomized trial in antihypertensive care.", "Work-site treatment of hypertension by specially trained nurses. A controlled trial.", "Use of a standardized personal medical record by patients with hypertension: a randomized controlled prospective trial.", "Implementing clinical guidelines in the treatment of hypertension in general practice. Evaluation of patient outcome related to implementation of a computer-based clinical decision support system.", "Randomized controlled trial on lifestyle modification in hypertensive patients.", "Five-year blood pressure control and mortality following health education for hypertensive patients.", "Effectiveness of patient education and psychosocial counseling in promoting compliance and control among hypertensive patients.", "Implementing clinical guidelines in the treatment of hypertension in general practice.", "An appointment reminder system's effect on reducing the number of hypertension patients who drop out from care.", "Impact of educational mailing on the blood pressure of primary care patients with mild hypertension.", "Targets and self monitoring in hypertension: randomised controlled trial and cost effectiveness analysis.", "Educational outreach in diabetes to encourage practice nurses to use primary care hypertension and hyperlipidaemia guidelines (EDEN): a randomized controlled trial." ]

[ "The effectiveness of two social support strategies designed to lower hypertensive patients' blood pressure were compared to each other and to a control group (N = 63) receiving routine care in a randomized clinical trial extending over a period of two years. Group 1 (N = 99) received visits and had family members actively participate in their care through home blood pressure monitoring; Group 2 (N = 56) received home visits from nurses and pharmacists. All groups were predominantly Black. After the first year of the trial, the proportion of patients with uncontrolled diastolic blood pressure (greater than or equal to 95mm Hg) had declined significantly for all three groups; no group showed a statistically significant advantage. However, during the last six months of the second year (after visiting had ended), both Groups 1 and 2 demonstrated clear superiority in DBP control over Group 3, achieving borderline statistical significance (p = .07) when multivariable analysis was performed to control for potential confounders. Supplementing routine care with periodic home visits produced an additional 21 per cent of patients with well-controlled DBP, while involving family members plus visits produced a 17 per cent improvement in the percentage of patients with DBP less than 95mm Hg. However, neither support strategy was clearly more effective than the other over time. The efficacy of the interventions is discussed with respect to cost and feasibility of implementation.", "A 1-year, randomized study was conducted to test the possibility of improving compliance with therapeutic regimens in hypertensives by means of certain simple arrangements. Patients were given written treatment instructions concerning hypertension, a personal blood-pressure follow-up card, and, for those who failed to attend their blood-pressure check-up, an invitation for a new check-up. Using matched pairs, 202 Finnish hypertensives were randomly allocated either to an ordinary or a reorganized treatment group. By means of the latter system, patient compliance could be significantly (p less than 0.01) improved: Only 4% of the patients in this group dropped out of treatment, compared with 19% in the ordinary treatment group. By the end of the year, blood pressure had been lowered by at least 10% in 95% of the patients in the reorganized group and in 78% of those in the ordinary group (p less than 0.01). This was achieved in approximately 60% of cases using chlorthalidone alone.", "To assess the effect of a physician and pharmacist teamwork approach to uncontrolled hypertension in a medical resident teaching clinic, for patients who failed to meet the recommended goals of the fifth Joint National Commission on Detection, Evaluation and Treatment of High Blood Pressure.\n Physician and pharmacist teamwork can improve the rate of meeting national blood pressure goals in patients with previously uncontrolled hypertension.\n A single-blinded randomized controlled trial lasting 6 months.\n A primary care outpatient teaching clinic.\n A sample of 95 adult hypertensive patients who failed to meet national blood pressure goals based on three consecutive visits over a 6-month period.\n Patients were randomly assigned to a control arm of standard medical care or to an intervention arm in which a physician and pharmacist worked together as a team.\n At study completion, the percentage of patients achieving national goals due to intervention was more than double the percentage in the control arm (55% vs 20%, p < .001). Systolic blood pressure declined 23 mm Hg in the intervention arm versus 11 mm Hg in the control arm (p < .01). Diastolic blood pressure declined 14 and 3 mm Hg in the intervention and control arms, respectively (p < .001). The intervention worked equally as well in men and women and demonstrated noticeable promise in a minority of mixed-ancestry Hawaiians in whom hypertension is of special concern.\n Patients who fail to achieve national blood pressure goals under standard outpatient medical care may benefit from a program that includes a physician and pharmacist teamwork approach.", "Pharmaceutical care programs may be an option to improve blood pressure (BP) control in patients with uncontrolled hypertension. The aim of this study was to evaluate the efficacy of pharmaceutical care programs in treating patients with resistant hypertension.\n In a double-blind randomized clinical trial, 71 patients with uncontrolled BP were enrolled in a pharmaceutical care program or in a control group and underwent a series of cognitive tests. The primary outcome was change in ambulatory BP (ABP) between the baseline evaluation and the final visit 6 months later. The secondary outcomes were the frequency of drug-related problems and adherence as determined by plasma levels of hydrochlorothiazide.\n The delta-values between the intervention and control groups for ABP in the different daily periods, with the corresponding 95% confidence limits, adjusted for age and baseline BP were: 3 (-1 to 5), 2 (-2 to 4), and 5 (-1 to 6) mm Hg for 24 h, daily and nightly systolic BP, respectively. The corresponding values for diastolic BP were 1 (-1 to 3), 0 (-2 to 2), and 3 (-1 to 4) mm Hg, respectively. Hydrochlorothiazide was detected in the plasma in 21 of 27 patients in the intervention group that attended to all appointments and 24 of 30 patients in the control group (P = .904).\n The pharmaceutical care program tested in this trial was feasible and showed a trend for better BP control in patients with uncontrolled hypertension.", "Standard office-based approaches to controlling hypertension show limited success. Such suboptimal hypertension control reflects in part the absence of both an infrastructure for patient education and frequent, regular blood pressure (BP) monitoring. We tested the efficacy of a physician-directed, nurse-managed, home-based system for hypertension management with standardized algorithms to modulate drug therapy, based on patients' reports of home BP.\n We randomized outpatients requiring drug therapy for hypertension according to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) criteria to receive usual medical care only (UC, n = 76) or usual care plus nurse care management intervention (INT, n = 74) over a 6-month period.\n Patients receiving INT achieved greater reductions in office BP values at 6 months than those receiving UC: 14.2 +/- 18.1 versus 5.7 +/- 18.7 mm Hg systolic (P < .01) and 6.5 +/- 10.0 versus 3.4 +/- 7.9 mm Hg diastolic, respectively (P < .05). At 6 months, we observed one or more changes in drug therapy in 97% of INT patients versus 43% of UC patients, and 70% of INT patients received two or more drugs versus 46% of UC. Average daily adherence to medication, measured by electronic drug event monitors, was superior among INT subjects (mean +/- SD, 80.5% +/- 23.0%) than among UC subjects (69.2 +/- 31.1%; t(113) = 2.199, P = .03). There were no significant adverse drug reactions in either group.\n Telephone-mediated nurse management can successfully address many of the systems-related and patient-related issues that limit pharmacotherapeutic effectiveness for hypertension.", "The effects of self-monitoring of blood pressure on the control of hypertension were examined in this study. Failure of patients to comply with treatment is presumably attributable in part to the fact that hypertension usually is asymptomatic until complications develop. Self-monitoring might make visible an otherwise asymptomatic condition, and thereby increase motivation. One hundred hypertensive patients beginning outpatient treatment were randomly assigned to experimental and control groups. Subjects were given a sphygmomanometer and instructed in its use. Both groups were given similar antihypertensive medications. After six months of treatment, mean systolic pressure was significantly lower (11.4 mm Hg, p smaller than 0.05) in the experimental than in the control subjects. However, the mean baseline systolic pressure in the control group was 3.9 mm Hg less than that of the experimental group. If this value is substracted from the difference between the last mean systolic pressures in the two groups, the 7.5 mm Hg difference is seen as a very modest effect of self-monitoring. Diastolic blood pressure was insignificantly lower for experimental subjects. Compared to the potent effectiveness of drugs in reducing blood pressure, self-monitoring was of little value.", "Two interventions designed to help physicians manage hypertensive patients were evaluated in a controlled trial: 1) computer-generated feedback to facilitate identification of poorly controlled patients; and 2) a physician education program on clinical management strategies, emphasizing patient compliance. Four physician practice teams received either computer feedback, the education program, both, or neither. Feedback team physicians received seven monthly listings of the latest visits and blood pressures of their hypertensive patients. The self-administered learning program included written clinical stimulations and associated didactic material. Experimental and control physicians were similar in baseline knowledge, patient mix and level of training. All feedback team physicians requested appointments for listed patients, and their patients made twice as many visits as control patients during the intervention period (p less than 0.05). Education team physicians showed significant gains on a content-specific post-intervention test: mean score 84 per cent compared with 74 per cent for the control group (p less than 0.005). All patient groups showed improvement in blood pressure over the study period. However, no differences between intervention teams could be detected (p greater than 0.20). The probability of missing a 10 mm interteam difference in outcome diastolic pressure was 1 per cent (power of 0.99). Strategies for further improvement in outpatient hypertension management may need to come from outside the traditional medical model.", "This study was planned in the context of a regional high blood pressure programme, to compare the efficacy of two educative methods. The group of 722 hypertensive patients (58.8% women), mean age 61 years, was randomly selected from 19 primary care centres. Initial assessment was based on a patient interview including 22 questions on high blood pressure, its consequences and treatment. Patients agreeing to participate in an active education team programme were distributed into three groups: individual education, team education and a control group. Those who declined to participate formed two groups: individual education and controls. Team education consisted of two audiovisual sessions attended by groups of 8-12 patients and conducted by treating physicians and nurses. Individual education included comments related to the 22 questions. Follow-up assessment was made after two months. An increase in the level of hypertension control was observed only in the accepting group, in which educative action was followed by increased knowledge. Results were similarly favourable for both the individual and team education groups and suggested the need to consider educational factors together with those influencing patient attitude towards an active educational programme.", "To evaluate the incremental effectiveness of a work-site blood pressure control program, we conducted a randomized, controlled trial at four work sites with established health promotion programs. Workers with blood pressures of 140/90 mm Hg or higher were eligible. Eighty subjects were assigned to receive a referral to a community physician, monthly 10-minute work-site counseling sessions including blood pressure readings, and personalized mailings, whereas 79 control subjects received only a physician referral. Results for 74 intervention and 71 control subjects were obtained after 1 year. As compared with control subjects, intervention subjects experienced average declines of 8.5/3.9 mm Hg. Adjusted for age, sex, and baseline blood pressure, the decreases were 7.6 mm Hg for systolic and 2.4 mm Hg for diastolic blood pressure. These results suggest that counseling of high-risk persons and personalized mailing programs can have an incremental benefit in controlling blood pressure.", "Hypertension is generally poorly controlled in primary care. One possible intervention for improving control is the harnessing of patient expertise through education and encouragement to challenge their care.\n To determine whether encouraging patients to manage their hypertension in an 'expert' manner, by providing them with information in a clear clinical guideline, coupled with an explicit exhortation to become involved in and to challenge their own care if appropriate, would improve their care.\n Single blind randomised controlled trial of detailed guideline versus standard information.\n Single urban general practice over 1 year.\n Patient-held guideline with written explicit exhortation to challenge care when appropriate. Two hundred and ninety-four of 536 eligible patients on the practice hypertension register were recruited, all of whom were randomised into one of two groups. Two hundred and thirty-six patients completed the study.\n Primary outcome: average systolic blood pressure. Secondary outcomes: proportion of patients with blood pressure < 150 mmHg systolic and < 90 mmHg diastolic, average cholesterol, proportion of patients prescribed statins and aspirin according to guideline, hospital anxiety and depression score. No clinically, or statistically significant differences were found between intervention and control with respect to all parameters or in anxiety and depression levels. Statin and aspirin use improved throughout the course of the study in both groups. Statin use showed a trend (P = 0.02) in favour of control.\n In this study there was no clinically significant perceived benefit to patients as a result of providing them with a hypertension guideline. Patient guidelines are currently planned for many chronic illnesses. It is important to determine the utility of such interventions before scarce resources are applied to them.", "The efficacy of self-recording of blood pressure in the management of hypertension was assessed in a randomized clinical trial involving 140 persons who had been receiving antihypertensive therapy for a year or more, but whose diastolic blood pressure had remained at 95 mm Hg or higher. To control for the increased attention implicit in self-recording, which might affect blood pressure, the patients were assigned at random to one of the four groups: self-recording and monthly home visits, self-recording only, monthly home visits only, and neither self-recording nor monthly home visits. This design also permitted assessment of the effect of home visits. During the 6-month experiment no significant differences were apparent between the groups in either compliance or diastolic blood pressure. However, both self-recording and monthly home visits produced a reduction in blood pressure among patients who admitted to difficulty remembering to take their pills; a reduction was not seen among patients who said they had no such difficulty. This confirmed an earlier observation suggesting that this easily identified group of patients may be the most responsive to intervention programs.", "The objective of this study was to determine whether a hypertension management program in which patients monitor their own blood pressure (BP) at home can reduce costs without compromising BP control. The prospective, randomized, controlled 1-year clinical trial was conducted at four medical centers of the Kaiser Permanente Medical Care Program in the San Francisco Bay Area. Of 467 patients with uncomplicated hypertension who were referred by their physicians, 37 declined to participate in the study; 215 were randomly assigned to a Usual Care (UC) group and 215 to a Home BP group. Twenty-five UC patients and 15 Home BP patients did not return for year-end BP measurements. Patients in the UC group were referred back to their physicians. Patients in the Home BP group were trained to measure their own BP and return the readings by mail. Patients were given a standard procedure to follow in case of unusually high or low BP readings at home. The number and type of outpatient medical services used were obtained from patient medical records for the study year and the prior year. Costs of care for hypertension were calculated by assigning relative value units to each outpatient service. Trained technicians measured each patient's BP at entry into the study and 1 year later. Home BP patients made 1.2 fewer hypertension-related office visits than UC patients during the study year (95% confidence interval (CI): 0.8, 1.7). Mean adjusted cost for physician visits, telephone calls, and laboratory tests associated with hypertension care was $88.76 per patient per year in the Home BP group, 29% less than in the UC group (95% CI: $16.11, $54.74). The annualized cost of implementing the home BP system was approximately $28 per patient during the study year and would currently be approximately $15. After 1 year, BP control in men in the Home BP group was better than in men in the UC group; BP control was equally good in women in both groups. Management of uncomplicated hypertension based on periodic home BP reports can achieve BP control with fewer physician visits, resulting in substantial cost savings.", "To assess whether an organised programme of prevention including the use of a health promotion nurse noticeably improved recording and follow up of cardiovascular risk factors and cervical smears in a general practice that had access to computerised cell and recall.\n Randomised controlled trial.\n General practice in inner London.\n All 3206 men and women aged 30-64 registered with the practice.\n The intervention group had their risk factors ascertained and followed up by the health promotion nurse and the general practitioner, whereas those in the control group were managed by the general practitioner alone.\n Recording and follow up of blood pressure and cervical smears after three years. Recording of smoking, family history of ischaemic heart disease, and serum cholesterol concentrations were also examined. MEASUREMENTS and\n When the trial was stopped after two years the measurements of blood pressure in the preceding five years were 93% (1511/1620) v 73% (1160/1586) (95% confidence interval for difference 17.5 to 22.7%) for intervention and control groups respectively. For patients with hypertension the figures were 97% (104/107) v 69% (80/116) (18.2 to 38.2%). For women the proportion who had had a cervical smear in the preceding three years were 76% (606/799) v 49% (392/806) (22.5 to 31.9%). Recording of smoking, family history of ischaemic heart disease, and serum cholesterol concentrations was also higher in the intervention group compared with the control group.\n An organised programme, which includes a nurse with specific responsibility for adult prevention, is likely to make an important contribution to recording of risk factors and follow up of those patients with known risks.", "This prospective, randomized, controlled study evaluated the impact of pharmacist-initiated home blood pressure monitoring and intervention on blood pressure control, therapy compliance, and quality of life (QOL). Subjects were 36 patients with uncontrolled stage 1 or 2 hypertension. Eighteen subjects received home blood pressure monitors, a diary, and instructions to measure blood pressure twice every morning. Home measurements were evaluated by a clinical pharmacist by telephone, and the patient's family physician was contacted with recommendations if mean monthly values were 140/90 mm Hg or higher. Eighteen control patients did not receive home monitors or pharmacist intervention. Office blood pressure measurements and QOL surveys (SF-36) were obtained at baseline and after 6 months. Mean absolute reductions in systolic and diastolic pressures were significantly reduced from baseline in intervention subjects (17.0 and 10.5 mm Hg, both p < 0.0001) but not in controls (7.0 and 3.8 mm Hg, p = 0.12 and p = 0.09). More intervention subjects (8) had blood pressure values below 140/90 at 6 months compared with controls (4). During the study 83.3% (15) of intervention subjects had drug therapy changes versus 33% (6) of controls (p < 0.01). Compliance and QOL were not significantly affected. Our data suggest that the combination of pharmacist intervention with home monitoring can improve blood pressure control in patients with uncontrolled hypertension. This may be related to increased modifications of drug regimens.", "A clinical trial of 204 untreated patients with mild hypertension was conducted to assess the effect of home blood pressure monitoring on blood pressure level, pharmacologic treatment, reduction of risk factors, and use of health services. After 1 year, no statistically significant differences were found between the treatment and control groups. The findings indicate that, while home blood pressure monitoring may be useful, it has no measurable short-term impact on these aspects of blood pressure management for patients with mild hypertension.", "Evaluation of a structured hypertension treatment and teaching programme in general practice.\n Prospective controlled trial; follow-up period 18 months.\n 10 primary health care practices. PRACTICES AND PATIENTS: From each practice 20 patients (30 to 60 years old, mean of the last two blood pressure measurements at or above 160 and/or 95 mmHg) were randomly selected; in 5 practices these patients were to participate in the treatment and teaching programme; in the remaining 5 practices hypertension care was continued without the availability of such a programme (controls).\n Structured treatment and teaching programme based upon four group sessions for patients mainly conducted by paramedical personnel.\n Blood pressure, body weight, prescription of antihypertensive drugs - as documented in the patient's records.\n Of the 100 control patients 26 and of the 100 intervention patients 14 were lost to observation; 46 patients had agreed to participate in the programme. The mean number of prescribed antihypertensive agents per patient decreased in the intervention group (1.8 +/- 1.3 at baseline, vs 1.2 +/- 1.2 at follow-up) compared to the control group (1.6 +/- 1.3 vs 1.8 +/- 1.6); difference 0.8 (95% CI 0.4 to 1.1), p < 0.0001. In the control group 9% and in the intervention group 33% of patients had documented reductions of body weight (p < 0.0001). Blood pressure decreased in the intervention group (162 +/- 14/100 +/- 7 mmHg at baseline, vs 154 +/- 16/95 +/- 9 mmHg at follow-up) compared to the control group (161 +/- 13/98 +/- 7 mmHg vs 158 +/- 18/96 +/- 11 mmHg); differences for systolic blood pressure 5 (95% CI 0 to 10) mmHg, p = 0.071; for diastolic blood pressure 4 (1 to 7) mmHg, p = 0.018.\n The introduction of a structured hypertension treatment and teaching programme in general practice may lead to significant improvements of hypertension care.", "38 hypertensive Canadian steelworkers who were neither compliant with medications nor at goal diastolic blood-pressure six months after starting treatment were allocated either to a control group or to an experimental group who were taught how to measure their own blood-pressures, asked to chart their home blood-pressures and pill taking, and taught how to tailor pill taking to their daily habits and rituals; these men were also seen fortnightly by a highschool graduate with no formal health professional training who reinforced the experimental manoeuvres and rewarded improvements in compliance and blood-pressure. Six months later, average compliance had fallen by 1.5% in the control group but rose 21.3% in the experimental group. Blood-pressures fell in 17 of 20 experimental patients (to goal in 6) and in 10 of 18 control patients (to goal in 2).", "To measure the effectiveness of a multifaceted educational intervention to improve ambulatory hypertension control.\n Cluster-randomized trial.\n Academic health system using an ambulatory electronic medical record.\n A total of 10,696 patients with a diagnosis of hypertension cared for by 93 primary care providers.\n Academic detailing, provision of provider-specific data about hypertension control, provision of educational materials to the provider, and provision of educational and motivational materials to patients.\n The primary outcome was blood pressure control, defined as a blood pressure measurement below 140/90 mm Hg, and was ascertained from electronic medical records over 6 months of follow-up. We determined the adjusted odds ratio for the association between the intervention and the achievement of controlled blood pressure. When we accounted for clustering by provider, this adjusted odds ratio was 1.13 (95% confidence interval 0.87-1.47). Adjusted odds ratios were 1.03 (95% confidence interval 0.78-1.36) in patients whose blood pressure was controlled at baseline and 1.25 (95% confidence interval 0.94-1.65) in those whose blood pressure was not. These odds ratios were not significantly different (p=0.11).\n These results were consistent with no effect or, at best, a relatively modest effect of the intervention among patients with hypertension. Had we not included a concurrent control group, the data would have provided an unduly optimistic view of the effectiveness of the program. The effectiveness of future interventions may be improved by focusing on patients whose blood pressure is uncontrolled at baseline.", "Lack of medication adherence is a common reason for poor control of blood pressure in the community, increasing the risk of heart attacks and strokes.\n To evaluate the effect of nurse-led adherence support for people with uncontrolled high blood pressure compared with usual care.\n We recruited 245 women and men with uncontrolled hypertension (> or = 150/90 mmHg) from 21 general practices in Bristol, UK. Participants were randomized to receive nurse-led adherence support or usual care alone. Main outcome measures were adherence to medication ('timing compliance') and blood pressure.\n Mean baseline timing compliance (+/- SD) was high in both the intervention (90.8 +/- 15.6%) and the control group (94.5 +/- 7.6%). There was no evidence of an effect of the intervention on timing compliance at follow-up (adjusted difference in means -1.0%; 95% confidence interval (CI) -5.1 to 3.1). There was also no difference at follow-up between the groups with regard to systolic blood pressure (-2.7 mmHg; 95% CI -7.2 to 1.8) or diastolic blood pressure (0.2 mmHg; 95% CI -1.9 to 2.3). Projected costs for the primary care sector per consultation were 6.60 pound sterling for the intervention compared with 5.08 pound sterling for usual care.\n In this study, adherence to blood pressure medication was much higher than previously reported. There was no evidence of an effect of nurse-led adherence support on medication adherence or blood pressure compared with usual care. Nurse-led adherence support was also more expensive from a primary care perspective.", "The practice of pharmaceutical care in primary care settings in Thailand is currently not generally accepted.\n To evaluate the effect of pharmacist involvement in treatment with hypertensive patients in primary care settings.\n The treatment objective was to stabilize the blood pressure (BP) of hypertensive patients in accordance with the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure guidelines. Patients were randomly assigned to a pharmacist-involved group (treatment) or a group with no pharmacist involvement (control). Pre- and post-test BPs, tablet counts, lifestyle modifications, and pharmacists' recommendations were recorded. The 6-month study was carried out in Mahasarakham University pharmacy and 2 primary care units. Patients were monitored monthly by reviewing their medications and supported by providing pharmaceutical care and counseling.\n From a total of 235 patients, the treatment group (n = 118) had a significant reduction in both systolic (S) and diastolic (D) BP compared with the 117 patients of the control group (p = 0.037, 0.027, respectively). The 158 patients (76 treatment, 82 control) with BPs >or=140/90 mm Hg at the beginning of the study showed significant BP reductions (p = 0.002 SBP, 0.008 DBP). The proportion of 158 patients whose BP became stabilized was higher in the treatment group (p = 0.017). The treatment group showed significantly better adherence (p = 0.014) and exercise control (p = 0.012) at the end of the study. Physicians accepted 42.72% of medication modifications and 5.34% of the suggestions for additional investigations.\n Hypertensive patients who received pharmacist input achieved a significantly greater benefit in BP reduction, BP control, and improvement in adherence rate and lifestyle modification.", "Technological advances in the distribution of information have opened new avenues for patient care. Few trials, however, have used telemedicine to improve blood pressure in patients with essential hypertension.\n To determine the efficacy of a telecommunication service in reducing blood pressure.\n Randomized, controlled trial.\n University-affiliated primary care outpatient clinics.\n 121 adults with essential hypertension who were under evaluation for a change in antihypertensive therapy.\n A home service consisting of automatic transmission of blood pressure data over telephone lines, computerized conversion of the information into report forms, and weekly electronic transmission of the report forms to physicians and patients.\n 24-hour ambulatory blood pressure monitoring at baseline and exit. The primary end point was change in mean arterial pressure from baseline to exit.\n Mean arterial pressure decreased by 2.8 mm Hg in patients receiving the home service and increased by 1.3 mm Hg in patients receiving usual care (P = 0.013 for the difference). Mean diastolic blood pressure decreased by 2.0 mm Hg for home service but increased by 2.1 mm Hg for usual care (P = 0.012 for the difference). Mean systolic blood pressure decreased by 4.9 mm Hg for home service and 0.1 mm Hg for patients receiving usual care (P = 0.047 for the difference). Among African-American patients, mean arterial pressure decreased by 9.6 mm Hg in those receiving home service and increased by 5.25 mm Hg in those receiving usual care (P = 0.047). Part of the decrease in blood pressure for home service was due to more frequent changes in the type or dose of antihypertensive medications.\n This telecommunication service was efficacious in reducing the mean arterial pressure of patients with established essential hypertension.", "230 Canadian steelworkers with hypertension took part in a randomised trial to see if compliance with antihypertensive drug regimens could be improved. For care and follow-up these men were randomly allocated to see either their own family doctors outside working-hours or industrial physicians during work shifts; the same men were randomly allocated to receive or not receive an educational programme aimed at instructing them about hypertension and its treatment. Surprisingly, the convenience of follow-up at work had no effect upon these men's compliance with antihypertensive drug regimens. Similarly, although men receiving health education learned a lot about hypertension, they were not more likely to take their medicine.", "nan", "This study assessed the effectiveness of enhanced tracking and follow-up services provided by community health workers in promoting medical follow-up of persons whose elevated blood pressures were detected during blood pressure measurement at urban community sites.\n In a randomized controlled trial, 421 participants received either enhanced or usual referrals to care. Participants were 18 years or older, were either Black or White, and had blood pressure greater than or equal to 140/90 mm Hg and income equal to or less than 200% of poverty. The primary outcome measure was completion of a medical follow-up visit within 90 days of referral.\n The enhanced intervention increased follow-up by 39.4% (95% confidence interval [CI] = 14%, 71%; P = .001) relative to usual care. Follow-up visits were completed by 65.1% of participants in the intervention group, compared with 46.7% of those in the usual-care group. The number needed to treat was 5 clients (95% CI = 3, 13) per additional follow-up visit realized.\n Enhanced tracking and outreach increased the proportion of persons with elevated blood pressure detected during community measurement who followed up with medical care.", "This exploratory study examined the effect of structured teaching about essential hypertension on control of the diastolic blood pressure in individuals with a diagnosis of essential hypertension. Using the pre-test, post-test design, study participants were measured on knowledge about essential hypertension and diastolic blood pressure before and after intervention. Six hypotheses were tested, three related to control of blood pressure, and three related to knowledge about essential hypertension. There was no significant difference between the experimental and control groups on diastolic blood pressure readings at the conclusion of the study. There was a significant difference between the experimental and control groups on post-test scores on knowledge of essential hypertension. It was concluded that structured teaching had no significant effect upon control of the diastolic blood pressure. Instruction increased knowledge, but not blood pressure control.", "nan", "Hypertension should be aggressively treated, especially in diabetic patients. But studies of physician prescribing habits reveal that physicians often delay making medication changes or initiating antihypertensive therapy. A chart-based reminder was designed to improve physician medication prescribing in this clinical situation.\n A randomized controlled trial was conducted at the Veterans Affairs Medical Center in Richmond, Virginia. Patients with diabetes and hypertension were selected. A highly visible chart reminder was applied to the front of outpatient charts in the intervention group practice. A chart review was conducted to assess physician-directed medication changes. A successful outcome was defined as any antihypertensive medication increase or addition at that same visit.\n Physicians were more likely to intensify antihypertensive medication as the blood pressure increased regardless of the reminder. Overall, only 33% of visits resulted in a medication change, even though 93% of patients had elevations over target blood pressure at the follow-up visit. Physicians in the intervention and control groups made changes to medication at similar rates (chi 2 = 0.621, p = .511).\n In this study, a chart reminder failed to improve physician compliance with the clinical guideline for hypertension management in diabetics, Sixth Report of the Joint National Committee on the Detection, Evaluation, Prevention and Treatment of High Blood Pressure. To inform the design of effective intervention strategies, further research should explore specific barriers to guideline adherence in this clinical situation.", "A single-blinded, randomized trial was conducted to determine whether a mailed postcard improved follow-up in uncontrolled hypertensives. One hundred and seven patients with a systolic blood pressure (BP) of 180 or more or a diastolic blood pressure of 110 or more at an inner-city, hospital-based walk-in clinic were enrolled; mean age was 56 years, 95 percent were African American, 73 percent were female, and mean BP was 193/106. Patients were required to be aware of their diagnosis and to have been informed of their need for medication at least a month before the trial. Of those who received postcard reminders, 45 percent followed up within 10 days, compared with 47 percent of controls (p = 0.93). At 30 days, 64 percent of the intervention group followed up, compared with 55 percent of controls (p = 0.36). In an adjusted logistic regression model, there was no difference in follow-up. Correlates of appointment noncompliance at one month included alcoholism and lack of insurance in an adjusted logistic regression model. Follow-up in severe hypertensives was poor, and a mailed postcard reminder had no effect in a walk-in setting.", "nan", "A controlled, randomized study was conducted in two chain pharmacies to determine the clinical value of comprehensive pharmacy services for hypertensive patients in a chain pharmacy setting. Twenty-seven patients were enrolled as intervention participants with 26 control subjects. Monthly services for the intervention group included blood pressure and heart rate assessments and counseling on lifestyle modifications and drug therapy. Control patients received initial and final blood pressure measurements and minimal counseling. Both study and control groups completed quality-of-life questionnaires upon entering and completing the study. Results showed that blood pressure control was significantly improved in the study group. Compliance rates as well as energy/fatigue scores (a quality-of-life scale) improved in the study group compared with the control population. Community pharmacists in chain stores could have a beneficial effect on the health care of large numbers of patients if pharmaceutical care programs were developed.", "Blood pressure self-measurement is increasing in most communities and yet its role in the management of hypertension is poorly understood. This study was devised to evaluate the behaviour of doctors in general practice when treating patients with poorly controlled essential hypertension who use self-measurement. Patients, most of whom were already taking antihypertensive medications were commenced on perindopril or indapamide at their doctor's discretion and were randomly allocated to self-measurement (SM) using an OMRON HEM706 oscillometric device or a continuation of their usual care (UC) over an 8-week period. This was an observational study without any specific or set treatment goals for the doctor to follow. Sixty of 62 subjects completed the study and the two groups were equally matched for age, body mass index, gender, and blood pressure (BP). While additional perindopril or indapamide produced a significant fall in BP in both groups over the study period, the systolic pressure remained significantly higher in the SM group (sitting 148 +/- 3 compared with 142 +/- 3; 145 +/- 3 compared with 138 +/- 3 mm Hg respectively; P < 0.05). Twenty-four hour and daytime ambulatory monitor systolic pressures were also significantly higher in the SM group. Differences in diastolic BP were not statistically significant. Furthermore, SM patients were less likely to have their medications increased and more likely to have them reduced or ceased. Doctors and patients found self-measurement convenient and useful. This study suggests that doctors prescribing decisions are influenced by evidence from self-measurement of BP with consequential increases in office BP related to reduced drug use. While self-BP measurement can offer reassurance about adequacy of control when away from a physicians office, our best evidence of understanding target blood pressures comes from large randomised studies using office blood pressures as an end-point. There is an urgent need for further study to provide arbitration between self-measurement and office blood pressures although each measurement must contribute to the management of hypertension.", "The Hypertension Detection and Follow-up Program (HDFP), in a community-based, randomized controlled trial involving 10,940 persons with high blood pressure (BP), compared the effects on five-year mortality of a systematic antihypertensive treatment program (Stepped Care [SC]) and referral to community medical therapy (Referred Care [RC]). Participants, recruited by population-based screening of 158,906 people aged 30 to 69 years in 14 communities througout the United States, were randomly assigned to SC or RC groups within each center and by entry diastolic blood pressure (DBP) (90 to 104, 105 to 114, and 115 + mm Hg). Over the five years of the study, more than two thirds of the SC participants continued to receive medication, and more than 50% achieved BP levels within the normotensive range, at or below the HDFP goal for DBP. Controls of BP was consistently better for the SC than for the RC group. Five-year mortality from all causes was 17% lower for the SC group compared to the RC group (6.4 vs 7.7 per 100, P less than .01) and 20% lower for the SC subgroup with entry DBP of 90 to 104 mm Hg compared to the corresponding RC subgroup (5.9 vs 7.4 per 100, P less than .01). These findings of the HDFP indicate that the systematic effective management of hypertension has a great potential for reducing mortality for the large numbers of people with high BP in the population, including those with \"mild\" hypertension.", "A radomized controlled trial was conducted in a metropolitan teaching hospital to determine whether improving follow-up of emergency room patients who had hypertension led to improvements in their medical care and blood pressure control. One hundred fourty four patients were randomly assigned into an intervention group and a control group. In the former, a follow-up clerk assigned patients in returning for follow-up care. Eighty-four percent of patients in this group and 63% of control patients returned to the clinic (P less than 0.1). However, five months after the patients' emergency room visits, 51% of patients in the intervention group and 53% of control patients were normotensive. There were more diagnostic and therapeutic measures in the intervention group, but long-term management was similar in both groups. Improvement in follow-up may not be by itself lead to blood pressure control among hypertensive patients.", "Hypertension is one of the most common diseases seen by the practicing physician. Yet, because of noncompliance, conditions of many hypertensive patients are not effectively controlled by treatment. The purpose of this study was to test the efficacy of a patient education program in reducing the blood pressure (BP) of hypertensive patients in a private, solo medical practice. The intervention program focused on three behavioral objectives-pill taking, appointment keeping, and dietary sodium reduction while stressing the need for taking responsibility for one's own care. It was hypothesized that patients receiving an educational intervention stressing self-care would benefit more than those receiving the usual medical care. A substantial reduction in BP was considered to be the measure of successful treatment. Thirty-nine hypertensive patients receiving drug therapy from a private, solo medical practice were randomized into either a treatment group or a control group. A comparison of means disclosed no pretreatment differences between the groups' average BPs. After following up both groups for six months, mean changes in BP were compared for both treatment and control patients using a two-sample t test for independent samples. The BP fell in the treatment group (-13 mm Hg, systolic; -8 mm Hg, diastolic) but rose slightly in the control group (3 mm Hg, systolic 0.5 mm Hg, diastolic). The difference in changes was significant for both the systolic and diastolic BP.", "First Nations people with diabetes mellitus and hypertension are at greater risk of renal and cardiovascular complications than are non-native patients because of barriers to health care services. We conducted this randomized controlled trial to assess whether a community-based treatment strategy implemented by home care nurses would be effective in controlling hypertension in First Nations people with existing hypertension and type 2 diabetes.\n We compared 2 community-based strategies for controlling hypertension in First Nations people with existing hypertension and diabetes. In the intervention group, a home care nurse followed a predefined treatment algorithm of pharmacologic antihypertensive therapy. In the control group, treatment decisions were made by each subject's primary care physician. The primary outcome measure was the difference between the 2 groups in the change in systolic blood pressure after 12 months. Secondary outcome measures were the change in diastolic blood pressure over time, the change in urine albumin status and the incidence of adverse events.\n Both groups experienced a significant reduction in systolic blood pressure by the final visit (by 24.0 [standard deviation (SD) 13.5] mm Hg in the intervention group and by 17.0 [SD 18.6] mm Hg in the control group); p < 0.001 in each case). However, the difference between the 2 groups in this change was not significant. Patients in the intervention group had a larger decrease in diastolic blood pressure over time than did those in the control group (by 11.6 [SD 10.6] mm Hg v. 6.8 [SD 11.1] mm Hg respectively; p = 0.05). The groups did not differ significantly in terms of changes in urine albumin excretion or incidence of adverse events.\n High rates of blood pressure control in the community were achieved in both groups in the DREAM 3 study. The addition of a home care nurse to implement a treatment strategy for blood pressure control was more effective in lowering diastolic than systolic blood pressure compared with home care visits for blood pressure monitoring alone and follow-up treatment by a family physician.", "nan", "The population aged 40 to 64 years of the municipality of Köyliö, situated in southwestern Finland, was screened for hypertension in 1973-74; a total of 1018 persons (92%) participated in the program. On the basis of two separate blood pressure measurements a total of 147 hypertensive individuals who were not under treatment were identified. These individuals were divided into two groups by randomization of matched pairs. One group (the control group) was merely advised by letter to see a physician for raised blood pressure, while the other group (the experimental group), in addition to being so notified, received written information explaining the nature of hypertension and the importance of its treatment. After two years, the individuals in both groups were invited for a follow-up blood-pressure measurement, with the object of investigating the number of individuals who had sought treatment and who had continued it, and the differences between the groups in treatment seeking and adherence. A total of 79% of those who were notified to seek medical care had done so. Antihypertensive drug therapy had been begun for 85% of these. After two years, 56% of those who had been found initially to be hypertensive and who were seen in the follow-up were still under treatment. In 43% of these the blood pressure was at the target level. No statistically significant differences in treatment seeking and adherence to it were found between the experimental and control groups, nor were differences found in the decline in the blood pressure or its target levels. Comparing with other studies shows, that results can be better if the health care system that carries out the screening procedure for hypertension also take active steps to bring the patient under treatment and keep him on the regimen.", "Hypertension often clusters with metabolic risk factors and its optimal treatment may involve a number of changes in lifestyle. Nurse-led care regarding lifestyle change may improve outcomes in cardiovascular disease prevention involving.\n To examine if lifestyle guidance given by a nurse improved components of the metabolic syndrome including blood pressure, lipids and waist circumference.\n Subjects that participated in a health screening with systolic blood pressure 140-169 mm Hg and diastolic blood pressure 90-99 mm Hg at a minimum of three separate readings treated or not treated with antihypertensive drugs were randomly allocated either to monthly nurse-led lifestyle counselling (intervention group, N=31) or to conventional primary care (control group, N=20) to be followed by lifestyle counselling.\n The mean (S.D.) baseline and end of study blood pressure was 157 (9)/94 (6) mm Hg and 147 (9)/91 (8) mm Hg, respectively, in the intervention group versus 153 (9)/94 (4) and 143 (10)/92 (8) mm Hg, respectively, in the control group (NS between the groups). Waist circumference increased significantly between baseline and 6 months in the control but not in the intervention (mean difference between the groups, 3.1 cm [95% CI 1.2-5.0], p=0.04) and serum triglyceride concentrations were reduced in the intervention compared with the control group (mean difference, 0.56 mmol/l [95% CI 0.22-0.90], p=0.03). The number of risk factors of the metabolic syndrome was 2.1 (S.D. 1.1) at baseline and 2.6 (S.D. 1.2) at 6 months in the control group versus 2.2 (S.D. 1.1) and 1.9 (S.D. 1.0), respectively, in the intervention group (p=0.01). Change in triglycerides was correlated with change in weight (Pearson's correlation coefficient=0.73, p=0.001) and waist circumference (Pearson's correlation coefficient=0.63, p=0.009) in the control group.\n Nurse counselling did not reduce blood pressure but was associated with a lesser gain in waist circumference and reduced triglyceride concentrations. Metabolic risk factors may worsen rapidly in patients with mild hypertension in the waiting period for lifestyle intervention.", "In the Hypertension Detection and Follow-up Program, 7825 (71.5 per cent) of the 10,940 participants had diastolic blood pressures averaging between 90 and 104 mm Hg on entry into the study and were designated Stratum 1. Half were referred to their usual source of care in the community (the referred-care group), and half were treated intensively in special clinics (the stepped-care group). Five-year mortality in the Stratum 1 patients given stepped care was 20.3 per cent lower than in those given referred care (P less than 0.01). Particularly noteworthy was the beneficial effect of stepped-care treatment on persons with diastolic pressures of 90 to 104 mm Hg who had no evidence of end-organ damage and were not receiving antihypertensive medication when they entered the study. This subgroup had 28.6 per cent fewer deaths at five years among those treated with stepped care than among those treated with referred care (P less than 0.01). These findings support a recommendation that in patients with mild hypertension, treatment should be considered early, before damage to end organs occurs.", "The majority of hypertensive patients do not reach the target blood pressure (BP). We sought to clarify whether intermittent self-monitoring of BP leads to better BP control compared to ordinary treatment in general practice.\n Two hundred sixty-nine hypertensive patients participated in this multicenter, randomized, parallel-group study in primary health care. Home BP was measured in the self-monitoring (SM) group at 0, 2, 4, and 6 months, and in the control (C) group at 0 and 6 months. The participating physicians were instructed to intensify the antihypertensive therapy when needed.\n At the beginning, both groups had similar home BP levels (SM 143.1 +/- 17.4/85.3 +/- 7.4 mm Hg v C 143.9 +/- 18.3/85.4 +/- 7.5 mm Hg). After 6 months, there were significant decreases in systolic (P <or= .0001), diastolic (P <or= .0029), and pulse pressures (P <or= .021) in both groups. Systolic (-7.8 +/- 13.1 mm Hg v -4.5 +/- 12.2 mm Hg, P = .047) and pulse pressure (-4.7 +/- 9.0 mm Hg v -2.2 +/- 10.0 mm Hg, P = .042) decreased significantly more than in the self-monitoring group. The decrease in diastolic pressure was similar in both groups (SM -3.1 +/- 6.2 mm Hg v C -2.3 +/- 8.3 mm Hg, P = not significant). The patients in the SM group reached home BP target more often than those in the C group (29% v 16%, P = .016). There was a nonsignificant trend toward lower office BP values in the SM group.\n Self-monitoring decreased systolic and pulse pressure significantly more than ordinary treatment and promoted achievement of target BP. This was most likely due to improved patient compliance and more active treatment by the physicians. Our results suggest that home measurement is useful in the control of hypertension.", "Research is needed to validate effective and practical strategies for improving the provision of evidence-based medicine in primary care.\n To determine whether a multimethod quality improvement intervention was more effective than a less intensive intervention for improving adherence to 21 quality indicators for primary and secondary prevention of cardiovascular disease and stroke.\n 2-year randomized, controlled clinical trial with the practice as the unit of randomization.\n 20 community-based family or general internal medicine practices in 14 states. All used the same electronic medical record.\n 44 physicians, 17 midlevel providers, and approximately 200 staff members; data from the electronic medical records of 87,291 patients.\n All practices received copies of practice guidelines and quarterly performance reports. Intervention practices also hosted quarterly site visits to help them adopt quality improvement approaches and participated in 2 network meetings to share \"best practice\" approaches.\n The percentage of indicators at or above predefined targets and the percentage of patients who had achieved each clinical indicator.\n Intervention practices improved 22.4 percentage points (from 11.3% to 33.7%) in the percentage of indicators at or above the target; control practices improved 16.4 percentage points (from 6.3% to 22.7%). The 6.0-percentage point absolute difference between the intervention and control group was not statistically significant (P > 0.2). Patients in intervention practices had greater improvements than those in control practices for diagnoses of hypertension (improvement difference, 15.7 percentage points [95% CI, 5.2 to 26.3 percentage points]) and blood pressure control in patients with hypertension (improvement difference, 8.0 percentage points [CI, 0.0 to 16.0 percentage points]).\n The study involved a small number of practices and lacked a pure control group.\n Primary care practices that use electronic medical records and receive regular performance reports can improve their adherence to clinical practice guidelines for cardiovascular disease and stroke prevention.", "This study was conducted to evaluate the effect of automated telephone patient monitoring and counseling on patient adherence to antihypertensive medications and on blood pressure control. A randomized controlled trial was conducted in 29 greater Boston communities. The study subjects were 267 patients recruited from community sites who were >or= 60 years of age, on antihypertensive medication, with a systolic blood pressure (SBP) of >or= 160 mm Hg and/or a diastolic blood pressure (DBP) of >or= 90 mm Hg. The study compared subjects who received usual medical care with those who used a computer-controlled telephone system in addition to their usual medical care during a period of 6 months. Weekly, subjects in the telephone group reported self-measured blood pressures, knowledge and adherence to antihypertensive medication regimens, and medication side-effects. This information was sent to their physicians regularly. The main study outcome measures were change in antihypertensive medication adherence, SBP and DBP during 6 months, satisfaction of patient users, perceived utility for physicians, and cost-effectiveness. The mean age of the study population was 76.0 years; 77% were women; 11% were black. Mean antihypertensive medication adherence improved 17.7% for telephone system users and 11.7% for controls (P = .03). Mean DBP decreased 5.2 mm Hg in users compared to 0.8 mm Hg in controls (P = .02). Among nonadherent subjects, mean DBP decreased 6.0 mm Hg for telephone users, but increased 2.8 mm Hg for controls (P = .01). For telephone system users, mean DBP decreased more if their medication adherence improved (P = .03). The majority of telephone system users were satisfied with the system. Most physicians integrated it into their practices. The system was cost-effective, especially for nonadherent patient users. Therefore, weekly use of an automated telephone system improved medication adherence and blood pressure control in hypertension patients. This system can be used to monitor patients with hypertension or with other chronic diseases, and is likely to improve health outcomes and reduce health services utilization and costs.", "This study aimed to compare the efficacy of a patient-directed management strategy with office-based management in maintaining blood pressure control in patients with chronic stable hypertension using a randomized trial of two months duration. The subjects had chronic stable essential hypertension without secondary causes or unstable cardiovascular disease and were selected through the offices of 11 family physicians and a tertiary care hypertension research unit. Patients were randomly assigned (2:1 ratio) to either a patient-directed management strategy using home blood pressure monitoring to adjust drug therapy if readings consistently exceeded defined limits, or office-based management through physician visits. The primary endpoint was the change from baseline in mean arterial pressure as determined by automatic ambulatory blood pressure monitoring. Secondary endpoints were changes in compliance, quality of life, and health care resource use. Ninety-one potential subjects were screened and 31 were randomized. Subjects in the patient-directed management group employed the drug adjustment protocols appropriately without complications. A significant difference in change in mean blood pressure was observed, favoring the patient-directed management (-0.95 mm Hg and +1.90 mm Hg, respectively, for patient-directed management and office-based management, P = .039). Compliance rates and quality of life scores were not significantly different between groups. Physician visits were more frequent in the patient-directed management group (1.05 v 0.20 visits/8 weeks, respectively, for patient-directed management and office-based management groups, P = .045). A patient-directed hypertensive management strategy may be feasible for patients with chronic stable hypertension. Such a strategy may improve blood pressure control compared with usual office-based care. However, physician visits may be increased using this strategy, at least in the short term.", "The value of patient education programmes in the control of hypertension is controversial. We have conducted a prospective study to investigate a patient education programme in our clinic. Every new patient was randomised into one of two different groups: a control group (CG, n = 149) and an intervention group (IG, n = 138); the latter group was invited to attend two educational talks and subsequently one tutorial meeting. Blood pressure, heart rate, Quetelet Index, attendance, knowledge level, analytical parameters and the prevalence of other risk factors were measured in both groups before and after 6 months follow-up. No significant differences were detected between the two groups initially. At 6 months, both groups significantly lowered their BP; the only differences observed between groups (IG vs. CG) were: the number of correct answers to the questionnaire (14.5 +/- 3.7 vs. 12.9 +/- 3.7, P less than 0.01), the rate of occasional therapeutic abandonment (10.3 vs. 25%, P less than 0.05), 24 h sodium excretion (97 +/- 45 vs. 127 +/- 68 mmol/l, P less than 0.01) and the number of withdrawals (39 vs. 25%, P less than 0.05). We conclude that in spite of increased knowledge, less frequent abandonment of drug treatment and better observance of a low salt diet, patients in the IG had an increase in the number of drop-outs. Our data suggest that education in hypertension clinics should play a supportive role rather than a primary one in the control of high blood pressure.", "Screening of 6,144 patients in a general practice clinic to assist physician case-finding uncovered 983 (16%) who were uncontrolled hypertensives. Following physician recommendation, 115 patients volunteered for a controlled trial to test the effectiveness of supplementary strategies to the pharmaceutical management of high blood pressure. A study of nonparticipants indicated that about 7% of the practice population was eligible for cardiovascular health education. One group received a health education program, a second was allocated to self-monitor their blood pressure for 6 months, a third group was allocated to both strategies, and the final group, acting as a control, continued to receive their usual care. Physician monitoring of patients continued for the duration of the study and blood pressures decreased in all patients. The study's most important outcome was the joint reduction of blood pressure and medication strength. These were assessed by a \"blind\" clinician before and after the interventions according to criteria set out in the \"stepped-care\" approach to management of high blood pressure. People allocated to a health education program conducted in the doctor's common room did twice as well on this measure as those who were not so educated. Daily self-monitoring of blood pressure for 6 months proved to be too much for the majority of those so instructed. It is concluded that the general practice setting remains an important place for health education to prevent cardiac disease and suggestions are made for incorporating this into everyday practice.", "Does free medical care lead to better health than insurance plans that require the patient to shoulder part of the cost? In an effort to answer this question, we studied 3958 people between the ages of 14 and 61 who were free of disability that precluded work and had been randomly assigned to a set of insurance plans for three or five years. One plan provided free care; the others required enrollees to pay a share of their medical bills. As previously reported, patients in the latter group made approximately one-third fewer visits to a physician and were hospitalized about one-third less often. For persons with poor vision and for low-income persons with high blood pressure, free care brought an improvement (vision better by 0.2 Snellen lines, diastolic blood pressure lower by 3 mm Hg); better control of blood pressure reduced the calculated risk of early death among those at high risk. For the average participant, as well as for subgroups differing in income and initial health status, no significant effects were detected on eight other measures of health status and health habits. Confidence intervals for these eight measures were sufficiently narrow to rule out all but a minimal influence, favorable or adverse, of free care for the average participant. For some measures of health in subgroups of the population, however, the broader confidence intervals make this conclusion less certain.", "A randomized controlled trial of an information and medical record booklet designed to improve patient understanding and participation in the management of hypertension was conducted in six inner London general practices. After one year there were no significant differences between the group who had received the booklets and the control group in mean systolic or diastolic blood pressure, but the study group scored significantly higher on knowledge about hypertension and its management. However, the difference between the two groups was small, possibly because both groups started with a high level of understanding about hypertension and its management. In addition, the mean diastolic blood pressure in the control group showed that the treatment provided was already satisfactory, and that there was little need for improvement. Nevertheless, the information booklet evaluated in this study provides health professionals with a highly acceptable method of informing the patient about hypertension and its management and could be used both in hospital and general practice.", "African Americans have a higher prevalence and greater severity of hypertension than do other minorities and whites. This fact is particularly problematic when one realizes that the rate of control and treatment of hypertension in the US population is getting worse rather than better. Alternative strategies to promote blood pressure control need to be tested.\n The purpose of this pilot study was to test the following hypothesis: Persons who participate in nurse-managed home telemonitoring (HT) plus usual care or who participate in nurse-managed community-based monitoring (CBM) plus usual care will have greater improvement in blood pressure from baseline to 3 months' follow-up than will persons who receive usual care only.\n This study used a randomized controlled design; participants were randomly assigned to 1 of 3 groups that were stratified by use or nonuse of antihypertension medication. One-way analysis of variance (ANOVA) and analysis of covariance (ANCOVA) controlling for age and body weight were used to determine changes in blood pressure from baseline to 3 months. The sample contained 26 African Americans with a mean age of 59 years.\n Both the HT group and the CBM group had clinically and statistically significant (P <.05) drops in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at 3 months' follow-up, with participants in the HT group demonstrating the greatest improvement (HT: baseline SBP 148.8 +/- 13.8, DBP 90.2 +/- 5.79; 3 months' follow-up SBP 124.1 +/- 13.82, DBP 75.58 +/- 11.4; CBM: baseline SBP 155.25 +/- 17.014, DBP 89.42 +/- 10.95; 3 months' follow-up SBP 142.3 +/- 12.1, DBP 78.25 +/- 6.86). There was little change in SBP or DBP at 3 months' follow-up in the usual care only group.\n These are important pilot results, which if replicated in a larger sample will significantly improve care for urban African Americans with hypertension.", "An automated surveillance system utilizing a computer-based medical record system (COSTAR) was designed to improve the follow-up of patients with newly identified elevated diastolic blood pressure. A population of patients was selected where, in the 6-month period following the initial measurement of an elevated diastolic blood pressure, there were fewer than two visits during which blood pressure was recorded. In a randomized controlled clinical trial, this poor follow-up population was divided into two groups, with computer-generated reminders being automatically generated for only patients in the experimental group. Follow-up was significantly improved in the group receiving the reminders, both in terms of rate of follow-up attempted or achieved by the responsible physician and in the repeated recording of blood pressure. We conclude that a computer-based reminder system improves follow-up of newly discovered elevation in diastolic blood pressure.", "To study the efficacy of telephone and mail intervention in therapeutic compliance among patients with mild to moderate hypertension.\n A prospective controlled multicenter clinical trial.\n Eighty-five primary care centers in Spain, with a duration of 6 months.\n A total of 636 patients with newly diagnosed or uncontrolled hypertension were included. Interventions. The patients were randomized and distributed between the following groups: (i) control (CG) - under routine clinical management; (ii) mail intervention (MIG) - received a mailed message reinforcing compliance and reminding of the visits (15 days, 2 and 4 months); (iii) telephone intervention (TIG) - received a telephone call at 15 days, then at 7 and 15 weeks.\n Five visits were scheduled, with the measurement of blood pressure and counting of tablets. Compliers were defined as subjects showing 80-110% drug consumption. Calculations were made of mean percentage compliance (MPC) and compliers, mean blood pressure and percentage controlled subjects.\n Five hundred and thirty-eight patients completed the study (261 males); 85.5% were compliers (CI = 82.5-88.5; n = 460). The MPC was 95.1+/-19.6% (CI = 93.28-96.92). The CG consisted of 182 individuals, MIG = 172 and TIG = 184. Compliers represented 69.2% of the CG (CI 62.5-75.9%), 91.3% (CI = 87.1-95.5) of the MIG (p = 0.0001) and 96.2% of the TIG (CI 93.5-98.9%); the final MPC was 89.6%+/-15 in CG, 96.6%+/-12 in MIG and 99.1+/-26.8 in TIG (p = 0.0001). The percentage of controlled subjects was 47.2% in CG (CI = 40-54.4), 61.3% in MIG (CI = 54.1-68.5%) and 63.3% in TIG (CI = 56.4-70.2%) (p<0.05).\n TIG and MIG are effective measures for improving patient compliance in hypertension.", "To investigate the effect of a computer based clinical decision support system and a risk chart on absolute cardiovascular risk, blood pressure, and prescribing of cardiovascular drugs in hypertensive patients.\n Cluster randomised controlled trial.\n 27 general practices in Avon.\n 614 patients aged between 60 and 79 years with high blood pressure.\n Patients were randomised to computer based clinical decision support system plus cardiovascular risk chart; cardiovascular risk chart alone; or usual care.\n Percentage of patients in each group with a five year cardiovascular risk >/=10%, systolic blood pressure, diastolic blood pressure, prescribing of cardiovascular drugs.\n Patients in the computer based clinical decision support system and chart only groups were no more likely to have cardiovascular risk reduced to below 10% than patients receiving usual care. Patients in the computer based clinical decision support group were more likely to have a cardiovascular risk >/=10% than chart only patients, odds ratio 2.3 (95% confidence interval 1.1 to 4.8). The chart only group had significantly lower systolic blood pressure compared with the usual care group (difference in means -4.6 mm Hg (95% confidence interval -8.4 to -0.8)). Reduction of diastolic blood pressure did not differ between the three groups. The chart only group were twice as likely to be prescribed two classes of cardiovascular drugs and over three times as likely to be prescribed three or more classes of drugs compared with the other groups.\n The computer based clinical decision support system did not confer any benefit in absolute risk reduction or blood pressure control and requires further development and evaluation before use in clinical care can be recommended. Use of chart guidelines are associated with a potentially important reduction in systolic blood pressure.", "Poor adherence to antihypertensive drug regimens is believed to be a major contributor to treatment failure. Electronic monitoring of adherence may improve adherence and allow differentiation between those who are nonadherent and those who are pharmacologically nonresponsive. This study was designed to evaluate the effectiveness of electronic monitoring of adherence in lowering blood pressure (BP) in comparison with usual care.\n A total of 258 patients with high BP despite use of antihypertensive medication were randomly assigned to either continuation of usual care (with adjustment in antihypertensive medication if necessary) or to the introduction of electronic monitoring. Adherence to antihypertensive medication was monitored for 2 months without medication changes. The primary outcome measure was the proportion of patients who reached target BP levels after a 5-month follow-up period.\n At 5 months, 50.6% of the patients in the usual care group reached adequate BP, v 53.7% in the electronic monitoring group (P = .73). The percentages of patients with drug additions or increases in dosage were higher in the usual care group compared with those in whom adherence was monitored (P < .01).\n These data show that electronic monitoring in comparison to usual care results in similar BP control but leads to fewer drug changes and less drug use. This result is likely to be achieved by improving adherence. Hence a strategy that includes electronic monitoring has the potential to prevent unnecessary treatment escalation in patients with poor adherence.", "The hypothesis that general practitioners would obtain better outcomes for patients with hypertension using a computer than doctors not using a computer was tested. Sixty family physicians were randomised to two treatment strategies. \"Test\" physicians completed a data collection form after each visit from a patient with hypertension and mailed the forms to the test centre for processing. Computer feedback on management was mailed to the doctors. This encouraged doctors to apply the \"stepped care\" protocol, supplied charts of diastolic blood pressure v time, and ranked patients' diastolic blood pressures by percentile. Letters were mailed to patients to remind them of appointments. \"Control\" doctors filled out the same data collection forms as test physicians, but neither doctors nor patients received computer feedback. Physicians who used the computer saw more patients per practice than control doctors (test 50 patients, control 40). For all patients the length of follow up was significantly longer in test practices (test 199 days, control 167), and a smaller percentage dropped out of active treatment in test practices (test 37.5%, control 42.1%). For patients with \"moderate\" hypertension of a baseline diastolic pressure of greater than 104 mm Hg the mean score of the last recorded pressure was below the goal of 90 mm Hg in test practices (88.5 mm Hg), but it failed to reach this goal in control practices (93.3 mm Hg). A greater average reduction of diastolic pressure was achieved in test practices (test 21.7 mm Hg, control 16.7 mm Hg). Though patients with \"moderate\" hypertension were better controlled in test practices than in control practices, the patients in test practices visited their doctors less often (test 13.3 visits per patient-year, control 17.4 visits). Among patients with newly detected hypertension test practices achieved a greater reduction in diastolic pressure than control practices (test 15.1 mm Hg v control 11.3 mm Hg) and more sustained control of hypertension (test 323 days per patient-year with a diastolic pressure of 90 mm Hg or less v control 259 days).", "In Mexico, hypertension is a major cause of disability and death in the elderly, but the most effective way to promote behaviour change in old people is unknown. Low resource interventions that are effective in normal healthcare settings are urgently needed. We report the results of a randomized trial of nurse-provided health and lifestyle advice during home visits to elderly people with hypertension in Mexico City.\n Subjects were 718 people with hypertension aged > or =60 years, who were residents of Mexico City and were registered with the Family Medicine Clinics of the Mexican Institute of Social Security (IMSS). A randomized controlled trial was carried out in which the intervention group was offered nurse visits over 6 months with blood pressure checks and negotiated lifestyle changes. The control group continued to receive usual care.\n After 6 months, 36.5% of the intervention versus 6.8% of the control group had a blood pressure of <160/90 mmHg. The difference in the mean change in systolic blood pressure was 3.31 mmHg (P = 0.03, 95% CI : 6.32, 0.29) and the same difference in diastolic blood pressure was 3.67 mmHg (P = 0.00, 95% CI : 5.22, 2.12). Weight and sodium excretion fell more in the intervention group, but the difference was not significant.\n Nurse home visits are effective in reducing blood pressure in hypertensive patients aged > or =60 years.", "nan", "Three educational interventions for the control of essential hypertension in ambulatory patients were based on analyses of the educational needs of patients and providers. The educational program increased reported compliance with medication, improved the proportion of patients losing weight, and improved appointment keeping. Most important, there was a favorable effect on blood pressure (BP) control. The proportion of patients with BP under control in the group assigned to all three interventions increased by 28% (from 38% to 66%), while the proportion in the control group receiving standard medical therapy with no educational interventions remained unchanged at 42%.", "Home measurement of blood pressure (BP) can improve compliance. The aim of this study was to evaluate if the efficacy of losartan in hypertension could be enhanced by providing patients with a device for home BP measurement. In this open, randomised, prospective, multi-centre study in 244 Swiss practices, patients with mild-to-moderate hypertension were randomised to a group receiving a home BP measuring device (OMRON) (group 2), or to a group where this device was not provided (group 1). After 8 weeks of treatment with losartan, the responder rates between subjects performing home measurement of BP were compared with those without self-measurement, whereby exclusively sphygmomanometric office BP values were considered. A total of 622 subjects completed the study. Treatment with losartan significantly reduced diastolic (DBP) and systolic BP (SBP) (P < 0.0001). Overall, the group with home BP measurement showed an increased responder rate (DBP < or =90 mm Hg) by 6.4% (59.8% vs 66.2%; 0.05 < P < 0.1). This difference was mainly due to female patients (64.1% vs 73.2%), where it reached statistical significance (P < 0.01). Pretreated patients showed a 9.0% improvement of response in the home measurement group as well (0.05 < P < 0.1). The responder rate in newly treated subjects was relatively high, reaching 79.5% (DBP < or =90 mm Hg or reduction > or =10 mm Hg DBP from baseline). However, home measurement did not significantly improve BP control in these new patients (81.4% vs 77.7%). Overall, home measurement can lead to a slight improvement of BP control. This improvement was most evident in females, reaching significance.", "Evidence is sparse concerning the value of the \"educational\" materials that physicians receive in the mail. We conducted a randomized trial of a mailed continuing education program on hypertension for primary care physicians. Although formal pretesting documented that the program led to significant improvements in physician knowledge over the short term, the current study showed no lasting effect on physician knowledge (mean scores on an end-of-study questionnaire were 50% and 52% for study and control physicians, respectively) and no influence on performance in lowering the blood pressures of patients referred from screening (mean blood pressure drop for study patients, 12.2/10.4 mm Hg vs 13.0/10.6 mm Hg for control patients). The chance that we missed a difference in diastolic blood pressure as great as 3 mm Hg is less than 5%. Resources spent on instructional materials mailed to physicians may be wasted.", "The clinical efficacy of using specially trained nurses to treat hypertension at the patient's place of work was compared in a controlled trial with management by the patient's family doctor. The 457 study participants were selected from 21 906 volunteers in industry and government whose blood-pressure was screened. The nurses were allowed to prescribe and change drug therapy at the work site without prior physician approval. Patients randomly allocated to receive care at work were significantly more likely to be put on antihypertensive medications (94.7% vs 62.7%, to reach goal blood-pressure in the first six months (48.5% vs 27.5%), and to take the drugs prescribed (67.6% vs 49.1%). Only 6% of patients were dissatisfied with the care provided by the nurses. Thus provision of care at work by specially tranined nurses was well accepted and resulted in significantly improved blood-pressure control and medication compliance among employees with asymptomatic and uncomplicated hypertension.", "It is widely believed that patients' compliance can be increased by persuading them to participate in their own care. We tested whether patients with hypertension could manage their own clinical records and whether their doing so would affect the quality of their care. Two hundred patients were randomly assigned to an intervention or a control group. Those in the intervention group were asked to complete a 10-page booklet containing a personal standardized medical record. All patients were scheduled for a follow-up appointment at the end of one year and were referred to their general practitioners for interim care. At the end of the follow-up period, the proportion of patients seen was comparable in the two groups. More of the patients in the intervention group than in the control group filled out a questionnaire as requested, and more added comments. Within the intervention group, the proportion of patients seen and the fall in systolic blood pressure were significantly higher among the 44 patients who had completed the personal record as requested than among the 57 who had not. Patients who completed the personal record also had fewer compliance problems.", "To evaluate the implementation of clinical guidelines for hypertension in general practice by use of a computer-based clinical decision support system (CDSS) and a specific implementation strategy. Evaluation of patient outcome.\n Randomised study with health centres as units. The intervention group had the CDSS installed and made ready for use, doctors and assistants were trained and received a user-manual, the doctors were offered telephone repetitions, a seminar in risk intervention and, at the same seminar, further demonstration of the CDSS. The doctors received baseline registrations with information of how they treated their own hypertensive patients, and use of the CDSS was checked repeatedly.\n General practice in Sør- and Nord-Trøndelag counties in Norway, 380,000 inhabitants.\n Seventeen health centres with 24 doctors and 984 patients in the intervention group. Data from 879 patients used in the final analyses. Twelve health centres with 29 doctors and 1255 patients in the control group. Data from 1119 patients used in the final analyses.\n After an intervention period of 18 months, group differences in level of systolic and diastolic blood pressure, serum cholesterol, body mass index, and risk score for myocardial infarction were calculated, as well as group differences in fractions of smokers.\n Significant group difference in favour of intervention group: diastolic blood pressure 1 mmHg (95% CI -1.89, -0.17). However, a significant baseline difference in systolic blood pressure in favour of control group of 2.7 mmHg (95% CI 1.0, 4.5) had been reduced to 1.2 mmHg (95% CI -0.6, 3.0) after intervention.\n Implementation of clinical guidelines in the treatment of hypertensive patients in general practice by means of a CDSS and several other procedures for implementation did not affect patient outcome in any clinically significant way.", "The authors examined the effects of a comprehensive lifestyle modification intervention on blood pressure (BP) and other cardiovascular risk factors in hypertensive patients. A total of 70 participants were randomly placed into either a lifestyle intervention or a control group. Four education classes and individual counseling sessions were held for the intervention group. Participants in the control group were provided with routine outpatient services and were asked to maintain their usual lifestyle. Data were gathered at baseline and at the end of 6 months. At the end of 6 months, BP, body weight, body mass index, waist circumference, and fasting lipids, apart from high-density lipoprotein cholesterol, significantly declined in the intervention group. Healthpromoting lifestyle scores of the intervention group had increased significantly compared to those of the control group. In conclusion, the results demonstrate the feasibility of comprehensive lifestyle modification and show its beneficial effects.", "Three health education interventions for urban poor hypertensive patients were introduced sequentially in a randomized factorial design: 1) an exit interview to increase understanding of and compliance with the prescribed regimen; 2) a home visit to encourage a family member to provide support for the patient's regimen; and 3) invitations to small group sessions to increase the patient's confidence and ability to manage his/her problem. Previous evaluation of the initial two-year experience demonstrated a positive effect of the educational program on compliance with the medical treatment and blood pressure control. Data accumulated over an additional three years, including mortality analysis, are now presented. The study group consisted of the same cohort of 400 ambulatory hypertensive outpatients in the eight experimental and control groups. The five-year analysis shows a continuing positive effect on appointment keeping, weight control, and blood pressure control. All-cause life table mortality rate was 57.3 per cent less for the experimental group compared to the control group (12.9/100 vs 30.2/100, p less than .05), while the hypertension-related mortality rate was 53.2 per cent less (8.9/100 vs 19.0/100, p less than .01). The results from this longitudinal study provide evidence to encourage health practitioners to utilize such educational programs in the long-term management and control of high blood pressure.", "Compliance with physician recommendations among long-term hypertensive patients can be a chronic and difficult treatment problem. This study evaluated the relative effectiveness of additional patient education and psychosocial counseling in improving patient compliance. At a family practice clinic, 123 low income, rural, black hypertensive patients were pretested on several psychological characteristics and randomly assigned to one of three groups: vigorous, group patient education and family physician appointments; supportive, individualized psychosocial counseling and family physician appointments; or family physician appointments only, which was the baseline medical care. Intervention and follow-up each lasted three months, and the intervention was in addition to the patients' baseline medical care. Compliance was measured by: keeping follow-up appointments; bringing antihypertension medications to each appointment; consuming these medications; and diastolic blood pressure. Analysis of variance of group mean and change scores, t tests, and chisquare analysis indicated that neither additional patient education nor additional psychosocial counseling improved compliance or blood pressure control significantly better than regular family physician visits alone.", "Discrepancies between clinical guidelines and clinical practice call for practical implementation strategies. This study evaluates the implementation of clinical guidelines for hypertension in general practice with a specific computer-based clinical decision support system (CDSS) as part of the intervention. We carried out a randomized study of general practice health centres in Sør- and Nord-Trøndelag counties in Norway (population 380000). A total of 17 health centres were included, with 24 doctors and 984 patients in the intervention group. Data from 887 patients was used in the analyses. There were 12 health centres with 29 doctors and 1255 patients in the control group. Data from 1127 control patients was used in the analyses. The main outcome measures were doctor's behaviour, measured by adherence to registration of recommended variables in the Norwegian clinical guidelines for hypertension. The aim of the intervention was to lower the fractions of patients without registrations. However, there were no clinically significant differences between the intervention group and the control group for fractions of patients without registration of blood pressure (intervention group 14.3%, control group 14.2%) or serum cholesterol (62.3% vs. 56.8%) during 12 months, nor, during 18 months, for fractions of patients without a registration of cigarette smoking (82.9% vs. 87.1%), cardiovascular inheritance (79.5% vs. 73.4%) and body mass index (81.5% vs. 89.2%). One or several variables necessary for calculation of risk score for myocardial infarction were missing in 91.7% of patients in the intervention group and 91.9% of patients in the control group. Large centre variations were shown for all variables. Implementation of clinical guidelines in the treatment of hypertensive patients in general practice, by means of a CDSS and several procedures for implementation did not result in clinically significant changes in the doctors' behaviour. Of importance are both the lack of user-friendliness of the specific CDSS and problems in performing time-consuming multidimensional procedures.", "We evaluated the effects of an appointment reminder system on the appointment-keeping behavior and blood pressure control status of hypertensive patients receiving care in an urban medical clinic. The study population consisted of 973 adult hypertensive patients receiving medical care at a family practice clinic affiliated with the Wayne State University School of Medicine, Detroit, Michigan. Of the 973 patients enrolled in the study, 486 were randomly assigned to a group that received appointment reminder cards and telephone calls to reschedule missed appointments, and 487 were assigned to a nonintervention control group. Patients were followed-up with regard to their appointment-keeping behavior and blood pressure control status, five to eight months after being entered in the study. The study results indicate that patients in the appointment reminder group kept significantly more appointments and were less likely to drop out of treatment than patients in the control group. The dropout rate was 46 percent lower among patients in the appointment reminder group than in the control group. Patients in the appointment reminder group also demonstrated slightly better blood pressure control at the end of the study compared with patients in the control group, although none of the differences in blood pressure levels between groups were statistically significant at the 5 percent level.", "To assess the effectiveness of mailed hypertension educational materials.\n Prospective, randomized, controlled single-blind trial.\n Primary care practice-based research network in which 9 clinics located in Portland, Oregon participated.\n Patients with mildly uncontrolled hypertension as defined as a last blood pressure of 140 to 159/90 to 99 mmHg from query of an electronic medical record database.\n Patients randomized to intervention were mailed 2 educational packets approximately 3 months apart. The first mailer included a letter from each patient's primary care provider. The mailer included a booklet providing an overview of hypertension and lifestyle modification and a refrigerator magnet noting target blood pressure. The second mailing also included a letter from the patient's primary care provider, a second educational booklet focused on medication compliance and home blood pressure monitoring, and a blood pressure logbook. The control group consisted of similar patients receiving usual care for hypertension.\n Patients from each group were randomly selected for invitation to participate in a study visit to measure blood pressure and complete a survey (intervention n= 162; control n= 150). No significant difference was found in mean blood pressure between intervention and control patients (135/77 mmHg vs 137/77 mmHg; P=.229). Patients in the intervention arm scored higher on a hypertension knowledge quiz (7.48 +/- 1.6 vs 7.06 +/- 1.6; P=.019), and reported higher satisfaction with several aspects of their care. No significant difference was seen in the prevalence of home blood pressure monitoring ownership or use.\n In patients with mildly uncontrolled hypertension, educational mailers did not yield a significant decrease in blood pressure. However, significant improvement in patient knowledge, frequency of home monitoring, and satisfaction with care were demonstrated.", "To assess whether blood pressure control in primary care could be improved with the use of patient held targets and self monitoring in a practice setting, and to assess the impact of these on health behaviours, anxiety, prescribed antihypertensive drugs, patients' preferences, and costs.\n Randomised controlled trial.\n Eight general practices in south Birmingham.\n 441 people receiving treatment in primary care for hypertension but not controlled below the target of < 140/85 mm Hg.\n Patients in the intervention group received treatment targets along with facilities to measure their own blood pressure at their general practice; they were also asked to visit their general practitioner or practice nurse if their blood pressure was repeatedly above the target level. Patients in the control group received usual care (blood pressure monitoring by their practice).\n Primary outcome: change in systolic blood pressure at six months and one year in both intervention and control groups. Secondary outcomes: change in health behaviours, anxiety, prescribed antihypertensive drugs, patients' preferences of method of blood pressure monitoring, and costs.\n 400 (91%) patients attended follow up at one year. Systolic blood pressure in the intervention group had significantly reduced after six months (mean difference 4.3 mm Hg (95% confidence interval 0.8 mm Hg to 7.9 mm Hg)) but not after one year (mean difference 2.7 mm Hg (- 1.2 mm Hg to 6.6 mm Hg)). No overall difference was found in diastolic blood pressure, anxiety, health behaviours, or number of prescribed drugs. Patients who self monitored lost more weight than controls (as evidenced by a drop in body mass index), rated self monitoring above monitoring by a doctor or nurse, and consulted less often. Overall, self monitoring did not cost significantly more than usual care (251 pounds sterling (437 dollars; 364 euros) (95% confidence interval 233 pounds sterling to 275 pounds sterling) versus 240 pounds sterling (217 pounds sterling to 263 pounds sterling).\n Practice based self monitoring resulted in small but significant improvements of blood pressure at six months, which were not sustained after a year. Self monitoring was well received by patients, anxiety did not increase, and there was no appreciable additional cost. Practice based self monitoring is feasible and results in blood pressure control that is similar to that in usual care.", "To determine the effectiveness of specialist nurse delivered education in primary care to improve control of hypertension and hyperlipidaemia in patients with diabetes.\n Practice-level randomized controlled trial, Salford, England.\n From 44 practices, 10 303 subjects presenting in general practice with raised blood pressure (= 140/80 mmHg), raised total cholesterol (= 5.0 mmol/l) or both.\n Practices were randomized to receive either the intervention for hyperlipidaemia or for hypertension; practices acted as control for the intervention not received. Specialist nurses arranged a schedule of visits with general practitioners and general practice nurses, reminding them of diabetes protocols and clinical targets. They provided educational materials and protocols used in secondary care for nurse and doctor interventions including stepping up pharmacotherapy when necessary. Practices received a list of patients in their practice who were poorly controlled at their last annual review; new and recalled patients were targeted.\n At subsequent annual review, blood pressure and total cholesterol values were obtained from the Salford electronic diabetes register for patients from participating practices.\n Overall, specialist nurse-led educational outreach to primary care was associated with no improvement in patients achieving target after 1 year-odds ratio (OR): 1.03 (95% CI 0.95-1.11; P = 0.52). Similar results were achieved with hyperlipidaemia OR: 1.04 (95% CI 0.88-1.23; P = 0.62) and hypertension OR: 1.01 (95% CI 0.80-1.27; P = 0.93).\n This study provides evidence that the use of specialist nurses to perform educational outreach to improve target adherence to patients with diabetes in primary care is not effective." ]

[ "17233688", "17924246", "15994575", "11427243", "17375319" ]

[ "Treatment and prevention of depression after surgery for hip fracture in older people: randomized, controlled trials.", "Trial of interpersonal counselling after major physical trauma.", "Effectiveness of providing self-help information following acute traumatic injury: randomised controlled trial.", "Collaborative interventions for physically injured trauma survivors: a pilot randomized effectiveness trial.", "Quality of life after multiple trauma: the effect of early onset psychotherapy on quality of life in trauma patients." ]

[ "To evaluate the effect of a psychiatric intervention in treating depression (treatment study) and the effect of a psychological treatment in preventing depression (prevention study) after hip fracture in older people.\n Two linked randomized, controlled trials.\n Orthopedic units in Manchester, England.\n Two hundred ninety-three older people who had undergone surgery for a fractured hip: 121 in the treatment study and 172 in the prevention study.\n The Geriatric Depression Scale and Hospital Anxiety and Depression Scale for mood, functional tests for mobility and pain measures.\n There was a slight reduction in depressive symptoms in the active arm of the treatment study. In the prevention study, there was no significant difference in incident depression between the psychological intervention and treatment as usual. There were no differences in the functional and pain outcomes.\n The results from these two randomized, controlled trials show that, after hip fracture surgery, no statistically significant benefits can be achieved from a psychiatric intervention in people who are depressed or a psychological intervention to prevent the onset of depression.", "The purpose of the present study was to determine if interpersonal counselling (IPC) was effective in reducing psychological morbidity after major physical trauma.\n One hundred and seventeen subjects were recruited from two major trauma centres and randomized to treatment as usual or IPC in the first 3 months following trauma. Measures of depressive, anxiety and post-traumatic symptoms were taken at baseline, 3 months and 6 months. The Structured Clinical Interview for DSM IV diagnoses was conducted at baseline and at 6 months to assess for psychiatric disorder.\n Fifty-eight patients completed the study. Only half the patients randomized to IPC completed the therapy. At 6 months the level of depressive, anxiety and post-traumatic symptoms and the prevalence of psychiatric disorder did not differ significantly between the intervention and treatment-as-usual groups. Subjects with a past history of major depression who received IPC had significantly higher levels of depressive symptoms at 6 months.\n IPC was not effective as a universal intervention to reduce psychiatric morbidity after major physical trauma and may increase morbidity in vulnerable individuals. Patient dropout is likely to be a major problem in universal multi-session preventative interventions.", "Patients attending an accident and emergency department may exhibit psychological disturbances post-injury. Early interventions have been suggested to reduce the risk of post-injury disorder, including psychoeducation.\n We assessed the efficacy of providing such self-help information.\n Patients who had experienced trauma were randomised to two groups: those given (n=75) and not given (n=67) a self-help booklet. Psychological assessments were completed within 2, 10-12 and 24-26 weeks.\n Post-traumatic stress disorder (PTSD), anxiety and depression decreased (P < 0.05) with time but there were no group differences in PTSD or anxiety. The controls were less depressed (P < 50.05) at follow-up. There was a reduction in PTSD caseness within the control (50%) compared with the intervention (20%) group which was almost significant (P < 0.06).\n This trial failed to support the efficacy of providing self-help information as a preventive strategy to ameliorate PTSD.", "Posttraumatic behavioral and emotional disturbances occur frequently among physically injured hospitalized trauma survivors. This investigation was a pilot randomized effectiveness trial of a 4-month collaborative care intervention for injured motor vehicle crash and assault victims. As surgical inpatients, intervention subjects (N=16) were assigned to a trauma support specialist who provided counseling, consulted with surgical and primary care providers, and attempted postdischarge care coordination. Control subjects (N=18) received usual posttraumatic care. For all participants, posttraumatic stress disorder (PTSD) and depressive symptoms, episodic alcohol intoxication, and functional limitations were evaluated during the hospitalization and 1 and 4 months postinjury. Study logs and field notes revealed that over 75% of intervention activity occurred in the first month after the trauma. One-month post-trauma intervention subjects when compared to controls demonstrated statistically significant decreases in PTSD symptoms as well as a reduction in depressive symptoms. However, at the 4-month assessment, intervention subjects evidenced no significant improvements in PTSD and depressive symptoms, episodic alcohol intoxication, or functional limitations. Future larger scale trials of stepped collaborative care interventions for physically injured trauma survivors are recommended.", "The aim of this study was to improve health-related quality of life (HRQOL) related to depression, anxiety, pain, physical functioning and social aspects for severely injured trauma survivors by early onset cognitive behavioural therapy applied on the surgical ward.\n The study was a randomised, controlled study. Of 298 primary screened patients 171 were eligible and randomised. Ninety-two patients adhered to follow-up investigations at 6 and 12 months. Main outcome measure was a sum score according to O'Brien calculated of five different questionnaires (BDI, SF-36, STAI, SCL 90R, F-SOZU-22).\n The sum score for overall HRQOL did not show significant group differences at follow-up. Effects on HRQOL sub-dimensions within groups have been found. In the dimension of depression therapy group showed significant improvement from the first measurement to discharge from hospital (p < 0.001), 6 MFU (p = 0.004) and to 12 MFU (p = 0.013). Measures of anxiety showed significant improvement for the therapy group at discharge from hospital (p = 0.001). In the control group there was only a significant reduction in depression and anxiety from surgical ward to discharge (p = 0.013/p = 0.031).\n Early onset cognitive therapy is not effective in improving overall HRQOL of severely injured patients but shows promising effects on depression and anxiety up to 12 months after trauma." ]

[ "9568790", "8971064", "3474437", "19064517", "7707436", "11121464", "19066370", "18444146", "4068802", "11696701", "1834125", "9486468", "14679373", "8423627", "2722382", "3594351", "14684401", "15986117", "9719083", "6475911", "15126606", "10798212", "9829869", "8000296", "3773937", "2332904", "19531680", "16123147", "17209198", "16175184", "12433737", "9367064", "18444134", "19687417", "6134981", "18299496", "11588133", "11860943", "3578124", "3610461", "10710196", "9152515", "3124081", "1726411", "3366933", "3046338", "15704105", "19005970", "10453813", "3788940" ]

[ "The association between baseline vitamin E, selenium, and prostate cancer in the alpha-tocopherol, beta-carotene cancer prevention study.", "Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group.", "Serum selenium and the risk of cancer, by specific sites: case-control analysis of prospective data.", "Plasma selenium concentration and prostate cancer risk: results from the European Prospective Investigation into Cancer and Nutrition (EPIC).", "Prospective study of toenail selenium levels and cancer among women.", "Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer.", "Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).", "The nutritional prevention of cancer: 400 mcg per day selenium treatment.", "Is serum selenium a risk factor for cancer?", "Plasma selenium level before diagnosis and the risk of prostate cancer development.", "Selenium in human mammary carcinogenesis: a case-cohort study.", "Relationships of serum carotenoids, retinol, alpha-tocopherol, and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States)", "Serum selenium and cancer mortality: a nested case-control study within an age- and sex-stratified sample of the Belgian adult population.", "A prospective cohort study on toenail selenium levels and risk of gastrointestinal cancer.", "Prediagnostic serum selenium in a case-control study of thyroid cancer.", "Serum selenium and risk of cancer. A prospective follow-up of nine years.", "Prospective study of serum selenium concentrations and esophageal and gastric cardia cancer, heart disease, stroke, and total death.", "Antioxidants and basal cell carcinoma of the skin: a nested case-control study.", "Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer.", "Association between serum selenium and the risk of cancer.", "A prospective study of plasma selenium levels and prostate cancer risk.", "Selenoprotein P in plasma in relation to cancer morbidity in middle-aged Swedish men.", "Is low selenium status a risk factor for lung cancer?", "Prediagnostic serum selenium and zinc levels and subsequent risk of lung and stomach cancer in Japan.", "Serum beta-carotene, vitamins A and E, selenium, and the risk of lung cancer.", "Serum selenium and subsequent risk of cancer among Finnish men and women.", "Association of plasma micronutrient levels and urinary isoprostane with risk of lung cancer: the multiethnic cohort study.", "Selenium and mortality in the elderly: results from the EVA study.", "Serum selenium and risk of prostate cancer-a nested case-control study.", "Toenail selenium concentrations and bladder cancer risk in women and men.", "No Association between toenail selenium levels and bladder cancer risk.", "The risk of developing lung cancer associated with antioxidants in the blood: ascorbic acid, carotenoids, alpha-tocopherol, selenium, and total peroxyl radical absorbing capacity.", "Dietary supplement use and risk of neoplastic progression in esophageal adenocarcinoma: a prospective study.", "Antioxidant supplementation and risk of incident melanomas: results of a large prospective cohort study.", "Prediagnostic serum selenium and risk of cancer.", "Serum selenium levels and all-cause, cancer, and cardiovascular mortality among US adults.", "Predictors of serum selenium in cigarette smokers and the lack of association with lung and prostate cancer risk.", "[The prevention of primary liver cancer by selenium in high risk populations].", "Essential micronutrients in relation to carcinogenesis.", "Selenium levels in nails of premenopausal breast cancer patients assessed prediagnostically in a cohort-nested case-referent study among women screened in the DOM project.", "Serum tocopherols, selenium and lung cancer risk among tin miners in China.", "Protective role of selenium against hepatitis B virus and primary liver cancer in Qidong.", "Low plasma selenium as a risk factor for cancer death in middle-aged men.", "A preliminary report on the intervention trials of primary liver cancer in high-risk populations with nutritional supplementation of selenium in China.", "Serum selenium concentration associated with risk of cancer.", "Serum levels of selenium and retinol and the subsequent risk of cancer.", "Toenail selenium and risk of hepatocellular carcinoma mortality in Haimen City, China.", "The role of antioxidants and vitamin A in ovarian cancer: results from the Women's Health Initiative.", "Plasma selenium levels and risk of hepatocellular carcinoma among men with chronic hepatitis virus infection.", "Is serum selenium a risk factor for cancer in men only?" ]

[ "The association between prostate cancer and baseline vitamin E and selenium was evaluated in the trial-based cohort of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (n = 29,133). During up to 9 years of follow-up, 317 men developed incident prostate cancer. Multivariate Cox proportional hazards models that adjusted for intervention group, benign prostatic hyperplasia, age, smoking, and urban residence were used to evaluate associations between prostate cancer and exposures of interest. There were no significant associations between baseline serum alpha-tocopherol, dietary vitamin E, or selenium and prostate cancer overall. The associations between prostate cancer and vitamin E and some of the baseline dietary tocopherols differed significantly by alpha-tocopherol intervention status, with the suggestion of a protective effect for total vitamin E among those who received the alpha-tocopherol intervention (relative risk was 1.00, 0.68, 0.80, and 0.52 for increasing quartiles; P = 0.07).", "To determine whether a nutritional supplement of selenium will decrease the incidence of cancer.\n A multicenter, double-blind, randomized, placebo-controlled cancer prevention trial.\n Seven dermatology clinics in the eastern United States.\n A total of 1312 patients (mean age, 63 years; range, 18-80 years) with a history of basal cell or squamous cell carcinomas of the skin were randomized from 1983 through 1991. Patients were treated for a mean (SD) of 4.5 (2.8) years and had a total follow-up of 6.4 (2.0) years.\n Oral administration of 200 microg of selenium per day or placebo.\n The primary end points for the trial were the incidences of basal and squamous cell carcinomas of the skin. The secondary end points, established in 1990, were all-cause mortality and total cancer mortality, total cancer incidence, and the incidences of lung, prostate, and colorectal cancers.\n After a total follow-up of 8271 person-years, selenium treatment did not significantly affect the incidence of basal cell or squamous cell skin cancer. There were 377 new cases of basal cell skin cancer among patients in the selenium group and 350 cases among the control group (relative risk [RR], 1.10; 95% confidence interval [CI], 0.95-1.28), and 218 new squamous cell skin cancers in the selenium group and 190 cases among the controls (RR, 1.14; 95% CI, 0.93-1.39). Analysis of secondary end points revealed that, compared with controls, patients treated with selenium had a nonsignificant reduction in all-cause mortality (108 deaths in the selenium group and 129 deaths in the control group [RR; 0.83; 95% CI, 0.63-1.08]) and significant reductions in total cancer mortality (29 deaths in the selenium treatment group and 57 deaths in controls [RR, 0.50; 95% CI, 0.31-0.80]), total cancer incidence (77 cancers in the selenium group and 119 in controls [RR, 0.63; 95% CI, 0.47-0.85]), and incidences of lung, colorectal, and prostate cancers. Primarily because of the apparent reductions in total cancer mortality and total cancer incidence in the selenium group, the blinded phase of the trial was stopped early. No cases of selenium toxicity occurred.\n Selenium treatment did not protect against development of basal or squamous cell carcinomas of the skin. However, results from secondary end-point analyses support the hypothesis that supplemental selenium may reduce the incidence of, and mortality from, carcinomas of several sites. These effects of selenium require confirmation in an independent trial of appropriate design before new public health recommendations regarding selenium supplementation can be made", "From 1971 to 1975, serum specimens were obtained from 6,860 men of Japanese ancestry in Hawaii. Since then, the following numbers of newly diagnosed cases with epithelial cancer have been identified: 82 colon, 71 lung, 66 stomach, 32 rectum, and 29 urinary bladder. The stored sera of the 280 cases and of 293 randomly selected controls were tested to determine their levels of selenium. There was no association of serum selenium with lung, stomach, or rectal cancer. An increase in relative risk (RR) was noted only for subjects in the lowest quintile of selenium values, as compared to the RR for subjects in the highest quintile, for colon (RR = 1.8) and urinary bladder cancer (RR = 3.1), but neither of these RR estimates was statistically significant (P = .09 and P = .07, respectively). Further work is needed to determine whether the antioxidant properties of selenium protect against specific types of cancer.", "Some evidence indicates that a low selenium intake may be associated with an increased risk of prostate cancer.\n The aim of this study was to investigate the association of plasma selenium concentration with subsequent prostate cancer risk and to examine this association by stage and grade of disease and other factors.\n A nested case-control study was performed among men in the European Prospective Investigation into Cancer and Nutrition (EPIC). The association between plasma selenium concentration and prostate cancer risk was assessed in 959 men with incident prostate cancer and 1059 matched controls.\n Overall, plasma selenium concentration was not associated with prostate cancer risk; the multivariate relative risk for men in the highest fifth of selenium concentration compared with the lowest fifth was 0.96 (95% CI: 0.70, 1.31; P for trend = 0.25). There were no significant differences in the association of plasma selenium with risk when analyzed by stage or grade of disease. Similarly, the association of selenium with risk did not differ by smoking status or by plasma alpha- or gamma-tocopherol concentration.\n Plasma selenium concentration was not associated with prostate cancer risk in this large cohort of European men.", "Inverse associations between selenium status and cancer risk have been observed in animal studies, ecologic studies, and some case-control and prospective studies. Whereas results of some prospective studies have suggested an overall inverse relationship between selenium levels and cancer, other prospective studies have failed to confirm this finding. Prospective data on women are particularly limited because fewer women than men have been studied prospectively.\n The aim of this study was to prospectively examine the relationship between selenium levels in toenails (previously shown to reflect selenium intake) and incidence of cancer among women.\n The Nurses' Health Study cohort began in 1976 with 121,700 female nurses aged 30-55 years living in 11 U.S. states. In 1982, we requested toenail clippings from the members of the cohort, and 62,641 participants with no history of cancer returned these clippings. During 41 months of follow-up, 503 cases of cancer other than breast cancer (results previously reported) or nonmelanoma skin cancer were analyzed. For each case patient, a control subject was chosen from women who remained free of diagnosed cancer, matched by age and by date of nail return.\n No inverse association was observed between selenium levels in toenails and cancer risk. The age- and smoking-adjusted relative risk (RR), comparing the highest with the lowest quintile of toenail selenium level, was 1.44 (95% confidence interval [CI] = 0.97-2.13), and the trend across quintiles was marginally significant (two-sided P = .06). Comparing the highest with the lowest decile, the RR (age- and smoking-adjusted) was 1.77 (95% CI = 1.04-3.02). When these data were combined with the data from 434 breast cancer case patients and their matched control subjects identified in parallel from this same cohort, the RR comparing the highest with the lowest quintile was 1.24 (95% CI = 0.93-1.65). Toenail selenium level was not inversely associated with cancer at any major site, including uterine cancer, colorectal cancer, melanoma, ovarian cancer, or lung cancer (after adjusting for smoking); in fact, nonsignificant positive associations were observed at several sites.\n Toenail selenium levels were not inversely associated with cancer risk in this study.\n These data, in conjunction with previous findings of no association between toenail selenium status and breast cancer risk, strongly suggest that higher selenium intake within the range consumed by most U.S. women (as reflected by toenail selenium levels) is not protective against overall cancer incidence in women.", "Selenium and alpha-tocopherol, the major form of vitamin E in supplements, appear to have a protective effect against prostate cancer. However, little attention has been paid to the possible role of gamma-tocopherol, a major component of vitamin E in the U.S. diet and the second most common tocopherol in human serum. A nested case-control study was conducted to examine the associations of alpha-tocopherol, gamma-tocopherol, and selenium with incident prostate cancer.\n In 1989, a total of 10,456 male residents of Washington County, MD, donated blood for a specimen bank. A total of 117 of 145 men who developed prostate cancer and 233 matched control subjects had toenail and plasma samples available for assays of selenium, alpha-tocopherol, and gamma-tocopherol. The association between the micronutrient concentrations and the development of prostate cancer was assessed by conditional logistic regression analysis. All statistical tests were two-sided.\n The risk of prostate cancer declined, but not linearly, with increasing concentrations of alpha-tocopherol (odds ratio (highest versus lowest fifth) = 0.65; 95% confidence interval = 0.32--1.32; P(trend) =.28). For gamma-tocopherol, men in the highest fifth of the distribution had a fivefold reduction in the risk of developing prostate cancer than men in the lowest fifth (P:(trend) =.002). The association between selenium and prostate cancer risk was in the protective direction with individuals in the top four fifths of the distribution having a reduced risk of prostate cancer compared with individuals in the bottom fifth (P(trend) =.27). Statistically significant protective associations for high levels of selenium and alpha-tocopherol were observed only when gamma-tocopherol concentrations were high.\n The use of combined alpha- and gamma- tocopherol supplements should be considered in upcoming prostate cancer prevention trials, given the observed interaction between alpha-tocopherol, gamma-tocopherol, and selenium.", "Secondary analyses of 2 randomized controlled trials and supportive epidemiologic and preclinical data indicated the potential of selenium and vitamin E for preventing prostate cancer.\n To determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men.\n A randomized, placebo-controlled trial (Selenium and Vitamin E Cancer Prevention Trial [SELECT]) of 35,533 men from 427 participating sites in the United States, Canada, and Puerto Rico randomly assigned to 4 groups (selenium, vitamin E, selenium + vitamin E, and placebo) in a double-blind fashion between August 22, 2001, and June 24, 2004. Baseline eligibility included age 50 years or older (African American men) or 55 years or older (all other men), a serum prostate-specific antigen level of 4 ng/mL or less, and a digital rectal examination not suspicious for prostate cancer.\n Oral selenium (200 microg/d from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/d of all rac-alpha-tocopheryl acetate) and matched selenium placebo, selenium + vitamin E, or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years.\n Prostate cancer and prespecified secondary outcomes, including lung, colorectal, and overall primary cancer.\n As of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17-7.33 years). Hazard ratios (99% confidence intervals [CIs]) for prostate cancer were 1.13 (99% CI, 0.95-1.35; n = 473) for vitamin E, 1.04 (99% CI, 0.87-1.24; n = 432) for selenium, and 1.05 (99% CI, 0.88-1.25; n = 437) for selenium + vitamin E vs 1.00 (n = 416) for placebo. There were no significant differences (all P>.15) in any other prespecified cancer end points. There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group (P = .06) and type 2 diabetes mellitus in the selenium group (relative risk, 1.07; 99% CI, 0.94-1.22; P = .16) but not in the selenium + vitamin E group.\n Selenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men.\n clinicaltrials.gov identifier: NCT00006392.", "Nonexperimental studies suggest that individuals with higher selenium (Se) status are at decreased risk of cancer. The Nutritional Prevention of Cancer (NPC) study randomized 1,312 high-risk dermatology patients to 200-mcg/day of Se in selenized yeast or a matched placebo; selenium supplementation decreased the risk of lung, colon, prostate, and total cancers but increased the risk of nonmelanoma skin cancer. In this article, we report on a small substudy in Macon, GA, which began in 1989 and randomized 424 patients to 400-mcg/day of Se or to matched placebo. The subjects from both arms had similar baseline Se levels to those treated by 200 mcg, and those treated with 400-mcg attained plasma Se levels much higher than subjects treated with 200 mcg. The 200-mcg/day Se treatment decreased total cancer incidence by a statistically significant 25%; however, 400-mcg/day of Se had no effect on total cancer incidence.", "A narrow band of counties extending along the southeastern Atlantic coast from Jacksonville, Florida to Charleston, South Carolina were found to have excessively high incidence rates for esophageal cancer in non-white males. White males in the same areas have a 30% higher incidence rate for lung cancer but only average incidence rates were found for non-white males. Selenium is considered to decrease cancer risk in the animal model. In this coastal region, a study of 130 cancer patients who developed a malignancy 2-12 years after baseline examination showed no dose response relationship between baseline serum selenium levels and risk of subsequent cancer.", "Epidemiological studies and a randomized intervention trial suggest that the risk of prostate cancer may be reduced by selenium intake. We investigated whether plasma selenium level before diagnosis correlated with the risk of later developing prostate cancer.\n A case control study was performed on men from the Baltimore Longitudinal Study of Aging registry, including 52 with known prostate cancer and 96 age matched controls with no detectable prostatic disease. Plasma selenium was measured at an average time plus or minus standard deviation of 3.83 +/- 1.85 years before the diagnosis of prostate cancer by graphite furnace atomic absorption spectrophotometry. Adjusted odds ratio and 95% confidence interval were computed with logistic regression.\n After correcting for years before diagnosis, body mass index, and smoking and alcohol use history, higher selenium was associated with a lower risk of prostate cancer. Compared with the lowest quartile of selenium (range 8.2 to 10.7 microg./dl.), the odds ratios of the second (10.8 to 11.8), third (11.9 to 13.2) and fourth (13.3 to 18.2) quartiles were 0.15 (95% confidence interval 0.05 to 0.50), 0.21 (0.07 to 0.68) and 0.24 (0.08 to 0.77, respectively, p =0.01). Furthermore, plasma selenium decreased significantly with patient age (p <0.001).\n Low plasma selenium is associated with a 4 to 5-fold increased risk of prostate cancer. These results support the hypothesis that supplemental selenium may reduce the risk of prostate cancer. Because plasma selenium decreases with patient age, supplementation may be particularly beneficial to older men.", "In a prospective study conducted on the island of Guernsey a cohort of 5162 ostensibly healthy women was enrolled between 1967 and 1976. Blood samples were drawn from each participant, who also completed a questionnaire, which provided information on established risk indicators in human mammary carcinogenesis. Plasma selenium levels were measured in 46 breast cancer cases diagnosed a mean of 11 (S.D. 4) years after entry into the study cohort and in an age-stratified sample of 138 women drawn from the study base. Plasma selenium level in the cases was 109 (28) micrograms/l and in the base sample 103 (22) micrograms/l (95% confidence interval for the overall difference, -2 to 14 micrograms/l). The adjusted relative risk of developing breast cancer in the different quartiles of the selenium distribution was 0.80, 0.79, 0.72 and 1.00, respectively. Thus, in the present study selenium was not a strong indicator of human breast cancer risk.", "To evaluate relationships of serum carotenoids, alpha-tocopherol, selenium, and retinol with breast cancer prospectively, we conducted a case-control study nested in a cohort from the Breast Cancer Serum Bank in Columbia, Missouri (United States). Women free of cancer donated blood to this bank in 1977-87. During up to 9.5 years of follow-up (median = 2.7 years), 105 cases of histologically confirmed breast cancer were diagnosed. For each case, two women alive and free of cancer at the age of the case's diagnosis and matched on age and date of blood collection were selected as controls. A nonsignificant gradient of decreasing risk of breast cancer with increasing serum beta-cryptoxanthin was apparent for all women. Serum lycopene also was associated inversely with risk, and among women who donated blood at least two years before diagnosis, a significant gradient of decreasing breast cancer risk with increasing lycopene concentration was evident. A marginally significant gradient of decreasing risk with increasing serum lutein/zeaxanthin also was apparent among these women. We did not observe any evidence for protective effects of alpha- and beta-carotene, alpha-tocopherol, retinol, or selenium for breast cancer. Results of this study suggest that the carotenoids beta-cryptoxanthin, lycopene, and lutein/zeaxanthin may protect against breast cancer.", "To study the predictive power of serum selenium with regard to cancer mortality in a large sample of the Belgian population given the lack of coherence in the results of observational epidemiological studies in this domain.\n A prospective case-control study within a stratified sample of the Belgian male and female population.\n A total of 201 cases randomly selected from all cancer deaths (N=343) during a 10-y mortality follow-up of a large age- and sex-stratified sample of the total Belgian population aged 25-74 y were matched for age and gender with 603 controls.\n Conditional logistic regression for both univariate and multivariate analyses using tertile distribution of serum selenium in controls. Odds ratios (ORs) are adjusted for 10 baseline characteristics.\n Unadjusted ORs of cancer deaths taking the highest tertile of serum selenium as a reference: in male subjects T1/T3 is 2.2 (CI 1.3-3.7) (P for trend 0.011), whereas in female subjects a nonsignificant OR of 0.8 is observed. In multivariate analyses, no significant modifications of the ORs are observed for the predictive relation of serum selenium with cancer mortality. Besides serum selenium, beta-carotene intake and smoking are independent predictors in male subjects.\n In this nested case-control study of a stratified sample from the Belgian population, serum selenium is an independent predictor of cancer mortality in male subjects only, in a country with rather high serum selenium levels with respect to most other European countries.", "Various animal studies and ecologic studies suggest an inverse association between low dietary selenium intake and risk of various types of cancer.\n The goal of this prospective cohort study was to investigate the association between toenail selenium levels and risks of stomach cancer and colorectal cancer.\n Our cohort study on diet and cancer started in The Netherlands in 1986 with enrollment of 120,852 subjects aged 55-69 years. Of this number, 58,279 were men and 62,573 were women. Following the case-cohort approach for analysis of the data, we randomly selected from the cohort a subcohort of 3500 subjects (1688 men and 1812 women). After 3.3 years of follow-up, 155 incident cases of microscopically confirmed stomach cancer, 313 cases of colon cancer, and 166 cases of rectal cancer had been detected in the cohort. Toenail selenium data were available for 104 patients with stomach cancer, 234 with colon cancer, and 113 with rectal cancer and for 2459 subjects from the subcohort.\n In a multivariate analysis, the relative rates (RRs) of stomach cancer for subjects in increasing quintiles of toenail selenium level were 1.00, 0.44, 0.59, 0.84, and 0.64 (trend, P = .491). For men, there was some evidence for an inverse association between toenail selenium levels and stomach cancer: The RR for those in the highest compared with the lowest quintile of toenail selenium was 0.40 (95% confidence interval = 0.17-0.96), but the trend was not statistically significant (P = .136). For stomach cancer in women, there was no negative association with toenail selenium levels. Toenail selenium level was not associated with the risk of colon or rectal cancer. After exclusion of cases diagnosed in the 1st year of follow-up, the RRs of colon cancer for increasing quintiles of toenail selenium were 1.00, 1.27, 1.17, 0.75, and 1.07 (trend, P = .544); for rectal cancer, RR estimates were 1.00, 1.73, 0.83, 1.58, and 1.12 (trend, P = .890).\n These data support a suggestive but inconsistent inverse association between selenium levels and risk of stomach cancer. Our findings, like those of other studies, do not suggest an inverse association with risk of colorectal cancer.", "Sera from 43 persons who developed thyroid cancer on an average 4.8 years after blood sampling were compared with sera from controls. Three controls per case matched for sex, age, place of residence and year of blood sampling, with regard to serum selenium and serum copper. Cases were significantly lower in serum selenium than controls, and the estimated odds ratio of thyroid cancer increased from 1 for levels greater than or equal to 1.65 mumol/l, to 6.1 for levels 1.26-1.64 mumol/l, to 7.7 for levels less than or equal to 1.25 mumol/l. When time from blood sampling to diagnosis of the case was considered, it could be shown that the protective effect of high serum selenium concentrations was restricted to the last (less than 7) years prior to the diagnosis of thyroid cancer. The serum selenium concentration of cases tended to decrease relative to controls the shorter time was from blood sampling to the diagnosis. There was no difference between cases and controls with regard to serum copper.", "The association between serum selenium concentration and the risk of cancer was studied in 1110 men aged 55 to 74 years in two rural areas of Finland. The men were followed-up prospectively for 9 years and there were 109 new cases of cancer, with the cases of the first follow-up year excluded. The serum selenium concentrations were adjusted for age, area, smoking, serum cholesterol, and alcohol intake. The patients had a slightly lower adjusted mean serum selenium than the subjects without cancer at the end of the follow-up (+/- standard error of mean) 53.9 +/- 1.5 and 55.3 +/- 0.5 micrograms/l, respectively. The relative risks of cancer were essentially the same when these were calculated in the tertiles of the serum selenium distribution. Thirty-seven men had a history of cancer at baseline or had cancer diagnosed during the first follow-up year and their adjusted mean serum selenium was 49.4 +/- 2.6 micrograms/l, which was significantly lower (P less than 0.05) than that of the subjects without cancer during the follow-up.", "We previously reported an inverse association between prediagnostic serum selenium concentrations and the risk of esophageal squamous cell carcinoma (ESCC) and gastric cardia cancer (GCC) but not gastric noncardia cancer (GNCC) in a nested study from the Nutrition Intervention Trial in Linxian, China.\n We examined the relation between baseline serum selenium and the subsequent risk of death from ESCC, GCC, GNCC, heart disease (HD), stroke, and total death over 15 y of follow-up (1986-2001).\n We measured baseline serum selenium concentrations in 1103 subjects randomly selected from a larger trial cohort. We identified 516 deaths during the 15-y follow up, including 75 from ESCC, 36 from GCC, 116 from HD, and 167 from stroke. Relative risks (RRs) and 95% CIs were estimated by using Cox proportional hazards regression models. Reported RRs estimated the change in risk conferred by a 25% increase in serum selenium relative to the population distribution. All estimates were adjusted for sex, age, smoking, drinking, and serum cholesterol.\n We found significant inverse associations between baseline serum selenium and death from ESCC (RR: 0.83; 95% CI: 0.71, 0.98) and GCC (0.75; 0.59, 0.95). Trends toward inverse associations were noted for death from HD (0.89; 0.78, 1.01; P = 0.07), but no association was noted for total death (0.96; 0.90, 1.02) or stroke (0.99; 0.88, 1.11).\n Population-wide selenium supplementation in the region of China with low serum selenium and high incidences of ESCC and GCC merits serious consideration.", "To investigate the relationship between basal cell carcinoma (BCC) and antioxidant nutrients, specifically carotenoids, vitamin E and selenium.\n The Nambour Skin Cancer Study is an ongoing, community-based study of randomly selected adult residents of a township in sub-tropical Queensland, Australia. Using a nested case-control design, incident cases of BCC (n=90) were compared with age and sex matched controls (n=90). Dietary exposure was measured using food frequency questionnaire estimates of intake as well as serum biomarkers. Other determinants of skin cancer including sun exposure were also considered. Dietary intakes were adjusted for energy intake, and serum carotenoids and vitamin E were adjusted for serum cholesterol. Odds ratios were calculated across quartiles of dietary intake and serum biomarkers and linear trends were assessed using logistic regression, adjusting for age, sex and supplement use.\n In this prospective study no significant associations were found between BCC and carotenoids, vitamin E or selenium, as measured by serum biomarkers or dietary intake, although there was a suggestion of a positive association with lutein intake.", "In a recent randomized intervention trial, the risk of prostate cancer for men receiving a daily supplement of 200 microg selenium was one third of that for men receiving placebo. By use of a nested case-control design within a prospective study, i.e., the Health Professionals Follow-Up Study, we investigated the association between risk of prostate cancer and prediagnostic level of selenium in toenails, a measure of long-term selenium intake.\n In 1986, 51,529 male health professionals aged 40-75 years responded to a mailed questionnaire to form the prospective study. In 1987, 33,737 cohort members provided toenail clippings. In 1988, 1990, 1992, and 1994, follow-up questionnaires were mailed. From 1989 through 1994, 181 new cases of advanced prostate cancer were reported. Case and control subjects were matched by age, smoking status, and month of toenail return. Selenium levels were determined by neutron activation. All P values are two-sided.\n The selenium level in toenails varied substantially among men, with quintile medians ranging from 0.66 to 1.14 microg/g for control subjects. When matched case-control data were analyzed, higher selenium levels were associated with a reduced risk of advanced prostate cancer (odds ratio [OR] for comparison of highest to lowest quintile = 0.49; 95% confidence interval [CI] = 0.25-0.96; P for trend = .11). After additionally controlling for family history of prostate cancer, body mass index, calcium intake, lycopene intake, saturated fat intake, vasectomy, and geographical region, the OR was 0.35 (95% CI = 0.16-0.78; P for trend = .03).\n Our results support earlier findings that higher selenium intakes may reduce the risk of prostate cancer. Further prospective studies and randomized trials of this relationship should be conducted.", "A matched-pair analysis was conducted with data based on a prospective six-year follow-up of a random population sample to study the association between serum selenium and the risk of cancer. Case-control pairs were from a population, after exclusions, of 8,113 persons examined in 1972 from two counties in eastern Finland. Cases were 31- to 59-year-old men and women initially free of cancer. One control was matched to each case according to age, gender, daily tobacco consumption, and serum cholesterol concentration. The mean serum selenium of the 128 cases was 50.5 micrograms/liter and that of the controls was 54.3 micrograms/liter (p = 0.012 for difference). When the residual variation in tobacco consumption and serum cholesterol as well as that in four other possible confounders was allowed for in a multiple logistic model, serum selenium of less than 45 micrograms/liter was associated with a relative risk of cancer of 3.1 (95% confidence interval, 1.5-6.7, p less than 0.01). These data support the hypothesis that selenium deficiency increases the risk of certain cancers in middle-aged persons.", "Epidemiologic studies suggest that low selenium levels are associated with an increased incidence of prostate cancer, although results are conflicting. We examined the association between pre-diagnostic plasma selenium levels and risk of prostate cancer in men enrolled in the Physicians' Health Study.\n Using plasma samples obtained in 1982 from healthy men enrolled in the study, we conducted a nested case-control study among 586 men diagnosed with prostate cancer during 13 years of follow-up and 577 control subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of prostate cancer in pre- (before October 1990) and post- (after October 1990) prostate-specific antigen (PSA) screening eras were calculated using multivariable logistic regression.\n Pre-diagnostic plasma selenium levels were inversely associated with risk of advanced prostate cancer (5th versus 1st quintile OR = 0.52, 95% CI = 0.28 to 0.98; P(trend) =.05), even among men diagnosed after 1990 (5th versus 1st quintile OR = 0.39, 95% CI = 0.16 to 0.97). The inverse association with prostate cancer risk was observed only for case subjects with elevated baseline PSA levels (PSA >4 ng/mL, 5th versus 1st quintile OR = 0.49, 95% CI = 0.28 to 0.86; P(trend) =.002). These inverse associations were observed in both pre- and post-PSA eras.\n The inverse association between baseline plasma selenium levels and risk of advanced prostate cancer, even among men diagnosed during the post-PSA era, suggests that higher levels of selenium may slow prostate cancer tumor progression. Ongoing randomized trials of selenium supplements may help to further evaluate this issue.", "The premorbid level of selenoprotein P in plasma from subjects with cancer at different sites was compared with that from control subjects in a nested case-control study. A health screening of 12,500 middle-aged men was performed during 1974-1982 in Malmö, Sweden, and from the 400 cancer cases that were identified during follow-up until the end of 1988, 302 plasma samples were available for analysis of selenoprotein P. Two living controls per case of the same screening day and age were chosen. Selenoprotein P levels in subgroups of major cancer sites were lower in cases than in controls for the respiratory tract (1.20 and 1.30 arbitrary units, respectively; p < 0.05) cancer group. The odds ratio for overall cancer risk in the lowest quintile of selenoprotein P level compared with that in the highest was 5.2 [p (for trend) = 0.01]. In subgroups of major cancer sites, the odds ratios for cancer risk in the lowest tertile compared with the highest were 6.0 [p (for trend) = 0.004] in the respiratory tract and 3.4 [p (for trend) = 0.002] in the digestive tract. In cases + controls, selenoprotein P was lower in smokers than in nonsmokers (p < 0.05). Selenoprotein P was significantly correlated to plasma albumin, fasting blood glucose, and body mass index and inversely correlated to plasma alpha 1-antitrypsin and gamma-glutamyl transferase. The results suggest that a low plasma selenoprotein P level is associated with higher future risk of respiratory and digestive tract cancer in middle-aged men.", "The hypothesis that low selenium may in some circumstances be a risk factor for lung cancer was investigated in a case-control study nested within a longitudinal study. Serum samples from 9,101 cancer-free individuals were collected and stored at -20 degrees C by the Finnish Mobile Clinic in 1968-1971 and 1973-1976. During follow-up until the end of 1991, 95 cases of lung cancer were diagnosed. Selenium concentrations were determined from the serum samples of the cases and 190 controls, individually matched for sex, age, and place of residence. Mean levels of serum selenium in cases and controls were 53.2 microg/liter and 57.8 microg/liter, respectively. The relative risk of lung cancer between the highest and lowest tertiles of serum selenium, adjusted for smoking, serum alpha-tocopherol, serum cholesterol, serum copper, serum orosomucoid, and body mass index (kg/m2), was 0.41 (95% confidence interval (CI) 0.17-0.94). The association was stronger at lower levels (<5.9 mg/liter) of alpha-tocopherol (relative risk=0.24, 95% CI 0.07-0.85). The association was also pronounced among current smokers and at higher levels of serum orosomucoid and serum copper. The relative risk for smokers who were twice ranked in higher selenium tertiles, at an interval of 4-7 years, in comparison with smokers who remained in the lowest tertile was 0.16 (95% CI 0.04-0.74). In accordance with the hypothesis, the findings suggest that very low selenium status may contribute to the risk of lung cancer.", "Serum samples were collected in Hiroshima and Nagasaki, Japan, from 1970 to 1972 for 208 persons who in 1973-1983 developed stomach cancer; for 77 who in 1973-1983 developed lung cancer; and for controls matched for age, sex, city, and season of blood collection. Average serum levels of selenium and zinc were slightly (< 5%) but not significantly lower among the cancer cases than among controls. Smoking-adjusted risks of lung cancer were elevated only among those in the lowest quartiles of serum selenium [odds ratio (OR) = 1.8] and zinc (OR = 1.3); the trends in risk of this cancer with decreasing serum levels were neither linear nor significant. Little or no excess risk of stomach cancer was observed among those with lowest levels of selenium (OR = 1.0) or zinc (OR = 1.2). These exploratory findings add to limited data available from other reports showing slightly increased risks of lung cancer associated with low blood levels of selenium, but suggest little association with either lung or stomach cancer across normal selenium or zinc ranges in this Japanese population.", "We studied the relation of serum vitamin A (retinol), beta-carotene, vitamin E, and selenium to the risk of lung cancer, using serum that had been collected during a large blood-collection study performed in Washington County, Maryland, in 1974. Levels of the nutrients in serum samples from 99 persons who were subsequently found to have lung cancer (in 1975 to 1983) were compared with levels in 196 controls who were matched for age, sex, race, month of blood donation, and smoking history. A strong inverse association between serum beta-carotene and the risk of squamous-cell carcinoma of the lung was observed (relative odds, 4.30; 95 percent confidence limits, 1.38 and 13.41). Mean (+/- SD) levels of vitamin E were lower among the cases than the controls (10.5 +/- 3.2 vs. 11.9 +/- 4.90 mg per liter), when all histologic types of cancer were considered together. In addition, a linear trend in risk was found (P = 0.04), so that persons with serum levels of vitamin E in the lowest quintile had a 2.5 times higher risk of lung cancer than persons with levels in the highest quintile. These data support an association between low levels of serum vitamin E and the risk of any type of lung cancer and between low levels of serum beta-carotene and the risk of squamous-cell carcinoma of the lung.", "The association between the serum selenium level and the subsequent incidence of cancer was investigated in a longitudinal study of 39,268 men and women participating in the Social Insurance Institution's Mobile Clinic Health Examination Survey in Finland. The baseline examinations, including the collection of blood samples, were performed in 1968-1972. During a median follow-up of 10 years, 1,096 new cancer cases were identified from the files of the Finnish Cancer Registry. Selenium concentrations were measured from the stored serum samples collected from these cancer cases and from two controls per case, matched for sex, municipality, and age. The mean serum selenium level was 59.1 micrograms/L among all male cancer cases and 62.5 micrograms/L among controls. The difference was statistically significant (P less than .001). Corresponding values among women were 63.6 and 63.9 micrograms/L, respectively. Low serum selenium levels were associated with an increased risk of developing cancer at several sites, especially cancers of the stomach and lung among men. The relative risk of lung cancer between the highest and lowest decile of serum selenium was 0.11, and it differed significantly from unity (P less than .001). These findings are in agreement with the hypothesis that low selenium intake may increase the risk of some cancers among men.", "Although smoking is the primary risk factor for lung cancer, there is evidence to suggest that fruit and vegetable intake are important cofactors. The present case-control study, nested within the Multiethnic Cohort Study, examined the associations of biomarkers of fruit and vegetable intake (individual plasma micronutrient levels), serum selenium, and a urinary biomarker for total lipid peroxidation with lung cancer risk. Two hundred seven incident cases were matched to 414 controls on age, sex, ethnicity, study location (Hawaii or California), smoking status, date/time of collection, and hours of fasting. We measured prediagnositic circulating levels of individual tocopherols and carotenoids, retinol, and serum selenium, and urinary 15-isoprostane F(2t). Conditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI). For men, strong reductions in risk were seen with increasing tertiles of each plasma carotenoid, with the ORs for the third tertile, compared with the first tertile, ranging from 0.24 to 0.45 (P(trends), 0.002-0.04). No associations were found among women for carotenoids or among either sex for tocopherols, selenium, and retinol. A doubling in risk was seen for men in the second and third tertiles, compared with the first tertile of urinary 15-isoprostane F(2t) (OR, 2.31; 95% CI, 1.02-5.25; and OR, 2.16; 95% CI, 0.98-4.78). This study supports the previously observed association between circulating carotenoids and lung cancer risk in men, and adds to the limited literature regarding urinary 15-isoprostane F(2t) as a marker of cancer risk. Future research examining the possible relationship between isoprostanes and lung cancer is warranted.", "Inadequate plasma selenium can adversely affect the maintenance of optimal health; therefore, reported decreases in plasma selenium in an aging population are cause for concern. To further examine this hypothesis, we explored the relationships between plasma selenium and mortality in an elderly population: the EVA (Etude du Vieillissement Artériel) study.\n The EVA study was a 9-year longitudinal study with 6 periods of follow-up. During the 2-year period from 1991 to 1993 (EVA0), 1389 men and women born between 1922 and 1932 were recruited. The effects of plasma selenium at baseline on mortality were determined by Cox proportional hazards regression analysis, adjusting for the following variables: sociodemographic characteristics, dietary habits, health, and cognitive factors.\n During the 9-year follow-up, 101 study participants died. Baseline plasma selenium was higher in individuals who were alive at the end of follow-up [mean (SD), 1.10 (0.20) micromol/L] than in those who died during the follow-up [1.01 (0.20) micromol/L; P <10(-4)]. Mortality rates were significantly higher in individuals with low selenium [increments = 0.2 micromol/L; relative risk (RR) = 1.56 (95% confidence interval, 1.28-1.89)]. After we controlled for various potential confounding factors, this association remained significant [RR = 1.54 (1.25-1.88)]. When the underlying causes of death were considered, we found an association with cancer-related mortality [adjusted RR = 1.79 (1.32-2.44)].\n Even if it is premature to present selenium as a longevity indicator in an elderly population, our results are in accordance those of large, interventional, randomized trials with selenium, which suggest that this essential trace element plays a role in health maintenance in aging individuals.", "Selenium is a potential chemopreventive agent against prostate cancer, whose chemoprotective effects are possibly mediated through the antioxidative properties of selenoenzymes. Interrelations with other antioxidative agents and oxidative stressors, such as smoking, are poorly understood.\n The aims were to investigate the association between serum selenium and prostate cancer risk and to examine interactions with other antioxidants and tobacco use.\n A nested case-control study was performed within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Serum selenium in prospectively collected samples was compared between 724 incident prostate cancer case subjects and 879 control subjects, frequency-matched for age, time since initial screen, and year of blood draw. The men were followed for up to 8 y.\n Overall, serum selenium was not associated with prostate cancer risk (P for trend = 0.70); however, higher serum selenium was associated with lower risks in men reporting a high (more than the median: 28.0 IU/d) vitamin E intake [odds ratio (OR) for the highest compared with the lowest quartile of selenium: 0.58; 95% CI: 0.37, 0.91; P for trend = 0.05; P for interaction = 0.01] and in multivitamin users (OR for highest compared with the lowest quartile of selenium: 0.61; 95% CI: 0.36, 1.04; P for trend = 0.06; P for interaction = 0.05). Furthermore, among smokers, high serum selenium concentrations were related to reduced prostate cancer risk (OR for the highest compared with the lowest quartile of selenium: 0.65; 95% CI: 0.44, 0.97; P for trend = 0.09; P for interaction = 0.007).\n Greater prediagnostic serum selenium concentrations were not associated with prostate cancer risk in this large cohort, although greater concentrations were associated with reduced prostate cancer risks in men who reported a high intake of vitamin E, in multivitamin users, and in smokers.", "Prediagnostic selenium concentrations measured in archived toenails were inversely associated with bladder cancer risk in women (P for trend = 0.02), but not in men, in a nested case-control study of 338 cases and 341 matched controls. These findings may be due to chance and more studies are needed to determine whether associations between selenium and bladder cancer risk differ by sex.", "nan", "Lung cancer cases diagnosed during the period 1975 through 1993 and matched controls were identified in the rosters of Washington County, Maryland residents who had donated blood for a serum bank in 1974 or 1989. Plasma from participants in the 1989 project was assayed for ascorbic acid; serum or plasma was assayed for participants in either project for alpha- and beta-carotene, cryptoxanthin, lutein/zeaxanthin, lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity. Among the total group of 258 cases and 515 controls, serum/plasma concentrations were significantly lower among cases than controls for cryptoxanthin, beta-carotene, and lutein/zeaxanthin with case-control differences of -25.5, -17.1, and -10.1%, respectively. Modest nonsignificant case-control differences in a protective direction were noted for alpha-carotene and ascorbic acid. There were only trivial differences for lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity. Findings are reported for males and females and for persons who had never smoked cigarettes, former smokers, and current smokers at baseline. These results and those from previous studies suggest that beta-carotene is a marker for some protective factor(s) against lung cancer; that cryptoxanthin, alpha-carotene, and ascorbic acid need to be investigated further as potentially protective factors or associates of a protective factor; and that lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity are unlikely to be associated with lung cancer risk. Until specific preventive factors are identified, the best protection against lung cancer is still the avoidance of airborne carcinogens, especially tobacco smoke; second best is the consumption of a diet rich in fruits and vegetables.", "The incidence of esophageal adenocarcinoma (EA) and its precursor condition, Barrett's esophagus, has risen rapidly in the United States for reasons that are not fully understood. Therefore, we evaluated the association between use of supplemental vitamins and minerals and risk of neoplastic progression of Barrett's esophagus and EA. The Seattle Barrett's Esophagus Program is a prospective study based on 339 men and women with histologically confirmed Barrett's esophagus. Participants underwent baseline and periodic follow-up exams, which included endoscopy and self-administered questionnaires on diet, supplement use, and lifestyle characteristics. Use of multivitamins and 4 individual supplements was calculated using time-weighted averages of reported use over the observational period. Cox proportional-hazards models were used to calculate hazard ratios (HR) for each endpoint: EA, tetraploidy, and aneuploidy. During a mean follow-up of 5 yr, there were 37 cases of EA, 42 cases of tetraploidy, and 34 cases of aneuploidy. After controlling for multiple covariates including diet, nonsteroidal anti-inflammatory drug use, obesity, and smoking, participants who took 1 or more multivitamin pills/day had a significantly decreased risk of tetraploidy [HR = 0.19; 95% confidence interval (CI) = 0.08-0.47) and EA (HR = 0.38; 95% CI = 0.15-0.99] compared to those not taking multivitamins. Significant inverse associations were also observed between risk of EA and supplemental vitamin C (> or = 250 mg vs. none: HR = 0.25; 95% CI = 0.11-0.58) and vitamin E (> or = 180 mg vs. none: HR = 0.25; 95% CI = 0.10-0.60). In this cohort study, use of multivitamins and single antioxidant supplements was associated with a significantly reduced risk of EA and markers of neoplastic progression among individuals with Barrett's esophagus.", "To examine whether antioxidant supplement use is associated with melanoma risk in light of recently published data from the Supplementation in Vitamins and Mineral Antioxidants (SUVIMAX) study, which reported a 4-fold higher melanoma risk in women randomized to receive a supplement with nutritionally appropriate doses of antioxidants.\n Population-based prospective study (Vitamins and Lifestyle [VITAL] cohort).\n Western Washington State.\n A total of 69 671 men and women who self-reported (1) intake of multivitamins and supplemental antioxidants, including selenium and beta carotene, during the past 10 years and (2) melanoma risk factors on a baseline questionnaire. Main Outcome Measure Incident melanoma identified through linkage to the Surveillance, Epidemiology, and End Results (SEER) cancer registry.\n Cox proportional hazards regression models were used to estimate multivariable relative risks (RRs) and 95% confidence intervals (CIs) for multivitamin, supplemental selenium, and supplemental beta carotene use. After adjusting for melanoma risk factors, we did not detect a significant association between multivitamin use and melanoma risk in women (RR, 1.14; 95% CI, 0.78-1.66) or in men (RR, 1.09; 95% CI, 0.83-1.43). Moreover, we did not observe increased melanoma risk with the use of supplemental beta carotene (RR, 0.87; 95% CI, 0.48-1.56) or selenium (RR, 0.98; 95% CI, 0.69-1.41) at doses comparable with those of the SUVIMAX study. Conclusion Antioxidants taken in nutritional doses do not seem to increase melanoma risk.", "Selenium levels in serum samples collected in 1973 from 111 subjects in whom cancer developed during the subsequent 5 years were compared with those in serum samples from 210 cancer-free subjects matched for age, race, sex, and smoking history. The mean selenium level of cases (0.129 +/- SEM 0.002 micrograms/ml) was significantly lower than that of controls (0.136 +/- 0.002 micrograms/ml). The risk of cancer for subjects in the lowest quintile of serum selenium was twice that of subjects in the highest. Multivariate adjustment for geographical area and serum levels of lipids, vitamins A and E, and carotene, did not alter this relation. The association between low selenium level and cancer was strongest for gastrointestinal and prostatic cancers. Serum levels of vitamins A and E compounded the effect of low selenium; relative risks for the lowest tertile of selenium were 2.4 and 3.9 in the lowest tertiles of vitamins E and A, respectively.", "Selenium, an essential trace element involved in defense against oxidative stress, may prevent cancer and cardiovascular disease. We evaluated the association between selenium levels and all-cause and cause-specific mortality in a representative sample of US adults.\n Serum selenium levels were measured in 13,887 adult participants in the Third National Health and Nutrition Examination Survey. Study participants were recruited from 1988 to 1994 and followed up for mortality for up to 12 years.\n The mean serum selenium level was 125.6 ng/mL. The multivariate adjusted hazard ratios comparing the highest (> or = 130.39 ng/mL) with the lowest (< 117.31 ng/mL) serum selenium level tertile were 0.83 (95% confidence interval [CI], 0.72-0.96) for all-cause mortality, 0.69 (95% CI, 0.53-0.90) for cancer mortality, and 0.94 (95% CI, 0.77-1.16) for cardiovascular mortality. However, based on spline regression models, the association between serum selenium levels and all-cause and cancer mortality was nonlinear, with an inverse association at low selenium levels (< 130 ng/mL) and a modest increase in mortality at high selenium levels (> 150 ng/mL). There was no association between serum selenium levels and cardiovascular mortality.\n In a representative sample of the US population, we found a nonlinear association between serum selenium levels and all-cause and cancer mortality. Increasing serum selenium levels were associated with decreased mortality up to 130 ng/mL. Our study, however, raises the concern that higher serum selenium levels may be associated with increased mortality.", "Epidemiological studies have suggested that low levels of selenium are associated with a higher incidence of both lung and prostate cancer. We analyzed the selenium serum concentration in 356 Carotene and Retinol Efficacy Trial (CARET) participants who later developed lung cancer and 356 matched controls and in 235 prostate cancer cases and 456 matched controls. Serum samples were obtained a mean of 4.7 years before diagnosis for both tumor types. Controls were matched to cases by year of randomization, age, smoking status, treatment arm, exposure population (asbestos workers or cigarette smokers), and year of blood draw. In the control population (n = 820), significant predictors of low serum selenium concentration were current smoking status and East Coast locations of the study center. Overall, there was no significant difference in mean serum selenium in lung cancer cases versus controls (11.91 microg/dl versus 11.77 microg/dl) or prostate cancer cases versus controls (11.48 microg/dl versus 11.43 microg/dl). No statistically significant trend in odds ratio was seen across quartiles of serum selenium for lung cancer (P = 0.49) or prostate cancer (P = 0.69). In a subpopulation of 174 prostate cancer patients who had clinical and pathological staging material reviewed, there was no association between serum selenium and Gleason score or clinical or pathological stage. In the CARET population of current and former smokers consuming an ad libitum diet, the serum concentration of selenium was not a risk factor for either lung cancer or prostate cancer.", "To study the preventive effects of selenium on primary liver cancer.\n After screening of blood samples in 18,000 males from 20 to 65 years-old in Qidong, Jiangsu province (a high risk area for liver cancer), 2,065 cases of HBsAg positive, AFP negative and normal liver function (normal ALT values) were found. The subjects were randomly divided into two groups, based on their residence areas; 1,112 subjects (experimental group) received one tablet of sodium selenite (0.5 mg Se) every day and 953 subjects (control group) received one placebo tablet every day.\n During three years of intervention and follow up, the blood selenium concentration and glutathione peroxidase activity of the subjects in the experimental group were increased and had significant difference as compared with those of the control group (P < 0.01). At the same time, the prevalence rate of micronucleus cells in peripheral blood lymphocytes in the experimental group was significantly lower than that of the control group (P < 0.01), and the incidence of new liver cancer in the experimental group (3 057.55/10(6), 34 cases out of 1,112 subjects) was significantly lower than the control group (5 981.11/10(6); 57 cases out of 953 subjects) (P < 0.01).\n The results confirms that selenium supplementation in general populations lived in high risk is effective in the prevention of liver cancer and the using of selenium tablets is simple and feasible.", "nan", "To determine the possible role of selenium in the pathogenesis of breast cancer, prediagnostic Se 77 m isotope levels in toenail clippings in premenopausal women were measured. The study was designed as a case-referent study nested in a cohort. Participants were recruited from the DOM-project breast-cancer screening cohorts. No decreased selenium levels were found up to two years prior to diagnosis, nor were Se levels different between prevalent and/or incident breast cancer cases, referents and women with benign breast disease. Se levels measured in nails could not detect women at higher risk for breast cancer. This study does not support the idea that Se supplementation could have a preventive potential for premenopausal breast cancer in women in the Netherlands.", "To evaluate the association of prediagnostic serum antioxidants and lung cancer risk we conducted a case-control study nested in an occupational cohort of tin miners.\n Male workers free of cancer enrolled in the cohort. During up to 6 years of follow-up, 339 lung cancer cases were diagnosed and, among these cases, those who donated blood prospectively (n = 108) were eligible for this study. For each case, two controls alive and free of cancer at the time of case diagnosis were matched on age and date of blood collection.\n Overall, we observed no association between serum alpha-tocopherol, gamma-tocopherol or selenium levels and lung cancer risk. However, a significant gradient of decreasing lung cancer risk with increasing serum alpha-tocopherol was apparent for men less than 60 years old (odds ratio by tertile: 1.0, 0.9, 0.2; trend p = 0.002). Alpha-tocopherol was also protective in men who reported no alcohol drinking (OR by tertile: 1.0, 0.6, 0.3; trend p = 0.008).\n Although there were no significant overall associations between prospectively collected serum alpha-tocopherol, gamma-tocopherol or selenium and incidence of lung cancer, results from this study suggest that higher alpha-tocopherol levels may be protective in men less than 60 years old and in those who do not drink alcohol.", "High rates of hepatitis B virus (HBV) infection and primary liver cancer (PLC) are present in Qidong county. Epidemiological surveys demonstrated an inverse association between selenium (Se) level and regional cancer incidence, as well as HBV infection. Four-year animal studies showed that dietary supplement of Se reduced the HBV infection by 77.2% and liver precancerous lesion by 75.8% of ducks, caused by exposure to natural environmental etiologic factors. An intervention trial was undertaken among the general population of 130,471. Individuals in five townships were involved for observation of the preventive effect of Se. The 8-yr follow-up data showed reduced PLC incidence by 35.1% in selenized table salt supplemented vs the nonsupplemented population. On withdrawal of Se from the treated group, PLC incidence rate began to increase. However, the inhibitory response to HBV was sustained during the 3-yr cessation of treatment. The clinical study among 226 Hepatitis B Surface Antigen (HBsAg)-positive persons provided either 200 micrograms of Se in the form of selenized yeast tablet or an identical placebo of yeast tablet daily for 4 yr showed that 7 of 113 subjects were diagnosed as having PLC in the placebo group, whereas no incidence of PLC was found in 113 subjects supplemented with Se. Again on cessation of treatment, PLC developed at a rate comparable to that in the control group, demonstrating that a continuous intake of Se is essential to sustain the chemopreventive effect.", "In a population study, 10,000 men (aged 46-48 years) were invited to a health screening program. At follow-up, which was up to eight years later, 61 subjects had died from cancer; from 35 of these subjects, plasma samples were available that were obtained at the initial screening. These samples, together with samples from two living controls for each case, were analyzed for selenium, retinol, cholesterol, triglyceride, and a number of plasma proteins. Plasma selenium was significantly lower (p less than 0.05) in cases than in controls (means: 1.06 vs. 1.12 mumol/l). The proportion of cases increased significantly from the highest to the lowest quintile of plasma selenium, and the relative risk for cancer death was 3.8 times higher in the lowest quintile compared with the highest. Mean plasma retinol was similar in cases (2.53 mumol/l) and controls (2.56 mumol/l). Cases and controls also had similar values for plasma cholesterol, triglyceride, uric acid, apolipoprotein B, orosomucoid, prealbumin, retinol-binding protein, and beta 2-microglobulin. Apolipoprotein AI in plasma was lower among cases (p less than 0.025). Cases smoked significantly more than controls did (p less than 0.05). Data indicate that low plasma selenium was a risk factor for cancer death in middle-aged men who lived in the same area. Further studies are necessary to establish whether differences in selenium intake, selenium metabolism, or other factors related to selenium are responsible for the relations observed. At present, the available data do not justify selenium supplementation programs in the whole population.", "The purpose of this study was to evaluate the effect of selenium (Se) in the prevention of human primary liver cancer. Three intervention trials were conducted among the residents at high risk to primary liver cancer (PLC) in Qidong county, Jiang-su province, the People's Republic of China. This area has the second highest rate of PLC in China. One trial was undertaken among the general population in a township with supplement of table salt fortified with 15 ppm anhydrous sodium selenite (Se-salt) for 5 y and the other four townships with similar PLC incidence rate served as the controls using normal table salt. The second trial was undertaken among hepatitis B virus surface antigen carriers (HBVsAg+) receiving supplement of 200 micrograms Se in form of selenized yeast (Se-yeast) daily vs placebo for 4 y. The third trial was carried out in members of families with high PLC incidence using Se-yeast (200 micrograms of Se daily) vs placebo for 2 y. The results showed that nutritional supplement of Se could reduce the PLC incidence significantly.", "The association between serum selenium concentration and risk of cancer was studied in a nested case control study. Case control pairs came from a population of 9364 people examined in 1979. During the six year follow up, 60 men and women aged between 20-54 at the time of blood sampling, who had been free of malignant disease, developed cancer. The mean serum selenium concentration of 1.56 mumol/l (123.2 micrograms/l) in patients was not significantly different from that in controls (1.63 mumol/l (128.7 micrograms/l]. The difference in mean selenium concentration was largest and most significant for haematological malignancies alone. The difference in selenium concentrations in cases of fatal cancer compared with controls was significant (p less than 0.01). The risk of developing adenocarcinomas does not seem to be influenced by serum selenium concentration.", "A nested case-control study was conducted to assess the relation between serum levels of selenium and retinol and the subsequent risk of cancer. During the years 1972-1984, in northwest Washington State, 156 cases of cancer were identified among members of two employee cohorts from whom specimens had been previously obtained and stored. Two hundred eighty-seven controls were selected from these cohorts and matched to cases on the basis of employer, age, sex, race, and date of blood draw. Selenium and retinol levels were measured by neutron activation and high pressure liquid chromatography, respectively. Information on known cancer risk factors was collected by telephone interviews of subjects and next of kin. Levels of selenium and retinol were unassociated with the incidence of cancer of all sites combined, both overall and within subgroups defined by age, sex, levels of the other micronutrient, time between blood draw and diagnosis, smoking status, and family history of cancer. These findings suggest that neither serum levels of selenium nor those of retinol have an appreciable effect on the risk of cancer.", "Selenium (Se) is an essential trace mineral with known anticarcinogenic properties in humans. However, few studies have examined the association between Se nutrient status and risk of liver cancer. We conducted a nested case-control study comparing the Se content in toenail clippings of 166 individuals (154 men, 12 women) with hepatocellular carcinoma (HCC) to 394 healthy controls (360 men, 34 women) in Haimen City, China, where HCC is a leading cause of mortality. Toenail Se concentration was measured by inductively coupled plasma-optical emission spectroscopy. Median toenail Se was lower for HCC cases than controls (p = 0.03). Adjusted odds ratios and 95% confidence intervals for HCC mortality by increasing quartile of toenail Se were 1.00 (reference), 0.58 (0.32-1.03), 0.83 (0.48-1.42) and 0.50 (0.28-0.90), with a marginally significant trend in risk observed (p for trend = 0.06). This inverse association appeared stronger among those who did not consume alcohol and among women. Future studies are needed to examine the interrelationship between Se, viral hepatitis infection and HCC in order to better understand the etiologic mechanisms involved and evaluate the true chemopreventive potential of Se compounds for liver diseases.\n Copyright 2005 Wiley-Liss, Inc.", "Antioxidant nutrients and carotenoids have been inconsistently associated with ovarian cancer risk. We examined the relationship between intake of dietary and supplemental antioxidant nutrients including vitamins C, E, and selenium as well as carotenoids and vitamin A and ovarian cancer in 133,614 postmenopausal women enrolled in the Women's Health Initiative (WHI) study. Dietary intake was assessed using a food frequency questionnaire, and ovarian cancer endpoints were centrally adjudicated. Cox regression models were used to estimate the risk for invasive ovarian cancer in relation to each of the antioxidant nutrients and carotenoids under consideration using models stratified for a WHI study component. A total of 451 cases of invasive ovarian cancer were diagnosed over 8.3 yr of follow-up. Dietary intake at baseline was not significantly different for cases vs. controls. Cases reported greater intake of supplemental vitamin C (358.0 mg/day vs. 291.6 mg/day, respectively; P = 0.024). Multivariate modeling (P for trend) of the risk for developing ovarian cancer did not suggest any significant relationships among dietary factors and ovarian cancer risk. The results from this prospective study of well-nourished, postmenopausal women suggest that intake of dietary antioxidants, carotenoids, and vitamin A are not associated with a reduction in ovarian cancer risk.", "Both experimental and epidemiologic studies have linked a low dietary intake of selenium with an increased risk of cancer. The authors examined the association between plasma selenium levels and risk of hepatocellular carcinoma (HCC) among chronic carriers of hepatitis B and/or C virus in a cohort of 7,342 men in Taiwan who were recruited by personal interview and blood draw during 1988-1992. After these men were followed up for an average of 5.3 years, selenium levels in the stored plasma were measured by using hydride atomic absorption spectrometry for 69 incident HCC cases who were positive for hepatitis B surface antigen (HBsAg) and/or antibodies against hepatitis C virus (mostly HBsAg positive) and 139 matched, healthy controls who were HBsAg positive. Mean selenium levels were significantly lower in the HCC cases than in the HBsAg-positive controls (p = 0.01). Adjusted odds ratios of HCC for subjects in increasing quintiles of plasma selenium were 1.00, 0.52, 0.32, 0.19, and 0.62, respectively. The inverse association between plasma selenium levels and HCC was most striking among cigarette smokers and among subjects with low plasma levels of retinol or various carotenoids. There was no clear evidence for an interaction between selenium and alpha-tocopherol in relation to HCC risk.", "The association of serum selenium with the subsequent risk of death from cancer was investigated in a case-control study that was nested in a prospective nine-year follow-up study in the Netherlands. In 1975-1978, 10,532 persons in the Dutch town of Zoetermeer who were aged five years or more participated in a medical survey. Serum samples were collected and stored at -20 C. For the 82 persons who died of cancer since the baseline examination, 164 cohort members still alive by the end of 1983 were selected as controls and matched for age, sex, and smoking. Cancer deaths that occurred in the first year of follow-up were excluded, leaving 69 cases for statistical analyses. The mean serum selenium level of 116.7 +/- 4.0 micrograms/liter among male cancer deaths (n = 40) was significantly different (p = 0.04) from that in the control subjects (126.4 +/- 3.1 micrograms/liter). In females, selenium levels were similar among cases and controls. The adjusted risk of death from cancer for men in the lowest quintile of serum selenium (below 100.8 micrograms/liter) was more than twice that of subjects with higher levels (relative risk = 2.7,90% confidence interval = 1.2-6.2). These data support recent findings of an increased cancer risk associated with low serum selenium levels in men but not in women." ]

[ "20381871", "19365011" ]

[ "Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study.", "Pegaptanib sodium for macular edema secondary to central retinal vein occlusion." ]

[ "To assess the efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after central retinal vein occlusion (CRVO).\n Prospective, randomized, sham injection-controlled, double-masked, multicenter clinical trial.\n A total of 392 patients with macular edema after CRVO.\n Eligible patients were randomized 1:1:1 to receive monthly intraocular injections of 0.3 or 0.5 mg of ranibizumab or sham injections.\n The primary efficacy outcome measure was mean change from baseline best-corrected visual acuity (BCVA) letter score at month 6. Secondary outcomes included other parameters of visual function and central foveal thickness (CFT).\n Mean (95% confidence interval [CI]) change from baseline BCVA letter score at month 6 was 12.7 (9.9-15.4) and 14.9 (12.6-17.2) in the 0.3 mg and 0.5 mg ranibizumab groups, respectively, and 0.8 (-2.0 to 3.6) in the sham group (P<0.0001 for each ranibizumab group vs. sham). The percentage of patients who gained > or =15 letters in BCVA at month 6 was 46.2% (0.3 mg) and 47.7% (0.5 mg) in the ranibizumab groups and 16.9% in the sham group (P<0.0001 for each ranibizumab group vs. sham). At month 6, significantly more ranibizumab-treated patients (0.3 mg = 43.9%; 0.5 mg = 46.9%) had BCVA of > or = 20/40 compared with sham patients (20.8%; P<0.0001 for each ranibizumab group vs. sham), and CFT had decreased by a mean of 434 microm (0.3 mg) and 452 microm (0.5 mg) in the ranibizumab groups and 168 microm in the sham group (P<0.0001 for each ranibizumab group vs. sham). The median percent reduction in excess foveal thickness at month 6 was 94.0% and 97.3% in the 0.3 mg and 0.5 mg groups, respectively, and 23.9% in the sham group. The safety profile was consistent with previous phase III ranibizumab trials, and no new safety events were identified in patients with CRVO.\n Intraocular injections of 0.3 mg or 0.5 mg ranibizumab provided rapid improvement in 6-month visual acuity and macular edema following CRVO, with low rates of ocular and nonocular safety events.\n Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.", "To assess the safety and efficacy of intravitreous pegaptanib sodium for the treatment of macular edema following central retinal vein occlusion (CRVO).\n This dose-ranging, double-masked, multicenter, phase 2 trial included subjects with CRVO for 6 months' or less duration randomly assigned (1:1:1) to receive pegaptanib sodium or sham injections every 6 weeks for 24 weeks (0.3 mg and 1 mg, n=33; sham, n=32).\n Visual acuity at week 30.\n In the primary analysis at week 30, 12 of 33 (36%) subjects treated with 0.3 mg of pegaptanib sodium and 13 of 33 (39%) treated with 1 mg gained 15 or more letters from baseline vs 9 of 32 (28%) sham-treated subjects (P= .48 for 0.3 mg and P= .35 for 1 mg of pegaptanib sodium vs sham). In secondary analyses, subjects treated with pegaptanib sodium were less likely to lose 15 or more letters (9% and 6%; 0.3-mg and 1-mg pegaptanib sodium groups, respectively) compared with sham-treated eyes (31%; P= .03 for 0.3 mg and P= .01 for 1 mg of pegaptanib sodium vs sham) and showed greater improvement in mean visual acuity (+7.1 and +9.9, respectively, vs -3.2 letters with sham; P= .09 for 0.3 mg and P= .02 for 1 mg of pegaptanib sodium vs sham). By week 1, the mean central retinal thickness decreased in the 0.3-mg and 1-mg pegaptanib sodium groups by 269 microm and 210 microm, respectively, vs 5 microm with sham (P< .001).\n Based on this 30-week study, intravitreous pegaptanib sodium appears to provide visual and anatomical benefits in the treatment of macular edema following CRVO.\n Benefits accrued with intravitreous pegaptanib sodium treatment of macular edema following CRVO suggest a role for vascular endothelial growth factor in the pathogenesis of this condition.\n clinicaltrials.gov Identifier: NCT00088283." ]

[ "18286501", "19783136", "10561355" ]

[ "Treatment of children with metastatic soft tissue sarcoma with oral maintenance compared to high dose chemotherapy: report of the HD CWS-96 trial.", "Sequential high-dose chemotherapy for children with metastatic rhabdomyosarcoma.", "High-dose melphalan with autologous stem-cell rescue in metastatic rhabdomyosarcoma." ]

[ "We prospectively studied the efficacy of high dose therapy (HDT) versus an oral maintenance treatment (OMT) in patients with stage IV soft tissue sarcoma (STS).\n Both groups were pretreated with the CEVAIE combination consisting of carboplatin, etoposide, vincristine, actinomycin D, ifosfamide, and epirubicin. HDT consisted of a tandem cycle of thiotepa (600 mg/m(2)) plus cyclophosphamide (4,500 mg/m(2)) and melphalan (120 mg/m(2)) plus etoposide (1,800 mg/m(2)). This treatment was compared with OMT, consisting of four cycles trofosfamide (10 days 2 x 75 mg/m(2)/day) plus etoposide (10 days 2 x 25 mg/m(2)/day), and 4 cycles trofosfamide (10 days 2 x 75 mg/m(2)/day) plus idarubicin (10 days 4 x 5 mg/m(2)). Eligibility criteria were: diagnosis confirmed by reference pathology, primary stage IV, below 22 years of age, and having completed the study therapy.\n From 96 patients 45 were treated with HDT and 51 with OMT. The main risk parameters were equally distributed in both arms. After a median follow-up of 57.4 months, 11/45 (24.4%) patients in the HDT-arm and 26/51 (57.8%) patients in OMT-arm were alive. Kaplan-Meier analysis demonstrated an overall survival for the whole group of 0.27 (OMT group: 0.52, HDT group 0.27, log rank P = 0.03). The proportional hazard analysis for patients with rhabdomyosarcoma (RMS) or \"RMS-like\" tumors (77.1% of all patients) demonstrated an independent benefit of OMT on outcome.\n Oral maintenance therapy seems to be a promising option for patients with RMS-like stage IV tumors.\n (c) 2008 Wiley-Liss, Inc.", "The RMS4.99 study was designed to explore the role of multiple sequential high-dose chemotherapy cycles administered early in the treatment of children with metastatic rhabdomyosarcoma.\n Seventy patients were enrolled and received three cycles of initial standard chemotherapy, followed by a course of cyclophosphamide and etoposide to obtain peripheral blood stem cells (PBSC), then three consecutive high-dose combinations followed by PBSC rescue. This was followed by surgery and/or radiotherapy, after which a final maintenance treatment with six courses of vincristine, actinomycin D and cyclophosphamide was administered.\n Sixty-two patients underwent the high-dose chemotherapy phase. The 3-year overall survival (OS) and progression free survival (PFS) rates for the 70 patients were 42.3% (95% confidence interval [CI] 39.5-53.6) and 35.3% (95% CI, 24.3-46.5), respectively. By multivariate analysis survival correlated strongly with age > 10 years. In a subset of patients with only one or no unfavourable prognostic factors (age > 10 years, unfavourable site of primary tumour, bone or bone marrow involvement and number of metastatic sites >2) the PFS was significantly higher, i.e. 60.5% at 3 years.\n Our study confirms that patients with favourable prognostic characteristics have a better survival. The use of sequential cycles of high-dose chemotherapy did not appear of benefit for patients with metastatic rhabdomyosarcoma.", "The European Collaborative MMT4-91 trial was conducted as a prospective nonrandomized study to evaluate the potential benefit of high-dose melphalan as consolidation of first complete remission in children with stage IV rhabdomyosarcoma.\n Fifty-two patients in complete remission after six courses of chemotherapy received \"megatherapy\": 42 received melphalan alone, whereas 10 received melphalan in combination with etoposide, carboplatin/etoposide, or thiotepa/busulfan and etoposide. The outcome of this group of patients was compared with that observed in 44 patients who were also in complete remission after six courses of identical chemotherapy (plus surgery or radiotherapy) but went on to receive a total of up to 12 courses of conventional chemotherapy (four cycles). No differences were found between the two groups regarding clinical characteristics, chemotherapy received before complete remission, or response to chemotherapy. In particular, there was no significant difference between the groups for site of primary tumor, histologic subtype, age at presentation, presence of bone or bone marrow metastases, or number of metastases.\n The 3-year event-free survival (EFS) and overall survival (OS) rates were 29.7% and 40%, respectively, for those receiving high-dose melphalan or other multiagent high-dose regimens and 19.2% and 27.7%, respectively, for those receiving standard chemotherapy. The difference was not statistically significant (P =.3 and P =.2 for EFS and OS, respectively). There was a significant prolongation in the time from the last day of high-dose chemotherapy or the end of chemotherapy cycle 4 to the time of relapse in those receiving megatherapy (168 days for patients receiving megatherapy v 104 days for those receiving standard therapy; P =.05).\n The addition of a high-dose alkylating agent to consolidation therapy may have prolonged progression-free survival in this poor-risk patient group, but it did not significantly improve the ultimate outcome." ]

[ "18718992", "20973677", "15111355", "8718912", "17803414", "8548092", "19284264", "4002313" ]

[ "Letter to editor: an observational study of red cell transfusion in specialist palliative care.", "Assessment of fatigue after blood transfusion in palliative care patients: a feasibility study.", "Use of red blood cell transfusion in palliative care services: is it still up to date or is cancer-related anaemia controlled better with erythropoietic agents?", "Use of red blood cell transfusions in terminally ill cancer patients admitted to a palliative care unit.", "Survey of blood transfusion practice for palliative care patients in Yorkshire: implications for clinical care.", "Blood transfusion and its benefits in palliative care.", "Effects of red blood cell transfusion on anemia-related symptoms in patients with cancer.", "The use of transfusion in terminal cancer patients. Hospice versus conventional care setting." ]

[ "nan", "Blood transfusions are often used as a potential treatment for cancer-related fatigue in anaemic palliative care patients. However, evidence of benefit using validated outcomes measures is lacking.\n The aim of this study was to test the feasibility of using two such tools; the Brief Fatigue Inventory and FACT F-fatigue subscale, to measure change in fatigue following a blood transfusion.\n Anemic cancer patients receiving specialist palliative care and undergoing transfusion for fatigue, completed the tools pre- and 3 days post-transfusion.\n Thirty patients with cancer-related fatigue who received a blood transfusion completed the study. Both measures were capable of detecting statistical and clinically significant change in fatigue following transfusion. Furthermore, the measures showed significant differences between patients that did, or did not, report an overall improvement in fatigue. Patients found the measures easy to complete with no preference for one over another. Future clinical trials of blood transfusion for the management of fatigue should incorporate these validated outcome measures.", "nan", "Anemia is often associated with neoplastic disorders. Blood transfusions are used to alleviate the discomfort of anemic cancer patients. Of 246 terminally ill cancer patients admitted to our palliative care unit from October 1991 to December 1993 (128 women and 118 men), 31 patients (12.6%) (17 men and 14 women; age, 69.5 +/- 12 years) received on average 2.8 units of packed red blood cells (PRBCs) (range, 2-7 units/patient) in 35 separate admissions. PRBCs were transfused in the presence of low hemoglobin (Hb) levels ( < or = 8 g/dL) and/or severe fatigue or dyspnea. Pre-transfusion performance status, cognitive function, dyspnea, and fatigue at rest (evaluated by a four-point scale), complete blood count, serum albumin, and C-reactive protein were determined. The day after transfusion, subjective well-being was recorded as \"yes/no\" improvement in comparison with the pre-transfusion day. Improved subjective well-being after blood transfusion was reported in 51.4%, without significant relationship to pre-transfusion Hb levels or performance status. The influence of blood transfusion on subjective well-being was not related to the severity of dyspnea or fatigue. Twenty-one patients (60%), including seven with subjective improvement, died during the same hospitalization, a median of 49 days after transfusion. Pre-transfusion Hb level did not differ significantly in patients who benefited and did not benefit from transfusion, whereas time before death was significantly (P < 0.001) shorter in patients who did not benefit. In the discharged patients (40%), the median interval between transfusion and discharge was 13 days and the frequency of subjective improvement in well-being was 78.6%. Our data suggest that two main areas should be investigated, namely the relation between low Hb levels and symptoms and signs in terminally ill cancer patients, and the correct timing for effective blood transfusion. A combination of criteria is needed for effective transfusion; they must include not only Hb levels but also type and severity of anemic symptoms and signs. Furthermore, the identification of reliable prognostic indicators for survival would be useful.", "Blood transfusions can be used to palliate the symptoms of fatigue or dyspnea in the presence of anemia. We studied the transfusion practices of 8 hospices in our cancer network over a 1-year period. We identified 164 patients who received 650 units of blood in 230 transfusions. The majority of patients received a single transfusion (71%), of 2 or 3 units of blood (76%), as an inpatient (83%). Blood transfusions occurred in 140 (5.7%) of 2460 hospice admissions. Median survival following first transfusion was 42 days and significantly longer for outpatients compared to inpatients (median of 104 days and 36 days, respectively, p = 0.006).", "The value of blood transfusion as a supportive treatment in haematological disease and oncology is well established and is seen as an essential part of treatment. The place of blood transfusion in the alleviation of symptoms within palliative care units is less well established. There has been no evaluation of its benefits in terms of symptom relief and impact on the quality of life. This study was designed to identify the benefit achieved by transfusion as well as possible indicators for its appropriate use in the future. Ninety-seven patients were recruited over one year, from the beginning of September 1992 to the end of August 1993, from eight centres, all members of the South West Thames Palliative Medicine Collaborative Audit Group. Patients completed visual analogue scales before and on two occasions after transfusion, to assess its impact on dyspnoea, weakness and overall sense of well-being. Results indicated that a significant proportion showed improvement in all three parameters. Those whose main indication for transfusion was weakness showed a particular benefit. The group of patients entered into the study were anaemic in comparison with our normal patient population, but the degree of improvement seen did not correlate with the degree of anaemia prior to transfusion. We conclude that transfusion does offer symptom relief and improvement in well-being in patients with advanced malignant disease. It should be considered as a worthwhile option in palliative treatment of weakness, dyspnoea and impaired overall sense of well-being, when associated with anaemia.", "The aim of this study was to assess the effects of red blood cell transfusion, and the subsequent increase in hemoglobin values, on anemia-related symptoms in a cohort of patients with cancer with different survival times. A red blood cell transfusion was recommended to a consecutive sample of patients with hemoglobin levels of 8 +/- 0.5 g/dL. The number of units to be ordered was decided according the hemoglobin values with a mean target of increasing the hemoglobin values by approximately 2 g/dL. Hemoglobin values, anemia-related signs and symptoms, including well-being, fatigue, and dyspnea, were recorded at admission (T0), 1 day after the last transfusion (T1), and 15 days afterward (T2) by telephone contact or visit. Well-being, fatigue, and dyspnea were measured on a numerical scale of 0-10. Sixty-one patients were recruited in the period of study. One hundred thirty-three units of red blood cells were transfused (mean 2.18, 95% confidence interval [CI] 0.6). Complete data were available for 40 patients. Hemoglobin values and well-being significantly increased after transfusion (T1), maintaining acceptable values 15 days afterward (T2). Significant changes in fatigue and dyspnea were found immediately after transfusion, although the effect was partially lost 15 days after transfusion. No statistical differences were found between patients with different survival times. Fatigue was significantly lower in patients with longer survival times in comparison with patients with shorter survival times (p = 0.04). Blood transfusion in patients with hemoglobin values of approximately 8 g/dL improved anemia-related symptoms on a short-term basis. This benefit is independent of the stage of disease and survival. However, the effects on dyspnea and fatigue tend to decrease within 15 days, despite the maintenance of hemoglobin values attained after transfusions, suggesting that other factors may play a role.", "This study examines the usage of blood component products by terminal cancer patients in hospice and conventional care settings. Our results show that patients in conventional care settings are five times more likely to be transfused than are patients in hospital-based hospices and ten times more likely to be transfused than are patients in home-care hospices (p = 0.003). Since the outcome of care was comparable for the three types of care settings, the transfusion of blood component products to terminal cancer patients may be overused in conventional care settings." ]

[ "20156949", "19108787", "15378666", "19132781", "20496365" ]

[ "A European multicenter randomized double-blind placebo-controlled monotherapy clinical trial of milnacipran in treatment of fibromyalgia.", "Milnacipran for the treatment of fibromyalgia in adults: a 15-week, multicenter, randomized, double-blind, placebo-controlled, multiple-dose clinical trial.", "A double-blind placebo-controlled trial of milnacipran in the treatment of fibromyalgia.", "The efficacy and safety of milnacipran for treatment of fibromyalgia. a randomized, double-blind, placebo-controlled trial.", "Efficacy and safety of milnacipran 100 mg/day in patients with fibromyalgia: results of a randomized, double-blind, placebo-controlled trial." ]

[ "This randomized, double-blind, placebo-controlled, multicenter study investigated the efficacy and safety of milnacipran in the treatment of fibromyalgia (FM) in a European population.\n Outpatients diagnosed with FM according to 1990 American College of Rheumatology criteria (N = 884) were randomized to placebo (n = 449) or milnacipran 200 mg/day (n = 435) for 17 weeks (4-week dose escalation, 12-week stable dose, 9-day down-titration), followed by a 2-week posttreatment period. The primary efficacy criterion was a 2-measure composite responder analysis requiring patients to achieve simultaneous improvements in pain (>or= 30% improvement from baseline in visual analog scale, 24-hour morning recall) and a rating of \"very much\" or \"much\" improved on the Patient Global Impression of Change scale. If responder analysis was positive, Fibromyalgia Impact Questionnaire (FIQ) was included as an additional key primary efficacy measure.\n At the end of the stable dose period (Week 16), milnacipran 200 mg/day showed significant improvements from baseline relative to placebo in the 2-measure composite responder criteria (p = 0.0003) and FIQ total score (p = 0.015). Significant improvements were also observed in multiple secondary efficacy endpoints, including Short-Form 36 Health Survey (SF-36) Physical Component Summary (p = 0.025), SF-36 Mental Component Summary (p = 0.007), Multidimensional Fatigue Inventory (p = 0.006), and Multiple Ability Self-Report Questionnaire (p = 0.041). Milnacipran was safe and well tolerated; nausea, hyperhidrosis, and headache were the most common adverse events.\n Milnacipran is an effective and safe treatment for pain and other predominant symptoms of FM. Registered as trial no. NCT00436033.", "Preclinical and clinical studies have suggested that milnacipran, a dual norepinephrine-serotonin reuptake inhibitor, may be efficacious in the treatment of fibromyalgia (FM).\n This study was conducted to evaluate the efficacy and tolerability of milnacipran in treating the multiple domains of FM.\n This was a multicenter, double-blind, placebo-controlled trial. Adult patients (age 18-70 years) who met 1990 American College of Rheumatology criteria for FM were randomized to receive milnacipran 100 mg/d, milnacipran 200 mg/d, or placebo for 15 weeks. Because this was a pivotal registration trial, the primary end points were chosen to investigate efficacy for 2 potential indications: the treatment of FM and the treatment of FM pain. Thus, the 2 primary efficacy end points were rates of FM composite responders and FM pain composite responders. FM composite responders were defined as patients concurrently experiencing clinically meaningful improvements in the following 3 domain criteria: pain (> or = 30% improvement, as recorded in an electronic diary); patients' global status (a rating of very much improved or much improved on the Patient Global Impression of Change [PGIC] scale); and physical function (a > or = 6-point improvement on the 36-item Short-Form Health Survey [SF-36] Physical Component Summary score). FM pain composite responders were defined as those who met the pain and PGIC criteria. Adverse events reported by patients or observed by investigators were recorded throughout the trial.\n Of 2270 patients screened, 1196 were randomized to receive milnacipran 100 mg/d (n = 399), milnacipran 200 mg/d (n = 396), or placebo (n = 401). The majority of patients were female (96.2%) and white (93.5%). The population had a mean age of 50.2 years, a mean baseline weight of 180.8 pounds, and a mean baseline body mass index of 30.6 kg/m(2). Compared with placebo, significantly greater proportions of milnacipran-treated patients were FM composite responders (100 mg/d: P = 0.01; 200 mg/d: P = 0.02) and FM pain composite responders (100 mg/d: P = 0.03; 200 mg/d: P = 0.004). Milnacipran was associated with significant improvements in pain after 1 week of treatment (100 mg/d: P = 0.004; 200 mg/d: P = 0.04), as well as significant improvements in multiple secondary efficacy end points, including global status (PGIC: P<0.001 for both doses), physical function (SF-36 physical functioning domain-100 mg/d: P < 0.001; 200 mg/d: P = 0.02), and fatigue (Multidimensional Fatigue Inventory- 100 mg/d: P = 0.04). The most commonly reported adverse events with milnacipran were nausea (100 mg/d, 34.3%; 200 mg/d, 37.6%), headache (18.0% and 17.7%, respectively), and constipation (14.3% and 17.9%). Adverse events resulted in premature study discontinuation in 19.5% and 23.7% of those who received milnacipran 100 and 200 mg/d, respectively, compared with 9.5% of placebo recipients.\n In these adult patients with FM, both doses of milnacipran (100 and 200 mg/d) were associated with significant improvements in pain and other symptoms. Clinical Trials Identification Number: NCT00098124.", "Fibromyalgia syndrome is a systemic disorder of widespread pain which is thought to result from abnormal pain processing within the central nervous system. There are no currently approved treatments for this indication. Antidepressants appear, however, to be effective, especially those with an action on noradrenergic neurotransmission. The objective of the present study was to test the efficacy of the dual action noradrenaline and serotonin reuptake inhibitor antidepressant, milnacipran, in the treatment of fibromyalgia. The 125 patients, who were enrolled in a double-blind, placebo-controlled, flexible dose escalation trial, were randomized to receive placebo or milnacipran for 4 weeks of dose escalation (up to 200 mg/day), followed by 8 weeks at a constant dose. The study evaluated the efficacy and safety of milnacipran for the treatment of pain and associated symptoms such as fatigue, depressed mood and sleep. 75% of milnacipran-treated patients reported overall improvement, compared with 38% in the placebo group (p < 0.01). Furthermore, 37% of twice daily milnacipran-treated patients reported at least 50% reduction in pain intensity, compared with 14% of placebo-treated patients (p < 0.05). 84% of all milnacipran patients escalated to the highest dose (200 mg/day) with no tolerability issues. Most adverse events were mild to moderate in intensity, and transient in duration. These results suggest that milnacipran may have the potential to relieve not only pain but several of the other symptoms associated with fibromyalgia.\n 2004 John Wiley & Sons, Ltd.", "To evaluate the safety and efficacy of milnacipran, a dual norepinephrine and serotonin reuptake inhibitor, in the treatment of fibromyalgia (FM).\n A 27-week, randomized, double-blind, multicenter study compared milnacipran 100 and 200 mg/day with placebo in the treatment of 888 patients with FM. Two composite responder definitions were used to classify each patient's individual response to therapy. \"FM responders\" concurrently satisfied response criteria for improvements in pain (visual analog scale 24-h morning recall), patient global impression of change (PGIC), and physical functioning (SF-36 Physical Component Summary); while \"FM pain responders\" concurrently satisfied response criteria for improvements in pain and PGIC.\n At the primary endpoint, after 3-month stable dose treatment, a significantly higher percentage of milnacipran-treated patients met criteria as FM responders versus placebo (milnacipran 200 mg/day, p = 0.017; milnacipran 100 mg/day, p = 0.028). A significantly higher percentage of patients treated with milnacipran 200 mg/day also met criteria as FM pain responders versus placebo (p = 0.032). Significant pain reductions were observed after Week 1 with both milnacipran doses. At 15 weeks, milnacipran 200 mg/day led to significant improvements over placebo in pain (realtime, daily and weekly recall; all measures, p < 0.05), PGIC (p < 0.001), fatigue (p = 0.016), cognition (p = 0.025), and multiple SF-36 domains. Milnacipran was safe and well tolerated by the majority of patients during 27 weeks of treatment; nausea and headache were the most common adverse events.\n Milnacipran is safe and effective for the treatment of multiple symptoms of FM.", "To assess the efficacy and safety of milnacipran at a dosage of 100 mg/day (50 mg twice daily) for monotherapy treatment of fibromyalgia.\n A double-blind, placebo-controlled trial was performed to assess 1,025 patients with fibromyalgia who were randomized to receive milnacipran 100 mg/day (n = 516) or placebo (n = 509). Patients underwent 4-6 weeks of flexible dose escalation followed by 12 weeks of stable-dose treatment. Two composite responder definitions were used as primary end points to classify the response to treatment. The 2-measure composite response required achievement of ≥30% improvement from baseline in the pain score and a rating of \"very much improved\" or \"much improved\" on the Patient's Global Impression of Change (PGIC) scale. The 3-measure composite response required satisfaction of these same 2 improvement criteria for pain and global status as well as improvement in physical function on the Short Form 36 (SF-36) physical component summary (PCS) score.\n After 12 weeks of stable-dose treatment, a significantly greater proportion of milnacipran-treated patients compared with placebo-treated patients showed clinically meaningful improvements, as evidenced by the proportion of patients meeting the 2-measure composite responder criteria (P < 0.001 in the baseline observation carried forward [BOCF] analysis) and 3-measure composite responder criteria (P < 0.001 in the BOCF). Milnacipran-treated patients also demonstrated significantly greater improvements from baseline on multiple secondary outcomes, including 24-hour and weekly recall pain score, PGIC score, SF-36 PCS and mental component summary scores, average pain severity score on the Brief Pain Inventory, Fibromyalgia Impact Questionnaire total score (all P < 0.001 versus placebo), and Multidimensional Fatigue Inventory total score (P = 0.036 versus placebo). Milnacipran was well tolerated by most patients, with nausea being the most commonly reported adverse event (placebo-adjusted rate of 15.8%).\n Milnacipran administered at a dosage of 100 mg/day improved pain, global status, fatigue, and physical and mental function in patients with fibromyalgia." ]

[ "1877512", "16522919", "7913157", "8632216", "8100345", "9846855", "11498488", "8102720", "7819847", "10390287" ]

[ "Diarrhea, respiratory infections, and growth are not affected by a weekly low-dose vitamin A supplement: a masked, controlled field trial in children in southern India.", "A double-blind, randomized, clinical trial of the effect of vitamin A and zinc supplementation on diarrheal disease and respiratory tract infections in children in Mexico City, Mexico.", "Effect of vitamin A supplementation on diarrhoea and acute lower-respiratory-tract infections in young children in Brazil.", "Vitamin A supplementation fails to reduce incidence of acute respiratory illness and diarrhea in preschool-age Indonesian children.", "Vitamin A supplementation in northern Ghana: effects on clinic attendances, hospital admissions, and child mortality. Ghana VAST Study Team.", "Randomized placebo-controlled clinical trial of the effect of a single high dose or daily low doses of vitamin A on the morbidity of hospitalized, malnourished children.", "Simultaneous zinc and vitamin A supplementation in Bangladeshi children: randomised double blind controlled trial.", "Vitamin A supplementation and increased prevalence of childhood diarrhoea and acute respiratory infections.", "Impact of massive dose of vitamin A given to preschool children with acute diarrhoea on subsequent respiratory and diarrhoeal morbidity.", "The beneficial effects of weekly low-dose vitamin A supplementation on acute lower respiratory infections and diarrhea in Ecuadorian children." ]

[ "Incidence, duration, and severity of diarrhea and respiratory symptoms were monitored weekly for 1 y in 15,419 children 6-60 mo of age in a randomized, placebo-controlled, masked clinical trial conducted in southern India. Half the children received weekly doses of 8.7 mumol (2500 microgram) vitamin A and 46 mumol (20 mg) vitamin E (treated) and the other half, 46 mumol vitamin E (control). Medical and ocular examinations and anthropometric measurements were obtained before and after 52 wk of intervention. Ocular examinations also were obtained after 26 wk. Supplements were delivered weekly from calibrated dispenser bottles by community health volunteers who also recorded each mother's recall of daily morbidity of her child during the previous week. Baseline characteristics of treated and control subjects were similar and documented a prevalence of 11% xerophthalmia and 72% undernutrition. Weekly treatment with the low-dose vitamin A supplement did not influence the incidence, severity, or duration of diarrhea or respiratory infections and did not influence linear or ponderal growth.", "The efficacy of micronutrient supplementation in improving childhood health and survival in developing countries may be specific to the micronutrient used and health outcome measured.\n We evaluated the effect of vitamin A and zinc supplementation on overall rates of childhood diarrheal disease and respiratory tract infections and rates stratified by household and personal characteristics.\n A double-blind, randomized, placebo-controlled trial was carried out in which 736 children aged 6-15 mo living in a periurban area of Mexico City were assigned to receive vitamin A every 2 mo, zinc daily, vitamin A and zinc together, or placebo. Children were followed for 12 mo to determine overall counts of diarrheal episodes and respiratory tract infections.\n Vitamin A supplementation was associated with a 27% increase in diarrheal disease [risk ratio (RR): 1.27; 95% CI: 1.10, 1.45; P < 0.001] and a 23% increase in cough with fever (RR: 1.23; 95% CI: 1.02, 1.47; P = 0.02), whereas zinc had no effect on these outcomes. Vitamin A supplementation decreased diarrhea in children from households with dirt floors but increased diarrhea in children from households with nondirt floors, piped water, and indoor bathrooms. Zinc supplementation decreased diarrhea in children from households with dirt floors and whose mothers were more educated. Vitamin A supplementation increased cough with fever in children from less-crowded households that lacked indoor bathrooms and in children of less-educated mothers.\n Vitamin A increases diarrheal disease and respiratory tract infections in young children in periurban areas of Mexico City. Vitamin A and zinc have more heterogeneous effects in different subgroups of children.", "A beneficial effect of periodic vitamin A supplementation on childhood mortality has been demonstrated, but the effect on morbidity is less clear. We investigated the effect of vitamin A supplementation on diarrhoea and acute lower-respiratory-tract infections (ALRI) in children from northeastern Brazil in a randomised, double-blind, placebo-controlled community trial. 1240 children aged 6-48 months were assigned vitamin A or placebo every 4 months for 1 year. They were followed up at home three times a week, and data about the occurrence and severity of diarrhoea and ALRI were collected. Any child with cough and respiratory rate above 40 breaths per min was visited by a paediatrician. The overall incidence of diarrhoea episodes was significantly lower in the vitamin-A-supplemented group than in the placebo group (18.42 vs 19.58 x 10(-3) child-days; rate ratio 0.94 [95% Cl 0.90-0.98]). The benefit of supplementation was greater as regards severe episodes of diarrhoea; the incidence was 20% lower in the vitamin A group than in the placebo group (rate ratio 0.80 [0.65-0.98]). With the standard definition of diarrhoea (> or = 3 liquid or semi-liquid stools in 24 h) the effect of vitamin A on mean daily prevalence did not reach significance, but as the definition of diarrhoea was made more stringent (increasing number of stools per day), a significant benefit became apparent, reaching for diarrhoea with 6 or more liquid or semi-liquid stools in 24 h a 23% lower prevalence. We found no effect of vitamin A supplementation on the incidence of ALRI. The reduction in severity of diarrhoea may be the most important factor in the lowering of mortality by vitamin A supplementation.", "Vitamin A supplementation of populations of vitamin A-deficient preschool-age children has been shown to reduce childhood mortality, but the primary preventive effects of such supplements on childhood infectious diseases have not been carefully evaluated. We conducted an individually randomized, placebo-controlled, double-masked trial among 1,407 Indonesian preschool-age children, to measure the effects of high dose vitamin A on acute respiratory and diarrheal illnesses. Signs and symptoms of morbidity were monitored using every other day home surveillance by trained interviewers. High dose vitamin A supplements increased the incidence of acute respiratory illnesses (ARI) by 8%, and acute lower respiratory illnesses (ALRI) by 39%. These detrimental effects on acute lower respiratory illnesses were most marked in children with adequate nutritional status (rate ratio 1.83, 95% confidence interval 1.257-2.669). In contrast, vitamin A tended to be protective of ALRI in chronically malnourished children (rate ratio 0.71, 95% confidence interval 0.375-1.331). There was no overall effect of high-dose vitamin A supplements on the incidence of diarrheal disease (rate ratio 1.06, 95% confidence interval 0.920-1.225). However, we found a significant interaction between supplementation and age: vitamin A increased the incidence of diarrhea in children < 30 mo of age, but tended to reduce the incidence in older children. The finding of a significant adverse effect of vitamin A supplements in adequately nourished children highlights the need to review the criteria for selecting populations of preschool-age children for vitamin A supplementation.", "Although most studies on the effect of vitamin A supplementation have reported reductions in childhood mortality, the effects on morbidity are less clear. We have carried out two double-blind, randomised, placebo-controlled trials of vitamin A supplementation in adjacent populations in northern Ghana to assess the impact on childhood morbidity and mortality. The Survival Study included 21,906 children aged 6-90 months in 185 geographical clusters, who were followed for up to 26 months. The Health Study included 1455 children aged 6-59 months, who were monitored weekly for a year. Children were randomly assigned either 200,000 IU retinol equivalent (100,000 IU under 12 months) or placebo every 4 months; randomisation was by individual in the Health Study and by cluster in the Survival Study. There were no significant differences in the Health Study between the vitamin A and placebo groups in the prevalence of diarrhoea or acute respiratory infections; of the symptoms and conditions specifically asked about, only vomiting and anorexia were significantly less frequent in the supplemented children. Vitamin-A-supplemented children had significantly fewer attendances at clinics (rate ratio 0.88 [95% CI 0.81-0.95], p = 0.001), hospital admissions (0.62 [0.42-0.93], p = 0.02), and deaths (0.81 [0.68-0.98], p = 0.03) than children who received placebo. The extent of the effect on morbidity and mortality did not vary significantly with age or sex. However, the mortality rate due to acute gastroenteritis was lower in vitamin-A-supplemented than in placebo clusters (0.66 [0.47-0.92], p = 0.02); mortality rates for all other causes except acute lower respiratory infections and malaria were also lower in vitamin A clusters, but not significantly so. Improving the vitamin A intake of young children in populations where xerophthalmia exists, even at relatively low prevalence, should be a high priority for health and agricultural services in Africa and elsewhere.", "The effect of high-dose vitamin A supplementation on recovery from morbidity and on recovery from nosocomial morbidity of hospitalized children has been poorly studied and results are conflicting. The effect of daily, low doses has never been assessed. We investigated the effect of a single high dose and daily, low doses of vitamin A on diarrhea, acute lower respiratory tract infections (ALRIs), and all-cause fevers in 900 hospitalized preschool-age children in the Democratic Republic of Congo in a randomized, double-blind, placebo-controlled clinical trial. The high-dose treatment group received 200,000 IU vitamin A (100,000 IU if aged <12 mo) orally on the day of admission, the low-dose treatment group received 5000 IU vitamin A/d until discharge. Data on all-cause morbidity were collected daily. Mortality rates were not significantly different among the 3 groups. High-dose vitamin A supplementation had no significant effect on the duration of moderate or severe diarrhea nor on the duration and incidence of ALRIs and all-cause fevers. Children in the high-dose group with no edema had an increased risk of severe nosocomial diarrhea (relative risk: 2.42; 95% CI: 1.15, 5.11). Low-dose vitamin A supplementation significantly reduced the incidence of severe diarrhea in severely malnourished children (relative risk: 0.21; 95% CI: 0.07, 0.62) but showed no significant effect on the duration of moderate or severe diarrhea or on the duration and incidence of ALRIs and all-cause fevers. Supplementation with high doses of vitamin A did not reduce morbidity in this population of malnourished and subclinically vitamin A-deficient children; daily, low doses appeared more beneficial for severely malnourished children.", "To evaluate the effect of simultaneous zinc and vitamin A supplementation on diarrhoea and acute lower respiratory infections in children.\n Randomised double blind placebo controlled trial.\n Urban slums of Dhaka, Bangladesh.\n 800 children aged 12-35 months were randomly assigned to one of four intervention groups: 20 mg zinc once daily for 14 days; 200 000 IU vitamin A, single dose on day 14; both zinc and vitamin A; placebo. The children were followed up once a week for six months, and morbidity information was collected.\n The incidence and prevalence of diarrhoea were lower in the zinc and vitamin A groups than in the placebo group. Zinc and vitamin A interaction had a rate ratio (95% confidence interval) of 0.79 (0.66 to 0.94) for the prevalence of persistent diarrhoea and 0.80 (0.67 to 0.95) for dysentery. Incidence (1.62; 1.16 to 2.25) and prevalence (2.07; 1.76 to 2.44) of acute lower respiratory infection were significantly higher in the zinc group than in the placebo group. The interaction term had rate ratios of 0.75 (0.46 to 1.20) for incidence and 0.58 (0.46 to 0.73) for prevalence of acute lower respiratory infection.\n Combined zinc and vitamin A synergistically reduced the prevalence of persistent diarrhoea and dysentery. Zinc was associated with a significant increase in acute lower respiratory infection, but this adverse effect was reduced by the interaction between zinc and vitamin A.", "There is uncertainty over whether vitamin A supplementation reduces morbidity among children with subclinical deficiency of the vitamin. Hence a double-blind, placebo-controlled trial of the effect of vitamin A supplementation on childhood morbidity was conducted among 11,124 children aged 6-83 months in the northwest of Haiti. After a random start, children were sequentially assigned by household units to receive either megadose vitamin A or placebo in three distribution cycles 4 months apart. 2 to 8 weeks after each administration of the vitamin A and placebo capsules, indicators of childhood morbidity were reassessed through interviews conducted in the homes of participating families. The vitamin A group was found to have an increased 2-week prevalence of all symptoms and signs of childhood morbidity assessed, including diarrhoea (rate ratio [RR] = 1.09, 95% confidence interval 1.05-1.14), rhinitis (RR = 1.02, 95% confidence interval 1.00-1.04), cold/flu symptoms (RR = 1.04, 95% confidence interval 1.01-1.06), cough (RR = 1.07, 95% confidence interval 1.03-1.11), and rapid breathing (RR = 1.18, 95% confidence interval 1.09-1.27). The study shows an increased 2-week prevalence of diarrhoea and the symptoms of respiratory infections after vitamin A supplementation.", "To assess the impact of vitamin A supplementation on morbidity from acute respiratory tract infections and diarrhoea.\n Double blind randomised placebo controlled field trial.\n An urban slum area in New Delhi, India.\n 900 children aged 12-60 months attending a local health facility for acute diarrhoea of less than seven days' duration randomly allocated to receive vitamin A 200,000 IU or placebo.\n Incidence and prevalence of acute lower respiratory tract infections and diarrhoea during the 90 days after termination of the enrolment diarrhoeal episode measured by twice weekly household surveillance.\n The incidence (relative risk 1.07; 95% confidence interval 0.92 to 1.26) and average number of days spent with acute lower respiratory tract infections were similar in the vitamin A supplementation and placebo groups. Among children aged 23 months or less there was a significant reduction in the incidence of measles (relative risk 0.06; 95% confidence interval 0.01 to 0.48). The incidence of diarrhoea was also similar (relative risk 0.95; 0.86 to 1.05) in the two groups. There was a 36% reduction in the mean daily prevalence of diarrhoea associated with fever in the vitamin A supplemented children older than 23 months.\n Results were consistent with a lack of impact on acute lower respiratory tract related mortality after vitamin A supplementation noted in other trials and a possible reduction in the severity of diarrhoea.", "Previous studies of large-dose vitamin A supplementation on respiratory morbidity have produced conflicting results in a variety of populations. The influence of malnutrition has not been examined in the majority of these trials. We hypothesized that weekly low-dose vitamin A supplementation would prevent respiratory and diarrheal disease morbidity and that malnutrition might influence the efficacy of vitamin A supplementation.\n In a randomized, double-blind, placebo-controlled field trial of 400 children, 6 to 36 months of age in a high Andean urban slum, half of the children received 10 000 IU of vitamin A weekly and half received placebo for 40 weeks. Children were visited weekly at home by physicians and assessed for acute diarrheal disease and acute respiratory infections.\n Acute diarrheal disease and acute respiratory infection did not differ globally or by severity between supplement-treated and placebo groups. However, the incidence of acute lower respiratory infection (ALRI) was significantly lower in underweight (weight-for-age z score [WAZ] <-2 SD) supplement-treated children than in underweight children on placebo (8.5 vs 22.3 per 10(3) child-weeks; rate ratio: 0.38 [95% CI: 0.17-0.85]). ALRI incidence was significantly higher in normal-weight (WAZ >-2 SD) supplement-treated children than in normal-weight children on placebo (9.8 vs 4.4 per 10(3) child-weeks; rate ratio: 2.21 [95% CI: 1.24-3.93]). By logistic regression analysis the risk of ALRI was lower in underweight supplement-treated children than in underweight children on placebo (point estimate 0.148 [95% CI: 0.034-0.634]). In contrast, risk of ALRI was higher in normal-weight supplement-treated children (WAZ >-1 SD to mean) than in normal-weight children on placebo in the same WAZ stratum (point estimate: 2.51 [95% CI: 1.24-5.05]). The risk of severe diarrhea was lower in supplement-treated children 18 to 23 months of age than in children on placebo in this age group (point estimate: 0.26 [95% CI: 0.06-1.00]).\n Weekly low-dose (10 000 IU) vitamin A supplementation in a region of subclinical deficiency protected underweight children from ALRI and paradoxically increased ALRI in normal children with body weight over -1 SD. Protection from severe diarrhea was consistent with previous trials. Additional research is warranted to delineate potential beneficial and detrimental interactions between nutritional status and vitamin A supplementation regarding ALRI." ]

[ "9603794", "14932560", "9175946", "7943128" ]

[ "Lack of efficacy of light reduction in preventing retinopathy of prematurity. Light Reduction in Retinopathy of Prematurity (LIGHT-ROP) Cooperative Group.", "Retrolental fibroplasia; the negative role of light, mydriatrics, and the ophthalmoscopic examination in its etiology.", "Light reduction and the electroretinogram of preterm infants.", "A controlled clinical trial of light and retinopathy of prematurity." ]

[ "Hospital-nursery lighting has been suggested as a factor in causing retinopathy of prematurity. Despite ongoing debate, a causal relation has not been established.\n We conducted a prospective, randomized, multicenter study of the effects of light reduction on 409 premature infants with birth weights of less than 1251 g and gestational ages of less than 31 weeks. Two hundred five infants were exposed to reduced light, and 204 to typical nursery lighting. The amount of light reaching the infants' eyes was reduced within 24 hours after birth by placing goggles on the infants that reduced visible-light exposure by 97 percent and ultraviolet-light exposure by 100 percent. The babies wore the goggles until 31 weeks' postconceptional age or 4 weeks after birth, whichever was longer. Once the goggles were removed, ophthalmologists masked to the treatment assignments assessed the infants for retinopathy of prematurity at least biweekly for up to 13 weeks.\n There were 188 infants in the group that wore goggles and 173 in the control group who survived and were available for follow-up. The mean birth weights were 906 g in the goggles group and 914 g in the control group; the mean gestational ages were 27.4 weeks and 27.2 weeks, respectively. The mean ambient-light level adjacent to the infants' faces was 399 lux for the goggles group and 447 lux for the control group. Retinopathy of prematurity was diagnosed in 102 infants (54 percent) in the goggles group and 100 (58 percent) in the control group (relative risk, 0.9; 95 percent confidence interval, 0.8 to 1.1; P=0.50).\n A reduction in ambient-light exposure does not alter the incidence of retinopathy of prematurity.", "nan", "To examine the effects of light on retinal development and function in preterm infants as measured by the electroretinogram (ERG). Secondary outcomes included visual acuity testing, the incidence of retinopathy of prematurity, and general wellbeing, reflected in feeding tolerance, rate of weight gain, and length of hospital stay.\n Eligibility criteria for enrollment were birthweight < or = 1250 g and gestational age < or = 31 weeks. Sixty one infants were randomly allocated by 6 hours after birth to a control or treatment group which wore 97% light filtering goggles for a minimum of four weeks or until the infant reached 31 weeks postmenstrual age.\n There were no significant differences between the two groups in the numbers of electroretinograms performed at 36 weeks of postmenstrual age. Although the sample size was not large enough to exclude clinically important differences in secondary outcomes, no significant differences were observed between the groups in visual acuity testing at 4-6 months corrected age, incidence of retinopathy of prematurity, weight gain, or length of stay.\n These data support the safety and feasibility of this intervention. A much larger study will be needed to determine whether light reduction to the eyes of very low birthweight infants will reduce the incidence of retinopathy of prematurity or enhance general well-being.", "Bright continuous light has been implicated in the pathogenesis of retinopathy of prematurity. To investigate the influence of light on the incidence and severity of retinopathy of prematurity, we enrolled 127 preterm infants (birth weight < or = 1,500 g; gestational age < or = 32 weeks) in a controlled clinical study. Randomization was done separately for three birth-weight groups (< 1,000 g; 1,000 to 1,249 g; 1,250 to 1,500 g). The babies' eyes were patched all day and night from birth to a gestational age of 35 weeks. The infants in the control group were exposed to cycled lighting conditions (that is, reduced light level during the night). Of 62 infants with patched eyes, 26 (42%) developed retinopathy of prematurity. In the control group, 25 of 65 infants (39%) showed retinopathy of prematurity (P = .596). There were also no statistically significant differences in the incidences of retinopathy of prematurity in the birth-weight subgroups or in the severity of retinopathy of prematurity. Thus, patching of the eyes from birth to 35 weeks of postconceptional age does not decrease the risk of retinopathy of prematurity in preterm infants when compared to a control group exposed to cycled lighting conditions." ]

[ "16784743", "16154059" ]

[ "Randomized controlled trial assessing a traditional Chinese medicine remedy in the treatment of primary dysmenorrhea.", "Rose tea for relief of primary dysmenorrhea in adolescents: a randomized controlled trial in Taiwan." ]

[ "A proof-of-concept study to assess the safety and efficacy of a traditional Chinese medicine formula as treatment for primary dysmenorrhea showed no statistically significant benefit over placebo. However, some efficacy parameters suggested possible superiority of the active treatment and so a larger study needs to be performed to determine whether this remedy has a role in the treatment of dysmenorrhea.", "Primary dysmenorrhea occurs in as many as 50% of female adolescents and is associated with significant decreases in academic performance, sports participation, and socialization with peers. Complementary and alternative medicine treatment options are of interest to patients and health care providers. The use of rose tea to alleviate menstrual pain has long been a part of folk knowledge around the world but has not been studied scientifically. To determine the effectiveness of drinking rose tea as an intervention for reducing pain and psychophysiologic distress in adolescents with primary dysmenorrhea, 130 female adolescents were randomly assigned to an experimental (n = 70) and a control (n = 60) group. Preintervention and postintervention data at 1 month, 3 months, and 6 months were gathered on the biopsychosocial outcomes of dysmenorrhea. The results showed that compared with the control group, the experimental group perceived less menstrual pain, distress, and anxiety and showed greater psychophysiologic well-being through time, at 1, 3, and 6 months after the interventions. Findings suggest that drinking rose tea is a safe, readily available, and simple treatment for dysmenorrhea, which female adolescents may take to suit their individual needs." ]

[ "17240233", "18041414", "16318970", "11169347" ]

[ "Does local anesthesia decrease pain perception in women undergoing amniocentesis?", "The efficacy of lidocaine-prilocaine cream to reduce pain in genetic amniocentesis.", "Reducing pain with genetic amniocentesis-A randomized trial of subfreezing versus room temperature needles.", "Does local anesthesia at mid-trimester amniocentesis decrease pain experience? A randomized trial in 220 patients." ]

[ "The null hypothesis is that local anesthesia does not decrease pain perception during amniocentesis.\n We performed a prospective randomized study comparing local anesthesia (1% lidocaine) with no anesthesia before amniocentesis in a racially diverse population. Immediately after the procedure, subjects were asked to assess their pain using both a Visual Analogue Scale and a 101-point Numerical Rating Scale.\n Two hundred four women were enrolled; 101 women received local, 102 women received no local, and 1 woman declined the amniocentesis after randomization. There was no difference in pain perception between the 2 groups as measured by either the visual analogue scale or the numeric rating scale (P = .28 and .18 respectively). The correlation coefficient between the 2 pain scales was strong with 0.86 for the local group and 0.92 for the no local group, (P < .001).\n Administration of local anesthesia before amniocentesis does not decrease maternal pain perception.", "Evaluate whether local anesthesia by lidocaine-prilocaine cream decreases maternal pain during mid-trimester genetic amniocentesis.\n This randomized controlled study of mid-trimester genetic amniocentesis was conducted between 1 October 2006 and 30 April 2007. Pregnant women were randomized to receive lidocaine-prilocaine cream or placebo cream 30 minutes prior to amniocentesis. Patients, blinded to allocation, recorded anticipated and actual pain before and after the procedure. The visual analog score (VAS) was evaluated, using a 0-10 scale.\n One hundred and twenty women participated in the present study. Sixty women were randomized to lidocaine-prilocaine group. The two groups were similar with respect to clinical correlations and procedure characteristics. Anticipated pain was 6.1 +/- 2.0 in the lidocaine-prilocaine group and 6.3 +/- 2.3 in the placebo group (p = 0.61). Actual pain was 2.3 +/- 2.2 in the lidocaine-prilocaine group and 2.9 +/- 2.5 in the placebo group (p = 0. 16).\n Lidocaine-prilocaine cream does not decrease pain during mid-trimester genetic amniocentesis.", "To determine whether pain associated with second trimester genetic amniocentesis is decreased by using subfreezing rather than room temperature needles.\n Subjects were randomized to a -14 degrees C or room temperature (20-22 degrees C) 22-gauge spinal needle. Patients, blinded to allocation, recorded anticipated and actual pain before and after the procedure, respectively, using a 0-10 visual analog scale with 0 = no pain and 10 = excruciating pain.\n Thirty-three subjects were randomized to room temperature and 29 subjects to subfreezing needles. Anticipated pain was similar in room temperature, 5.1 +/- 1.7, and subfreezing groups, 4.9 +/- 2.0, respectively (p = 0.6). Actual pain was also similar in the room temperature, 3.6 +/- 2.0, and subfreezing groups, 2.8 +/- 2.0, respectively (p = 0.14). Similar numbers of subjects in the room temperature and subfreezing groups reported less actual pain (20 vs. 18), greater actual pain (4 vs. 4) or no difference in pain (9 vs. 5) than anticipated (p = 0.6).\n A subfreezing 22-gauge spinal needle does not decrease perceived pain associated with second trimester genetic amniocentesis.", "To evaluate whether local anesthesia decreases patients' pain experience during mid-trimester amniocentesis.\n In a randomized trial, one group did not receive local anesthesia while, in another group, lignocaine 1% was injected subcutaneously prior to amniocentesis. Five different scoring systems were used to evaluate patients' pain experience.\n Two hundred and twenty women entered the study: 114 received local anesthesia, while 106 did not. The mean (SD) Visual Analog Scale was 1.4 (1.5) on a 0-10 scale (range 0-7.6). Some 97% of patients described the procedure as not painful or bearable, 79% had expected the procedure to be more painful and 59% reported the amniocentesis to have a comparable discomfort as venous blood sampling; 98% of women declared they would undergo an amniocentesis again if indicated. There were no statistical differences between both randomization groups.\n Mid-trimester amniocentesis is not a painful procedure. Local anesthesia does not affect pain experience during amniocentesis." ]

[ "9164365", "10359888", "3353895", "17359604", "4710748", "9192919", "10981523", "16136910", "12002728", "9074278", "11149991", "14656350", "6106739", "19650848", "12867606", "8732235", "9574889", "8454796", "7809773", "8596961", "8511730", "15480327", "6342456", "12728474", "16374022", "10697255", "7662102", "10629456", "9298177", "8814042", "12079502", "10520054", "7677828", "54740", "1629503", "9042633", "2253088", "12532114", "3041876", "3520626", "1560167", "7846339", "10452769", "7001667", "7001668", "7838620", "1789401" ]

[ "Continuous avoidance measures with or without acaricide in dust mite-allergic asthmatic children.", "House dust mite avoidance for children with asthma in homes of low-income families.", "Effect of house dust mite avoidance measures on adult atopic asthma.", "House dust mite allergen avoidance and self-management in allergic patients with asthma: randomised controlled trial.", "Use of laminar control device as adjunct to standard environmental control measures in symptomatic asthmatic children.", "Allergen reduction measures in houses of allergic asthmatic patients: effects of air-cleaners and allergen-impermeable mattress covers.", "The effect of high-efficiency and standard vacuum-cleaners on mite, cat and dog allergen levels and clinical progress.", "[The efficacy of controlling of house dusts in attacks of mite sensitive asthmatics].", "The effect of anti-allergic mattress encasings on house dust mite-induced early- and late-airway reactions in asthmatic patients. A double-blind, placebo-controlled study.", "Effects of Microstop-treated anti-mite bedding on children with mite-sensitive asthma.", "Eradication of house dust mite from homes of atopic asthmatic subjects: a double-blind trial.", "A randomized controlled trial of mite allergen-impermeable bed covers in adult mite-sensitized asthmatics.", "Controlled trial of an electrostatic precipitator in childhood asthma.", "Effect of improved home ventilation on asthma control and house dust mite allergen levels.", "Control of exposure to mite allergen and allergen-impermeable bed covers for adults with asthma.", "The respiratory effects of reduction of mite allergen in the bedrooms of asthmatic children--a double-blind controlled trial.", "Clinical effects of benzyl benzoate in the prevention of house-dust-mite allergy. Results of a prospective, double-blind, multicenter study.", "A double-blind, placebo controlled trial of solidified benzyl benzoate applied in dwellings of asthmatic patients sensitive to mites: clinical efficacy and effect on mite allergens.", "The effects of a single treatment of an acaricide, Acarosan, and a detergent, Metsan, on Der p 1 allergen levels in the carpets and mattresses of asthmatic children.", "Accumulation of house-dust mite (Der-p-1) levels on mattress covers.", "Double blind trial of ionisers in children with asthma sensitive to the house dust mite.", "Clinical effectiveness of a mite allergen-impermeable bed-covering system in asthmatic mite-sensitive patients.", "Preventive measures in mite asthma. A controlled trial.", "Effect of bedding control on amount of house dust mite allergens, asthma symptoms, and peak expiratory flow rate.", "Encasement of bedding does not improve asthma in atopic adult asthmatics.", "An evaluation of mattress encasings and high efficiency particulate filters on asthma control in the tropics.", "Efficacy of the acaricide: acardust for the prevention of asthma and rhinitis due to dust mite allergy, in children.", "Mechanical ventilation and high-efficiency vacuum cleaning: A combined strategy of mite and mite allergen reduction in the control of mite-sensitive asthma.", "Allergen-avoidance measures in homes of house-dust-mite-allergic asthmatic patients: effects of acaricides and mattress encasings.", "Effect of application of benzyl benzoate on house dust mite allergen levels.", "House dust mite barrier bedding for childhood asthma: randomised placebo controlled trial in primary care [ISRCTN63308372].", "Effects of house dust mite avoidance measures on Der p 1 concentrations and clinical condition of mild adult house dust mite-allergic asthmatic patients, using no inhaled steroids.", "House dust mite allergen avoidance: a randomized controlled trial of surface chemical treatment and encasement of bedding.", "Anti-mite measurements in mite-sensitive adult asthma. A controlled trial.", "Reducing domestic exposure to dust mite allergen reduces bronchial hyperreactivity in sensitive children with asthma.", "Effect of a bed covering system in children with asthma and house dust mite hypersensitivity.", "House dust mite allergen levels and an anti-mite mattress spray (natamycin) in the treatment of childhood asthma.", "Effect of mattress and pillow encasings on children with asthma and house dust mite allergy.", "Laminar flow air cleaner bed attachment: a controlled trial.", "Allergen avoidance in house dust mite sensitive adult asthma.", "Effective education of adults with asthma who are allergic to dust mites.", "Domiciliary air filtration units, symptoms and lung function in atopic asthmatics.", "Clinical effects of air cleaners in homes of asthmatic children sensitized to pet allergens.", "Effects of anti-mite measures on children with mite-sensitive asthma: a controlled trial.", "Effect of a change to mite-free bedding on children with mite-sensitive asthma: a controlled trial.", "Benzyl-benzoate foam: effects on mite allergens in mattress, serum and nasal secretory IgE to Dermatophagoides pteronyssinus, and bronchial hyperreactivity in children with allergic asthma.", "Efficacy of an air-cleaning device equipped with a high efficiency particulate air filter in house dust mite respiratory allergy." ]

[ "Improvement in the quality of life in the Western world and increased time spent indoors by children have enhanced the spread of house dust mites and increased the exposure time for sensitive children. Also, exposure to house dust mites in infancy and subsequent development of childhood asthma have been clinically linked. Recently, new acaricides have been developed.\n To test the efficacy of the new acaricide (esdepallethin and piperonyl butoxide--\"Acardust\") combined with environmental control compared with continuous house dust mite avoidance measures.\n Forty-six house dust mite-allergic, asthmatic children were evaluated for 6 months in a prospective, randomized, double-blind, and placebo-controlled study. Patients were randomly allocated to active and placebo acaricide treatment combined with avoidance measures, whereas only continuous avoidance measures were taken in the third group. Symptom score, medication usage, and peak flow measurements were recorded daily. The amount of house dust mite allergen in the dust vacuumed from the bedrooms was also measured.\n Morning and evening peak expiratory flow rates and forced expiratory volume in one second remained unchanged throughout the study period. In all groups, the symptom scores improved significantly, whereas the amount of house dust mite allergen decreased significantly at the end of the trial.\n Continuous house dust mite avoidance measures have a significant positive effect on the symptomology of children with mild or moderate asthma. \"Acardust\" combined with continuous house dust mite avoidance measures is not more effective than continuous house dust mite avoidance measures alone in the treatment of house dust mite-allergic, asthmatic children.", "Home exposure to high levels of house dust mite allergen has been shown to aggravate airways reactivity and asthma.\n The purpose of this study was to determine whether specific house dust mite control measures could reduce exposure levels and asthma severity.\n This double-blinded, randomized trial compared asthma progression over 1 year in children whose homes received standard environmental control intervention with those whose homes received aggressive intervention for dust mite elimination. The primary end point was doubling in PD20 methacholine.\n Symptom scores and quality-of-life scores were similar for the standard and aggressive intervention groups. PD20 methacholine doubling occurred in 9 members of the aggressive intervention group vs 4 control patients (P <.05). Dust mite levels decreased in the aggressive intervention homes compared with the standard intervention homes (P <.05).\n Aggressive dust mite intervention decreased dust mite levels and improved bronchial hyperresponsiveness.", "Twenty one adult patients with asthma, with positive skin test responses to the European house dust mite, Dermatophagoides pteronyssinus, were randomly allocated to a control group or to a group applying house dust mite avoidance measures. These included an initial application of liquid nitrogen to mattresses and bedroom carpets to kill the live house dust mite population. Histamine airway responsiveness, symptom scores, peak expiratory flow rates (PEF), and house dust mite numbers were determined during the two week pretrial and eight week trial periods. Nine patients in each group completed the study. By the end of the study there was a significant reduction in live mites in the \"avoidance\" group but not in the control group. The avoidance group showed a significant improvement in symptom scores measured on a linear analogue scale, in the number of hours each day spent wheezing (mean reduced from 8.6 to 4.5 hours), and in PEF (l/min) both in the morning (from 364 to 388) and in the evening (from 368 to 392). These changes were not found in the control group. The provocative concentration (PC) of histamine causing a 20% fall in FEV1 (PC20FEV1) had increased significantly in the avoidance group at eight weeks (from 0.58 to 2.3 mg/ml), whereas no change was seen in the control group (from 0.93 to 1.21 mg/ml). These results show that house dust mite avoidance, combined with initial killing of the mite by liquid nitrogen, diminishes airway responsiveness and improves asthma symptom control over an eight week period in adult asthmatic patients with house dust mite allergy.", "The efficacy of bed covers that are impermeable to house dust mites has been disputed.\n The aim of the present study was to investigate whether the combination of 'house dust mite impermeable' covers and a self-management plan, based on peak flow values and symptoms, leads to reduced use of inhaled corticosteroids (ICS) than self-management alone.\n Prospective, randomised, double blind, placebo-controlled trial.\n Primary care in a south-eastern region of the Netherlands.\n Asthma patients aged between 16 and 60 years with a house dust mite allergy requiring ICS were randomised to intervention and placebo groups. They were trained to use a self-management plan based on peak flow and symptoms. After a 3-month training period, the intervention commenced using house dust mite impermeable and placebo bed covers. The follow-up period was 2 years. Primary outcome was the use of ICS; secondary outcomes were peak expiratory flow parameters, asthma control, and symptoms.\n One hundred and twenty-six patients started the intervention with house dust mite impermeable or placebo bed covers. After 1 and 2 years, significant differences in allergen exposure were found between the intervention and control groups (P<0.001). No significant difference between the intervention and control groups was found in the dose of ICS (P = 0.08), morning peak flow (P = 0.52), peak flow variability (P = 0.36), dyspnoea (P = 0.46), wheezing (P = 0.77), or coughing (P = 0.41). There was no difference in asthma control between the intervention and control groups.\n House dust mite impermeable bed covers combined with self-management do not lead to reduced use of ICS compared with self-management alone.", "nan", "Recommendations for allergen avoidance or allergen reduction measures play an important part in the treatment of allergic asthmatic patients. The purpose of this study was to test recently developed air-cleaners with respect to their capacity to capture airborne allergen particles and to improve clinical parameters of asthmatic patients sensitized to aeroallergens. Forty five allergic asthmatic patients were studied in a double-blind procedure for 6 months. The patients were divided into three groups of 15 patients. In Group 1, the intervention consisted of the application of active air-cleaners in living-rooms and bedrooms. In Group 2, placebo air-cleaners were used in combination with allergen-impermeable mattress covers. In Group 3, the same intervention was performed as in Group 2 but with active air-cleaners. Allergen levels in mattress and floor dust were measured before, and 3 and 6 months after the interventions. After 6 months, the air-cleaners were dismantled and the filters were analysed for the amount of dust collected and allergen content. Immunological and lung function parameters were measured before, and 3 and 6 months after the interventions. Considerable amounts of airborne dust and allergenic particles were captured in the filters of the air-cleaners. Up to the 18.9 g of dust, 4,513 ng of house dust mite allergen, Der p 1, and 50,000 mU of cat allergen, Fel d 1, (in houses with cats) were collected by air-cleaners in living-rooms. Only in Group 3 (in which both active air-cleaners and mattress covers were used) was a small (less than 1 doubling dose) but statistically significant improvement of provocative concentration of histamine causing a 20% fall in forced expiratory volume in one second (PC20) observed (from 5.96 to 9.02 mg x mL(-1)). The amount of dust and house dust mite allergen collected in the filters was significantly correlated with an improvement of peak flow variation. In combination with other allergen avoidance measures, the examined air-cleaners can contribute to diminished allergen exposure and improvement of airway hyperresponsiveness in asthmatic patients.", "The major triggers for allergic asthma are exposure to allergens of the house dust mite, Dermatophagoides pteronyssinus, and of pets. Unfortunately studies of techniques designed to reduce house dust mite and pet allergens have had mixed results. However, new so-called 'improved' products continue to appear on the market and require subjective evaluation. The homes of 60 house dust mite-allergic patients were studied to compare the effects of high-efficiency and standard vacuum-cleaners on allergen concentration. Der p 1 (house dust mite), Fel d 1 (cat) and Can f 1 (dog) allergens were measured in four separate locations in each home. Clinical analysis was by lung function, bronchodilator usage and histamine challenge techniques. There was a significant reduction in Fel d 1 (ng/m2) in dust samples from the living-room carpet (p = 0.046), bedroom carpet (p = 0.003) and mattress (p = 0.013) and living-room sofa (p = 0.005) after 12 months of using the high-efficiency cleaners, but only in the mattress sample using the standard cleaners (p = 0.014). Can f 1 (ng/g dust) was reduced in the mattress sample after using the high-efficiency vacuum-cleaners (p = 0.028), but not at other sites. Der p 1 levels were not significantly changed over this period. Clinically, patients in the high-efficiency group showed improvements in peak expiratory flow rate (PEFR) (p = 0.004), FEV1 (p = 0.026) and bronchodilator usage (p = 0.005) after 12 months. When the cat-sensitive patients were analyzed separately, improvements in histamine PC20 (p = 0.039) were also seen. Reducing Fel d 1 concentrations, in the absence of any change in Der p 1 concentrations, can produce significant improvements in the lung function of atopic, asthmatic patients. This effect was primarily achieved in those patients with cat sensitivity, but who did not possess a cat themselves.", "To study the effect of controlling of house dusts in attacks of mite sensitive asthmatics (DMSA).\n Dust in mattresses, sofas, beddings and pillows were calculated for 43 cases of DMSA every season meanwhile the asthmatic symptoms, amount of drugs taken, PEF value in morning and evening were daily recorded by patients, then the patients were divided into two groups i.e. treatment group (A group, 22 cases) and no treatment group ( B group, 21 cases) randomly. The controlling measures included well-ventilation, washing clothes and bedclothes and catching dust frequently and exposing of clothing or bedclothes in the sun.\n Correlation was found between house dust density and asthmatic attacks. The number of dust mites was lower after treatment than before in A group [(N/g): spring 62 vs 103, summer 105 vs 132, autumn 163 vs 231, winter 9 vs 13]. Concomitant asthmatic symptoms and amount of drugs taken and total IgE reduced [(0.6 vs 1.6) mg/L] and PEF values or PEF difference improved.\n Control of dust mites growth could alleviate the asthmatic symptoms and decrease the attacks.", "Anti-allergic mattress encasing may provide clinical benefit in asthmatic patients. However, the effect of mattress encasings on allergen-specific parameters, such as bronchial reactions to house dust mite (HDM) challenge, is not clear.\n To investigate the effect of anti-allergic mattress encasings on allergen sensitivity in patients with moderate to severe asthma.\n Twenty-seven patients with asthma and HDM allergy were studied in a double-blind, placebo-controlled study. Concentrations of Dermatophagoides pteronyssinus (Der p 1) were measured in mattress dust before and after 1 year of treatment; bronchial histamine challenge, bronchial challenge with HDM and intradermal skin challenges with HDM were performed. The number of eosinophils in peripheral blood was assessed.\n In the active group, but not in the placebo group, there was a significant reduction in Der p 1 concentration in the dust collected from the mattresses after 1 year of treatment compared to before. There was a significant difference between the groups with respect to HDM-induced early-reaction (ER) in the airways and the number of blood eosinophils, which reflected an increase in ER and eosinophils in the placebo group without significant change in the active group. No significant improvement in PC20 histamine, late-reaction (LR) and skin tests was found in either groups.\n Our data suggest that encasings protect against a further increase in allergen sensitivity in asthmatic patients, so their use should be recommended.", "Seventy-one children with mite-sensitive asthma were randomly divided into three groups. Group 1 was comprised of 28 patients who were provided with new Microstop-treated bedding including matresses, quilts, pillows, bed linens and quilt covers. The Microstop mattresses and pillows were made of impermeable Polyurethane coated nylon ticking. Group 2 included 28 patients who were provided with new, conventional, mat Polyurethane mattresses, quilts, pillows, bed linens and quilt covers made of cotton and polyester which had not been Microstop treated. Group 3 included 15 patients who used their old bedding. Mite counts were performed on samples of dust collected from the old mattresses, pillows and quilts before the bedding was changed. After changing the bedding, mite counts were performed on dust from the same three bed sites at the end of months 1, 2, 3, 6, 9, and 12. Morning and evening peak expiratory flow, asthma symptom scores, were recorded by each patient at least 1 month before entering the study and every month during the one-year study period. Mattress mite counts were significantly reduced in Group 1 but not in Groups 2 or 3. However, quilt mite counts were significantly reduced in both Group 1 and Group 2 throughout the 12-monthstudy while mite counts in Group 3 quilts remained unchanged. The results provide evidence that the PU-coated nylon material was effective in reducing house dust mites, but do not demonstrate that the Microstop treatment had an obvious anti-mite effect. One-year follow-up of asthma symptom scores showed significant improvement in Group 1, but not in Groups 2 or 3. This suggests that the Microstop-treated bedding, as a system, was effective in asthma prevention.", "House dust mite (HDM) allergens can accumulate to very high levels in homes. From the observed sensitivity of HDMs to heat and their allergens to steam, a novel treatment of furnishings has been developed.\n We sought to determine whether combined steam and heat treatment of home furnishings reduced asthmatic patients' bronchial hyperreactivity (BHR) and lowered HDM antigen loads.\n The homes of 30 asthmatic subjects aged 18 to 45 years were randomly allocated into 3 groups. In groups 1 and 2 mattresses and duvets were treated with hot air (110 degrees C), followed by steam and then heat again. All their carpets were steam cleaned. Group 2 also had a special ventilation system installed above each patient's bedroom. The homes of subjects in group 3 were sham treated. Neither patient nor laboratory staff was aware of the types of treatment. Der p 1 and 2 levels in the household dust from the lounge, bedroom carpet, and beds were determined before and after treatment and then at 6 and 12 months. BHR, measured by using histamine PD(20) values, was recorded during the 4-week run-in period and at 3, 6, 9, 12 months after treatment.\n Active heat-steam treatment of homes caused a sustained reduction of Der p 1 (P =.003) and Der p 2 (P =.001) compared with no change in sham-treated group 3 homes. Patients whose homes were treated showed a 4-fold reduction in BHR at 9 months in group 1 and throughout the posttreatment period in group 2. No change was observed in the asthmatic subjects whose homes were not treated. These improvements were sustained for 12 months in the homes with bedroom ventilation units.\n A single treatment of home furnishings reduced mite allergen load to below the risk level for sensitization and improved the asthmatic patients' BHR by 4-fold.", "Mite-allergic patients with allergic disease should benefit from avoiding mite allergens. Many physicians, however, are yet to be convinced that allergen avoidance can make a significant contribution to asthma management in these patients. Many allergen-avoidance regimes include multiple measures of allergen reduction, but as mite exposure in the home is most likely to be greatest in bed dust, bedding is usually the first target for intervention.\n This study selected adult patients considered to be most likely to benefit from avoiding mite allergens, namely diagnosed asthmatics, sensitized to house dust mites and exposed to mite allergen in their mattresses. Patients were randomized into a placebo-controlled trial of the use of allergen-impermeable bed covers for 12 months, without any other form of mite-reduction measures.\n Adults with asthma were selected from general practices and asthma clinics in south-east London. Their serum IgE to mite allergens and allergen content of mattress dust samples were measured. Those with >0.70 kU/L mite-specific IgE and >2 microg/g Der p 1 were randomized into active or placebo treatments. Information was collected on allergic symptoms and medication use and quarterly peak flow diaries were kept throughout the trial. Dog or cat allergic patients were excluded if they had a pet at home to which they were sensitized.\n The mean decrease in microg/g Der p 1 was 25.7 (95% CI 8.9, 74.1) in the active group and 4.5 (95% CI 1.8, 11.5) in the placebo group. Der p 1 concentrations in the active and placebo groups at the end of the trial were not significantly different. There was no effect on peak flow or asthma symptoms in a simple comparison of the treatment and placebo groups.\n In this group of patients, mite allergen avoidance in the bed by the use of allergen-impermeable bedding alone cannot be recommended as an effective way of relieving asthma symptoms.", "A cross-over trial was conducted on 10 children with moderate to severe asthma, who had positive skin tests to Dermatophagoides pteronyssinus and nocturnal wheeze. An electrostatic precipitator was used during the night to remove airborne particles from the bedroom. During use of the precipitator peak expiratory flow rates were no better than in a control period.", "The warm, humid environment in modern homes favours the dust mite population, but the effect of improved home ventilation on asthma control has not been established. We tested the hypothesis that a domestic mechanical heat recovery ventilation system (MHRV), in addition to allergen avoidance measures, can improve asthma control by attenuating re-colonization rates.\n We conducted a randomized double-blind placebo-controlled parallel group trial of the installation of MHRV activated in half the homes of 120 adults with asthma, allergic to Dermatophagoides pteronyssinus. All homes had carpets steam cleaned and new bedding and mattress covers at baseline. The primary outcome was morning peak expiratory flow (PEF) at 12 months.\n At 12 months, the primary end-point; change in mean morning PEF as compared with baseline, did not differ between the MHRV group and the control group (mean difference 13.5 l/min, 95% CI: -2.6 to 29.8, P = 0.10). However, a secondary end-point; evening mean PEF, was significantly improved in the MHRV group (mean difference 24.5 l/min, 95% CI: 8.9-40.1, P = 0.002). Indoor relative humidity was reduced in MHRV homes, but there was no difference between the groups in Der p 1 levels, compared with baseline.\n The addition of MHRV to house dust mite eradication strategies did not achieve a reduction in mite allergen levels, but did improve evening PEF.", "The effectiveness of avoidance of house-dust-mite allergen (Dermatophagoides pteronyssinus 1 [Der p1]) in the management of asthma is uncertain.\n We conducted a double-blind, randomized, placebo-controlled study of allergen-impermeable bed covers involving 1122 adults with asthma. The primary outcomes were the mean morning peak expiratory flow rate over a four-week period during the run-in phase and at six months and the proportion of patients who discontinued inhaled corticosteroid therapy as part of a phased-reduction program during months 7 through 12. Der p1 was measured in mattress dust in a 10 percent random subsample of homes at entry and at 6 and 12 months.\n The prevalence of sensitivity to dust-mite allergen was 65.4 percent in the group supplied with allergen-impermeable bed covers (active-intervention group) and 65.1 percent in the control group supplied with non-impermeable bed covers. The concentration of Der p1 in mattress dust was significantly lower in the active-intervention group at 6 months (geometric mean, 0.58 microg per gram vs. 1.71 microg per gram in the control group; P=0.01) but not at 12 months (1.05 microg per gram vs. 1.64 microg per gram; P=0.74). The mean morning peak expiratory flow rate improved significantly in both groups (from 410.7 to 419.1 liters per minute in the active-intervention group, P<0.001 for the change; and from 417.8 to 427.4 liters per minute in the control group, P<0.001 for the change). After adjustment for base-line differences (by analysis of covariance), there was no significant difference between the groups in the peak expiratory flow rate at six months (difference in means, active-intervention group vs. control group, -1.6 liters per minute [95 percent confidence interval, -5.9 to 2.7] among all patients [P=0.46] and -1.5 liters per minute [95 percent confidence interval, -6.9 to 3.9] among mite-sensitive patients [P=0.59]). There was no significant difference between the groups in the proportion in whom complete cessation of inhaled corticosteroid therapy was achieved (17.4 percent in the active-intervention group and 17.1 percent in the control group) or in the mean reduction in steroid dose, either among all patients or among mite-sensitive patients.\n Allergen-impermeable covers, as a single intervention for the avoidance of exposure to dust-mite allergen, seem clinically ineffective in adults with asthma.\n Copyright 2003 Massachusetts Medical Society", "Inhalation of house dust mite (HDM) allergen may provoke attacks of asthma.\n We investigated whether a double-blind placebo-controlled community-based study aimed at reducing the HDM allergens in the bedrooms of HDM sensitive asthmatic children using the best methods available would prove beneficial to the children's health.\n The children (mean age 9.9 years, 34 boys) were recruited by a questionnaire submitted to 7386 families in a geographically-defined area of the UK. Subjects were chosen to take part in the double-blind placebo-controlled trial if they were asthmatic, skin sensitive to mites, and had mite allergen in their mattresses. Seventy children were randomly allocated to groups. In the active group, the children's bedrooms were treated with an acaricide (Acarosan) and the mattresses, pillows and duvets were encased in exclusion covers. The control group received placebo treatments.\n Forty-nine complete data sets were obtained. Applying bedding covers and Acarosan led to a median reduction of 480 ng (100%) in mite allergen on the mattress vs 215 ng (53%) reduction in placebo-treated group by 6 weeks. No evidence was found that the acaricide reduced mite allergen level. A change in bronchial reactivity to histamine was observed in the children after 6 weeks. This was not associated with any change in thrice-daily records of peak expiratory flow rate. By 24 weeks, the actively-treated children had improved forced expiratory volume in 1s (FEV1) and fewer required bronchodilator therapy or reported asthmatic symptoms than did the controls.\n The results suggest that mite removal procedures may modestly improve mite-sensitive asthmatics and could perhaps be of value in exceptionally mite-sensitive and/or highly mite-exposed individuals whose response to the attempted removal should be measured.", "The efficacy of the acaricide benzyl benzoate as an additive to a chemically and technically defined cleaning substance (Acarosan) was tested in a multicentric, prospective, randomized, controlled study on 118 outpatients with bronchial asthma due to house-dust-mite allergy. Subjective reports from patients and doctors revealed an improvement in clinical complaints in more than 50%, with only small differences between the verum and the placebo group. Objective parameters such as titrated skin tests, RAST, and bronchial challenge tests with histamine and Dermatophagoides pteronyssinus (D. pt.) did not reveal any significant changes either during the year of testing or between the two groups. A clinical improvement as observed in either group could not be assessed by objective parameters. Additional questions as to the merits of the possible prophylactic use of benzyl benzoate over more than 1 year remain unanswered.", "The aim of this double-blind, randomized study was to investigate the effectiveness of an acaricidal cleaning product in modifying both clinical symptoms and mite allergen levels over a period of at least 1 year.\n Twenty-six asthmatic patients with proven Dermatophagoides pteronyssinus (Dp) asthma were selected; three were withdrawn from the trial. The patients' homes were divided into two groups; 11 homes were treated with solidified benzyl benzoate and tenside agents (A), and 12 were treated with a placebo (P). Two applications were performed at the beginning of the trial and at least 6 months later. Patients were examined 1 month before the trial, at the beginning of the trial, and every 3 months over a period of 1 year. Indoor mite exposure was evaluated by three methods: semiquantitative guanine determinations, quantitative guanine determinations, and the measurement of Der p I + Der f 1 (antigen P, of Dp + antigen F1 of D. farinae) levels.\n The symptom scores established at the beginning of the trial and 12 months later showed a statistically significant improvement only in the A group (p < 0.01). The visual analog scale also showed a statistically significant difference both in the A (p < 0.05) and P groups (p < 0.01). No statistical differences were found between medication scores in the A or P groups. A statistically significant increase was also observed for forced expiratory volume in 1 second and maximal expiratory flow rate 25/75 in the two groups (p < 0.05 for P group; p < 0.01 for A group). The mean decreases in Der p I + Der f 1 in patient mattresses between the beginning of the trial and after 12 months were 20% for the acaricide group and 17% for the placebo group, respectively (NS). For house dust samples with origins other than the patients' mattresses we found significant decreases in Der p I+Der f 1 in the A group (p < 0.01 for carpets and p < 0.05 for upholstery elements).", "Baseline levels of the house-dust mite allergen, Der p 1, were measured on the carpets and mattresses of 60 pure-mite-sensitive asthmatic children in the Cape Peninsula, by means of an enzyme-linked immunosorbent assay (ELISA). High levels of mite allergens were recorded (range 2-50 micrograms Der p 1/g dust). In order to investigate the efficacy of the application of acaricides to carpets and bedding, 3 groups of 20 children were studied. Carpets and mattresses in group A were treated with a detergent, Metsan (Snowchem), and in group B with Metsan combined with the acaricide, Acarosan (Noristan). Group C was a control group in which no treatment was applied. The level of airway hyperreactivity (PC20) to histamine was measured at the beginning of the study and again 3 months after acaricide treatment. Significant reductions in carpet Der p 1 levels were achieved in group A (22.83 v. 13.26 micrograms Der p 1/g dust; P = 0.04) and group B (21.76 v. 13.26 micrograms Der p 1/g dust; P = 0.01), but mite levels were not reduced in any of the mattresses treated. There was also no improvement in airway hyperreactivity in any of the groups. This study clearly demonstrates that at present it is not possible to reduce Der p 1 antigen levels in mattresses in the Cape Peninsula with the available acaricides, even when one of these is combined with a detergent solution. Until strategies are developed which will significantly reduce Der p 1 levels in the bedding of sensitive individuals, a reduction in ongoing airway inflammation and airway hyperreactivity cannot be expected.", "Mattresses serve as a large reservoir for house-dust mite antigens and harbour the highest mite levels within the household. Mite reduction measures have previously been shown to be unsuccessful. The effect of mattress covers and acaracides on Der-p-1 levels in the mattresses of 60 patients with mite-allergic asthma was studied. Der-p-1 levels were measured using monoclonal antibodies (ELISA method). Baseline levels were recorded and re-assessed at 8-week intervals over a 6-month period. Patients were randomised into three equal groups. In group A mattresses were treated with Metsan (Snowchem) and benzylbenzoate only; group C had their mattresses covered with mattress covers (Allergy Control Products). Group B was the control group. We were unable to demonstrate any reduction of mite levels in the beds of all 3 groups. In fact all 3 groups demonstrated an increase in Der-p-1 levels over the study period, viz. group A (mean pre: 14.28, post: 34.18 micrograms/g dust); group C (mean pre: 8.26, post: 20.80 micrograms/g dust) and group B (mean pre: 18.21, post 38.47 micrograms/g dust). However, 12 patients in group C had their mattress covers washed in hot water at weekly intervals over a 5-week period at the end of the study. The results demonstrated a significant reduction in mite levels (mean pre: 41.95, post: 26.2 micrograms/g dust; P = 0.027). We therefore conclude that the use of mattress covers per se does not reduce Der-p-1 levels. The regular application of benzylbenzoate and Metsan does not prevent the accumulation of Der-p-1 on mattresses either.(ABSTRACT TRUNCATED AT 250 WORDS)", "Manufacturers of ionisers claim many benefits from the use of their devices, including the relief of asthma. Particles removed from the air are likely to include airborne allergens, so ionisers may achieve an effect by reducing the allergen load.\n The effect of ionisers on airborne concentrations of house dust mite allergen Der p I was investigated in a double blind, crossover, placebo controlled trial in the homes of 20 children with allergic asthma. Subjects recorded their peak expiratory flow rate (PEFR) twice daily and completed a daily symptom score and treatment schedule on a diary card for two six week periods, one with an active ioniser and the other with a placed ioniser (randomly allocated) used in the living room and the bedroom.\n Airborne Der p I concentrations fell significantly during the active period compared with the placebo period, but there was no significant change in PEFR, symptom scores, or treatment usage. There was an increase in night time cough which almost reached significance during the active period.\n This study indicates that the use of ionisers cannot be recommended in the homes of asthmatic subjects to improve their symptoms. The significant reduction of airborne allergen concentrations may be of use as part of a multidevice allergen avoidance regimen, but the increase in night time cough requires further study.", "Exposure to allergens plays a role in the development of bronchial hyperresponsiveness and in the chronic inflammatory response seen in asthmatic patients. House dust mites (HDMs) are an important source of allergen. Reduction of these allergens might lead to better lung function and reduction of asthma symptoms.\n The effect of HDM-impermeable covers on HDM allergen levels, peak flow values, and asthma symptoms were measured. Therefore a randomized clinical trial was carried out.\n Fifty-two allergic asthmatic patients were randomly allocated to use the HDM-impermeable or placebo covers. During the study period, daily peak flow and asthma symptom scores were recorded. Dust samples were taken from the mattresses.\n We observed a significant reduction in HDM allergen levels on the mattresses after encasing them with HDM-impermeable covers (reduction of 87% of Der p 1 in micrograms per gram of dust; P <.001). Baseline symptoms were so low that no improvement could be established. Morning peak expiratory flow is significantly higher in the intervention group compared with that seen in the placebo group during the study period (beta=20.2; P <.01).\n HDM-impermeable covers significantly decreased the level of HDM allergens. Furthermore, morning peak flow was significantly increased during the intervention period. This study indicates that HDM allergen-avoidance measures might have beneficial effects on allergen reduction and asthma outcome.", "To evaluate the effect of preventive measures 46 patients, all allergic to house-dust mites (Dermatophagoides spp.), were randomly allocated to a study and a control group. According to the patients' subjective recordings of symptom score and use of medicine, compared with the control group, the study group had improved. There was, however, no improvement when comparing the objective recordings of morning and evening peak flow and use of medicine, and it is concluded that the preventive measures in this programme are not very effective for patients allergic to house-dust mites. The reduction in indoor humidity in the study group was limited and, as a high indoor humidity is the cause of huge populations of house-dust mites in homes, it is emphasized that future programmes of preventive measures should focus more on damp problems, particularly those related to bad housing construction.", "This quasi-experimental study was designed to investigate the effect of bedding control on the amount of house dust mite (HDM) allergens, asthma symptoms, and peak expiratory flow rate (PEFR) in asthmatics sensitive to HDMs. The subjects in the study were drawn from patients receiving treatment at the allergy clinics of three university-affiliated hospitals in Seoul. Forty-two patients without prior practice of the bedding control used in this study were selected. They commonly showed bronchial asthma caused by HDMs, and exhibited strong positive points (more than 3 points) in skin prick test (D. farinae, D. pteronyssinus), and positive response in both fluoro-allergosorbent test (FAST), and PC20 methacholine test. Of the subjects, alternatively, 22 were assigned to the experimental group and 20 to control group. Bedding control consisted of the use of outer cotton covers, boiling them for 10 minutes fortnightly, and disinfecting bedding by sunlight fortnightly. The experimental group was under bedding control for 4 weeks. The data were collected from October 2000 to January 2001. The results were as follows: 1. After bedding control, the total amount of HDM allergens decreased significantly in the experimental group. However there was no significant difference in the decrease of the amount of HDM allergens between the two groups. 2. Of the asthma symptoms, there was significant difference only in the decrease of the frequency of dyspnea, and in the increase of sleeping disturbance between the two groups after bedding control. 3. After bedding control, PEFR increased in the experimental group whereas it decreased in the control group. However, neither change was significant. The above findings indicate that bedding control improved several asthma symptoms in asthmatics sensitive to HDMs. Accordingly, we suggest that bedding control is adopted as a useful nursing intervention in the field.", "We evaluated the impact of impermeable bed covers on asthma in asthmatics with clinically relevant house dust mite (HDM) sensitization.\n The study included 32 HDM-sensitized asthmatics in whom HDM allergy was considered as a significant factor in their asthma. They were randomized into either an intervention group whose bedding was encased with impermeable covers, or a control group who received cotton covers. Before and 3 and 6 months after encasement, dust samples were collected from the bedding and assayed for Der p 1. Clinical outcomes included quality of life, lung function, bronchial reactivity to methacholine, symptoms, medications and peak flow rates.\n Baseline Der p 1 levels in both the active and the placebo groups were comparable and high (19.2 vs 18.9 microg/g of dust). There was a significant reduction in Der p 1 levels in the active group after 6 months, but not in the placebo group (7.3 vs 21.9 microg/g of dust). Quality of life improved significantly in both the intervention and control groups, but there was no significant difference in the improvements between the groups. There was no significant change in lung function, symptoms, and requirements for medications.\n Encasement of bedding significantly reduced the Der p 1 levels. However, this was not sufficient to produce worthwhile clinical improvement in those in whom dust mite avoidance might well have been recommended as part of their clinical management.\n Copyright (c) 2006 S. Karger AG, Basel.", "The effect of two allergen avoidance modalities, Allergy Control Covers (ACC) and High Efficiency Particulate Filters (HEPA) on asthma control in children were evaluated. This was an open study involving 24 dust mite sensitive asthmatic children. Following a 4 week run-in period, the subjects were randomly allocated to use mattresses fitted with ACC (n = 6), HEPA filters in their bedrooms (n = 12) or act as controls (n = 6) for a study duration of 4 months. Measurements of the major Dermatophagoides spp. mite allergens, Der p 1 and Der f 1, levels in dust samples obtained from mattresses were made at baseline, 1, 2 and 4 months post implementation. Daily symptom scores including morning and evening peak flow readings, and monthly spirometry and exercise bronchoprovocation tests were carried out Our results showed that dust mite allergen levels in mattresses fell at 1 and 2 months post implementation in the ACC group (p<0.05). In contrast, no decrease in allergen levels was seen in the HEPA and control group. At the end of the 16 weeks, only the ACC group showed improvement in FEV1 and reduction in diurnal peak expiratory flow rate (p<0.05). Improvement in mean symptom scores was also observed for both the ACC and HEPA groups, but not the control groups (p<0.05). Although the numbers in this study were small, the results Indicate that the effectiveness on mite exposure barrier covers was short-lived, and the improvement in asthma control though documented was not obvious.", "A double blind, randomized, comparative study versus placebo, was done during 6 months in 32 children, aged 4-12 years, who suffer from either allergic asthma or rhinitis or both, slept in a bedroom rich in dust mite, have well documented allergy solely to house dust mite (H.D.M.), and a condition severe enough to require continuous medication. After thorough cleaning, their bedrooms were sprayed on day 0 and day 90 with the total content of a canister containing either Acardust or Placebo. Rooms were cleaned regularly throughout the study period. Each child completed an individual daily score card (scales from 0-3) for asthma, and rhinitis symptoms, medication taken, and any additional symptoms. Peak flow was recorded twice weekly. All the children were examined every month (at the clinic) when also PFF, FEVI, doctor's and patient's opinion of clinical symptoms were recorded according to the same scale (0-3) and dust samples from child's bedroom were examined for H.D.M. antigen content. At day 0, 90 and 180, total IgE and dust mite specific IgE determination was done. At the end of the study, patient's and doctor's opinion about the spray's efficacy were recorded on a scale from 0-3. The results were in favor of Acardust for asthma, according to patient's opinion (p = 0.001), doctor's opinion (p = 0.04) and individual score cards (p = 0.03), and for nasal secretion (p = 0.01), sneezing and lacrimation (p = 0.02); concurrent medication dropped significantly (p = 0.01) in the Acardust group. No side-effects were reported. We consider Acardust a safe and valuable preventive treatment in H.D.M. allergy.", "The relationship between exposure to house dust mite (HDM) allergens and prevalence of sensitization to these allergens in patients with asthma has been confirmed in many studies. Mite population growth is regulated by humidity. Reducing humidity and removing allergen by efficient vacuuming should control mite allergen and reduce symptoms.\n We sought to investigate the effect of mechanical ventilation and high-efficiency vacuuming on HDM numbers and Der p 1 concentrations in the homes of mite-sensitive asthmatic subjects and to evaluate the effect of any reductions on symptoms.\n The homes of 40 HDM-sensitive asthmatic subjects were randomized to receive (1) mechanical ventilation and a high-efficiency vacuum cleaner (HEVC); (2) mechanical ventilation alone; (3) an HEVC alone; and (4) no intervention. Homes and patients were monitored for 12 months. Change in absolute humidity, mite numbers, Der p 1 concentrations, lung function, bronchial hyperresponsiveness, and symptom scores were analyzed.\n Homes with mechanical ventilation achieved significantly lower humidity levels than those without (P <.001), with an associated reduction of mite numbers (P <.05) and Der p 1 concentrations (P <.001 ¿in nanograms per gram, P =.006 ¿in milligrams per square meter) in bedroom carpets and some other mite sources in the ventilated areas of the homes. The addition of a vacuum cleaner enhanced this effect. There was a trend for an improvement in histamine PC(20) (P =.085) in the patients whose homes were ventilated.\n The use of a mechanical ventilation system in suitable homes resulted in some reduction in numbers of HDM and Der p 1 concentrations. The addition of an HEVC slightly enhanced the effect but not sufficiently to see an improvement in symptoms.", "This double-blind, placebo-controlled study investigated whether the application of an acaricide (Acarosan) on mattresses and on textile floor coverings in living rooms and bedrooms can contribute to improvement in lung function and airway hyperresponsiveness in 40 adult asthmatic patients sensitized to house-dust mite. In a second group of 19 patients who refused chemical intervention, the clinical effects of application of allergen-impermeable mattress encasings were studied. In all three treatment groups, Der p 1 levels in mattress dust were statistically significantly decreased after 12 months. However, this decrease was much greater in the group who received mattress encasings (final mean level 430 ng/g) than in groups with acaricide- or placebo-treated mattresses (final mean levels 1730 and 2100 ng/g, respectively). Treatment of textile floors with either Acarosan or placebo chemical caused a statistically significant decrease in the level of the house-dust-mite allergen Der p1 in floor dust. In the group with mattress encasings, no significant changes of floor dust Der p 1 were found. Airway hyperresponsiveness (as measured by the PC20 histamine) improved significantly in the mattress cover group after 6 months. The Acarosan group also showed a small but statistically significant improvement after 12 months.", "Several acaricides have become available for reducing house dust mite allergen levels.\n The purpose of this study was to assess whether the use of benzyl benzoate (Acarosan) provides additional benefit to the usual mite control measures including encasement of mattress and pillows with vinyl covers.\n A randomized controlled trial was carried out in 26 homes (14 control versus 12 treatment) of asthmatic patients in two cities (Vancouver and Winnipeg). The control group had the usual house dust mite control measures including the use of vinyl covers for mattresses and pillows while the treatment group had application of benzyl benzoate to mattresses and carpets in the bedroom and the most commonly used room, in addition to the above control measures. Mite allergen levels were measured 3 months and immediately before, 1 week, and 1 and 3 months after the application of house dust mite control measures. Patients kept diary cards on asthma symptoms and peak expiratory flow rates morning and evening one month before and three months after the onset of mite allergen control measures.\n A reduction of mite allergen level was found in mattress samples in both groups, statistically significant at all times in the treatment group and at one and three months in the control group. Mite allergen levels on floor carpets also showed progressive reduction in both groups, but were significantly different in the treatment group (compared with controls) at 1 week, and were lower compared with baseline in the treatment group up to 3 months. No significant changes in asthma symptoms, peak expiratory flow rates, spirometric measurements, or bronchial hyperresponsiveness were observed among treatment or control group subjects.\n The addition of benzyl benzoate to conventional house dust mite control measures resulted in a significant reduction in floor carpet dust mite levels that persisted for 3 months. The results of this study should be confirmed in a larger and longer study.", "The house dust mite is the most important environmental allergen implicated in the aetiology of childhood asthma in the UK. Dust mite barrier bedding is relatively inexpensive, convenient to use, and of proven effectiveness in reducing mattress house dust mite load, but no studies have evaluated its clinical effectiveness in the control of childhood asthma when dispensed in primary care. We therefore aimed to evaluate the effectiveness of house dust mite barrier bedding in children with asthma treated in primary care.\n Pragmatic, randomised, double-blind, placebo controlled trial conducted in eight family practices in England. Forty-seven children aged 5 to 14 years with confirmed house dust mite sensitive asthma were randomised to receive six months treatment with either house dust mite barrier or placebo bedding. Peak expiratory flow was the main outcome measure of interest; secondary outcome measures included asthma symptom scores and asthma medication usage.\n No difference was noted in mean monthly peak expiratory flow, asthma symptom score, medication usage or asthma consultations, between children who received active bedding and those who received placebo bedding.\n Treating house dust mite sensitive asthmatic children in primary care with house dust mite barrier bedding for six months failed to improve peak expiratory flow. Results strongly suggest that the intervention made no impact upon other clinical features of asthma.", "Exposure to house dust mite (HDM) allergens often results in worsening of asthma. Therefore, avoidance of exposure to HDM allergens is often proposed. Unfortunately, the most effective and feasible avoidance strategy is still not completely assessed. Consequently, we investigated the effects of a combined HDM avoidance strategy on HDM allergen concentrations and clinical condition of allergic, mild asthmatic, patients using no inhaled steroids.\n Asthmatic patients, allergic to HDM, using no inhaled corticosteroids, were randomly allocated to an active (n = 76) or a placebo allergen-avoidance group (n = 81). Avoidance measures consisted of applying Acarosan(R) (placebo: water) to the living room and bedroom floors, and the use of HDM-impermeable covers for mattresses and bedding (placebo: cotton covers for mattresses only). Effects on allergen concentrations (Der p 1), FEV1, bronchial hyperresponsiveness, peak flow parameters and asthma symptom scores were studied during 20 weeks and controlled for the allergic status of the patients.\n The active covers reduced Der p 1 concentrations to 9.4% (P = 0.0001), and were always significant lower than in the placebo group (P = 0.0002). Acarosan(R) resulted in slight but significant decreases (twofold, P = 0.0001), both on living room and bedroom floors, but concentrations were never significantly lower than the placebo group. Although the combined avoidance strategy resulted in a considerable reduction in allergen load in the active group, no differences were seen between the two groups in any of the clinical parameters during the follow-up period in this group of allergic asthmatics, using no inhaled corticosteroids. Corrections for the allergic status did not alter these results.\n The combined avoidance strategy was effective in reducing HDM allergen concentration. This was especially achieved by the allergen-impermeable covers, while the effects of Acarosan(R) were only marginal. However, this allergen reduction was not reflected in a convincing improvement in clinical condition in this group of mild allergic asthmatics, using no inhaled steroids. Perhaps, a longer follow-up period would have resulted in more pronounced effects.", "To test the effectiveness of a house dust mite (HDM) allergen avoidance strategy we conducted a randomized controlled trial in 35 atopic subjects with asthma, aged 13 to 60 living in Sydney - a high HDM allergen environment. After a 3 month run-in period, subjects were randomized to active allergen avoidance treatment (n = 17) or placebo (n = 18) groups and followed for 6 months. The active treatment involved placing impermeable covers over the mattress, pillows and duvet and spraying the remaining bedding, as well as the carpets and furniture, with a tannic acid/acaricidal spray. Subjects kept a daily record of symptoms and peak expiratory flow rates and had 3 monthly assessments of lung function and airway hyperresponsiveness (AHR). Dust samples were collected from the bed, the bedroom floor and the living room floor at 3 monthly intervals and 2 weeks after the treatment. Mean HDM allergen levels at baseline at these sites were, in the active group, 15.5, 9.6 and 10.2 micrograms Der p I/g of fine dust, and, in the placebo group 25.7, 11.8 and 6.3 micrograms/g. Two weeks after the allergen avoidance treatment the HDM allergen level in the beds was reduced to 29% of baseline (95% CI 16-50%, P = 0.038 compared with placebo), but was not significantly different at 3 or 6 months. There was also no significant effect of the allergen avoidance treatment on symptom scores, peak flow variability, lung function or AHR P > 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)", "A cross-over controlled trial has been conducted among 32 adult patients with mite-sensitive asthma. The bedclothes and pillows of each subject were laundered and vacuum-cleaned and a plastic cover applied to the mattress for six weeks in an attempt to reduce exposure to mites. No improvement in daily peak-flow reading or drug usage was found in comparison with a control period.", "nan", "Allergen avoidance is regarded as an important approach to management of atopic asthma. The effect of Intervent bed covering systems on house dust mite (HDM) allergen exposure, asthma symptoms and markers of inflammation was investigated in 31 HDM sensitive asthmatic children. Dust concentrations of Dermatophagoides pteronyssinus allergen 1 (Der p 1) were monitored before and after covering the mattress, duvet and pillow with active and placebo covers for 3 months, in a single-blind, cross-over trial. Twice daily peak expiratory flow rate (PEFR), daily symptom scores and treatment schedule were recorded. Bronchial hyperresponsiveness was monitored by histamine challenge (provocative concentration of histamine causing a 20% fall in forced expiratory volume in one second (PC20)), and inflammation by measuring eosinophil cationic protein (ECP), eosinophil protein X (EPX), eosinophil peroxidase (EPO), and soluble interleukin-2 receptor (sIL-2R) in serum. There was a significant reduction in Der p 1 when the mattress, duvet and pillow were covered with the active bedding. There was no significant improvement in symptoms of asthma, PEFR, bronchodilator usage of PC20. Also, ECP, EPX, sIL-2R concentrations did not change for either treatment. EPO concentrations were significantly lower in the active compared to the placebo period. The active bed covers reduced retrievable Dermatophagoides pteronyssinus allergen 1 (Der p 1) from the bedding, with short term clinical benefit.", "Natamycin, a fungicide marketed as Tymasil, is claimed to reduce house dust mite numbers and would therefore be expected to improve asthma in children with mite sensitivity. We have tested this assertion by a double-blind, placebo-controlled trial. There was no significant effect on levels of Der p I in mattress dust between active and placebo groups at the end of the spraying period. Histamine inhalation challenge PC20, clinic visit symptom scores and lung function tests reflecting either large or small airways obstruction were also unchanged. Therefore this product is not a therapeutic option for mite-allergic patients using the manufacturer's recommended dose and method of administration. Other factors influencing the Der p I levels were also investigated. Of these, only month of measurement and bedroom wall humidity showed any association.", "House dust mite (HDM) allergy is a frequent cause of allergic asthma in children. Reduction of exposure seems to be the most logical way to treat these patients.\n Our aim was to investigate whether mattress and pillow encasings resulted in an effective long-term control of HDM allergen levels, thereby reducing the need for asthma medication in children with asthma and HDM allergy.\n In a prospective, double-blind, placebo-controlled study 60 children (age range, 6-15 years) with asthma and HDM allergy were randomized to active (allergy control) or placebo mattress and pillow encasings. After a 2-week baseline period, follow-up was performed every 3 months for 1 year. During the entire study period, the dose of inhaled steroids was tapered off to the lowest effective dose according to well-defined criteria.\n Fifty-two patients completed the trial, and 5 were excluded, leaving data from 47 children (26 in the active treatment group and 21 in the placebo group) for analysis. A significant perennial reduction in HDM allergen concentrations was seen only for the active treatment group. Also, a significant decrease in the dose of inhaled steroids (mean, 408 to 227 microg/d; P <.001) was found for the active treatment group only, with significant differences between groups after 9 and 12 months. After 1 year, the dose of inhaled steroids was reduced by at least 50% in significantly more children in the active treatment group than in the placebo group (73% vs 24%, P <.01).\n Encasing of mattresses and pillows resulted in a significant long-term reduction in HDM allergen concentrations in mattresses and in the need for inhaled steroids in children with asthma and HDM allergy.", "Thirteen house dust mite-allergic young asthmatics were entered into a double-blind, crossover clinical trial to compare \"in use\" with \"non-use\" of a laminar flow air cleaner bed attachment. The study design encouraged maintenance of symptom control by adjustment of the dose of medications used. There was a significant reduction in the amount of medications required by the patients during the trial period that the air cleaner was in use. Histamine airway responsiveness was significantly decreased for a group of eight of the subjects tested at the end of a 3-month open trial.", "Fifty adult asthmatic patients with strongly positive skinprick tests to the house dust mite were admitted into a prospective randomised controlled trial of house dust mite avoidance in the community. Twenty-two of the experimental group completed one year of dust avoidance and 19 of these tolerated the use of plastic mattress and pillow covers. Twenty of the control group (who did not alter their housecleaning habits) also completed one year of study. A fall in mite and dust levels was noted in the homes of the experimental but not the control group. Fifteen of the experimental group who completed the study were strongly RAST positive (score 3 or more) to the house dust mite. These patients had a significant improvement in FEV1/FVC, PEFR, PC20, use of treatment, and symptom score at one year, whilst the seven experimental patients who were not strongly RAST positive (score 2 or less) did not, suggesting that the change noted in the former patients was not merely due to a placebo effect. Fifteen of the control group who completed the study were also strongly RAST positive for the house dust mite and these patients showed no change in any of the parameters. This study demonstrates that adult asthmatic patients can successfully carry out house dust eradication procedures in the community over a long period of time, and that those patients who are allergic to the house dust mite appear to have both subjective and objective improvement in their asthma.", "The effects of supplementary computer instruction in house dust mite-avoidance measures on adherence to implementing measures, on home dust mite-allergen levels, and on symptomatology were investigated in 52 adult patients with mite-associated asthma. Twenty-six patients received conventional instruction (counseling and written instruction) and the other 26 patients received conventional plus 22 minutes of interactive computer-assisted instruction. Instructions were aimed at mite-avoidance measures. Pre- and postinstruction dust samples were collected, and adherence was monitored. All patients kept symptom diaries twice a day. Patients' progress was followed for 12 weeks, and all patients completed the study. Adherence, number of observed and self-reported mite-avoidance measures implemented after visit, was higher for the computer group (p = 0.023). The computer-instructed group achieved significantly lower levels of mite allergen in bedroom carpets (p = 0.004) with mean levels of mite allergen declining from 6.5 +/- 7.6 to 2.2 +/- 4.3 micrograms/gm of dust (two-site monoclonal antibody assays), whereas levels for the conventional-instructed group did not change. Moreover, by study weeks 9 and 10, the computer-instructed group was significantly less symptomatic (p = 0.033). Mean symptom scores for this group decreased from 12.4 to 7.7, compared with 16.4 to 14.3. Conventional instruction supplemented with computer instruction is suggested in mite education.", "Air infiltration units (AFUs) incorporating a high efficiency particulate air filter are theoretically able to remove almost all potential airborne allergens. This may have implications for subjects with allergic lower respiratory disease. AFUs were placed in the living room of 12 atopic asthmatics, and the internal filters were inserted and removed in a double-blind fashion. No difference in subjective symptom scoring, spirometry or bronchial reactivity was demonstrated. Peak expiratory flow rate (PEFR) variability was significantly improved from baseline readings, and there was a trend towards higher mean PEFRs when the filters were present in the AFU. Trends towards lower levels of airborne micro-organisms were also demonstrated when the filters were present, however no effect upon total airborne dust and airborne Der pI could be demonstrated.", "Exposure to cat and dog allergens is very common in the Western World and is a serious cause of asthma in sensitized subjects.\n We sought to study the clinical effects of air cleaners in living rooms and bedrooms of asthmatic children sensitized to cat or dog allergens.\n Twenty asthmatic children sensitized to pet allergens (cat/dog) and with an animal at home participated in a double-blind, placebo-controlled, cross-over study in which the effects of air cleaners placed in the living room and bedroom for 3 months were compared with the effects of sham air cleaners. Before and after each study period, lung function, airway hyperresponsiveness (adenosine monophosphate), and peak flow variation were recorded. Cat and dog allergen levels were assessed in the filters of the air cleaners.\n After a 3-month intervention with active air cleaners, airway hyperresponsiveness decreased significantly, showing a 1.2 doubling dose increase of PC(20 )adenosine (P =.003). Peak flow amplitude also decreased (P =. 045). Substantial amounts of airborne cat and dog allergen were captured by the air cleaners in living rooms and bedrooms as well. Allergen levels in floor dust were not changed.\n In young asthmatic patients sensitized and exposed to pets in the home, application of air cleaners in living rooms and bedrooms was accompanied by a significant improvement in airway hyperresponsiveness and a decrease in peak flow amplitude.", "Mite counts and tests for mite antigen were performed on samples of dust taken from the bedding of 53 children with mite-sensitive asthma. The samples from damp houses and the beds or enuretic children had markedly more mites and mite-antigen than those from dry houses. although the predominant species was usually Dermatophagoides pteronyssinus, some of the beds in the damp houses were heavily infested with another pyroglyphid mite Euroglyphus maynei, so that this was the species found in the greatest numbers. D pteronyssinus antigen was found to be correlated broadly with the total mite count, but more antigen was present for a given number of mites in the mattresses than in the blankets. The children were randomly allocated into two groups, one of which carried out rigorous anti-mite measures. The amounts of dust and mite antigen were reduced, though not the numbers of mites. Peak flow readings were monitored in the two groups for eight weeks and a final assessment made by a paediatrician who was unaware of the allocation of each patient in the trial. No significant differences emerged in the progress of the two groups, both tending to improve. Measures designed to remove mites from bedding do not greatly benefit the majority of children with mite-sensitive asthma.", "Twenty-one children with mite-sensitive asthma took part in a crossover randomised controlled trial of mite-free bedding. Each child was issued with a new sleeping bag and pillow for a month, and twice-daily peak flow readings were compared with those obtained during a month in the child's ordinary bedding. Seventeen of the children had higher mean peak flow readings during the period in the mite-free bedding (p < 0.01). The overall improvement was only modest, however, and some mites had appeared in most of the bedding by the end of the trial. New bedding may be helpful to patients with mite-sensitive asthma, but methods are needed to prevent colonisation by mites.", "Home mattresses of 24 asthmatic children with house dust mite allergy were sprayed with either benzyl-benzoate foam or placebo in a double blind fashion, 10 days before the children left the residential house for asthmatic children Istituto Pio XII (located in the Italian Alps in an environment free of mites) and went back to their own home for the Christmas and Easter holidays. A further group of 8 children, whose mattresses received no treatment, was kept as an absolute control. Two days after spraying, benzyl-benzoate or placebo were vacuumed from the mattresses. Acarex test was performed immediately before spraying and at the end of each holiday period of 20 and 10 days, respectively. Bronchial hyperreactivity as well as serum and nasal secretory specific IgE for Dermatophagoides pteronyssinus were assessed in all children immediately before leaving and within 48 hr after returning to the residential house. The results of the study show that sprayed benzyl-benzoate foam was no more effective than placebo in reducing the level of house dust mite recovered from patients' mattresses, or in reducing bronchial hyperreactivity and IgE concentration in serum and nasal secretions.", "The efficacy of an air-cleaning device equipped with a high efficiency particulate air (HEPA) filter (without further avoidance measures) was studied in patients allergic to house dust mite. The effects of the air-cleaner on indoor Dermatophagoides sp. levels, symptom score and bronchial hyperresponsiveness in nine mite-allergic patients were assessed using a cross-over controlled study. No significant effect was demonstrated on indoor Dermatophagoides sp. levels when comparing the period of air-cleaner activity (2 months) with the control period (2 months). The Dermatophagoides sp. levels in the houses studied were lower than the risk level for asthmatic attacks, making it difficult to assess any effect on asthma; however, neither bronchial hyperresponsiveness nor rhinitis symptom score were changed by air-cleaner activity. During the trial period, however the mean level of Dermatophagoides sp. allergen in the houses changed spontaneously from 4.4 micrograms/g (mean level in the first 2 trial months) to 1.75 micrograms/g of dust (second 2 months) (P less than 0.05). Owing to this change, the mean rhinitis symptom score also decreased (P less than 0.05), even if no significant correlation was demonstrated (r = 0.4 P = 0.089). HEPA filter air-cleaners appear insufficient as substitutes for standard avoidance measures in mite allergic patients." ]

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[ "Effect of infection control measures on the frequency of upper respiratory infection in child care: a randomized, controlled trial.", "Proper handwashing promotes wellness in child care.", "A randomized, controlled trial of a multifaceted intervention including alcohol-based hand sanitizer and hand-hygiene education to reduce illness transmission in the home.", "Evaluation of control measures implemented in the severe acute respiratory syndrome outbreak in Beijing, 2003.", "The effect of hand hygiene on illness rate among students in university residence halls.", "Reducing absenteeism from gastrointestinal and respiratory illness in elementary school students: a randomized, controlled trial of an infection-control intervention.", "Alcohol-free instant hand sanitizer reduces elementary school illness absenteeism.", "[Effectiveness of personal protective measures in prevention of nosocomial transmission of severe acute respiratory syndrome].", "Evaluation of a handwashing intervention to reduce respiratory illness rates in senior day-care centers.", "Nosocomial respiratory syncytial virus infections: the cost-effectiveness and cost-benefit of infection control.", "Which preventive measures might protect health care workers from SARS?", "Dispersal of respiratory droplets with open vs closed oxygen delivery masks: implications for the transmission of severe acute respiratory syndrome.", "Prospective controlled study of four infection-control procedures to prevent nosocomial infection with respiratory syncytial virus.", "Why did outbreaks of severe acute respiratory syndrome occur in some hospital wards but not in others?", "Reduction of illness absenteeism in elementary schools using an alcohol-free instant hand sanitizer.", "Impact of an infection control program in a specialized preschool.", "Preliminary findings of a randomized trial of non-pharmaceutical interventions to prevent influenza transmission in households.", "Effect of handwashing on child health: a randomised controlled trial.", "Prevention of upper respiratory tract infections by gargling: a randomized trial.", "Healthy Hands: Use of alcohol gel as an adjunct to handwashing in elementary school children.", "Handwashing education can decrease illness absenteeism.", "Evaluation of an hygienic intervention in child day-care centers.", "Interruption of experimental rhinovirus transmission.", "Rapid awareness and transmission of severe acute respiratory syndrome in Hanoi French Hospital, Vietnam.", "Effectiveness of a training program in reducing infections in toddlers attending day care centers.", "Modes of transmission of respiratory syncytial virus.", "Adverse skin reactions to personal protective equipment against severe acute respiratory syndrome--a descriptive study in Singapore.", "[Hand-hygiene and sickness among small children attending day care centers. An intervention study].", "Factors associated with transmission of severe acute respiratory syndrome among health-care workers in Singapore.", "The use of gowns and masks to control respiratory illness in pediatric hospital personnel.", "Screening for respiratory syncytial virus and assignment to a cohort at admission to reduce nosocomial transmission.", "Two randomized controlled trials of virucidal nasal tissues in the prevention of natural upper respiratory infections.", "Effect of a comprehensive infection control program on the incidence of infections in long-term care facilities.", "Prevention of nosocomial transmission of respiratory syncytial virus in a newborn nursery.", "Using an integrated infection control strategy during outbreak control to minimize nosocomial infection of severe acute respiratory syndrome among healthcare workers.", "Exploration of the effectiveness of social distancing on respiratory pathogen transmission implicates environmental contributions.", "Use of surgical face masks to reduce the incidence of the common cold among health care workers in Japan: a randomized controlled trial.", "Impact of non-pharmaceutical interventions on URIs and influenza in crowded, urban households.", "Risk factors for SARS among persons without known contact with SARS patients, Beijing, China.", "Face mask use and control of respiratory virus transmission in households.", "Scheduled hand washing in an elementary school population.", "SARS transmission, risk factors, and prevention in Hong Kong.", "Nosocomial respiratory syncytial virus infection: impact of prospective surveillance and targeted infection control.", "Nosocomial respiratory syncytial viral infections. Should gowns and masks be used?", "Respiratory syncytial virus (RSV) infection rate in personnel caring for children with RSV infections. Routine isolation procedure vs routine procedure supplemented by use of masks and goggles.", "Prevention of nosocomial respiratory syncytial virus infections through compliance with glove and gown isolation precautions.", "Cohorting of infants with respiratory syncytial virus.", "Surgical mask vs N95 respirator for preventing influenza among health care workers: a randomized trial.", "Handwashing and cohorting in prevention of hospital acquired infections with respiratory syncytial virus.", "Influence of school closure on the incidence of viral respiratory diseases among children and on health care utilization.", "Entry screening to delay local transmission of 2009 pandemic influenza A (H1N1).", "Facemasks and hand hygiene to prevent influenza transmission in households: a cluster randomized trial.", "Protecting healthcare staff from severe acute respiratory syndrome: filtration capacity of multiple surgical masks.", "Efficacy of organic acids in hand cleansers for prevention of rhinovirus infections.", "Interruption of transmission of rhinovirus colds among human volunteers using virucidal paper handkerchiefs.", "Efficacy of virucidal nasal tissues in interrupting familial transmission of respiratory agents. A field trial in Tecumseh, Michigan.", "Gowning does not affect colonization or infection rates in a neonatal intensive care unit.", "Handwashing and respiratory illness among young adults in military training.", "Mask use, hand hygiene, and seasonal influenza-like illness among young adults: a randomized intervention trial.", "Effectiveness of precautions against droplets and contact in prevention of nosocomial transmission of severe acute respiratory syndrome (SARS).", "The use of eye-nose goggles to control nosocomial respiratory syncytial virus infection." ]

[ "Acute upper respiratory infections are common in children who attend child care, and preventing transmission of disease in this setting depends on actions by child care staff. We set out to discover whether transmission of respiratory infections in child care could be reduced by improved infection control procedures.\n We performed a cluster, randomized, controlled trial of an infection control intervention conducted in child care centers in 1 city in Australia. The intervention was training of child care staff about transmission of infection, handwashing, and aseptic nosewiping technique. Implementation of the intervention was recorded by an observer. Illness was measured by parent report in telephone interviews every 2 weeks.\n There were 311 child-years of surveillance for respiratory symptoms. By multivariable analysis, there was no significant reduction in colds in intervention center children across the full age range. However, a significant reduction in respiratory illness was present in children 24 months of age and younger. When compliance with infection control practices was high, colds in these children were reduced by 17%.\n This trial supports the role of direct transmission of colds in young children in child care. The ability of infection control techniques to reduce episodes of colds in children in child care was limited to children 24 months of age and under.", "The purpose was to determine the effectiveness of an instructional program on handwashing. The hypothesis stated that an instructional program on germs and handwashing in child care could significantly reduce the spread of infectious diseases in the test center.\n A longitudinal study was conducted in a field setting with a test group and a control group of 3- to 5-year-old children and their teachers in two similar child care settings. For 21 weeks illnesses and symptoms of infectious diseases were assessed with a health assessment checklist. The test group received a developmentally appropriate instructional program on germs and handwashing. The teachers in the test group attended workshops on infectious diseases and handwashing. The control group maintained their usual handwashing procedures.\n At weeks 1 through 11 benchmark data were collected. At weeks 12 through 21, peak cold and flu season, the test group had significantly fewer colds than the control group (chi-squared analysis, 4.338, 1 df, p < .05); thus the hypothesis was confirmed.\n Handwashing has been recognized as one way to manage the spread of infectious diseases in child care centers. Handwashing helped to reduce colds at the test center where frequent and proper handwashing practices were incorporated into the curriculum through an intervention program.", "Good hand hygiene may reduce the spread of infections in families with children who are in out-of-home child care. Alcohol-based hand sanitizers rapidly kill viruses that are commonly associated with respiratory and gastrointestinal (GI) infections. The objective of this study was to determine whether a multifactorial campaign centered on increasing alcohol-based hand sanitizer use and hand-hygiene education reduces illness transmission in the home.\n A cluster randomized, controlled trial was conducted of homes of 292 families with children who were enrolled in out-of-home child care in 26 child care centers. Eligible families had > or =1 child who was 6 months to 5 years of age and in child care for > or =10 hours/week. Intervention families received a supply of hand sanitizer and biweekly hand-hygiene educational materials for 5 months; control families received only materials promoting good nutrition. Primary caregivers were phoned biweekly and reported respiratory and GI illnesses in family members. Respiratory and GI-illness-transmission rates (measured as secondary illnesses per susceptible person-month) were compared between groups, adjusting for demographic variables, hand-hygiene practices, and previous experience using hand sanitizers.\n Baseline demographics were similar in the 2 groups. A total of 1802 respiratory illnesses occurred during the study; 443 (25%) were secondary illnesses. A total of 252 GI illnesses occurred during the study; 28 (11%) were secondary illnesses. The secondary GI-illness rate was significantly lower in intervention families compared with control families (incidence rate ratio [IRR]: 0.41; 95% confidence interval [CI]: 0.19-0.90). The overall rate of secondary respiratory illness was not significantly different between groups (IRR: 0.97; 95% CI: 0.72-1.30). However, families with higher sanitizer usage had a marginally lower secondary respiratory illness rate than those with less usage (IRR: 0.81; 95% CI: 0.65-1.09).\n A multifactorial intervention emphasizing alcohol-based hand sanitizer use in the home reduced transmission of GI illnesses within families with children in child care. Hand sanitizers and multifaceted educational messages may have a role in improving hand-hygiene practices within the home setting.", "Beijing, China, experienced the world's largest outbreak of severe acute respiratory syndrome (SARS) beginning in March 2003, with the outbreak resolving rapidly, within 6 weeks of its peak in late April. Little is known about the control measures implemented during this outbreak.\n To describe and evaluate the measures undertaken to control the SARS outbreak.\n Data were reviewed from standardized surveillance forms from SARS cases (2521 probable cases) and their close contacts observed in Beijing between March 5, 2003, and May 29, 2003. Procedures implemented by health authorities were investigated through review of official documents and discussions with public health officials.\n Timeline of major control measures; number of cases and quarantined close contacts and attack rates, with changes in infection control measures, management, and triage of suspected cases; and time lag between illness onset and hospitalization with information dissemination.\n Health care worker training in use of personal protective equipment and management of patients with SARS and establishing fever clinics and designated SARS wards in hospitals predated the steepest decline in cases. During the outbreak, 30 178 persons were quarantined. Among 2195 quarantined close contacts in 5 districts, the attack rate was 6.3% (95% confidence interval [CI], 5.3%-7.3%), with a range of 15.4% (95% CI, 11.5%-19.2%) among spouses to 0.36% (95% CI, 0%-0.77%) among work and school contacts. The attack rate among quarantined household members increased with age from 5.0% (95% CI, 0%-10.5%) in children younger than 10 years to 27.6% (95% CI, 18.2%-37.0%) in adults aged 60 to 69 years. Among almost 14 million people screened for fever at the airport, train stations, and roadside checkpoints, only 12 were found to have probable SARS. The national and municipal governments held 13 press conferences about SARS. The time lag between illness onset and hospitalization decreased from a median of 5 to 6 days on or before April 20, 2003, the day the outbreak was announced to the public, to 2 days after April 20 (P<.001).\n The rapid resolution of the SARS outbreak was multifactorial, involving improvements in management and triage in hospitals and communities of patients with suspected SARS and the dissemination of information to health care workers and the public.", "Several studies have indicated a connection between hand sanitization and infection control in numerous settings such as extended care facilities, schools, and hospitals. The purpose of this study was to assess the effectiveness of both a hand-hygiene message campaign and the use of an alcohol gel hand sanitizer in decreasing the incidence of upper-respiratory illness among students living in university residence halls.\n This study involved a total of 430 students recruited from 4 residence halls during the fall semester at the University of Colorado at the Boulder campus. Dormitories were paired into control and product groups. In the product groups, alcohol gel hand-sanitizer dispensers were installed in every room, bathroom, and dining hall. The data were statistically analyzed for the differences between product and control groups in reported symptoms, illness rates, and absenteeism from classes.\n The overall increase in hand-hygiene behavior and reduction in symptoms, illness rates, and absenteeism between the product group and control group was statistically significant. Reductions in upper respiratory-illness symptoms ranged from 14.8% to 39.9%. Total improvement in illness rate was 20%. The product group had 43% less missed school/work days.\n Hand-hygiene practices were improved with increased frequency of handwashing through increasing awareness of the importance of hand hygiene, and the use of alcohol gel hand sanitizer in university dormitories. This resulted in fewer upper respiratory-illness symptoms, lower illness rates, and lower absenteeism.", "Students often miss school because of gastrointestinal and respiratory illnesses. We assessed the effectiveness of a multifactorial intervention, including alcohol-based hand-sanitizer and surface disinfection, in reducing absenteeism caused by gastrointestinal and respiratory illnesses in elementary school students.\n We performed a school-based cluster-randomized, controlled trial at a single elementary school. Eligible students in third to fifth grade were enrolled. Intervention classrooms received alcohol-based hand sanitizer to use at school and quaternary ammonium wipes to disinfect classroom surfaces daily for 8 weeks; control classrooms followed usual hand-washing and cleaning practices. Parents completed a preintervention demographic survey. Absences were recorded along with the reason for absence. Swabs of environmental surfaces were evaluated by bacterial culture and polymerase chain reaction for norovirus, respiratory syncytial virus, influenza, and parainfluenza 3. The primary outcomes were rates of absenteeism caused by gastrointestinal or respiratory illness. Days absent were modeled as correlated Poisson variables and compared between groups by using generalized estimating equations. Analyses were adjusted for family size, race, health status, and home sanitizer use. We also compared the presence of viruses and the total bacterial colony counts on several classroom surfaces.\n A total of 285 students were randomly assigned; baseline demographics were similar in the 2 groups. The adjusted absenteeism rate for gastrointestinal illness was significantly lower in the intervention-group subjects compared with control subjects. The adjusted absenteeism rate for respiratory illness was not significantly different between groups. Norovirus was the only virus detected and was found less frequently on surfaces in intervention classrooms compared with control classrooms (9% vs 29%).\n A multifactorial intervention including hand sanitizer and surface disinfection reduced absenteeism caused by gastrointestinal illness in elementary school students. Norovirus was found less often on classroom surfaces in the intervention group. Schools should consider adopting these practices to reduce days lost to common illnesses.", "BACKGROUND AND HYPOTHESES: A substantial percentage of school absenteeism among children is related to transmissible infection. Rates of transmission can be reduced by hand washing with soap and water, but such washing occurs infrequently. This study tested whether an alcohol-free instant hand sanitizer (CleanHands) could reduce illness absenteeism in school-age children.\n A 10-week, open-label, crossover study was performed on 420 elementary school-age children (ages 5-12). Students were given a brief orientation immediately prior to the start of the study on the relationship of germs, illness, and hand washing. Each student in the treatment group then received the test product in individual bottles, with instructions to apply one to two sprays to the hands after coming into the classroom, before eating, and after using the restroom, in addition to their normal hand washing with soap and water. The control group was instructed to continue hand washing as normal with non-medicated soap. After 4 weeks of treatment and a 2-week wash-out period, the control and experimental groups were reversed. Data gathered on absenteeism were classified as gastrointestinal or respiratory related and normalized for nonillness-related absenteeism and school holidays.\n Compared to the hand washing-only control group, students using CleanHands were found to have 41.9% fewer illness-related absence days, representing a 28.9% and a 49.7% drop in gastrointestinal- and respiratory-related illnesses, respectively. Likewise, absence incidence decreased by 31.7%, consisting of a 44.2% and 50.2% decrease in incidence of gastrointestinal- and respiratory-related illnesses, respectively. No adverse events were reported during the study.\n Daily use of the instant hand sanitizer was associated with significantly lower rates of illness-related absenteeism.", "To evaluate the effectiveness of personal protective measures of health care workers (HCWs) against severe acute respiratory syndrome (SARS).\n A case-control study from ten hospitals in Guangdong, with 180 non-infected and 77 infected staff members that accessed the isolation unit every day, and participated in direct first aid for severe SARS patients. All participants were surveyed about how they were using personal protective equipment (PPE), protective drugs and hygiene habits when caring for patients with SARS. Statistical analysis was done with either chi(2) or Fisher's exact test for univariate analysis, whereas we used forward stepwise selection (Waldesian) for logistic regression.\n Univariate analysis showed that mask, gown, gloves, goggles, footwear, \"hand-washing and disinfecting\", gargle, \"membrane protection\", \"taking shower and changing clothing after work\", \"avoid from eating and drinking in ward\", oseltamivir phospha tall had protective effects (P < 0.05), but stepwise logistic regression showed significant differences for mask (OR = 0.78, 95% CI: 0.60 - 0.99), goggles (OR = 0.20, 95% CI: 0.10 - 0.41) and footwear (OR = 0.58, 95% CI: 0.39 - 0.86). Analysis for linear trend in proportions showed that dose response relationship existed in mask, gown, gloves, goggles, footwear, gargle, \"membrane protection\" and \"taking shower and changing dree after work\" (P < 0.01). The attack rate of HCWs who were rescuing severe SARS patients without any PPE was 61.5% (16/26). It seemed that the more the protective measures were used, the higher the protective effect was (P < 0.001), and could reach 100% if mask, gown, gloves, goggles, footwear, \"hand-washing and disinfecting\" were all used at the same time.\n Nosocomial infection of SARS can be prevented effectively by precautions against droplets and personal contact. HCWs must take strict protection according to the guidance of WHO or Chinese MOH and pay attention to personal hygiene.", "To decrease respiratory infections in senior day care, staff were educated on viral transmission and the value of hand washing. Fanny packs with alcohol foam supplemented hand washing and were alternated monthly between centers. Infection rates were unchanged with alcohol foam use. The intervention year's infection rate was significantly lower than the previous 3 years, suggesting a benefit of education.", "To determine the cost-effectiveness and cost-benefit of an infection control program to reduce nosocomial respiratory syncytial virus (RSV) transmission in a large pediatric hospital.\n RSV nosocomial infection (NI) was studied for 8 years, before and after intervention with a targeted infection control program. The cost-effectiveness of the intervention was calculated, and cost-benefit was estimated by a case-control comparison.\n Children's Hospital of Philadelphia, a 304-bed pediatric hospital.\n All inpatients with RSV infection, both community- and hospital-acquired.\n Consisted of early recognition of patients with respiratory symptoms, confirmation of RSV infection by laboratory testing, establishing cohorts of patients and nursing staff, gown and glove barrier precautions, and monitoring and education of staff.\n The incidence density of RSV NI before and after the intervention was calculated as the rate per 1000 patient days-at-risk for infection. Intervention costs included laboratory testing, isolation, and administration of the program. The cost of RSV NI was estimated by comparing hospital charges for 30 cases and matched uninfected controls.\n A total of 148 patients acquired NI (88 before and 60 after the intervention). The Mantel-Haenszel stratified relative risk for NI in the period before the infection control program, compared with the postintervention period, was.61 (95% confidence interval:.53-.69). By applying the preintervention stratum-specific rates of infection to the days-at-risk in the postintervention period, an estimated 100 NIs would have been expected, which in comparison to the 60 NIs observed, yielded an estimated program effectiveness of 10 RSV NIs prevented per season. The total cost of the program per season was $15 627 or $1,563/NI prevented. In comparison, the mean cost to the hospital was $9,419/case of RSV NI, resulting in a cost-benefit ratio of 1:6.\n A targeted infection control intervention was cost-effective in reducing the rate of RSV NI. For every dollar spent on the program, approximately $6 was saved.", "Despite the use of a series of preventive measures, a high incidence of severe acute respiratory syndrome (SARS) was observed among health care workers (HCWs) during the SARS epidemic. This study aimed to determine which preventive measures may have been effective in protecting HCWs from infection, and which were not effective.\n A retrospective study was performed among 758 'frontline' health care workers who cared for SARS patients at the Second Affiliated Hospital and the Third Affiliated Hospital of Sun Yat-sen University. The HCWs with IgG against SARS and those without IgG against SARS were respectively defined as the \"case group\" and the \"control group\", and logistic regression was conducted to explore the risk factors for SARS infection in HCWs.\n After adjusting for age, gender, marital status, educational level, professional title, and the department in which an individual worked, the results of a multivariate logistic regression analysis indicated that incidence of SARS among HCWs was significantly and positively associated with: performing tracheal intubations for SARS patients, methods used for air ventilation in wards, avoiding face-to-face interaction with SARS patients, the number of pairs of gloves worn by HCWs, and caring for serious SARS cases.\n Some measures, particularly good air ventilation in SARS wards, may be effective in minimizing or preventing SARS transmission among HCWs in hospitals.", "Nosocomial transmission of droplet-borne respiratory infections such as severe acute respiratory syndrome (SARS) may be influenced by the choice of oxygen face mask. A subject inhaled saline mist and exhaled through three oxygen masks to illustrate the pattern of dispersal of pulmonary gas. In two commonly used masks, exhaled gas formed a plume emanating from the side vents, while a third mask with a valved manifold, which was modified by adding a respiratory filter, retained the droplets. Maintaining respiratory isolation during the administration of oxygen may reduce the risk of the nosocomial transmission of respiratory infections such as SARS.", "To determine the most effective infection control procedure in preventing nosocomial infection with respiratory syncytial virus (RSV), we did a prospective controlled study of four infection-control strategies in four wards in a large paediatric hospital in the west of Scotland. All children under two years old admitted to four general wards during three winter RSV epidemics (1989-92) were screened for RSV infection (by nasopharyngeal aspirate and direct immunofluorescence) within 18 hours of admission. The main outcome measure was the occurrence of nosocomial infection, defined as the number of children initially RSV negative who became RSV positive 7 days or more after hospital admission (incubation period for RSV infection is 5-8 days). Without special precautions, there was a high rate of nosocomial RSV infection (26%). Nosocomial infection was significantly reduced by the combination of cohort nursing with the wearing of gowns and gloves for all contacts of RSV-infected children (p = 0.0022). Neither the use of gowns and gloves alone nor cohort nursing alone produced a significant reduction in cross-infection. In the final year, general clinical use of a policy of cohort nursing with gowns and gloves resulted in a reduction in the cross-infection rate by two-thirds of its original value (9.5% vs 26%). Combined with rapid laboratory diagnosis, cohort nursing and the wearing of gowns and gloves for all contacts with RSV-infected children can significantly reduce the risk of nosocomial RSV infection.", "Most documented \"superspreading events\" of severe acute respiratory syndrome (SARS) occurred in hospitals, but the underlying causes remain unclear. We systematically analyzed the risk factors for nosocomial outbreaks of SARS among hospital wards in Guangzhou and Hong Kong, China.\n A case-control study was conducted. Case wards were hospital wards in which superspreading events of SARS occurred, and control wards were wards in which patients with SARS were admitted, but no subsequent nosocomial outbreaks occurred. Information on environmental and administrative factors was obtained through visits to the wards and interviews with ward managers or nursing officers. Relevant information about host factors was abstracted from the medical records. Logistic regression analyses were used to identify the major risk factors for superspreading events.\n Eighty-six wards in 21 hospitals in Guangzhou and 38 wards in 5 hospitals in Hong Kong were included in the study. Six risk factors were significant in the final multiple-logistic regression model: minimum distance between beds of < or = 1 m (odds ratio [OR], 6.94; 95% confidence interval [CI], 1.68-28.75), availability of washing or changing facilities for staff (OR, 0.12; 95% CI, 0.02-0.97), whether resuscitation was ever performed in the ward (OR, 3.81; 95% CI, 1.04-13.87), whether staff members worked while experiencing symptoms (OR, 10.55; 95% CI, 2.28-48.87), whether any host patients (index patient or the first patient with SARS admitted to a ward) required oxygen therapy (OR, 4.30; 95% CI, 1.00-18.43), and whether any host patients required bi-level positive airway pressure ventilation (OR, 11.82; 95% CI, 1.97-70.80).\n Our results revealed that factors that were associated with the ward environment and administration were important in nosocomial outbreaks of SARS. The lessons learned from this study remain very important and highly relevant to the daily operation of hospital wards if we are to prevent nosocomial outbreaks of other respiratory infections in the future.", "Hand washing is the most effective way to prevent the spread of communicable disease. The purpose of this double-blind, placebo-controlled study was to assess whether an alcohol-free, instant hand sanitizer containing surfactants, allantoin, and benzalkonium chloride could reduce illness absenteeism in a population of 769 elementary school children and serve as an effective alternative when regular soap and water hand washing was not readily available. Prior to the study, students were educated about proper hand washing technique, the importance of hand washing to prevent transmission of germs, and the relationship between germs and illnesses. Children in kindergarten through the 6th grade (ages 5-12) were assigned to the active or placebo hand-sanitizer product and instructed to use the product at scheduled times during the day and as needed after coughing or sneezing. Data on illness absenteeism were tracked. After 5 weeks, students using the active product were 33% less likely to have been absent because of illness when compared with the placebo group.", "The purpose of this study was to design and implement a comprehensive infection control program and measure its effects on the number and types of infectious illnesses experienced by children attending a specialized preschool program.\n Participants in the study were children with Down syndrome enrolled in a school-based early intervention program. The ages of the children ranged from 6 weeks to 5 years. Through a series of parental questionnaires, the number and types of infections in the children were chronicled for a year before and a year after the implementation of an infection control intervention program. Interventions included infection control lectures, handouts, posters, and attention to environmental cleaning and disinfection, with an emphasis on toys. Compliance with these measures was monitored and recorded.\n During the interventional year the median number of total illnesses/child/month decreased significantly from the baseline year (0.70 vs 0.53, p < 0.05), with a trend toward a decrease in the number of respiratory illnesses (0.67 vs 0.42, p < 0.07). Significant decreases were also seen for the median number of physician visits (0.50 vs 0.33, p < 0.05), courses of antibiotics administered (0.33 vs 0.28, p < 0.05), and days of school missed as a result of respiratory illness (0.75 vs 0.40, p < 0.05).\n This study demonstrates a decrease in infection rates with the implementation of a comprehensive educational and environmental infection control program in a day care setting.", "There are sparse data on whether non-pharmaceutical interventions can reduce the spread of influenza. We implemented a study of the feasibility and efficacy of face masks and hand hygiene to reduce influenza transmission among Hong Kong household members.\n We conducted a cluster randomized controlled trial of households (composed of at least 3 members) where an index subject presented with influenza-like-illness of <48 hours duration. After influenza was confirmed in an index case by the QuickVue Influenza A+B rapid test, the household of the index subject was randomized to 1) control or 2) surgical face masks or 3) hand hygiene. Households were visited within 36 hours, and 3, 6 and 9 days later. Nose and throat swabs were collected from index subjects and all household contacts at each home visit and tested by viral culture. The primary outcome measure was laboratory culture confirmed influenza in a household contact; the secondary outcome was clinically diagnosed influenza (by self-reported symptoms). We randomized 198 households and completed follow up home visits in 128; the index cases in 122 of those households had laboratory-confirmed influenza. There were 21 household contacts with laboratory confirmed influenza corresponding to a secondary attack ratio of 6%. Clinical secondary attack ratios varied from 5% to 18% depending on case definitions. The laboratory-based or clinical secondary attack ratios did not significantly differ across the intervention arms. Adherence to interventions was variable.\n The secondary attack ratios were lower than anticipated, and lower than reported in other countries, perhaps due to differing patterns of susceptibility, lack of significant antigenic drift in circulating influenza virus strains recently, and/or issues related to the symptomatic recruitment design. Lessons learnt from this pilot have informed changes for the main study in 2008.\n ClinicalTrials.gov NCT00425893 HKClinicalTrials.com HKCTR-365.", "More than 3.5 million children aged less than 5 years die from diarrhoea and acute lower respiratory-tract infection every year. We undertook a randomised controlled trial to assess the effect of handwashing promotion with soap on the incidence of acute respiratory infection, impetigo, and diarrhoea.\n In adjoining squatter settlements in Karachi, Pakistan, we randomly assigned 25 neighbourhoods to handwashing promotion; 11 neighbourhoods (306 households) were randomised as controls. In neighbourhoods with handwashing promotion, 300 households each were assigned to antibacterial soap containing 1.2% triclocarban and to plain soap. Fieldworkers visited households weekly for 1 year to encourage handwashing by residents in soap households and to record symptoms in all households. Primary study outcomes were diarrhoea, impetigo, and acute respiratory-tract infections (ie, the number of new episodes of illness per person-weeks at risk). Pneumonia was defined according to the WHO clinical case definition. Analysis was by intention to treat.\n Children younger than 5 years in households that received plain soap and handwashing promotion had a 50% lower incidence of pneumonia than controls (95% CI (-65% to -34%). Also compared with controls, children younger than 15 years in households with plain soap had a 53% lower incidence of diarrhoea (-65% to -41%) and a 34% lower incidence of impetigo (-52% to -16%). Incidence of disease did not differ significantly between households given plain soap compared with those given antibacterial soap.\n Handwashing with soap prevents the two clinical syndromes that cause the largest number of childhood deaths globally-namely, diarrhoea and acute lower respiratory infections. Handwashing with daily bathing also prevents impetigo.", "Gargling to wash the throat is commonly performed in Japan, and people believe that such hygienic routine, especially with gargle medicine, prevents upper respiratory tract infections (URTIs). Its effectiveness, however, has not been established by clinical trials.\n Randomized controlled trial carried out in 2002-2003 winter season and analyzed in 2003 and 2004.\n Healthy volunteers (387) aged 18 to 65 years.\n Participants were randomly assigned to water gargling, povidone-iodine gargling, and usual care (control). Subjects in the two gargling groups were requested to gargle with water or diluted povidone-iodine at least three times a day. Participants were followed for 60 days.\n The primary outcome measure was first URTI incidence. Severity of URTI symptoms among incident cases was also evaluated. Both outcomes were assessed with a self-administered symptom record. Analyses were performed on an intention-to-treat basis.\n A total of 130 participants contracted URTIs. The incidence rate of first URTI was 0.26 episodes/30 person-days among control subjects. The rate decreased to 0.17 episodes/30 person-days in the water gargling group, and 0.24 episodes/30 person-days in the povidone-iodine gargling group. Respective incidence rate ratios against controls were 0.64 (95% confidence interval [CI]=0.41-0.99) and 0.89 (95% CI=0.60-1.33). A Cox regression (proportional hazard model) revealed the efficacy of water gargling (hazard ratio=0.60, 95% CI=0.39-0.95). Even when a URTI occurred, water gargling tended to attenuate bronchial symptoms (p=0.055).\n Simple water gargling was effective to prevent URTIs among healthy people. This virtually cost-free modality would appreciably benefit the general population.", "Elementary school-age children are particularly vulnerable to infections. While handwashing is the best method of preventing infections, many elementary schools are housed in buildings that have barriers to effective hand hygiene. The purpose of this study was to determine the effectiveness of an alcohol gel as an adjunct to handwashing in reducing absenteeism secondary to infectious illness. Two-hundred and fifty-three elementary school children were randomized by classroom into an experimental or control group. With a crossover design, all children participated in both groups, with a one-week washout period between phases. A 45-minute \"Germ Unit\" was taught to all children as they started the experimental phase and a standard unit on hand hygiene was taught as they started the control phase. Sixty-nine children were absent due to illness while in the control group. Thirty-nine children became ill while in the experimental group. Alcohol gel as an adjunct to handwashing was shown to be effective in reducing absenteeism due to infectious illness by 43%.", "A handwashing program for elementary school students was developed and implemented by the school nurse in a suburban elementary school. The program consisted of surveying teachers, inspecting handwashing facilities, and providing classroom presentations and follow-up activities. Absenteeism records indicated a significant decrease in absenteeism for illness during the two months following the presentations.", "nan", "Aqueous iodine (2%) applied to the fingers was effective in blocking had transmission of experimental rhinovirus infection. None of eight volunteers became infected when exposed to rhinovirus immediately after treatment of the fingers with iodine. All of seven similarly exposed subjects treated with a placebo preparation became infected (P less than 0.001, Fisher's exact test). One of 10 volunteers became infected when exposed 2 hr after treatment of fingers with iodine, compared with six of 10 who became infected in the control group (P = 0.06, Fisher's exact test). Virus was recovered from three (11%) of 27 hand rinses from volunteers using iodine and from 11 (41%) of 27 hand rinses from volunteers using the placebo preparation (P less than 0.03), Fisher's exact test).", "A case-control study was conducted to examine the relationship between severe acute respiratory syndrome (SARS) and the time-dependent precautionary behaviors taken during an outbreak of SARS in Hanoi French Hospital (HFH), Vietnam. Masks (odds ratio [OR] = 0.3; 95% confidence interval [CI]: 0.1, 0.7) and gowns (OR = 0.2; 95% CI: 0.0, 0.8) appeared to prevent SARS transmission. The proportion of doctors and nurses who undertook each measure significantly improved (chi(2) = 9.8551, P = 0.043) after the onset of secondary cases. The impact of individual behaviors on an outbreak was investigated through mathematical approaches. The reproduction number decreased from 4.1 to 0.7 after notification. The basic reproduction number was estimated, and the use of masks alone was shown to be insufficient in containing an epidemic. Intuitive results obtained by means of stochastic individual-based simulations showed that rapid improvements in behavior and isolation would increase the probability of extinction.", "The objective of this study was to assess the effectiveness of a hygiene program in reducing the incidence of respiratory and diarrheal diseases in toddlers attending day care centers. A randomized field trial was conducted in 52 day care centers in Quebec, Canada, between September 1, 1996 and November 30, 1997. Absences for any reasons and the daily occurrence of colds and/or diarrhea in toddlers were recorded on calendars by the educators. The number of fecal coliforms on children's hands and on educators' hands was measured during three unannounced visits. Overall, 1,729 children were followed in 47 day care centers for a total of 153,643 child-days. The incidence rate of diarrhea was considerably reduced by the effect of monitoring (IRR = 0.73, 95% CI = 0.54,0.97), and the intervention reduced the incidence rate of upper respiratory tract infections (IRR = 0.80, 95% CI = 0.68,0.93). Monitoring alone also had an important effect in reducing the level of bacterial contamination on children's and educators' hands. The results indicate that both an intervention program and monitoring alone play a role in reducing infections in children attending day care centers.", "nan", "Severe acute respiratory syndrome (SARS) was first recognized in February 2003. It is the first severe and readily transmissible new disease to emerge in the 21st century. Healthcare workers in affected countries were exposed to the regular use of personal protective equipment (PPE) such as the N95 mask, gloves, and gowns. Our aim was to study the prevalence of adverse skin reactions to PPE among healthcare workers in Singapore during the SARS outbreak. Healthcare staff in the National Skin Centre and Tan Tock Seng Hospital were surveyed using questionnaires. Of those asked to participate, 322 (94.7%) agreed. 14.3% of the respondents were doctors, 73.0% nurses, and 12.7% other ancillary staff. Mean age of respondents was 32.4 years, with the majority being women (85.7%) and Chinese (53.7%). 109 (35.5%) of the 307 staff who used masks regularly reported acne (59.6%), facial itch (51.4%), and rash (35.8%) from N95 mask use. 64 (21.4%) of the 299 who used gloves regularly reported dry skin (73.4%), itch (56.3%), and rash (37.5%). The use of PPE is associated with high rates of adverse skin reactions. There is a need to find suitable alternatives for affected staff and to encourage awareness among staff of the role of dermatologists in their care.", "The purpose of the study was to evaluate the effect of intensified hygiene with frequent handwashing and several educational procedures in day-care centres. The study was conducted as a controlled trial, with an intervention group and an observation group. There was a 34% reduction in expected sickness in children in the intervention group. In the categories diarrhoea and eye-infection there was a significant drop in sickness. We conclude that broad intervention concerning hand-hygiene has a positive effect on sickness in children attending day-care centres.", "Between 1 and 22 March 2003, a nosocomial outbreak of Severe Acute Respiratory Syndrome (SARS) occurred at the Communicable Disease Centre in Tan Tock Seng Hospital, Singapore, the national treatment and isolation facility for patients with SARS. A case-control study with 36 cases and 50 controls was conducted of factors associated with the transmission of SARS within the hospital. In univariate analysis, contact with respiratory secretions elevated the odds ratio to 6.9 (95 % CI 1.4-34.6, P= 0.02). Protection was conferred by hand washing (OR 0.06, 95% CI 0.007-0.5, P=0.03) and wearing of N95 masks (OR 0.1, 95% CI 0.03-0.4, P=0.001). Use of gloves and gowns had no effect. Multivariate analysis confirmed the strong role of contact with respiratory secretions (adjusted OR 21.8, 95 % CI 1.7 274.8, P=0.017). Both hand washing (adjusted OR 0.07, 95 % CI 0.008-0.66, P=0.02) and wearing of N95 masks (adjusted OR 0.1, 95% CI 0.02-0.86, P=0.04) remained strongly protective but gowns and gloves had no effect.", "nan", "To limit nosocomial spread of respiratory syncytial virus (RSV) infection, a longitudinal intervention trial was instituted. Nasal secretions or washes were screened for RSV antigen by enzyme-linked immunosorbent assay, and patients were assigned to an RSV-infected or an RSV-uninfected cohort. The baseline (preintervention) rate of 7.17 nosocomial cases of RSV per 1000 patient-days of care was used for comparison. Despite continued infections in the community after screening was initiated, there were no cases of RSV infection in 1880 patient-days of care for 3 months (p = 0.039). During the fourth month, an RSV-infected child was erroneously assigned to the RSV-uninfected cohort, and three nosocomial cases occurred--5.33/1000 patient-days of care (p = 0.286). Overall, there were three nosocomial RSV infections in 2443 patient-days of care in the 1987 season after screening was introduced--1.23/1000 patient-days of care (p = 0.026). In the subsequent RSV season, there was one nosocomial case--0.461/1000 patient-days of care for 3 months (p = 0.0074). During the same period, nosocomial cases of RSV were observed in the pediatric and neonatal intensive care units, where assignment to a cohort was not possible. We conclude that entry into a cohort at the time of admission, on the basis of prospective RSV screening by enzyme-linked immunosorbent assay, effectively reduces nosocomial transmission of RSV.", "Two six-month randomized, controlled double-blind trials of the efficacy of virucidal nasal tissues in the prevention of natural colds were conducted in Charlottesville, Virginia, between 1983 and 1986. Tissues impregnated with malic and citric acids and sodium lauryl sulfate were used in both trials. Placebo tissues contained saccharin in the first trial and a mixture including succinic acid in the second. A total of 186 families were evaluable after completion of trial I, and 98 families were evaluable in trial II. The antiviral tissues were associated with 14 and 5% relative reductions in the overall rate of colds in the first and second trials, respectively. In the first study, this appeared to be due to an appropriate fall in secondary illnesses with a relative reduction in the ratio of secondary to primary illnesses of 32%. In trial II, however, the small and statistically insignificant reduction was primarily due to a drop in the rate of primary illness (which cannot be attributed to tissue efficacy), and the ratio of secondary to primary illness was actually 5% higher in the group with active tissues than in the placebo group. We conclude that when rigorously used in a study protocol, virucidal tissues may offer a modest reduction of secondary colds in the home, but for reasons currently unknown, do not have a major effect on the overall rate of colds.", "Control of infection within the long-term care facility is a daunting problem. Elderly patients are at high risk for contracting infection because of reduced innate immunity, malnutrition, and the presence of chronic medical conditions. This small study tested the effect of developing and implementing a comprehensive preventive infection control program in the long-term care setting and examined the resultant incidence of infections.\n Eight private, freestanding, long-term care facilities in urban and suburban settings were selected for the study. The 4 test sites had a total of 443 beds; there were 447 beds in 4 matched control sites. Data on infection rates were accrued in both preintervention and intervention years. The control homes maintained their existing infection control policies and procedures. The test homes were provided with an infection control educational program and replaced all currently used germicidal products with single-branded products for a 12-month period. A criteria-based standardized infection control surveillance system was used to monitor and report infections in all facilities.\n In the preintervention year, the test sites experienced 743 infections (incidence density rate, 6.33) and the control homes experienced 614 infections (incidence density rate, 3.39). In the intervention year, the test homes reported 621 infections, a decrease of 122 infections (incidence density rate, 4.15); in the control homes, the number of infections increased slightly, to 626 (incidence density rate, 3.15). The greatest reduction in infections in the test homes was in upper respiratory infections (P =.06).\n This study provides additional evidence that a comprehensive infection control program that includes handwashing and environmental cleaning and disinfecting may help reduce infections among the elderly residing in long-term care settings.", "During three winter seasons prior to 1984-1985 the special care nursery at New England Medical Center experienced respiratory syncytial virus (RSV) epidemics that required closure of the unit. Prior to and during the 1984-1985 winter season, several measures were taken to prevent recurrent nosocomial RSV transmission. In the winters of 1984-1985 and 1985-1986 there were 26 introductions of community-acquired RSV with no transmission of nosocomial cases during 1,688 patient days at risk as compared with 1983-1984 when there were seven cases of nosocomial RSV following six introductions of RSV during 875 patient days at risk (rate = 8 per 1,000 patient days) (P = 0.0016). The institution of many infection control measures including active surveillance, cohorting infected patients, a strict winter visiting policy, and gowning, gloving, and applying mask on contact, was associated with the successful prevention of nosocomial transmission of RSV in this nursery setting.", "Healthcare workers (HCWs) are at risk of acquiring severe acute respiratory syndrome (SARS) while caring for SARS patients. Personal protective equipment and negative pressure isolation rooms (NPIRs) have not been completely successful in protecting HCWs. We introduced an innovative, integrated infection control strategy involving triaging patients using barriers, zones of risk, and extensive installation of alcohol dispensers for glove-on hand rubbing. This integrated infection control approach was implemented at a SARS designated hospital ('study hospital') where NPIRs were not available. The number of HCWs who contracted SARS in the study hospital was compared with the number of HCWs who contracted SARS in 86 Taiwan hospitals that did not use the integrated infection control strategy. Two HCWs contracted SARS in the study hospital (0.03 cases/bed) compared with 93 HCWs in the other hospitals (0.13 cases/bed) during the same three-week period. Our strategy appeared to be effective in reducing the incidence of HCWs contracting SARS. The advantages included rapid implementation without NPIRs, flexibility to transfer patients, and re-inforcement for HCWs to comply with infection control procedures, especially handwashing. The efficacy and low cost are major advantages, especially in countries with large populations at risk and fewer economic resources.", "In both military and civilian settings, transmission of respiratory pathogens may be due to person-to-person and environmental contributions. This possibility was explored in a military training setting, where rates of febrile respiratory illness (FRI) often reach epidemic levels.\n Population size and FRI rates were monitored over 10 months in the units of 50-90 individuals. Some units were open to the influx of potentially infectious convalescents (hereafter referred to as \"open units,\" and some were closed to such an influx (hereafter referred to as \"closed units\"). Virologic testing and polymerase chain reaction analysis were used to detect adenovirus on surface structures.\n The odds ratio (OR) associated with FRI in closed units, compared with open units, was 1.13 (95% confidence interval [CI], 0.99-1.28). The OR in units with a population greater than the median size, compared with units with a population lower than the median size was 1.38 (95% CI, 1.23-1.55). Between 5% and 9% of surface samples obtained from selected units harbored viable adenovirus.\n FRI rates were not reduced in units that were closed to potentially contagious individuals. These findings imply that the primary source of the pathogen is likely environmental rather than human, and they underscore what is known about other virus types. Diligence in identifying the relative roles of different transmission routes is suggested for civilian settings similar to those described in the current study.", "Health care workers outside surgical suites in Asia use surgical-type face masks commonly. Prevention of upper respiratory infection is one reason given, although evidence of effectiveness is lacking.\n Health care workers in a tertiary care hospital in Japan were randomized into 2 groups: 1 that wore face masks and 1 that did not. They provided information about demographics, health habits, and quality of life. Participants recorded symptoms daily for 77 consecutive days, starting in January 2008. Presence of a cold was determined based on a previously validated measure of self-reported symptoms. The number of colds between groups was compared, as were risk factors for experiencing cold symptoms.\n Thirty-two health care workers completed the study, resulting in 2464 subject days. There were 2 colds during this time period, 1 in each group. Of the 8 symptoms recorded daily, subjects in the mask group were significantly more likely to experience headache during the study period (P < .05). Subjects living with children were more likely to have high cold severity scores over the course of the study.\n Face mask use in health care workers has not been demonstrated to provide benefit in terms of cold symptoms or getting colds. A larger study is needed to definitively establish noninferiority of no mask use.", "We compared the impact of three household interventions-education, education with alcohol-based hand sanitizer, and education with hand sanitizer and face masks-on incidence and secondary transmission of upper respiratory infections (URIs) and influenza, knowledge of transmission of URIs, and vaccination rates.\n A total of 509 primarily Hispanic households participated. Participants reported symptoms twice weekly, and nasal swabs were collected from those with an influenza-like illness (ILI). Households were followed for up to 19 months and home visits were made at least every two months.\n We recorded 5034 URIs, of which 669 cases reported ILIs and 78 were laboratory-confirmed cases of influenza. Demographic factors significantly associated with infection rates included age, gender, birth location, education, and employment. The Hand Sanitizer group was significantly more likely to report that no household member had symptoms (p < 0.01), but there were no significant differences in rates of infection by intervention group in multivariate analyses. Knowledge improved significantly more in the Hand Sanitizer group (p < 0.0001). The proportion of households that reported > or = 50% of members receiving influenza vaccine increased during the study (p < 0.001). Despite the fact that compliance with mask wearing was poor, mask wearing as well as increased crowding, lower education levels of caretakers, and index cases 0-5 years of age (compared with adults) were associated with significantly lower secondary transmission rates (all p < 0.02).\n In this population, there was no detectable additional benefit of hand sanitizer or face masks over targeted education on overall rates of URIs, but mask wearing was associated with reduced secondary transmission and should be encouraged during outbreak situations. During the study period, community concern about methicillin-resistant Staphylococcus aureus was occurring, perhaps contributing to the use of hand sanitizer in the Education control group, and diluting the intervention's measurable impact.", "Most cases of severe acute respiratory syndrome (SARS) have occurred in close contacts of SARS patients. However, in Beijing, a large proportion of SARS cases occurred in persons without such contact. We conducted a case-control study in Beijing that compared exposures of 94 unlinked, probable SARS patients with those of 281 community-based controls matched for age group and sex. Case-patients were more likely than controls to have chronic medical conditions or to have visited fever clinics (clinics at which possible SARS patients were separated from other patients), eaten outside the home, or taken taxis frequently. The use of masks was strongly protective. Among 31 case-patients for whom convalescent-phase (>21 days) sera were available, 26% had immunoglobulin G to SARS-associated coronavirus. Our finding that clinical SARS was associated with visits to fever clinics supports Beijing's strategy of closing clinics with poor infection-control measures. Our finding that mask use lowered the risk for disease supports the community's use of this strategy.", "Many countries are stockpiling face masks for use as a nonpharmaceutical intervention to control virus transmission during an influenza pandemic. We conducted a prospective cluster-randomized trial comparing surgical masks, non-fit-tested P2 masks, and no masks in prevention of influenza-like illness (ILI) in households. Mask use adherence was self-reported. During the 2006 and 2007 winter seasons, 286 exposed adults from 143 households who had been exposed to a child with clinical respiratory illness were recruited. We found that adherence to mask use significantly reduced the risk for ILI-associated infection, but <50% of participants wore masks most of the time. We concluded that household use of face masks is associated with low adherence and is ineffective for controlling seasonal respiratory disease. However, during a severe pandemic when use of face masks might be greater, pandemic transmission in households could be reduced.", "Hand washing prevents communicable illness. We evaluated the effect of a mandatory, scheduled hand-washing program in elementary school children on absenteeism due to acute communicable illness.\n The study was conducted at Trombley Elementary School in Grosse Pointe Park, Mich. The intervention group, approximately half of the school children (n = 143, including all grades 1-5), washed their hands a minimum of four scheduled times a day. The control group (n = 162) continued hand-washing practices as usual.\n Of the 37 school days examined, children in the hand-washing group were absent fewer days than the control group due to all acute communicable illness (relative risk = .75). There were less days of absence due to gastrointestinal symptoms (relative risk = .43). The difference in absence due to respiratory symptoms was not statistically significant.\n A scheduled hand-washing program will reduce acute communicable (gastrointestinal) illnesses in elementary school-age children.", "We analyzed information obtained from 1,192 patients with probable severe acute respiratory syndrome (SARS) reported in Hong Kong. Among them, 26.6% were hospital workers, 16.1% were members of the same household as SARS patients and had probable secondary infections, 14.3% were Amoy Gardens residents, 4.9% were inpatients, and 9.9% were contacts of SARS patients who were not family members. The remaining 347 case-patients (29.1%) had undefined sources of infection. Excluding those <16 years of age, 330 patients with cases from \"undefined\" sources were used in a 1:2 matched case-control study. Multivariate analysis of this case-control study showed that having visited mainland China, hospitals, or the Amoy Gardens were risk factors (odds ratio [OR] 1.95 to 7.63). In addition, frequent mask use in public venues, frequent hand washing, and disinfecting the living quarters were significant protective factors (OR 0.36 to 0.58). In Hong Kong, therefore, community-acquired infection did not make up most transmissions, and public health measures have contributed substantially to the control of the SARS epidemic.", "Nosocomially acquired respiratory syncytial virus (RSV) infections cause serious problems in hospitalized patients. An increased effort should be made to describe the problems connected with such infections in pediatric hospitals, with the aim of reducing the occurrence of nosocomial RSV infections (NI).\n A specialized database was introduced for surveillance and a multifaceted barrier concept based on the CDC recommendations was developed for the control of NI in a university children's hospital in Germany.\n Between 1999 and 2002 (November 1-April 30), 283 RSV infections (general population) were prospectively documented. Thirty-nine cases (13.8%) were nosocomial infections (NI) with an incidence density (ID) of 0.99/1000 patient days; 48.7% of all NI were found in prematurely born infants. Following the introduction of a surveillance and prevention policy, a 9-fold decrease of the ID (1.67 vs. 0.18/1000 patient-days) was found when comparing the first and the last season. Intensive care treatment was required in 18% of all documented RSV-infections, in 48.7% of all NI cases and in 43.5% of all RSV-infected prematurely born infants. Overall RSV-related mortality was 0.71%.\n Early diagnosis, a strict cohorting and contact isolation policy, and prospective surveillance contribute to the reduction of nosocomial RSV infection.", "The efficacy of infection control procedures utilizing gowns and masks in the control of nosocomial respiratory syncytial virus (RSV) infections was evaluated by comparing the rate of nosocomial RSV infections in infants and ward personnel during two sequential periods when gowns and masks were used (period 1) and not used (period 2). All patients (162) and staff (36) on our infants' ward were examined for signs of respiratory infection and had nasal washes obtained for viral isolation every two to four days for two months. Nosocomial RSV infection was identified in a total of 19 infants. Eight of these occurred in period 1 for a nosocomial infection rate of 32% of contact infants who were hospitalized for seven or more days. In comparison, 11 (41%) of the contact infants hospitalized for seven or more days in period 2 became infected. These findings suggest that the additional routine use of masks and gowns does not result in measurable benefit in controlling the nosocomial spread of RSV infection to infants or to ward personnel.", "Respiratory syncytial virus (RSV) infections in hospitalized children were identified by indirect fluorescent antibody technique. Patients with RSV infections were assigned to one of two isolation categories. In one category, the health care workers entering the child's room did not wear masks and goggles; in the other category, the workers did wear masks and goggles. The RSV illness rate in health care workers using masks and goggles was 5%, but the rate for those not using masks and goggles was 61%. In the no mask/goggles group, the RSV illness rates in the health care workers correlated directly with the number of exposures. In this modest study, the use of masks and goggles was associated with a significant reduction of RSV illnesses in pediatric health care workers.", "To determine whether increased compliance with a policy of glove and gown isolation precautions could reduce the high rate of nosocomial respiratory syncytial virus (RSV) infection on an infant and toddler ward, we conducted a longitudinal intervention trial during three RSV seasons, from 1982 to 1985, with an intervention to increase compliance introduced midway through the second season. The risk of acquiring RSV infection in the hospital was adjusted for the intensity of nosocomial exposure to the virus by assigning each study week to one of five strata, defined by the proportion of hospital days on which virus was shed by children on the ward. Overall, 37 patients acquired nosocomial RSV infections during 7547 days at risk. The adjusted relative risk, comparing the infection rate in the period before the intervention (when compliance with isolation precautions was noted in only 38.5 percent of the observed patient contacts) with the infection rate in the postintervention period (when compliance more than doubled) was 2.9 (95 percent confidence interval, 1.5 to 5.7). Rates of nosocomial RSV infection increased linearly with increasing levels of exposure to patients shedding virus, but the rise in the infection rate with increasing exposure was less than one fourth as great (P less than 0.001) in the period after the intervention as it was before. We conclude that glove and gown precautions can substantially reduce the nosocomial transmission of RSV, particularly with increasing exposure to patients shedding the virus.", "During two winter periods (1994-1995 and 1995-1996), nasopharyngeal aspirates were obtained from infants and young children with an acute respiratory illness, after initial assessment in an area with six cubicles which serves as an admissions unit. Aspirates were sent for rapid diagnostic testing. Respiratory syncytial virus (RSV) positive patients were cohorted into two six-bedded bays on the paediatric wards. Over the two successive winter periods studied, 347 RSV positive patients were assigned to the cohort. No nosocomial infections were identified during the first winter; in the second, two were identified. Cohorting at admission eased clinical management, with one area used for high-dependency care and cubicles being freed for children with other infectious diseases. Nosocomial infection was minimized.", "Data about the effectiveness of the surgical mask compared with the N95 respirator for protecting health care workers against influenza are sparse. Given the likelihood that N95 respirators will be in short supply during a pandemic and not available in many countries, knowing the effectiveness of the surgical mask is of public health importance.\n To compare the surgical mask with the N95 respirator in protecting health care workers against influenza.\n Noninferiority randomized controlled trial of 446 nurses in emergency departments, medical units, and pediatric units in 8 tertiary care Ontario hospitals.\n Assignment to either a fit-tested N95 respirator or a surgical mask when providing care to patients with febrile respiratory illness during the 2008-2009 influenza season.\n The primary outcome was laboratory-confirmed influenza measured by polymerase chain reaction or a 4-fold rise in hemagglutinin titers. Effectiveness of the surgical mask was assessed as noninferiority of the surgical mask compared with the N95 respirator. The criterion for noninferiority was met if the lower limit of the 95% confidence interval (CI) for the reduction in incidence (N95 respirator minus surgical group) was greater than -9%.\n Between September 23, 2008, and December 8, 2008, 478 nurses were assessed for eligibility and 446 nurses were enrolled and randomly assigned the intervention; 225 were allocated to receive surgical masks and 221 to N95 respirators. Influenza infection occurred in 50 nurses (23.6%) in the surgical mask group and in 48 (22.9%) in the N95 respirator group (absolute risk difference, -0.73%; 95% CI, -8.8% to 7.3%; P = .86), the lower confidence limit being inside the noninferiority limit of -9%.\n Among nurses in Ontario tertiary care hospitals, use of a surgical mask compared with an N95 respirator resulted in noninferior rates of laboratory-confirmed influenza.\n clinicaltrials.gov Identifier: NCT00756574", "Hospital acquired infections with respiratory syncytial virus are a major problem. The virus is spread predominantly by infected nasal secretions and we investigated whether we could reduce its incidence by cohorting babies on each ward into designated areas and encouraging staff and parents to wash their hands. We examined the incidence of hospital acquired infection due to respiratory syncytial virus in all children less than 2 years old and in those with congenital heart disease. In 1986-7, before any intervention, 18 (4.2%) of 425 hospitalised children less than 2 years old developed hospital acquired infection due to respiratory syncytial virus. In 1987-8, after intervention, five (0.6%) of 840 children developed hospital acquired infection but there were fewer ward admissions with community acquired infections due to the virus. In 1988-9, when there were more community acquired infections than 1986-7, six (1.1%) of 552 children developed hospital acquired infection. In 1986-7, eight (34.8%) of 23 children less than 2 years old with congenital heart disease developed hospital acquired infection due to respiratory syncytial virus; all eight were among 11 children with congenital heart disease hospitalised for more than 14 days. In 1987-8, one (3.3%) of 30 children with congenital heart disease developed hospital acquired infection due to respiratory syncytial virus and in 1988-9 there was one (2.1%) case out of 47 children with congenital heart disease. Handwashing and cohorting significantly reduce the incidence of nosocomial respiratory syncytial virus infection.", "We evaluated the effect of school closure on the occurrence of respiratory infection among children ages 6-12 years and its impact on health care services. During this period, there were significant decreases in the diagnoses of respiratory infections (42%), visits to physician (28%) and emergency departments (28%) and medication purchases (35%). The present study provides quantitative data to support school closure during an influenza pandemic.", "After the WHO issued the global alert for 2009 pandemic influenza A (H1N1), many national health agencies began to screen travelers on entry in airports, ports and border crossings to try to delay local transmission.\n We reviewed entry screening policies adopted by different nations and ascertained dates of official report of the first laboratory-confirmed imported H1N1 case and the first laboratory-confirmed untraceable or 'local' H1N1 case.\n Implementation of entry screening policies was associated with on average additional 7-12 day delays in local transmission compared to nations that did not implement entry screening, with lower bounds of 95% confidence intervals consistent with no additional delays and upper bounds extending to 20-30 day additional delays.\n Entry screening may lead to short-term delays in local transmission of a novel strain of influenza virus. The resources required for implementation should be balanced against the expected benefits of entry screening.", "Few data are available about the effectiveness of nonpharmaceutical interventions for preventing influenza virus transmission.\n To investigate whether hand hygiene and use of facemasks prevents household transmission of influenza.\n Cluster randomized, controlled trial. Randomization was computer generated; allocation was concealed from treating physicians and clinics and implemented by study nurses at the time of the initial household visit. Participants and personnel administering the interventions were not blinded to group assignment. (ClinicalTrials.gov registration number: NCT00425893)\n Households in Hong Kong.\n 407 people presenting to outpatient clinics with influenza-like illness who were positive for influenza A or B virus by rapid testing (index patients) and 794 household members (contacts) in 259 households.\n Lifestyle education (control) (134 households), hand hygiene (136 households), or surgical facemasks plus hand hygiene (137 households) for all household members.\n Influenza virus infection in contacts, as confirmed by reverse-transcription polymerase chain reaction (RT-PCR) or diagnosed clinically after 7 days.\n Sixty (8%) contacts in the 259 households had RT-PCR-confirmed influenza virus infection in the 7 days after intervention. Hand hygiene with or without facemasks seemed to reduce influenza transmission, but the differences compared with the control group were not significant. In 154 households in which interventions were implemented within 36 hours of symptom onset in the index patient, transmission of RT-PCR-confirmed infection seemed reduced, an effect attributable to fewer infections among participants using facemasks plus hand hygiene (adjusted odds ratio, 0.33 [95% CI, 0.13 to 0.87]). Adherence to interventions varied.\n The delay from index patient symptom onset to intervention and variable adherence may have mitigated intervention effectiveness.\n Hand hygiene and facemasks seemed to prevent household transmission of influenza virus when implemented within 36 hours of index patient symptom onset. These findings suggest that nonpharmaceutical interventions are important for mitigation of pandemic and interpandemic influenza.\n Centers for Disease Control and Prevention.", "Guidelines issued by the Centers for Disease Control and Prevention and the World Health Organisation state that healthcare workers should wear N95 masks or higher-level protection during all contact with suspected severe acute respiratory syndrome (SARS). In areas where N95 masks are not available, multiple layers of surgical masks have been tried to prevent transmission of SARS. The in vivo filtration capacity of a single surgical mask is known to be poor. However, the filtration capacity of a combination of masks is unknown. This was a crossover trial of one, two, three and five surgical masks in six volunteers to determine the in vivo filtration efficiency of wearing more than one surgical mask. We used a Portacount to measure the difference in ambient particle counts inside and outside the masks. The best combination of five surgical masks scored a fit factor of 13.7, which is well below the minimum level of 100 required for a half face respirator. Multiple surgical masks filter ambient particles poorly. They should not be used as a substitute for N95 masks unless there is no alternative.", "Direct hand-to-hand contact is an important mechanism of transmission of rhinovirus infection. The rhinoviruses are inactivated at a low pH. A survey of organic acids in vitro revealed that these compounds have antirhinoviral activity that persists for at least 3 h after application to the skin. In additional studies of salicylic acid (SA) and pyroglutamic acid (PGA), the hands of volunteers were contaminated with rhinovirus at defined times after application of the acid, and then volunteers attempted to inoculate the nasal mucosa with one hand and quantitative viral cultures were done on the other hand. In one study, 3.5% SA or 1% SA with 3.5% PGA was compared with controls 15 min after application to assess the efficacy of the inactivation of virus and prevention of infection. Virus was recovered from the hands of 28 out of 31 (90%) of the volunteers in the control group compared to 4 out of 27 (15%) and 0 out of 27 in the groups administered 3.5 and 1% SA, respectively (P < 0.05). Rhinovirus infection occurred in 10 out of 31 (32%) of the controls and 2 out of 27 (7%) of volunteers in both treatment groups (P < 0.05 compared with control). In a second study, the efficacy of 4% PGA was evaluated 15 min, 1 h, and 3 h after application. Significantly fewer volunteers had positive hand cultures at all time points compared with the control group, but the proportion that developed rhinovirus infection was not significantly reduced. These results suggest the feasibility of the prevention of rhinovirus transmission by hand treatments that are virucidal on contact and have activity that persists after application.", "nan", "A randomized field trial was conducted in Tecumseh, Michigan, to test the efficacy of virucidal nasal tissues in interrupting transmission of respiratory agents in the household. In the double-blinded trial, 296 households were stratified by household size and randomly assigned to the group using treated tissues and the group using placebo tissues. Households were recruited in late August to early September 1984, and the tissues were distributed in November 1984. A 10-week influenza A(H3N2) period was identified from January 13 to March 23, 1985, although there was also evidence of rhinovirus circulation during that period. A household-level infection transmission model was used to assess the effectiveness of the virucidal tissue in the household. The model was used to estimate the secondary attack rate for the placebo and treated tissue households during the influenza A(H3N2) period. The efficacy of the treated tissue in interrupting secondary transmission was found to vary from 30.1% to 36.9%, although it could be as high as 39.4% when historical comparisons are used. However, these differences were not statistically significant. In general, the use of virucidal nasal tissue in the household appears to result in the partial interruption of transmission of influenzavirus from an infected household member to another household member during an influenza epidemic.", "To study the effect of gowning in a neonatal intensive care unit on colonization patterns, necrotizing enterocolitis, respiratory syncytial virus and other infections, mortality, and traffic and handwashing patterns.\n Alternate 2-month gowning and no-gowning cycles were established in a 24-bed level III neonatal intensive care unit for 8 months, with respiratory site, umbilical, and stool surveillance cultures done weekly on all patients. Traffic flow and handwashing compliance were evaluated by direct observation.\n Demographic data did not differ between periods. There were no significant differences between the gowning and no-gowning periods in the rates of bacterial colonization, any type of infection, or mortality. There was no effect on traffic flow or handwashing compliance.\n Gowning in the neonatal intensive care unit is an unnecessary custom without benefit in neonatal colonization, infection rates, mortality, traffic patterns, and handwashing behavior.", "In response to increasing concerns about respiratory illness in military recruits, a simple handwashing program was developed and evaluated at a large Navy training center.\n Clinical records from 1996 through 1998 were reviewed to determine weekly rates of respiratory illness before and after program implementation (1,089,800 person-weeks reviewed). A supplemental survey was given to a sample of recruits to assess self-reported respiratory illness and compliance with the handwashing program.\n A 45% reduction in total outpatient visits for respiratory illness was observed after implementation of the handwashing program. No change was noted in hospitalization rates for respiratory illness, which remained low during the observation period. Survey data supported clinical observations, as frequent handwashers self-reported fewer respiratory illness episodes when compared to infrequent handwashers. Surveys also revealed challenges with handwashing compliance.\n Implementation of a handwashing program in this population of healthy young adults was associated with a marked reduction in outpatient visits for respiratory illness. Despite its success, maintenance of the handwashing program has been challenging in the time-constrained setting of military training.", "During the influenza A(H1N1) pandemic, antiviral prescribing was limited, vaccines were not available early, and the effectiveness of nonpharmaceutical interventions (NPIs) was uncertain. Our study examined whether use of face masks and hand hygiene reduced the incidence of influenza-like illness (ILI).\n A randomized intervention trial involving 1437 young adults living in university residence halls during the 2006-2007 influenza season was designed. Residence halls were randomly assigned to 1 of 3 groups-face mask use, face masks with hand hygiene, or control- for 6 weeks. Generalized models estimated rate ratios for clinically diagnosed or survey-reported ILI weekly and cumulatively.\n We observed significant reductions in ILI during weeks 4-6 in the mask and hand hygiene group, compared with the control group, ranging from 35% (confidence interval [CI], 9%-53%) to 51% (CI, 13%-73%), after adjusting for vaccination and other covariates. Face mask use alone showed a similar reduction in ILI compared with the control group, but adjusted estimates were not statistically significant. Neither face mask use and hand hygiene nor face mask use alone was associated with a significant reduction in the rate of ILI cumulatively.\n These findings suggest that face masks and hand hygiene may reduce respiratory illnesses in shared living settings and mitigate the impact of the influenza A(H1N1) pandemic.\n ClinicalTrials.gov identifier: NCT00490633.", "We did a case-control study in five Hong Kong hospitals, with 241 non-infected and 13 infected staff with documented exposures to 11 index patients with severe acute respiratory syndrome (SARS) during patient care. All participants were surveyed about use of mask, gloves, gowns, and hand-washing, as recommended under droplets and contact precautions when caring for index patients with SARS. 69 staff who reported use of all four measures were not infected, whereas all infected staff had omitted at least one measure (p=0.0224). Fewer staff who wore masks (p=0.0001), gowns (p=0.006), and washed their hands (p=0.047) became infected compared with those who didn't, but stepwise logistic regression was significant only for masks (p=0.011). Practice of droplets precaution and contact precaution is adequate in significantly reducing the risk of infection after exposures to patients with SARS. The protective role of the mask suggests that in hospitals, infection is transmitted by droplets.", "We evaluated an eye-nose goggle to determine its usefulness in reducing nosocomial RSV infection in patients and staff members on our infant ward. During a community outbreak of RSV in 1984, infection was assessed by biweekly routine viral cultures on all ward personnel and patients and also by seroconversion in personnel. For three weeks staff members wore the goggles; two (5%) adults and one (6%) child acquired nosocomial infection. During the subsequent three-week study period, goggles were not used and 34% of personnel and 43% of susceptible infants became infected. The use of the disposable eye-nose goggles was associated with a significant decrease in nosocomial RSV infections (P less than .003 for staff and P less than .05 for contact infants)." ]

[ "11813896", "3488978", "9726683", "3865493", "2341774", "7028896", "8806290", "7155965", "1766705", "2647105", "1876465", "1693411", "2589274", "9153098", "6757712", "2248740", "19434268", "2405348", "6389394", "2880294" ]

[ "A comparative study of azithromycin and pseudoephedrine hydrochloride for otitis media with effusion in children.", "Efficacy of oral antibiotics for the treatment of persistent otitis media with effusion.", "Epidemiology and treatment of otitis media with effusion in children in the first year of primary school.", "Cefaclor in the treatment of otitis media with effusion.", "Otitis media with effusion: can erythromycin reduce the need for ventilating tubes?", "A controlled trial of cotrimoxazole therapy in serous otitis media.", "Double-blind randomised trial of co-amoxiclav versus placebo for persistent otitis media with effusion in general practice.", "Trimethoprim-sulfamethoxazole treatment of persistent otitis media with effusion.", "Comparative efficacy of erythromycin-sulfisoxazole, cefaclor, amoxicillin or placebo for otitis media with effusion in children.", "Antibiotic treatment of children with secretory otitis media. A randomized, double-blind, placebo-controlled study.", "Resolution of otitis media with effusion with the use of a stepped treatment regimen of trimethoprim-sulfamethoxazole and prednisone.", "Otitis media with effusion and chronic upper respiratory tract infection in children: a randomized, placebo-controlled clinical study.", "Prophylaxis of recurrent acute otitis media and middle-ear effusion. Comparison of amoxicillin with sulfamethoxazole and trimethoprim.", "Single dose of betamethasone in combined medical treatment of secretory otitis media.", "Serous otitis media. A double-blind trial with sulfisoxazole.", "The efficacy of oral steroids in the treatment of persistent otitis media with effusion.", "Management for the children with otitis media with effusion in the tertiary hospital.", "A controlled trial comparing three treatments for chronic otitis media with effusion.", "Antimicrobial therapy of chronic otitis media with effusion.", "Efficacy of amoxicillin with and without decongestant-antihistamine for otitis media with effusion in children. Results of a double-blind, randomized trial." ]

[ "We compared the outcomes of two different regimens--azithromycin and pseudoephedrine hydrochloride (PHCl)--for the treatment of otitis media with effusion (OME) in children. In a double-blind randomized clinical study, a total of 90 children aged between 2 and 13 years with persistent OME were randomly assigned to one of 3 treatment groups. The first group received azithromycin at a dose of 10 mg/kg once daily for 3 days and this regimen was repeated weekly for up to 12 weeks according to the results of tympanometry and pneumatic otoscopy. The second group received azithromycin at a dose of 10 mg/kg once daily for 3 days for the first week, and this regimen was repeated for 1 day a week for the following 11 weeks. The third group received PHCl, 4 mg/kg, 3 times daily for up to 12 weeks. Each patient underwent pneumatic otoscopic and tympanometric investigations at baseline and at Weeks 4, 8 and 12. The outcomes in the azithromycin-treated groups were superior to that in the decongestant group. However, the difference between the outcomes in the azithromycin groups according to the treatment protocol was not statistically significant. Azithromycin therapy, particularly a once-weekly regimen, helps patients to comply with treatment and also helps us to achieve good results with minimal therapy.", "We followed 137 children who were found to have persistent otitis media with effusion (POME) one month after the diagnosis of acute otitis media. Subjects were randomly assigned to either treatment with erythromycin ethylsuccinate and sulfisoxizole or to no treatment. Follow-up utilizing pneumatic otoscopy and tympanometry showed that treated patients were more likely to have normal findings, and less likely to develop acute otitis media during the month following treatment. These data indicate that children with POME one month following acute otitis media may benefit from an additional course of antibiotics.", "In this multicentre study we evaluated the prevalence and risk factors of otitis media with effusion (OME) in Italian school-children and the effectiveness of medical treatment of chronic OME with a new cephalosporin, ceftibuten. During two winter periods, 3413 children, aged 5 to 7 years, were examined for the presence of OME by means of pneumotoscopy and a portable, hand-held tympanometer. The prevalence of asymptomatic OME was 14.2%, with no difference as regards sex, age, month of examination or geographic area. Younger children had significantly more bilateral than unilateral effusion. A recent episode of acute otitis media and previous tonsillectomy or adenoidectomy were associated with an increased risk of OME in multivariate logistic regression models. The presence of OME was unrelated to such factors as birthweight, prematurity, sibling or parental history of allergy, duration of daycare attendance, family history of ear infections. After 12 weeks, 26.6% of children with OME still had middle-ear fluid: 52 were randomized to ceftibuten (9 mg/kg q.d. for 14 days) and 59 to no treatment (nasal saline drops allowed). Children treated with ceftibuten had a significantly better resolution of middle-ear effusion after 4 and 8 weeks. As mass screening programmes for OME in the year of school entry are questioned, a focus only on children with known risk factors seems advisable. Ceftibuten can be useful in reducing the duration of middle-ear effusion.", "A randomized clinical trial in which 91 children with chronic OME participated was performed. Cefaclor 20 mg/kg body weight b.i.d. was given to the treated group (n = 46) during 10 days preceding the day appointed for surgery. The control group (n = 45) remained untreated. On the day scheduled for surgery 24 (52%) of the treated cases had healed, compared to 5 (11%) of the untreated cases, a significant difference (p less than 0.001). The long term effects showed that in the treated group 18 of the 24 primarily healed remained unoperated at a median follow-up period of 20 months. In the untreated group two of the five that originally resolved later relapsed and were subjected to surgery.", "Otitis media with effusion (OME) is a common condition among children and is characterized by nonpurulent fluid in the middle ear and fluctuating conductive hearing loss. Most children will spontaneously regain normal air-filled middle ears, but a certain number will have persistent problems. In our department we will treat annually about 500 children on an outpatient basis, with the insertion of ventilating tubes in the eardrum. The reason for this study was to evaluate the effect of erythromycin, instead of inserting a ventilation tube, in children with bilateral OME of longer duration than three months (double blind/placebo). The study comprises 147 children, 1-15 years of age, 83 boys and 64 girls, all with OME for more than three months. All the patients were candidates for tube insertion. In the group treated with erythromycin, 12 patients out of 69 had bilaterally air-filled middle ears after one month, as compared to 19 out of 72 in the group treated with the placebo. No difference was noted due to sex or age. The results support our indication and timing for ventilation tube insertion.", "nan", "The treatment of persistent otitis media with effusion (OME) remains controversial, but this condition is the commonest reason for children to require ear, nose, and throat (ENT) surgery. Trials of antibiotics are inconclusive, are often weak methodologically, and have not been done in general practice. Our aim was a trial of an antibiotic for OME in such a population.\n 433 children, aged 6 months to 6 years, with OME from 57 general practices entered a 3-month watchful waiting period. Of 223 (52%) with persistent bilateral OME, 162 were randomised double-blind to receive co-amoxiclav suspension (20 mg/kg amoxicillin, 5 mg/kg clavulanate potassium) or matching placebo, orally three times a day for 14 days. All cases also received xylometazoline 0.25% decongestant nosedrops thrice daily. Of the 61 not randomised, 13 children were referred to an ENT surgeon and parents refused consent in 48 cases. The main outcome measures were persistent OME in both ears and in one or both ears, as assessed clinically and by tympanometry. Analysis was by intention-to-treat.\n 79 children in the treatment group and 70 in the placebo group were analysed for efficacy. 3 withdrew in the co-amoxiclav group (2 lost to follow-up, 1 due to side-effects); 6 withdrew in the placebo group (5 and 1, respectively). In addition, 4 tympanograms were uninterpretable in the controls. Compliance was over 90% in both groups. Persistent OME in both ears and in one or both ears were found at significantly lower rates in the co-amoxiclav group than in the controls at the 2-week follow-up: 53 vs 84% and 77 vs 93%, respectively. Odds ratios adjusted for sex, history of adenoidectomy, and upper respiratory tract infection at follow-up were 0.25 (95% CI 0.11, 0.58, p = 0.001) and 0.30 (0.10, 0.89, p = 0.03), respectively. Parents of children in the co-amoxiclav group reported significantly more side-effects than those of control children (44 vs 22%, p = 0.03). Side-effects were mostly gastrointestinal and mild.\n Our study in a general-practice setting confirmed the positive short-term effect of antibiotic treatment for persistent middle-ear infection. Before referral to an ENT surgeon, children with persistent OME presenting to general practitioners could be considered for such treatment, depending on the individual child and possible adverse sequelae.", "Persistent otitis media with effusion (POME) is found in 50% of young children after 10 days of antimicrobial therapy for acute otitis media. Pathogenic bacteria are present in at least 25% of such effusions. We studied the effect of a 2-week course of trimethoprim-sulfamethoxazole (TMP-SMX) administered to 33 children who had POME and compared the results obtained to those of a similar group of children with POME who did not receive drug therapy. This study was designed to answer two questions: (1) Would TMP-SMX promote the resolution of POME? (2) Would TMP-SMX prevent an attack of acute otitis media (AOM) superimposed on POME? The diagnosis of POME was validated by obtaining a type B tympanogram, and AOM was diagnosed according to strict criteria. Each child was randomly assigned either to a treatment group that received a 14-day course of TMP-SMX or to a control group that received no medication. TMP-SMX failed to promote resolution of POME but did prevent recurrent AOM. During the second 2-week (follow-up) phase of the study, when no antimicrobial was given to either subject group, the incidence of AOM was similar in both groups.", "We randomly assigned children with otitis media with effusion to receive either erythromycin-sulfisoxazole, cefaclor, amoxicillin or placebo for a 2-week period, primarily to determine whether either erythromycin-sulfisoxazole or cefaclor would have greater short term efficacy than that found previously for amoxicillin, and secondarily to supplement earlier data on outcomes in placebo-treated subjects. Interim analyses showed no statistically significant (P less than 0.05) differences between the three antimicrobial treatment groups in the primary outcome measures, i.e. the prevalence of middle-ear effusion 2 and 4 weeks after entry, and indicated that postulated differences favoring the erythromycin-sulfisoxazole and cefaclor groups over the amoxicillin group were unlikely to be found even if the originally calculated sample size were attained. Subject accrual was therefore terminated. Final analysis showed no significant between-group differences in other outcome measures as well. In antimicrobial vs. placebo comparisons neither erythromycin-sulfisoxazole nor cefaclor gave more favorable outcomes than placebo, whereas more children were effusion-free in the amoxicillin group than in the placebo group at 2 weeks (31.6% vs. 14.1%, P = 0.007), but not at 4 weeks. We conclude that when antimicrobial treatment for otitis media with effusion is deemed advisable, neither erythromycin-sulfisoxazole nor cefaclor should replace amoxicillin as first line treatment.", "A double-blind, randomized, placebo-controlled clinical trial was conducted to evaluate one month of amoxicillin-clavulanate potassium treatment of children with secretory otitis media. In total, 264 children, aged 1 to 10 years, were randomly assigned to either antibiotic or placebo treatment; 43 patients were excluded during treatment, equally distributed in both groups, leaving 221 patients completing the trial. The inclusion criterion was a type C2 and type B tympanometry result of at least three months' duration. Tympanometry was performed every month for 12 additional months. At the end of the treatment period, the disease was reversed in 61% in the antibiotic-treated group compared with 30% in the placebo-treated group (P less than .0001), and the improvement was persistently significant in favor of antibiotic for eight months. The effect was present in all age groups and independent of laterality of disease. The middle-ear status at the end of treatment was the determining factor for the outcome of tympanometry the year following treatment. From the end of treatment, there was no difference between tympanometry in a patient having been treated with the antibiotic and a patient having been treated with placebo. Antibiotic treatment shifts the individual patient from poor to better tympanometric conditions, so antibiotics can be recommended in the treatment of secretory otitis media before inserting ventilating tubes.", "This double blind, placebo-controlled trial was designed to determine whether intervention with a stepped regimen of trimethoprim-sulfamethoxazole (TMP-SMX) and prednisone would prevent high risk children from developing chronic otitis media with effusion (OME) and recurrent acute otitis media. Forty-two children were enrolled, assigned to treatment with active drug or placebo and then examined at 2-week intervals. They received TMP-SMX (or placebo) during the first 2 weeks, TMP-SMX and prednisone (or placebo) during Weeks 3 and 4 for persistent OME and TMP-SMX (or placebo) for Weeks 5 and 6 if OME was still unresolved. After treatment 48% of active drug and 14% of placebo subjects resolved OME bilaterally (P less than 0.05). Active drug subjects also had fewer acute otitis media episodes than placebo subjects while receiving study treatment (P less than 0.01). Although this treatment regimen produced short term OME resolution, long term benefits were not demonstrated.", "This study was performed to investigate the course of spontaneous recovery from otitis media with effusion in children with chronic rhinosinusitis treated in various ways. One hundred forty-one children between 3 and 10 years of age were selected for the presence of chronic rhinosinusitis and unilateral or bilateral otitis media with effusion. The children were assigned at random to one of four treatment groups, i.e., placebo, amoxicillin combined with xylometazoline hydrochloride nose drops, maxillary sinus drainage, or a combination of the latter two forms of therapy. The follow-up period was 6 months. Drainage of the maxillary sinus had no effect on either the recovery of the chronic upper respiratory tract infection or otitis media with effusion. Amoxicillin combined with xylometazoline nose drops had no significant effect on recovery from the upper respiratory tract infection, but did have a small but significant effect on recovery from otitis media with effusion. However, the general tendency of the upper respiratory tract and ears to recover was poor. Persistence of the chronic upper respiratory tract infection during the follow-up period proved to be a negative prognostic factor with respect to cure of otitis media with effusion. Children with chronic rhinosinusitis as defined in this study appear to have a high risk of developing chronic otitis media with effusion. The results of the study are discussed.", "We compared the efficacy of amoxicillin with that of the combination drug sulfamethoxazole and trimethoprim in reducing recurrences of acute otitis media (AOM) in a single-blind, randomized, placebo-controlled trial involving 96 children. Each of the children had had three or more episodes of AOM in the preceding 6 months, and 97% (93/96) of them still had unilateral or bilateral effusion at the beginning of the study. During the 6-month study period, 9 (27%) of 33 of the children in the amoxicillin group developed 9 episodes of AOM, 9 (27%) of 33 of the children in the sulfamethoxazole and trimethoprim group experienced 11 episodes of AOM, and 19 (63%) of 30 of the children in the placebo group developed 25 episodes. Young age and day-care attendance characterized children for whom prophylaxis was more efficacious. Overall persistence of middle-ear effusion was shorter in treated children only as a consequence of the reduced number of new episodes of AOM.", "With the objective of evaluating the efficacy of cefixime and the combination of cefixime and betamethasone in the treatment of secretory otitis media (SOM), we enrolled 142 children 2 to 12 years old in a randomized, double-blind, placebo-controlled study. All children suffered from SOM, verified by otomicroscopy and tympanometry, of at least 3 months' duration. Active treatment was a 10-day course of cefixime with and without a single dose of 6 mg betamethasone. On hundred forty children were available for efficacy evaluation 14 to 23 days after the start of treatment. A statistically significant treatment effect was found in the group treated with cefixime plus betamethasone (n = 59), with a 44.1% cure rate as compared to 19.7% in the cefixime-treated group (n = 61; p < .005) and 5% in the placebo group (n = 20; p < .005). Relapse rates were high and no statistically differences between groups remained at last valid visit. Adverse events possibly or probably associated with active treatment were reported in 11 cases (9.2%). One patient reported a severe adverse event. No serious events occurred. The study did not show any significant long-term effect of cefixime treatment or any long-term treatment benefit with the addition of betamethasone to the antibiotic.", "nan", "One hundred thirty-six children with otitis media with effusion of at least 2 months' duration were investigated in a strict, double-blind, randomized prospective study to evaluate the efficacy of oral steroids in the treatment of this disease. The results of our study showed a significant complete and partial recovery from otitis media with effusion in the group treated by a combination of antibiotics (amoxicillin) and oral steroids (prednisone), compared with an amoxicillin-treated group and a placebo-treated group. We believe that this treatment mostly benefits children aged 4 to 10 years without oversized adenoids. The findings of our study imply that a combined course of antibiotics and oral steroids deserves its place as a routine conservative trial before surgery.", "Recently, new evidence-based recommendations have been introduced for diagnosing and managing otitis media with effusion (OME) in children. However, there are some difficulties to follow the general guidelines in the tertiary hospitals. The purpose is to evaluate the efficiency of antibiotics or antihistamines for treatment of children with OME in the tertiary hospital with a randomized prospective clinical study.\n Eighty-four children with OME who had been diagnosed in the tertiary hospital were randomized to receive 5 different medications for 2 weeks. We prescribed antibiotics (amoxicillin-clavulanate syrup) in Group I (n=16), antibiotics/steroids (prednisolone) in Group II (n=18), antibiotics/antihistamines (ebastine) in Group III (n=15), antibiotics/steroids/antihistamines in Group IV (n=17), and mucolytics (ivy leaf extract) in Group V (n=17) for control. We followed-up children every 2 weeks and evaluated the state of OME at 3 months.\n Thirty six (42.9%) of 84 children were resolved within average 6.9 weeks after the treatments. Thirty-six (42.9%) were treated with ventilation tube insertion and 12 patients (14.3%) were observed. There was no difference in the resolution rates of OME among the five different protocols (P>0.05). There was no difference in the resolution rates among groups who used steroids, antihistamines, steroids and antihistamines, or other medications to manage 42 children with allergies (P>0.05).\n In the tertiary hospital, the cure rate of children with OME was not as high as well-known, and antibiotics or anti-allergic medications were not more effective than control. We may, therefore, need any other guidelines which are different from the previous evidence-based recommendations, including early operation in the tertiary hospitals.", "A randomized, controlled clinical trial was conducted in 76 children to evaluate the efficacy of trimethoprim-sulfamethoxazole for 4 weeks, prednisone for 2 weeks and aluminum ibuprofen suspension for 2 weeks in resolving chronic otitis media with effusion which had persisted for more than 8 weeks. After 2 weeks of treatment resolution rates of chronic otitis media with effusion in the prednisone and trimethoprim-sulfamethoxazole groups were significantly greater than those in the control (no treatment) and ibuprofen groups. After 4 weeks the differences in resolution rates between the control, trimethoprim-sulfamethoxazole and prednisone groups became smaller. After 12 months of follow-up, differences in hearing sensitivity among study groups were not statistically significant, although 83% of patients had a 15-dB or greater hearing loss. Therefore short term antimicrobial and antiinflammatory treatment did not appear to have a long lasting effect on chronic middle ear inflammation.", "Otitis media with effusion is the most common cause of hearing loss in children. Prior studies have indicated that viable bacteria may be present in this process. A controlled clinical trial was therefore undertaken to assess the efficacy of antimicrobial agents in the treatment of this disease entity over a four week period. It appears that the use of antibiotics significantly improves the outcome in patients treated for four weeks when compared with patients observed over the same time period.", "In a randomized, double-blind, placebo-controlled trial involving 518 infants and children who had otitis media with effusion (\"secretory\" otitis media), we evaluated the efficacy of a two-week course of amoxicillin (40 mg per kilogram of body weight per day) with and without a four-week course of an oral decongestant-antihistamine combination. Among the 474 subjects who were evaluated at the four-week end point, the rate of resolution of middle-ear effusion was twice as high in those treated with amoxicillin, either with or without the decongestant-antihistamine, as in those who received placebo (P less than 0.001), but 69.8 percent of the amoxicillin-treated subjects still had effusion. Among both the amoxicillin-treated subjects and the placebo-treated subjects, resolution was more likely in those with initially unilateral effusion, in those who had had effusion for eight weeks or less, and in those without an upper respiratory tract infection at the four-week end point. Side effects were reported more often in subjects who received decongestant-antihistamine than in those who did not. Among the subjects without effusion at the four-week end point, recurrent effusion developed in approximately half those in both the amoxicillin and placebo groups during the subsequent three months. We conclude that in infants and children with otitis media with effusion, amoxicillin treatment increases to some extent the likelihood of resolution." ]

[ "4761204" ]

[ "[Tape-recorded hypnotic treatment of schizophrenia]." ]

[ "nan" ]

[ "20148739", "10634377", "19522426", "16501039", "15206484", "12734787", "16199429", "9637806", "11238496", "19396538", "16769748", "21722894", "19268929", "17803698", "17766923", "15921686", "11172832", "15840746", "18321486", "15063963", "16316811", "11994052", "16579997", "10219066", "11836287", "21193187", "11821265", "18505764", "20435692", "19158194", "14967373", "11473953", "20517830", "15482765", "16352680", "19463994", "15547527", "16827766", "15302293", "12070543" ]

[ "Clinical, metabolic, and endocrine parameters in response to metformin and lifestyle intervention in women with polycystic ovary syndrome: a randomized, double-blind, and placebo control trial.", "Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation.", "Metformin effects on clomifene-induced ovulation in the polycystic ovary syndrome.", "Endocrine and metabolic effects of rosiglitazone in overweight women with PCOS: a randomized placebo-controlled study.", "Effects of inositol on ovarian function and metabolic factors in women with PCOS: a randomized double blind placebo-controlled trial.", "Clinical, metabolic and endocrine parameters in response to metformin in obese women with polycystic ovary syndrome: a randomized, double-blind and placebo-controlled trial.", "Combined lifestyle modification and metformin in obese patients with polycystic ovary syndrome. A randomized, placebo-controlled, double-blind multicentre study.", "Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome.", "Insulin reduction with metformin increases luteal phase serum glycodelin and insulin-like growth factor-binding protein 1 concentrations and enhances uterine vascularity and blood flow in the polycystic ovary syndrome.", "Evaluating the equivalence of clomiphene citrate with and without metformin in ovulation induction in PCOS patients.", "Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial.", "The reproductive and metabolic effect of rosiglitazone on Chinese women with polycystic ovarian syndrome--a double-blind randomized placebo-controlled study.", "Metformin effects on ovarian ultrasound appearance and steroidogenic function in normal-weight normoinsulinemic women with polycystic ovary syndrome: a randomized double-blind placebo-controlled clinical trial.", "Total and high molecular weight (HMW) adiponectin levels and measures of glucose and lipid metabolism following pioglitazone treatment in a randomized placebo-controlled study in polycystic ovary syndrome.", "Efficacy of metformin in obese and non-obese women with polycystic ovary syndrome: a randomized, double-blinded, placebo-controlled cross-over trial.", "Ultra-short metformin pretreatment for clomiphene citrate-resistant polycystic ovary syndrome.", "Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone.", "Prospective parallel randomized, double-blind, double-dummy controlled clinical trial comparing clomiphene citrate and metformin as the first-line treatment for ovulation induction in nonobese anovulatory women with polycystic ovary syndrome.", "Comparison of clomiphene citrate, metformin, or the combination of both for first-line ovulation induction, achievement of pregnancy, and live birth in Asian women with polycystic ovary syndrome: a randomized controlled trial.", "The effects of metformin on insulin resistance, clomiphene-induced ovulation and pregnancy rates in women with polycystic ovary syndrome.", "Predictive value of glucose-insulin ratio in PCOS and profile of women who will benefit from metformin therapy: obese, lean, hyper or normoinsulinemic?", "Metformin does not enhance ovulation induction in clomiphene resistant polycystic ovary syndrome in clinical practice.", "Two weeks of metformin improves clomiphene citrate-induced ovulation and metabolic profiles in women with polycystic ovary syndrome.", "Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome.", "Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double blind placebo-controlled trial.", "The effects of metformin with lifestyle therapy in polycystic ovary syndrome: a randomized double-blind study.", "Co-administration of metformin during rFSH treatment in patients with clomiphene citrate-resistant polycystic ovarian syndrome: a prospective randomized trial.", "Extended-release metformin does not reduce the clomiphene citrate dose required to induce ovulation in polycystic ovary syndrome.", "PCOSMIC: a multi-centre randomized trial in women with PolyCystic Ovary Syndrome evaluating Metformin for Infertility with Clomiphene.", "Retinol-binding protein 4 in polycystic ovary syndrome--association with steroid hormones and response to pioglitazone treatment.", "Nonobese women with polycystic ovary syndrome respond better than obese women to treatment with metformin.", "Effects of metformin on ovulation rate, hormonal and metabolic profiles in women with clomiphene-resistant polycystic ovaries: a randomized, double-blinded placebo-controlled trial.", "[Indication of metformin in the management of hormonal dysfunction secondary to polycystic ovarian syndrome: prospective comparative study of 63 cases].", "Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity.", "Early effects of metformin in women with polycystic ovary syndrome: a prospective randomized, double-blind, placebo-controlled trial.", "An assessment of lifestyle modification versus medical treatment with clomiphene citrate, metformin, and clomiphene citrate-metformin in patients with polycystic ovary syndrome.", "Does metformin induce ovulation in normoandrogenic anovulatory women?", "The effect of metformin on fat distribution and the metabolic syndrome in women with polycystic ovary syndrome--a randomised, double-blind, placebo-controlled trial.", "A randomized, 48-week, placebo-controlled trial of intensive lifestyle modification and/or metformin therapy in overweight women with polycystic ovary syndrome: a pilot study.", "The effect of metformin plus clomiphene citrate on ovulation and pregnancy rates in clomiphene-resistant women with polycystic ovary syndrome." ]

[ "The aim of this study was to evaluate the effects of metformin in addition to diet and exercise on endocrine and metabolic disturbances in women with polycystic ovary syndrome (PCOS) in a prospective, double-blind, randomized, placebo (PBO) control trial. Thirty women with insulin resistance and PCOS received lifestyle modification and 1500 mg of metformin or placebo for 4 months. Before and after treatment, body mass index, waist/hip ratio, blood pressure, hirsutism, and menstrual patterns were evaluated. Serum concentrations of gonadotropins, androgens, progesterone, glucose, insulin, and lipids were measured. Lifestyle interventions resulted in similar weight and menstrual cycle's improvements in both groups. A significant reduction in serum fasting insulin, HOMA index, waist and testosterone levels was only observed with metformin. There were no significant changes in androstenedione, dehydroepiandrosterone sulfate, gonadotropins, and lipids levels. No other changes were observed in hirsutism or blood pressure. These findings suggest that metformin has an additive effect to diet and exercise to improve parameters of hyperandrogenism and insulin resistance. Although, a small decrease in body weight trough lifestyle changes could be enough to improve menstrual cycles in insulin-resistant women with PCOS.", "In the last few years some studies assessed the effects of attenuation of hyperinsulinemia and insulin resistance, obtained by insulin sensitizing agents, in women with polycystic ovary syndrome (PCOS), suggesting potential scope for these drugs in treating the whole spectrum of reproductive, endocrine, and metabolic abnormalities found in such subjects. However, the results of these studies, mostly uncontrolled and short-term, are still inconclusive, and there is no long-term follow-up. In the present study, 23 PCOS subjects [mean (+/- SE) body mass index 30.0+/-1.1 kg/m2] were randomly assigned to double-blind treatment with metformin (500 mg tid) or placebo for 6 months, while maintaining their usual eating habits. Before and after treatment, menstrual history, endocrine and metabolic profiles, serum 17-hydroxyprogesterone response to GnRH-agonist testing, and insulin sensitivity measured by the glucose clamp technique were assessed. Eighteen of these women, as well as 14 additional PCOS patients, were subsequently given metformin in an open trial for 11.0+/-1.3 months (range 4-26), to assess long-term effects of treatment and baseline predictors of metformin efficacy on reproductive abnormalities. After metformin treatment, mean frequency of menstruation improved (P = 0.002), due to striking amelioration of menstrual abnormalities in about 50% of subjects. Women given metformin showed reduced plasma insulin (at fasting: P = 0.057; during the clamp studies: P<0.01) and increased insulin sensitivity (P<0.05). Concurrently, ovarian hyperandrogenism was attenuated, as indicated by significant reductions in serum free testosterone (P<0.05) and in the 17-hydroxyprogesterone response to GnRH-agonist testing (P<0.05). No changes were found in the placebo group. Only comparable minor changes in body mass index were found both in the metformin group and in the placebo group. In the open, long-term trial 17 women (54.8%) showed striking improvements of their menstrual abnormalities and were considered as responders. Logistic regression analysis of baseline characteristics in responders and nonresponders showed that plasma insulin, serum androstenedione, and menstrual history were independent predictors of the treatment's clinical efficacy. In 10 subjects whose menses proved regular after treatment, the great majority of cycles became ovulatory (32 out of 39 assessed, 79%). In conclusion, in women with PCOS metformin treatment reduced hyperinsulinemia and hyperandrogenemia, independently of changes in body weight. In a large number of subjects these changes were associated with striking, sustained improvements in menstrual abnormalities and resumption of ovulation. Higher plasma insulin, lower serum androstenedione, and less severe menstrual abnormalities are baseline predictors of clinical response to metformin.", "Polycystic ovary syndrome (PCOS) is a common, complex endocrine disorder for women on reproductive age. A high incidence of ovulation failure is observed in PCO women and perhaps linked to insulin resistance related to metabolic features In the last few years some studies assessed hyperinsulinimea and insulin resistance attenuation effects, by insulin sensitizing agents such as metformin, in PCOS women suggesting potential scope for these drugs in CC ovulation induction quality improvement.\n Our prospective study aim is to compare the effectiveness of clomifene citrate plus metformin and clomifene citrate plus placebo in women with newly diagnosed polycystic ovary syndrome.\n From February 24 to September 29 (2007), PCOS was explored on women attending the Department of Obstetrics & Gynaecology sterility consultation unit (CHU Hedi Chaker-Sfax) according to the Rotterdam 2003 diagnostic criteria. PCOS patients were randomized to receive, in addition to clomifene citrate treatment, placebo or metformin 850 mg two times a day all ovulatory cycle for three trials maximum. Ovulation detection was done by the E2 serum measurements and ovarian transvaginal ultrasonography' evolution controlling on 7th, 11th and 13th day of the cycle.\n Within 7 months, 32 PCOS women were recruited in the study and equally allocated to the two groups. Baseline characteristics were similar in metformin group and placebo one. Ovulation was characterized by the presence of at least one mature follicle (> 16 mm), a circulating estradiol concentration in the edge of 150-250 pg and accessory an endometrial depth > 8 mm. The ovulation rate in the metformin group was 62.5% compared with 37.5% in the placebo group, a non-statistically significant (small study population) but important difference (1.66 times). Analyses show a higher mature follicle number and estradiol concentration in metformin group than in the placebo one. Metformin effect was, in our study, his only insulinosensitizer property consequence far away a 'making thinner' or Hyperandrogenism reducing ones.\n The ovulatory response to clomifene can be increased in polycystic ovary syndrome women by decreasing insulin secretion with metformin.", "The objective of the study was to assess the therapeutic effects of rosiglitazone in overweight women with polycystic ovary syndrome (PCOS).\n A double-blind, placebo-controlled study was conducted on 30 (BMI > 25 kg/m2, mean age 29.1 +/- 1.2 years) overweight women with PCOS treated with rosiglitazone or placebo for 4 months. Waist-to-hip ratios (WHRs), serum concentrations of sex hormones and binding proteins, blood glucose, serum insulin and serum C-peptide during a 75-g oral glucose tolerance test (OGTT), first-phase insulin secretion as determined by an intravenous glucose tolerance test (IVGTT), M values (expressing insulin sensitivity using a euglycaemic clamp) and calorimetric data were assessed at 0 and 4 months of treatment.\n Rosiglitazone improved menstrual cyclicity, increased serum sex hormone-binding globulin (SHBG) levels and decreased serum levels of androstenedione, 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEA-S). Glucose tolerance [expressed as AUC(glucose) during the OGTT] improved (P = 0.002) and peripheral insulin response (expressed as AUC(insulin)) decreased (P = 0.004) in the rosiglitazone group (ROSI group). M value improved in the ROSI group from 33.4 +/- 3.27 to 40.0 +/- 5.51 micromol/kg min (P = 0.04).\n Rosiglitazone, by improving menstrual cyclicity, hyperandrogenism, insulin resistance and hyperinsulinaemia, represents an alternative treatment for overweight anovulatory women with PCOS and no pregnancy desire.", "Women with oligomenorrhea and polycystic ovaries show a high incidence of ovulation failure perhaps linked to insulin resistance and related metabolic features. A small number of reports shows that inositol improves ovarian function. Futhermore, in these trials the quality of evidence supporting ovulation is suboptimal, and few studies have been placebo-controlled. The aim of this study was to use a double-blind, placebo-controlled approach with detailed assessment of ovarian activity (two blood samples per week) to assess the validity of this therapeutic approach in this group of women.\n Of the 283 patients randomized, 2 withdrew before treatment commenced, 147 received placebo, and 136 received inositol (100 mg, twice a day). The women which discontined the study prematurely were more numerous in the treatment group (n = 45) than the placebo group (n = 15; P < 0.05).\n The ovulation frequency estimated by the ratio of luteal phase weeks to observation weeks was significantly (P < 0.01) higher in the treated group (23%) compared with the placebo (13%). The time in which the first ovulation occurred was significantly (P < 0.05) shorter [23.6 d; 95% confidence interval (CI), 17, 30; compared with 41.8 d; 95% CI, 28, 56]. The number of patients failing to ovulate during the placebo-treatment period was higher (P < 0.05) in the placebo group, and in most cases ovulations were characterized by normal progesterone concentrations in both groups. The effect of inositol on follicular maturation was rapid, because the circulating concentration of E2 increased only in the inositol group during the first week of treatment. Significant (P < 0.01) weight loss (and leptin reduction) was recorded in the inositol group, whereas in the placebo group was recorded an increase of the weight (P < 0.05). A significant increase in circulating high-density lipoprotein was observed only in the inositol-treated group. Metabolic risk factor benefits of inositol treatment were not observed in the morbidly obese subgroup of patients (body mass index > 37). No change in fasting glucose concentrations, fasting insulin, or insulin responses to glucose challenge test was recorded after 14-wk of inositol and placebo therapy. There was an inverse relationship between body mass of the patients and the efficacy of the treatment.\n These data support a beneficial effect of inositol in improving ovarian function in women with oligomenorrhea and polycystic ovaries.", "There is still some controversy concerning the effects of metformin in the treatment of Polycystic Ovary Syndrome (PCOS). The aim of this study was to asses the effect of metformin on clinical, metabolic and hormone parameters in obese women with PCOS. Thirty obese, non-diabetic women with PCOS received 500 mg of metformin or placebo, TID, over 90 days. Assessed parameters included body mass index, waist-to-hip ratio, blood pressure, FSH, LH, total testosterone, SHBG, fasting insulinemia, insulin-to-glucose ratio, total, HDL and LDL cholesterol, triglycerides, and menstrual cycles before and after the use of the drugs. Before treatment, patients did not differ in the two groups. After 90 days of metformin use, PCOS women presented significantly lower levels of total testosterone (p = 0.030) and total cholesterol (p = 0.023) compared to the women that used placebo. The other parameters did not differ between the groups. In conclusion, obese women with PCOS may benefit from the use of metformin through the reduction of hyperandrogenemia, total cholesterol, and possibly by restoration of regular menstrual cycles. Further studies with longer follow-ups are necessary to determine cardiovascular and endometrial metformin benefits and insulin-resistance decrease in women with polycystic ovary syndrome.", "It has been reported that women with polycystic ovary syndrome (PCOS) benefit from metformin therapy.\n A randomized, placebo-controlled, double-blind study of obese (body mass index >30 kg/m2), oligo-/amenorrhoeic women with PCOS. Metformin (850 mg) twice daily was compared with placebo over 6 months. All received the same advice from a dietitian. The primary outcome measures were: (i) change in menstrual cycle; (ii) change in arthropometric measurements; and (iii) changes in the endocrine parameters, insulin sensitivity and lipid profile.\n A total of 143 subjects was randomized [metformin (MET) = 69; placebo (PL) = 74]. Both groups showed significant improvements in menstrual frequency [median increase (MET = 1, P < 0.001; PL = 1, P < 0.001)] and weight loss [mean (kg) (MET = 2.84; P < 0.001 and PL = 1.46; P = 0.011)]. However, there were no significant differences between the groups. Logistic regression analysis was used to analyse the independent variables (metformin, percentage of weight loss, initial BMI and age) in order to predict the improvement of menses. Only the percentage weight loss correlated with an improvement in menses (regression coefficient = 0.199, P = 0.047, odds ratio = 1.126, 95% CI 1.001, 1.266). There were no significant changes in insulin sensitivity or lipid profiles in either of the groups. Those who received metformin achieved a significant reduction in waist circumference and free androgen index.\n Metformin does not improve weight loss or menstrual frequency in obese patients with PCOS. Weight loss alone through lifestyle changes improves menstrual frequency.", "Obese women with the polycystic ovary syndrome are relatively unresponsive to the induction of ovulation by clomiphene. We hypothesized that reducing insulin secretion by administering metformin would increase the ovulatory response to clomiphene.\n We performed oral glucose-tolerance tests before and after the administration of 500 mg of metformin or placebo three times daily for 35 days in 61 obese women with the polycystic ovary syndrome. Women who did not ovulate spontaneously were then given 50 mg of clomiphene daily for five days while continuing to take metformin or placebo. Serum progesterone was measured on days 14, 28, 35, 44, and 53, and ovulation was presumed to have occurred if the concentration exceeded 8 ng per milliliter (26 nmol per liter) on any of these days.\n Twenty-one women in the metformin group and 25 women in the placebo group were given clomiphene because they did not ovulate spontaneously during the first phase of the study. Among the 21 women given metformin plus clomiphene, the mean (+/-SE) area under the serum insulin curve after oral glucose administration decreased from 6745+/-2021 to 3479+/-455 microU per milliliter per minute (40.5+/-12.1 to 20.9+/-2.7 nmol per liter per minute, P=0.03), but it did not change significantly in the 25 women given placebo plus clomiphene. Nineteen of the 21 women (90 percent) who received metformin plus clomiphene ovulated (mean peak serum progesterone concentration, 23.8+/-3.4 ng per milliliter [7.6+/-10.9 nmol per liter]). Two of the 25 women (8 percent) who received placebo plus clomiphene ovulated (P<0.001). Overall, 31 of the 35 women (89 percent) treated with metformin ovulated spontaneously or in response to clomiphene, as compared with 3 of the 26 women (12 percent) treated with placebo.\n The ovulatory response to clomiphene can be increased in obese women with the polycystic ovary syndrome by decreasing insulin secretion with metformin.", "We hypothesized that hyperinsulinemia contributes to early pregnancy loss in the polycystic ovary syndrome by adversely affecting endometrial function and environment. Serum glycodelin, a putative biomarker of endometrial function, is decreased in women with early pregnancy loss. Insulin-like growth factor-binding protein-1 may also play an important role in pregnancy by facilitating adhesion processes at the feto-maternal interface. We studied 48 women with polycystic ovary syndrome before and after 4 weeks of administration of 500 mg metformin (n = 26) or placebo (n = 22) 3 times daily. Oral glucose tolerance tests were performed, and serum glycodelin and insulin-like growth factor-binding protein-1 were measured during the follicular and clomiphene-induced luteal phases of menses. In the metformin group, the mean (+/-SE) area under the serum insulin curve after glucose administration decreased from 62 +/- 6 to 19 +/- 2 nmol/L.min (P < 0.001). Follicular phase serum glycodelin concentrations increased 20-fold from 150 +/- 46 to 2813 +/- 1192 pmol/L (P < 0.001), and serum insulin-like-growth factor-binding protein-1 concentrations increased from 936 +/- 152 to 2396 +/- 300 pmol/L (P < 0.001). Similarly, luteal phase serum glycodelin concentrations increased 3-fold from 3434 +/- 1299 to 10624 +/- 1803 pmol/L (P < 0.001), and serum insulin-like growth factor-binding protein-1 concentrations increased from 1220 +/- 136 to 4916 +/- 596 pmol/L (P < 0.001). Uterine vascular penetration also increased in the metformin group, as did blood flow of spiral arteries, as demonstrated by a 20% decrease in the resistance index from 0.71 +/- 0.02 to 0.57 +/- 0.03 (P < 0.001). These variables did not change in the placebo group. We conclude that insulin reduction with metformin increases follicular and luteal phase serum glycodelin and insulin-like growth factor-binding protein-1 concentrations and enhances luteal phase uterine vascularity and blood flow in the polycystic ovary syndrome. These changes may reflect an improved endometrial milieu for the establishment and maintenance of pregnancy.", "To evaluate the benefit of Metformin added to Clomiphene Citrate in a primary ovulation induction protocol in PCOS patients.\n Prospective randomised controlled study.\n Tygerberg Academic Hospital, Stellenbosch University and the Institute of Reproductive Medicine at Vincent Pallotti Hospital, Cape Town.\n 107 patients presenting with PCOS.\n Group A was pre-treated with metformin 850 mg twice a day for at least 6 weeks before clomiphene was added and the metformin was used throughout the study period. Group B received clomiphene without pre-treatment with metformin. In both groups clomiphene was given at a starting dose of 50 mg day 4-8 and increase with increments of 50 mg to a maximum of 150 mg if no response was achieved.\n The ovulation rate achieved in women in the M+C/C arm was 34/52 (65.4%) compared to 36/55 (65.5%) in the C/C arm. The treatment effect ((M+C/C) - C/C) is 0% with 95% confidence interval of -18.1% to 18%. The per protocol ovulation results were 34/42 (81%) in the M+C/C arm compared to 36/48 (75%) in the C/C arm. The ovulation rate difference was 6% with 95% confidence interval -11% to 22%. In a comparison of successful ovulating versus non-ovulating women from the trial the following were significant baseline determinants: lower median weight in the ovulating group (77 kg versus 86 kg, p = .021), lower median bmi (29.0 versus 32.9, p = .009), lower median DHEAS at baseline (4.6 compared to 7.0, p = .049), lower median 17OH-progesterone (2.2 versus 4.6, p = .027) and higher baseline median SHBG ( 37.8 compared to 28.5, p = .036).\n Although identical ovulation rates were observed in both arms equivalence could not be concluded with respect to the specified criteria.", "To compare the effectiveness of clomifene citrate plus metformin and clomifene citrate plus placebo in women with newly diagnosed polycystic ovary syndrome.\n Randomised clinical trial.\n Multicentre trial in 20 Dutch hospitals.\n 228 women with polycystic ovary syndrome.\n Clomifene citrate plus metformin or clomifene citrate plus placebo.\n The primary outcome measure was ovulation. Secondary outcome measures were ongoing pregnancy, spontaneous abortion, and clomifene resistance.\n 111 women were allocated to clomifene citrate plus metformin (metformin group) and 114 women were allocated to clomifene citrate plus placebo (placebo group). The ovulation rate in the metformin group was 64% compared with 72% in the placebo group, a non-significant difference (risk difference - 8%, 95% confidence interval - 20% to 4%). There were no significant differences in either rate of ongoing pregnancy (40% v 46%; - 6%, - 20% to 7%) or rate of spontaneous abortion (12% v 11%; 1%, - 7% to 10%). A significantly larger proportion of women in the metformin group discontinued treatment because of side effects (16% v 5%; 11%, 5% to 16%).\n Metformin is not an effective addition to clomifene citrate as the primary method of inducing ovulation in women with polycystic ovary syndrome.\n Current Controlled Trials ISRCTN55906981 [controlled-trials.com].", "To investigate whether an insulin sensitizer has any effect on amenorrhea and clinical and biochemical hyperandrogenism in Chinese women with polycystic ovarian syndrome (PCOS).\n Randomized controlled double-blind trial.\n A tertiary referral center, Hong Kong.\n Chinese women who fulfilled the Rotterdam criteria of PCOS (n = 70).\n Rosiglitazone 4 mg daily for the first month followed by 4 mg twice daily for 11 months.\n Menstrual status as well as clinical and biochemical hyperandrogenism.\n There is a significantly higher rate of regular menses among the treatment arm (16 [50.0%] of 32 vs 4 [11.8%] of 34) at 6 months and the improvement appeared to be sustained (10 [41.7%] of 24 vs 6 [20.0%] of 30) at 12 months. There was no change in the acne and hirsutism scores as well as serum T levels in both arms.\n We found a possible benefit in menstrual cyclicity but a lack of improvement in hyperandrogenism in our Chinese population.\n ChiCTR-TRC-09000670 (Chinese Clinical Trial Registry).\n Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.", "To investigate metformin effects on the endocrine-metabolic parameters and ovarian morphology in normoinsulinemic women with polycystic ovary syndrome (PCOS).\n Randomized double-blind study.\n Operative Division of Endocrinological Gynecology, Università Cattolica del Sacro Cuore.\n Twenty-eight normal-weight normoinsulinemic PCOS women.\n Patients were randomized to receive metformin 500 mg twice a day (group A, 15 subjects) or placebo (group B, 13 subjects) for 6 months. Ultrasonographic pelvic exams, hormonal and lipid features, and oral glucose tolerance test were performed at baseline and after 3 and 6 months of treatment.\n Hormonal and glycoinsulinemic assessment, ovarian ultrasound appearance.\n Glycoinsulinemic assessment remained unvaried in both groups. About 70% of patients in group A experienced a restoration of menstrual cyclicity. Metformin significantly decreased testosterone levels at 3 and 6 months) and 17-hydroxyprogesterone levels at 6 months, and improved hirsutism score at 6 months. No clinical or hormonal modifications occurred in group B. Metformin, but not placebo, reduced ovarian volume and stromal/total area ratio at 3 and 6 months.\n Metformin seems to improve the menstrual pattern and ultrasonographic ovarian features in normoinsulinemic PCOS women. These effects seem to be, at least in part, independent of the insulin-lowering properties of the drug.\n Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.", "Recent studies suggested that the effect of adiponectin on insulin-stimulated glucose metabolism is mediated primarily by the high molecular weight (HMW) form of adiponectin. In the present study we evaluated total and HMW adiponectin in polycystic ovary syndrome (PCOS) patients and controls and examined possible mechanisms for increased insulin sensitivity during pioglitazone treatment.\n Thirty PCOS patients randomized to pioglitazone, 30 mg/day, or placebo for 16 weeks and 14 weight-matched healthy females were studied.\n Total and HMW adiponectin levels were measured, and euglycaemic hyperinsulinaemic clamps and indirect calorimetry were performed. Delta-values denoted changes during pioglitazone treatment (16 weeks--basal).\n Pretreatment adiponectin levels were decreased in PCOS patients vs. controls (P < 0.05), whereas no significant differences were found in HMW adiponectin levels. Following pioglitazone treatment, total and HMW adiponectin increased (all P < 0.05), whereas no significant changes were observed with placebo. Delta-total adiponectin levels correlated positively with the rate of Delta-insulin-stimulated glucose disposal (R(d)) (r = 0.89) and Delta-oxidative glucose metabolism (r = 0.71) and inversely with Delta-fasting free fatty acid (FFA) levels (r = -0.69) and Delta-lipid oxidation (r = -0.73) during insulin stimulation (all P < 0.01). Weaker correlations were found between Delta-HMW adiponectin levels and Delta-measures of glucose and lipid metabolism during insulin stimulation than with Delta-total adiponectin.\n A close correlation between increased total adiponectin levels and increased insulin-stimulated glucose metabolism during pioglitzone treatment supports the hypothesis that the insulin-sensitizing effect of pioglitazone in PCOS is, at least in part, mediated by adiponectin. Measures of changes in HMW adiponectin did not add further information to this relationship.", "Our aim was to assess the effects of metformin on menstrual frequency, fasting plasma glucose (FPG), insulin resistance assessed as HOMA-index, weight, waist/hip ratio, blood pressure (BP), serum lipids, and testosterone levels in women with polycystic ovary syndrome (PCOS) METHODS: In a randomized, controlled, double-blinded setup, 56 women aged 18-45 with PCOS were treated with either metformin 850 mg or placebo twice daily for 6 months. After a wash-out period of 3 months participants received the alternate treatment for 6 months. The changes in the measured parameters were analysed by intention-to-treat and per protocol.\n There were no changes in menstrual frequency. In the intention-to-treat analysis, weight and systolic BP were reduced on metformin treatment (p=0.009 and 0.047, respectively), while high-density lipoprotein (HDL) increased (p=0.001). On placebo, weight and FPG increased (p<0.05). Post-hoc subgrouping according to BMI revealed reductions in testosterone (p=0.013), FPG (p=0.018), insulin (p=0.045) and HOMA-index (p=0.022) in obese women. Per protocol analysis showed the following differences between the changes on placebo and metformin (mean (5 - 95 % percentiles): weight (-4.2 (-7.0, -1.9) kg, p<0.001), FPG (-0.23 (-0.44, -0.01) mmol/l, p=0.041), insulin (-4.17 (-8.10, -0.23) mIU/l, p=0.039) and HOMA index (-1.50 (-2.53, -0.47) mIU/l*mmol/l, p=0.006). Weight, FPG and HOMA index were lower after metformin than after placebo.\n Metformin treatment lowered weight and systolic blood pressure and increased HDL in women with PCOS. In post-hoc analysis it increased insulin sensitivity and lowered testosterone in obese women. Non-obese women did not benefit from metformin.", "To evaluate the effect of ultra-short (12 days) metformin pretreatment in clomiphene-citrate (CC) resistant polycystic ovary syndrome (PCOS).\n Eighty women with CC-resistant PCOS were randomly allocated to metformin pretreatment or usual treatment. Forty women received 1500 mg metformin daily for 12 days, followed by clomiphene 150 mg daily for 5 days along with metformin. Forty women (control group) received the same dose of clomiphene but no metformin pretreatment.\n In the metformin group, 17 (42.5%) women ovulated, and 6 (15%) conceived. In the control group, 5 (12.5%) women ovulated but none conceived. Compared with the control group, the metformin group had significantly higher ovulation (P = 0.03) and pregnancy rates (P = 0.026).\n Twelve days of metformin pretreatment improves ovulation and pregnancy rates in women with CC-resistant PCOS.", "To determine whether metformin treatment increases the ovulation and pregnancy rates in response to clomiphene citrate (CC) in women who are resistant to CC alone.\n Randomized, double-blind, placebo-controlled trial.\n Multicenter environment.\n Anovulatory women with the polycystic ovary syndrome (PCOS) who were resistant to CC.\n Participants received placebo or metformin, 500 mg three times daily, for 7 weeks. Information on reproductive steroids, gonadotropins, and oral glucose tolerance testing was obtained at baseline and after treatment. Metformin or placebo was continued and CC treatment was begun at 50 mg daily for 5 days. Serum P level > or =4 ng/mL was considered to indicate ovulation. With ovulation, the daily CC dose was not changed, but with anovulation it was increased by 50 mg for the next cycle. Patients completed the study when they had had six ovulatory cycles, became pregnant, or experienced anovulation while receiving 150 mg of CC.\n Ovulation and pregnancy rates.\n In the metformin and placebo groups, 9 of 12 participants (75%) and 4 of 15 participants (27%) ovulated, and 6 of 11 participants (55%) and 1 of 14 participants (7%) conceived, respectively. Comparisons between the groups were significant.\n In anovulatory women with PCOS who are resistant to CC, metformin use significantly increased the ovulation rate and pregnancy rate from CC treatment.", "Although metformin has been shown to be effective in the treatment of anovulation in women with polycystic ovary syndrome (PCOS), clomiphene citrate (CC) is still considered to be the first-line drug to induce ovulation in these patients.\n The goal of this study was to compare the effectiveness of metformin and CC administration as a first-line treatment in anovulatory women with PCOS.\n We describe a prospective parallel randomized, double-blind, double-dummy controlled clinical trial.\n The study was conducted at the University \"Magna Graecia\" of Catanzaro, Catanzaro, Italy.\n One hundred nonobese primary infertile anovulatory women with PCOS participated.\n We administered metformin cloridrate (850 mg twice daily) plus placebo (group A) or placebo plus CC (150 mg for 5 d from the third day of a progesterone withdrawal bleeding) (group B) for 6 months each.\n The main outcome measures were ovulation, pregnancy, abortion, and live-birth rates.\n The subjects of groups A (n = 45) and B (n = 47) were studied for a total of 205 and 221 cycles, respectively. The ovulation rate was not statistically different between either treatment group (62.9 vs. 67.0%, P = 0.38), whereas the pregnancy rate was significantly higher in group A than group B (15.1 vs. 7.2%, P = 0.009). The difference found between groups A and B regarding the abortion rate was significant (9.7 vs. 37.5%, P = 0.045), whereas a positive trend was observed for the live-birth rate (83.9 vs. 56.3%, P = 0.07). The cumulative pregnancy rate was significantly higher in group A than group B (68.9 vs. 34.0%, P < 0.001).\n Six-month metformin administration is significantly more effective than six-cycle CC treatment in improving fertility in anovulatory nonobese PCOS women.", "To determine the first-line medication to be used in anovulatory patients with polycystic ovary syndrome (PCOS) for ovulation induction and pregnancy achievement.\n Randomized controlled trial.\n Infertility unit of a public hospital.\n One hundred fifteen newly diagnosed patients with PCOS based on ESHRE/ASRM criteria.\n These patients were assigned to three groups: group 1 (38 patients) received 500 mg of metformin three times a day; group 2 (39 patients) received clomiphene citrate (CC) at an incremental dose; group 3 (38 patients) received both medications.\n Rates of ovulation, pregnancy (PR), and live birth.\n The ovulation rate was 23.7% in the metformin group, 59% in the CC group, and 68.4% in the combination treatment group. This was translated into a similar PR and live birth rate, which were higher in the CC and combination groups compared to the metformin group (PR: 7.9%, 15.4%, and 21.1%; live birth rate: 7.9%, 15.4%, and 18.4% in metformin, CC, and combination treatment groups, respectively), although statistically the differences were not significant. There were no multiple pregnancies and the rate of spontaneous first trimester loss was similar to the general population.\n Clomiphene citrate should be the first-line treatment for ovulation induction in anovulatory patients with PCOS.", "To evaluate the effects of metformin on insulin resistance, ovarian androgen production, and clomiphene-induced ovulation and pregnancy rates in infertile women with polycystic ovary syndrome (PCOS).\n Twenty-one infertile women with PCOS were selected in this prospective randomized clinical study. Basal steroid and gonadotropin levels were measured, and oral glucose tolerance test (OGTT) was performed. The patients were divided randomly into group 1 (n = 11) and group 2 (n = 10). Group 1 patients were treated with 1700 mg per day of metformin for 3 months. The basal tests and OGTT were repeated after metformin therapy. Group 2 patients did not receive metformin. The patients in both groups received 100 mg of clomiphene citrate (CC) daily for 5 days until either a pregnancy occurred, or six CC cycles were reached. Metformin administration continued during CC therapy until the day of hCG in group 1. Serum progesterone (P) level >or=5 ng/ml was considered as confirmatory of ovulation. Ovulation and pregnancy rates after six cycles were determined.\n Serum androgens and insulin response to OGTT decreased significantly after metformin therapy. Midluteal serum P level was significantly higher in cycles treated with metformin plus CC (P < 0.05). The ovulation (38 of 51 cycles, 74.4% versus 34 of 55 cycles, 61.8%) and pregnancy rates (5 of 11 women, 45.5% versus 3 of 10 women, 30%) were higher, but not significantly, in the metformin plus CC group than in the CC alone group. All the patients who conceived had insulin resistance in group 1 whereas non-insulin resistance in group 2.\n Metformin improves insulin resistance and reduces androgen levels. Metformin did not increase significantly the ovulation and pregnancy rates.", "The aim of the present study is to evaluate sub-groups of PCOS patients who will benefit from metformin therapy and to find out any predictors of ovulation in PCOS sub-groups.\n In the current prospective-randomized, placebo-controlled, double-blind study, PCOS patients (n = 116) were divided into six main groups according to glucose to insulin ratio (G-I ratio mg/10(-4) U) and body mass index (BMI kg/m2) as: Group 1: normoinsulinemic (G-I ratio > or = 4.5 mg/10(-4) U), lean (BMI < 25) (n = 37); Group 2: normoinsulinemic, overweight (BMI: 25-29.9) (n = 19); Group 3: normoinsulinemic, obese (BMI > or = 30) (n = 18); Group 4: hyperinsulinemic (G-I ratio < 4.5 mg/10(-4) U), lean (n = 28); Group 5: hyperinsulinemic, overweight (n = 17); Group 6: hyperinsulinemic, obese (n = 20). Patients in each group were randomized onto placebo or metformin treatments (850 mg two to three times per day according to BMI). The rate of ovulation, biochemical profile, hormonal profile and clinical symptoms of hyperandrogenism were evaluated before and after 6 months of metformin and placebo treatments.\n We observed a significant decrease in WHR following metformin therapy in the normoinsulinemic overweight sub-group (P < 0.05). The duration of the menstrual cycle significantly decreased in the normoinsulinemic obese sub-group on metformin therapy (P < 0.05). Metformin had a significant effect on hirsutism scores in hyperinsulinemic lean women (P < 0.05) and decreased DHEAS levels significantly in the lean hyperinsulinemic and normoinsulinemic groups (P < 0.05). Metformin had significant effects on ovulation in only lean hyperinsulinemic women (P < 0.05).\n Clinical outcomes of metformin therapy may be categorized on the basis of basal BMI and insulin levels in PCOS patients.", "To determine whether metformin pretreatment has beneficial effects in clomiphene resistant infertile women with polycystic ovary syndrome (PCOS) in an infertility clinic.\n This was a randomized placebo controlled double-blind crossover study of 3 months metformin (1500 mg day-1)/placebo, followed by 3 months metformin/placebo together with clomiphene (50-100 mg for 5 days) for three cycles in clomiphene resistant women with PCOS. The primary outcomes were restoration of spontaneous menses, ovulation induction (spontaneous or clomiphene induced) and pregnancy. Secondary endpoints were changes in biochemical parameters related to androgens and insulin.\n Twelve women completed the metformin arm and 14 the placebo arm. Spontaneous menstruation resumed in five metformin treated patients and in six placebo treated women, P=0.63. No women given metformin spontaneously ovulated, although one patient given placebo did, P=0.30. There was no difference in the efficacy of clomiphene between the two groups with ovulation being induced in five (out of 12) metformin treated women and four (out of 14) placebo treated women, P=0.63. Pregnancy occurred in three (out of 12) women given metformin and two (out of 14) women given placebo, P=0.59.\n Metformin is not always beneficial when given to clomiphene resistant infertile women with PCOS in clinical practice.", "To determine if short courses of metformin (MET) administration in patients with polycystic ovary syndrome (PCOS) would reduce fasting insulin and improve the efficacy of clomiphene citrate (CC) to induce ovulation.\n A randomized prospective trial involving 31 subjects with PCOS and infertility.\n University-based medical center.\n Obese patients (body mass index > 29 kg/m2) with PCOS.\n Patients with PCOS were treated either with CC or CC+MET for 2 weeks.\n Ovulation as determined by serum P, serum insulin, and total and free T.\n In the CC/MET group, a significant increase in sex hormone-binding globulin (SHBG) levels, a decrease in fasting insulin, and an increase in fasting glucose/fasting insulin was detected on day 21 of the cycle. Of these parameters, only SHBG levels increased significantly in the CC group. In the CC/MET group, a significant increase in day 21 progesterone occurred, with 44% of subjects ovulating in the CC+MET group as compared with 6.7% in the CC group. Five subjects in the CC+MET group and none in the CC group conceived. Total and free testosterone levels did not change significantly for either group.\n In obese PCOS patients, 2 weeks of MET significantly reduces serum insulin and insulin resistance and increases SHBG levels, resulting in an improved response to CC. This regimen may be beneficial in noncompliant patients or those with intolerance to the side effects of MET.", "Women with the polycystic ovary syndrome have insulin resistance and hyperinsulinemia, possibly because of a deficiency of a D-chiro-inositol-containing phosphoglycan that mediates the action of insulin. We hypothesized that the administration of D-chiro-inositol would replenish stores of the mediator and improve insulin sensitivity.\n We measured steroids in serum and performed oral glucose-tolerance tests before and after the oral administration of 1200 mg of D-chiro-inositol or placebo once daily for six to eight weeks in 44 obese women with the polycystic ovary syndrome. The serum progesterone concentration was measured weekly to monitor for ovulation.\n In the 22 women given D-chiro-inositol, the mean (+/-SD) area under the plasma insulin curve after the oral administration of glucose decreased from 13,417+/-11,572 to 5158+/-6714 microU per milliliter per minute (81+/-69 to 31+/-40 nmol per liter per minute) (P=0.007; P=0.07 for the comparison of this change with the change in the placebo group); glucose tolerance did not change significantly. The serum free testosterone concentration in these 22 women decreased from 1.1+/-0.8 to 0.5+/-0.5 ng per deciliter (38+/-7 to 17+/-3 pmol per liter) (P=0.006 for the comparison with the change in the placebo group). The women's diastolic and systolic blood pressure decreased by 4 mm Hg (P<0.001 and P=0.05, respectively, for the comparisons with the changes in the placebo group), and their plasma triglyceride concentrations decreased from 184+/-88 to 110+/-61 mg per deciliter (2.1+/-0.2 to 1.2+/-0.1 mmol per liter) (P=0.002 for the comparison with the change in the placebo group). None of these variables changed appreciably in the placebo group. Nineteen of the 22 women who received D-chiro-inositol ovulated, as compared with 6 of the 22 women in the placebo group (P<0.001).\n D-Chiro-inositol increases the action of insulin in patients with the polycystic ovary syndrome, thereby improving ovulatory function and decreasing serum androgen concentrations, blood pressure, and plasma triglyceride concentrations.", "Women with oligomenorrhea and polycystic ovaries show a high incidence of ovulation failure perhaps linked to insulin resistance and related metabolic features. A number of reports show that the biguanide metformin improves ovarian function. However, in these trials the quality of evidence supporting ovulation is suboptimal, and few studies have been placebo-controlled. The aim of our study was to use a double-blind, placebo-controlled approach with detailed assessment of ovarian activity (two blood samples per week) to assess the validity of this therapeutic approach in this group of women. Of the 94 patients randomized, 2 withdrew before treatment commenced, 47 received placebo, and 45 received metformin (850 mg, twice a day). The numbers discontinuing the study prematurely were higher in the treatment group (n = 15) than the placebo group (n = 5; P < 0.05). The ovulation frequency assessed by the ratio of luteal phase weeks to observation weeks was significantly (P < 0.01) higher in the treated group (23%) compared with the placebo (13%), and the time to first ovulation was significantly (P < 0.05) shorter [23.6 d; 95% confidence interval (CI), 17, 30; compared with 41.8 d; 95% CI, 28, 56]. The proportion of patients failing to ovulate during the placebo-treatment period was higher (P < 0.05) in the placebo group, and the majority of ovulations were characterized by normal progesterone concentrations in both groups. The effect of metformin on follicular maturation was rapid, because the E2 circulating concentration increased over the first week of treatment only in the metformin group. Significant (P < 0.01) weight loss (and leptin reduction) was recorded in the metformin group, whereas the placebo group actually increased weight (P < 0.05). A significant increase in circulating high-density lipoprotein was observed only in the metformin-treated group. Metabolic risk factor benefits of metformin treatment were not observed in the morbidly obese subgroup of patients (body mass index > 37). No change in fasting glucose concentrations, fasting insulin, or insulin responses to glucose challenge was recorded after 14-wk metformin or placebo therapy. There was an inverse relationship between body mass and treatment efficacy. We show in a large randomized placebo-controlled trial that metformin treatment improves ovulation frequency in women with abnormal ovarian function and polycystic ovaries significantly but to a modest degree, and protracted treatment improves cardiovascular risk factors. These data support a beneficial effect of metformin in improving ovarian function in women with oligomenorrhea and polycystic ovaries.", "To determine if the combination of lifestyle (caloric restriction and exercise) and metformin (MET) would be superior to lifestyle and placebo (PBO) in improving the polycystic ovary syndrome (PCOS) phenotype.\n Double-blind randomized 6-month trial of MET versus PBO.\n Two academic medical centers.\n One hundred fourteen subjects with PCOS were randomized to MET (N = 55) or PBO (N = 59).\n Subjects collected urine daily for ovulation monitoring, had monthly monitoring of hormones and weight and determination of body composition by dual-energy x-ray absorptiometry, glucose tolerance, and were evaluated for quality of life at baseline and completion.\n Ovulation rates and testosterone levels.\n Dropout rates were high. There was no significant difference in ovulation rates. Testosterone levels were significantly lower compared with baseline in the MET group at 3 mos but not at 6 mos. There were no differences in weight loss between groups, but MET showed a significant decline at 6 months compared with baseline (-3.4 kg, 95% confidence interval -5.3 to -1.5 kg). We noted divergent effects of MET versus PBO on oral glucose tolerance test indices of insulin sensitivity (increased) and secretion (worsened). Total bone mineral density increased significantly in MET. There were no differences in quality of life measures between the groups. The MET group had increased diarrhea and headache, but fewer bladder infections and musculoskeletal complaints.\n The addition of metformin to lifestyle therapy produced little reproductive or glycemic benefit in women with PCOS, although our study had limited power owing to a high dropout rate. It is not possible at baseline to identify women likely to drop out.\n Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.", "This study aims to evaluate the impact of metformin on ovarian response when co-administered during recombinant (r)FSH using the low-dose step-up protocol in clomiphene citrate-resistant polycystic ovarian syndrome (PCOS) patients with normal glucose tolerance.\n Thirty-two patients were randomized to metformin (n = 16) and placebo (n = 16) groups. Hormonal assessment, a 75 g oral glucose tolerance test (OGTT) and a frequently sampled i.v. glucose tolerance test (FSIGTT) were performed before and after oral administration of metformin (850 mg twice daily) or placebo for 6 weeks. Recombinant FSH treatment was undertaken, thereafter, in women who did not ovulate on metformin (n = 10) or placebo (n = 15). There was no significant change in all insulin sensitivity indices in both groups. The only change noted was a decline in mean serum free testosterone concentration in the metformin group (P = 0.049). One patient on placebo and six patients on metformin ovulated spontaneously (P < 0.05). All parameters of ovarian response were comparable between the two groups during rFSH treatment. Combining the 6 week placebo or metformin-only period with a single rFSH treatment cycle, the overall ovulation rates were 75 and 94% in the placebo and metformin groups respectively (P > 0.05). The respective figures for pregnancy were 6.3 and 31.3% (P > 0.05).\n Metformin may restore ovulation with no improvement on insulin resistance in clomiphene citrate-resistant PCOS patients with normal glucose tolerance, but has no significant effect on ovarian response during rFSH treatment.", "When used for ovulation induction, higher doses of clomiphene may lead to antiestrogenic side effects that reduce fecundity. It has been suggested that metformin in combination with clomiphene can restore ovulation to some clomiphene-resistant anovulators with polycystic ovary syndrome (PCOS).\n Our objective was to determine if cotreatment with extended-release metformin (metformin XR) can lower the threshold dose of clomiphene needed to induce ovulation in women with PCOS.\n A secondary analysis of data from the National Institute of Child Health and Human Development Cooperative Multicenter Reproductive Medicine Network prospective, double-blind, placebo-controlled multicenter clinical trial, Pregnancy in Polycystic Ovary Syndrome, was performed.\n Study volunteers at multiple academic medical centers were included.\n Women with PCOS and elevated serum testosterone who were randomized to clomiphene alone or with metformin (n = 209 in each group) were included in the study.\n Clomiphene citrate, 50 mg daily for 5 d, was increased to 100 and 150 mg in subsequent cycles if ovulation was not achieved; half also received metformin XR, 1000 mg twice daily. Treatment was for up to 30 wk or six cycles, or until first pregnancy.\n Ovulation was confirmed by a serum progesterone more than or equal to 5 ng/ml, drawn prospectively every 1-2 wk.\n The overall prevalence of at least one ovulation after clomiphene was 75 and 83% (P = 0.04) for the clomiphene-only and clomiphene plus metformin groups, respectively. Using available data from 314 ovulators, the frequency distribution of the lowest clomiphene dose (50, 100, or 150 mg daily) resulting in ovulation was indistinguishable between the two treatment groups.\n Metformin XR does not reduce the lowest dose of clomiphene that induces ovulation in women with PCOS.", "Ovulation induction treatment with metformin, either alone or in combination with clomiphene citrate (CC), remains controversial even though previous randomized trials have examined this.\n A double blinded multi-centre randomized trial was undertaken including 171 women with anovulatory or oligo-ovulatory polycystic ovary syndrome. Women with high body mass index (BMI) > 32 kg/m(2) received placebo ('standard care') or metformin; women with BMI < or = 32 kg/m(2) received CC ('standard care'), metformin or both. Treatment continued for 6 months or until pregnancy was confirmed. Primary outcomes were clinical pregnancy and live birth.\n For women with BMI > 32 kg/m(2), clinical pregnancy and live birth rates were 22% (7/32) and 16% (5/32) with metformin, 15% (5/33) and 6% (2/33) with placebo. For women with BMI < or = 32 kg/m(2), clinical pregnancy and live birth rates were 40% (14/35) and 29% (10/35) with metformin, 39% (14/36) and 36% (13/36) with CC, 54% (19/35) and 43% (15/35) with combination metformin plus CC.\n There is no evidence that adding metformin to 'standard care' is beneficial. Pregnancy and live birth rates are low in women with BMI > 32 kg/m(2) whatever treatment is used, with no evidence of benefit of metformin over placebo. For women with BMI < or = 32 kg/m(2) there is no evidence of significant differences in outcomes whether treated with metformin, CC or both. ClinicalTrials.gov number NCT00795808; trial protocol accepted for publication November 2005: Johnson, Aust N Z Journal Obstet Gynaecol 2006;46:141-145.", "Polycystic ovary syndrome (PCOS) is frequently associated with insulin resistance.\n The aim of the study was to investigate a putative role of the adipokines retinol-binding protein 4 (RBP4), adiponectin, and visfatin in a cohort of patients with PCOS and their response to treatment with pioglitazone.\n We conducted a randomized, controlled, double-blind study at a tertiary referral center.\n Forty premenopausal women with PCOS were allocated to receive treatment with either pioglitazone (30 mg/d) or a placebo for a period of 3 months.\n Serum concentrations of RBP4, adiponectin, and visfatin were determined along with metabolic and hormonal parameters before and after treatment.\n Serum adiponectin concentrations were higher after treatment with pioglitazone (P = 0.003), whereas RBP4 levels tended to decrease (P = 0.06), and visfatin concentrations remained unchanged. We found RBP4 serum concentrations at baseline to be positively correlated with serum levels of testosterone (R = 0.446; P = 0.005), 17-OH progesterone (R = 0.345, P = 0.037), and dehydroepiandrosterone sulfate (R = 0.347; P = 0.041). However, these correlations were abolished after treatment with pioglitazone. Patients with high RBP4 levels had significantly higher hirsutism scores (P = 0.038 before and P = 0.034 after treatment). In contrast, serum adiponectin concentrations were related to parameters of impaired glucose metabolism, and no significant associations were detected for visfatin.\n Our results suggest that RBP4 may contribute to endocrine changes and to the phenotypic manifestation of patients with PCOS because higher RBP4 concentrations are associated with higher androgen levels and higher clinical hirsutism scores independently of pioglitazone treatment. The molecular involvement of RBP4 in human steroid metabolism requires further clarification.", "To determine the clinical, hormonal, and biochemical effects of metformin therapy in obese and nonobese patients with polycystic ovary syndrome (PCOS).\n Controlled clinical study.\n Department of Gynecology of Federal University of São Paulo, São Paulo, Brazil.\n Twenty-nine patients with PCOS.\n Patients were treated with 500 mg of p.o. metformin t.i.d. for 6 months.\n Clinical data as well as serum concentrations of sex steroids, sex hormone-binding globulin (SHBG), gonadotropins, leptin, GH, lipids, insulin, and glucose levels were assessed before and after treatment.\n In the metformin group of nonobese patients, the mean fasting serum insulin concentration decreased from a pretreatment value of 12.1 +/- 2.4 to 6.3 +/- 0.6 microU/mL after treatment, and the area under the curve of insulin decreased from 5,189.1 +/- 517.4 to 3,035.6 +/- 208.9 microU/mL per minute. Also in the metformin group of nonobese patients, the mean basal serum total testosterone, free testosterone, and androstenedione concentrations decreased by 38%, 58%, and 30%, respectively. In the obese patients treated with metformin, only free testosterone showed a statistically significant decrease (1.7 +/- 0.2).\n Our data suggest that nonobese patients respond better than obese patients to a 1.5 g/day metformin regimen.", "Metformin, an insulin-sensitizing agent, has been used successfully as the first-line drug to induce ovulation in women with polycystic ovary syndrome. There are, however, very few studies evaluating metformin treatment in women with clomiphene citrate (CC)-resistant polycystic ovaries (PCO).\n Twenty infertile Chinese women aged <40 years, who had ultrasound features of PCO and remained anovulatory on CC, were randomized by computer using the sealed envelope method to receive placebo or metformin 500 mg three times a day for 3 months. Hormonal and metabolic profiles were determined before the therapy and were repeated after 3 months for women who failed to become pregnant within this period. Clomiphene was then added for one cycle to those women who did not ovulate after taking placebo or metformin alone.\n The median ovulation rate in the placebo group was 0% (range: 0--50%) after placebo only and 6.9% (range: 0--50%) after placebo and CC, whereas the corresponding rates in the metformin group were 0% (range: 0--22%) and 0% (range: 0--22%) respectively. There was no improvement in the ovulation rate despite a significant reduction of body mass index, serum testosterone and fasting leptin concentrations in the metformin group.\n Metformin treatment may result in successful ovulation only in certain subgroups of these women.", "Polycystic ovarian syndrome (PCOS) is the most common hormonal dysfunction in women. It's a cause of female infertility by oligoanovulation, clinical and biochemical hyperandrogenism and polycystic ovaries. Weight loss, firstly proposed in overweight or obese patient suffering from PCOS, aims to reduce hyperinsulinism and hyperandrogenism. Recently, Metformin, an insulin sensitizer, has been proposed as an alternative first line treatment for polycystic ovarian syndrome by improving hyperinsulinemia and hyperandrogenism in these women.\n The aim of our study, and through a literature review, is to demonstrate if Metformin should be used as a first-line drug for infertile women with this syndrome or as an adjunction to Clomifene Citrate, the longest established treatment already used in this syndrome.\n A prospective comparative study including 63 patients with PCOS has been done during 2 years. Women were randomly allocated to clomifene + Metformin (Metformin group, Metformin took during 8 weeks, 850 mg twice a day, plus Clomifene 100 mg per day during five days) or Clomifene only (100 mg per day during five days). All patients underwent a two- month's diet.\n The middle age was about 30.63 years and the body mass index (BMI) was about 29.88 kg/ m(2). We noticed a 6.2% weight loss in both groups (a non significant difference in p=0.04). The median of infertility period was about 2.49 years. The ovulation rate in the Metformin group was 53.12% (significant difference for inducing ovulation p=0.02) and 32.25% in Clomifene group (non-significant difference 0.07). There was also a significant difference for ongoing pregnancies (p=0.04). In fact, 11 on 32 patients (34%) achieved a full-term pregnancy in Metformin group versus only 4 ones on 31 patients (12.9%) in Clomifene group.\n Our conclusion is that Metformin is an effective addition to Clomifene Citrate in term of reestablishment of ovulation and full-term pregnancies achievement, excluding ART cycles.", "To determine whether insulin-sensitizing drugs would improve ovulation and T levels in women with polycystic ovary syndrome (PCOS), without clinical or biochemical criteria indicating insulin resistance and whether the combination of two distinct insulin-sensitizing drugs would be of any benefit over either drug alone.\n Randomized controlled double-blind trial.\n A referral center in Caracas, Venezuela.\n One hundred twenty-eight nonobese PCOS women with normal indices of insulin sensitivity-that is, normal glucose tolerance, fasting insulin, peak insulin during an oral glucose tolerance test (OGTT), and fasting glucose-to-insulin ratio. Twenty-eight women were lost to follow-up initially and did not receive any intervention.\n One hundred women received twice daily one of the following for 6 months: metformin (850 mg), rosiglitazone (4 mg), combination of both drugs, or at least one placebo.\n Frequencies of ovulation and serum free T after 6 months.\n Frequencies of ovulation were higher after treatment with an insulin-sensitizing drug (ovulations per subject in 6 months: metformin, 3.3; rosiglitazone, 2.4; and combination, 3.4) than with placebo (0.4). Ovulatory frequencies increased significantly more with metformin than rosiglitazone, and the combination was not more potent. After treatment, serum free-T levels were comparable among all active treatment groups (metformin: 2.34 pg/mL, rosiglitazone: 3.06 pg/mL, and combination: 2.39 pg/mL) and were significantly lower than in the placebo group (7.26 pg/mL). Compared with placebo, fasting insulin levels, area under the insulin curve during OGTT, the homeostatic model assessment of insulin sensitivity, and OGTT-derived insulin sensitivity index improved significantly after metformin or combination therapies but not after rosiglitazone.\n These findings suggest that insulin-sensitizing drugs increase ovulatory frequency and ameliorate hyperandrogenemia, even in nonobese women with PCOS who appear to have normal insulin sensitivity.", "Metformin is successfully used in the treatment of cycle disorders and anovulation in women with polycystic ovary syndrome (PCOS). No data of the exact point and the impact of insulin resistance (IR) on metformin's efficacy exist.\n The objective of the study was to evaluate the early potential effects of metformin treatment, their time of onset, and the role of IR on metformin's efficacy.\n This was a prospective randomized, double-blind, placebo-controlled trial.\n The study was conducted at the University of Heidelberg, Heidelberg, Germany.\n The patient population was 45 oligo-/anovulatory PCOS women with typical ovaries.\n Women were stratified for IR (32 of 13) and then randomly allocated to receive either metformin (n = 22) or placebo (n = 23) and were assessed before and every 4 wk within a treatment period of 12 wk.\n Menstrual disturbance and markers of insulin metabolism were measured.\n The main outcome criterion menstrual disturbance was successfully improved in the metformin-treated group, depending on IR (12 of 15 vs. three of 17), whereas women without IR (four of seven vs. four of six) had no significant amelioration of their menstrual irregularities (P < 0.05). Estradiol levels increased continuously only in the treatment group (P < 0.005), indicating an improvement of ovulatory function. Sixty-seven percent of metformin-treated women had at least one ovulation, compared with only 45% in the placebo group, shown by biphasic body temperature curves. Insulin sensitivity improved within 4 wk after beginning of metformin as shown by an increased area under the curve glucose to insulin ratio, compared with baseline (P < 0.005).\n IR is a baseline predictor of clinical efficacy in metformin treatment in PCOS women measured by improved menstrual cyclicity and ovulatory function.", "To compare the effect of clomiphene citrate, metformin, and lifestyle modification on treatment of patients with polycystic ovary syndrome (PCOS).\n Prospective randomized double-blind study.\n University-based infertility clinic and research center.\n Three hundred forty-three overweight infertile women with PCOS.\n The participating women were assigned to four groups: clomiphene (n = 90), metformin (n = 90), clomiphene + metformin (n = 88), and lifestyle modification (n = 75). The patients in each group received standardized dietary and exercise advice from a dietitian.\n The primary outcome variables were change in menstrual cycle, waist circumference measurements, endocrine parameters, and lipid profile. The main secondary outcome variable was clinical pregnancy rate.\n The clinical pregnancy rate was 12.2% in clomiphene group, 14.4% in metformin group, 14.8% in clomiphene + metformin group, and 20% in lifestyle modification group. Lifestyle modification group achieved a significant reduction in waist circumference, total androgen, and lipid profile.\n Lifestyle modification improves the lipid profile in PCOS patients. Therefore, lifestyle modification may be used as the first line of ovulation induction in PCOS patients.\n Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.", "This study was undertaken to evaluate the efficacy of metformin in women with anovulation who do not have evidence for hyperandrogenism and classic polycystic ovary syndrome.\n A randomized trial of metformin (1500 mg daily) and placebo in 24 anovulatory women was undertaken for 3 months. Assessments of changes in hormone levels and insulin sensitivity were carried out. Abnormal hormonal values were defined by levels exceeding the range in normal ovulatory controls.\n Anovulatory women had normal androgen levels and luteinizing hormone but had higher serum insulin and lower insulin sensitivity compared with controls. Over 3 months, there were 16 ovulatory cycles with metformin and only 4 with placebo ( P < .05). Success of ovulation did not correlate with changes in androgen, insulin, or insulin sensitivity parameters.\n Metformin may be useful for inducing ovulation in anovulatory women who do not have hyperandrogenism. This effect may be independent of a lowering of androgen or insulin levels.", "To establish whether metformin has a significant action in reducing visceral fat and improving other metabolic parameters in women with polycystic ovary syndrome (PCOS).\n Randomised, double-blind, placebo-controlled trial.\n Reproductive medicine clinic.\n Forty women with anovulatory PCOS.\n Participants were randomised into receiving metformin 500 mg three times a day or placebo for 3 months.\n Fat distribution was measured by computed tomography scan. Secondary outcome measures included serum indices of the metabolic syndrome and evidence of ovulation.\n We found no significant differences in any of the measures of fat distribution between the placebo and metformin groups. The metformin group had significantly lower total cholesterol (P= 0.02), low-density lipoprotein cholesterol (P= 0.02) and cholesterol:high-density lipoprotein cholesterol ratio (P= 0.05), but there was no statistically significant treatment effect on androgens, insulin, insulin resistance, triglycerides, ovulation or pregnancy.\n Metformin has no clinically significant effect in reducing visceral fat mass, although it does have a beneficial effect on lipids. This trial lends support to the growing evidence that metformin is not a weight loss drug. Metformin might therefore be used as an adjunct to lifestyle modification in women with PCOS, but not as a substitute for it.", "To obtain data from a pilot randomized trial on the effect of metformin therapy and lifestyle modification on ovulation and androgen concentrations in women with polycystic ovary syndrome (PCOS).\n Prospective, randomized, placebo-controlled pilot trial.\n Academic medical center.\n Thirty-eight overweight or obese women with PCOS.\n All subjects were randomized to one of four 48-week interventions: metformin 850 mg two times per day, lifestyle modification plus metformin 850 mg two times per day, lifestyle modification plus placebo, or placebo alone.\n Recruitment, dropout, and compliance with a long-term lifestyle intervention in PCOS; preliminary estimates of treatment effect on ovulation, as measured by weekly urinary pregnanediol glucuronide, and on total T and free androgen index.\n It was necessary to screen seven women to have one subject randomized. The dropout rate was 39%, with the majority of dropouts occurring within the first 24 weeks. Mean body mass index was >39 mg/kg(2). Modest weight reduction was found in all treatment groups, with the most significant reduction occurring with the combination of metformin and lifestyle intervention. Significant androgen reduction occurred in the combination group only. Ovulation rates did not differ significantly between groups. However, when data were analyzed by presence or absence of weight reduction in subjects, independent of treatment group, the estimated odds ratio for weight loss was 9.0 (95% confidence interval 1.2-64.7) with respect to regular ovulation. If weight loss occurred during metformin therapy, the odds ratio for regular ovulation was 16.2 (95% confidence interval 4.4-60.2).\n Key methodologic issues for a large-scale, randomized trial of lifestyle intervention in PCOS include minimizing early dropout from the lifestyle intervention and including a range of body mass index that is not skewed toward severe obesity. Weight reduction might play the most significant role in restoration of ovulation in obese women with PCOS.", "To study the effect of metformin in combination with clomiphene citrate, as compared with placebo plus clomiphene citrate, on the ovulation and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome.\n This study was carried out at King Hussein Medical Center, Amman, Jordan, during the period January 2001 through to July 2001. Twenty-eight clomiphene citrate-resistant polycystic ovary syndrome women were evaluated prospectively for 6 treatment cycles by receiving metformin, 850mg twice daily throughout the cycle along with 50 mg clomiphene citrate, starting on day 5-9 of the same cycle (N=16), or by taking placebo with clomiphene citrate (N=12). During cycles 2-6, clomiphene citrate was added with increments of 50mg (up to 200 mg/day) for both groups. Progesterone level on day 21 and 28 >5ng/dl was indicative of ovulation.\n A statistically significant increase in the rates of ovulation (68.6% versus 25%, p<0.05) and pregnancy (56.3% versus 16.6%, p<0.05) were observed in the metformin-clomiphene citrate group as compared with the placebo-clomiphene citrate controls. Insignificant increase in the rate of ovarian hyperstimulation was noted in the placebo-clomiphene citrate group.\n Metformin-clomiphene citrate regimen in resistant-clomiphene citrate polycystic ovary syndrome women significantly increases the ovulation and pregnancy rates, and decreases the occurrence of ovarian hyperstimulation syndrome." ]

[ "12790954", "17198065", "10982049" ]

[ "Anal plug for faecal incontinence.", "Anal plugs for the management of fecal incontinence in children and adults: a randomized control trial.", "A new polyurethane anal plug in the treatment of incontinence after anal atresia repair." ]

[ "Despite the availability of pharmacological, behavioural and surgical treatments for faecal incontinence, many patients remain symptomatic. There are few devices designed specifically to cope with this, and perineal pads are inefficient and unacceptable for many patients. This study aimed to evaluate a new device in patients with intractable faecal incontinence.\n Two sizes of a purpose-designed anal plug were evaluated in 20 patients with intractable faecal incontinence for solid or liquid stool. Each plug size was tested for 2 weeks, with patients completing a structured questionnaire after each size.\n The majority [14/20] could not tolerate a plug due to discomfort. Four patients (20%) wished to continue to use a plug on a regular basis after the study, and two others on an occasional basis. However, for this minority who could tolerate a plug, it was highly successful at controlling faecal incontinence. There was no clear preference for the smaller or larger plug. There was no association between comfort in using the plug and anorectal sensitivity as measured by electrophysiological tests. It was not possible to predict which patients would benefit from plug use.\n The anal plug is effective in controlling faecal incontinence and is well tolerated in a minority of patients. Evaluation quickly reveals whether the patient will find it an effective and acceptable option. This device therefore offers a further management option for patients with faecal incontinence.", "To evaluate the contribution of the anal plug to the management of fecal incontinence in children and adults.\n Effective management of fecal incontinence remains problematic. Previous studies of an anal plug have yielded conflicting results.\n A randomized controlled trial was conducted. The intervention was the Conveen anal plug (Coloplast Limited) used for 12 months. Outcomes measures included: generic measures of child health [Functional Status II-R, Child Health Questionnaire (CHQ-PF50) and Dartmouth Primary Care Cooperative Information Project Charts]; generic measures of adult health for patients and carers (the SF-36, and Patient Generated and Carer Generated indices); condition-specific measures for adults and children; qualitative interviews, bowel charts, and diaries. The main outcome measure was a condition-specific score on a 0 to 100 scale, where 0 was the most severe and 100 was the least severe incontinence.\n Thirty-one intervention and 17 control patients were recruited. Fecal incontinence was due to 1 of 3 reasons: congenital, acquired, and neurogenic. At baseline, patients managed their condition preemptively or protectively. Intervention patients used the plug as a complete management substitute or as an adjunct to existing management. The majority of intervention respondents retained the plug most of the time. There was greater improvement from baseline in mean condition-specific score in intervention group compared with control group but this difference was not statistically significant (t test P=0.053). Complete data analysis using analysis of covariance showed the mean difference between the treatment groups in condition-specific score of 9.9 (95% confidence interval-1.4, 21.1). Intention to treat analyses using imputation showed similar results. There was generally greater improvement in intervention groups subjects using other measures for children, adults, and carers.\n The anal plug is of benefit to the majority of patients. It does not suit all eligible patients with in situ plug retention being a problem for some.", "38 totally or partially incontinent patients following imperforate anus repair (age 6-15 years) tested a new polyurethane (PU) anal plug against another, widely used anal plug (PVA) in a randomized crossover trial. Plugs were tested 3 weeks each, data concerning bowel habits, handling and plug-related problems were collected by questionnaire before trial, at time of product change and after trial.\n 15 of 38 patients did not complete the protocol, among them 6 with anal canal diameters too small for the smallest plug. During plug use, patients experienced enhanced awareness of repletion and urge. Stool consistence did not change in 82% of patients. There were no changes in children constipated prior to study (n = 8/23). 12,123 children were absolutely clean during use of either plug. 15 patients (68%) using the PU plug and 10 (45%) using the PVA plug felt secure from soiling during plug use. 74% of patients preferred the PU plug. Painful plug insertion, a feeling of pressure inside the anal canal and painful plug removal were reported with both plugs, but were less frequent with the PU plug.\n Anal plugs, regardless of their make, offer absolute cleanliness for periods of several hours to 66% of our incontinent patients. The PU plug (Conveen, Coloplast) is preferred by the patients and offers greater security than the PVA plug." ]

[ "15351164", "11741361", "17350451", "11792138", "11419424" ]

[ "Do men benefit more than women from an interventional strategy in patients with unstable angina or non-ST-elevation myocardial infarction? The impact of gender in the RITA 3 trial.", "ST depression in ECG at entry indicates severe coronary lesions and large benefits of an early invasive treatment strategy in unstable coronary artery disease; the FRISC II ECG substudy. The Fast Revascularisation during InStability in Coronary artery disease.", "Long-term outcome after an early invasive versus selective invasive treatment strategy in patients with non-ST-elevation acute coronary syndrome and elevated cardiac troponin T (the ICTUS trial): a follow-up study.", "Value of first day angiography/angioplasty in evolving Non-ST segment elevation myocardial infarction: an open multicenter randomized trial. The VINO Study.", "Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban." ]

[ "The RITA 3 trial randomized patients with non-ST-elevation myocardial infarction or unstable angina to strategies of early intervention (angiography followed by revascularization) or conservative care (ischaemia or symptom driven angiography). The aim of this analysis was to investigate the impact of gender on the effect of these two strategies.\n In total, 1810 patients (682 women and 1128 men) were randomized. The risk factor profile of women at presentation was markedly different to men. There was evidence that men benefited more from an early intervention strategy for death or non-fatal myocardial infarction at 1 year (adjusted odds ratios 0.63, 95% confidence interval 0.41-0.98 for men and 1.79, 95% confidence interval 0.95-3.35 for women; interaction p-value=0.007). Men who underwent the assigned angiogram were more likely to be put forward for coronary artery bypass surgery, even after allowing for differences in disease severity.\n An early intervention strategy resulted in a beneficial effect in men which was not seen in women although caution is needed in interpretation. Further research is needed to evaluate why women do not appear to benefit from early intervention and to identify treatments that improve the prognosis of women.", "In unstable coronary artery disease, ST-segment depression indicates a poor prognosis. We evaluated whether the effect of early revascularization and the extent of coronary lesions were related to ST-segment and T wave changes on admission.\n 2457 patients with unstable coronary artery disease were randomized to an early invasive strategy with coronary angiography/revascularization within 7 days or to a non-invasive strategy with coronary procedures only when symptoms or severe ischaemia recurred. ST depression was present in 1114 (45.5%) patients. In the invasive group, 45% of the patients with ST depression had three-vessel disease or left main stenosis compared with 22% if no ST-segment depression was present, PP=0.004 while mortality was changed from 5.8 to 3.3%, P=0.050. In patients without ST-segment depression the corresponding rates concerning death/myocardial infarction were 10.4 and 8.9, and for mortality 2.0 and 1.2% (non-significant).\n In unstable coronary artery disease, ST-segment depression is associated with a 100% increase in the occurrence of three-vessel/left main disease and to an increased risk of subsequent cardiac events. In these patients an early invasive strategy substantially decreases death/myocardial infarction.\n Copyright 2001 The European Society of Cardiology.", "The ICTUS trial was a study that compared an early invasive with a selective invasive treatment strategy in patients with non-ST-elevation acute coronary syndrome (nSTE-ACS). The study reported no difference between the strategies for frequency of death, myocardial infarction, or rehospitalisation after 1 year. We did a follow-up study to assess the effects of these treatment strategies after 4 years.\n 1200 patients with nSTE-ACS and an elevated cardiac troponin were enrolled from 42 hospitals in the Netherlands. Patients were randomly assigned either to an early invasive strategy, including early routine catheterisation and revascularisation where appropriate, or to a more selective invasive strategy, where catheterisation was done if the patient had refractory angina or recurrent ischaemia. The main endpoints for the current follow-up study were death, recurrent myocardial infarction, or rehospitalisation for anginal symptoms within 3 years after randomisation, and cardiovascular mortality and all-cause mortality within 4 years. Analysis was by intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN82153174.\n The in-hospital revascularisation rate was 76% in the early invasive group and 40% in the selective invasive group. After 3 years, the cumulative rate for the combined endpoint was 30.0% in the early invasive group compared with 26.0% in the selective invasive group (hazard ratio 1.21; 95% CI 0.97-1.50; p=0.09). Myocardial infarction was more frequent in the early invasive strategy group (106 [18.3%] vs 69 [12.3%]; HR 1.61; 1.19-2.18; p=0.002). Rates of death or spontaneous myocardial infarction were not different (76 [14.3%] patients in the early invasive and 63 [11.2%] patients in the selective invasive strategy [HR 1.19; 0.86-1.67; p=0.30]). No difference in all-cause mortality (7.9%vs 7.7%; p=0.62) or cardiovascular mortality (4.5%vs 5.0%; p=0.97) was seen within 4 years.\n Long-term follow-up of the ICTUS trial suggests that an early invasive strategy might not be better than a more selective invasive strategy in patients with nSTE-ACS and an elevated cardiac troponin, and implementation of either strategy might be acceptable in these patients.", "Direct angioplasty is an effective treatment for ST-elevation myocardial infarction. The role of very early angioplasty in non-ST-elevation infarction is not known. Thus, a randomized study of first day angiography/angioplasty vs early conservative therapy of evolving myocardial infarction without persistent ST-elevation was conducted.\n One hundred and thirty-one patients with confirmed acute myocardial infarction without ST-segment elevations were randomized within 24 h of last rest chest pain: 64 in the first day angiography/angioplasty group and 67 in the early conservative group (coronary angiography only after recurrent or stress induced myocardial ischaemia).\n All patients in the invasive group underwent coronary angiography on the day of admission (mean randomization-angiography time 6.2 h). First day angioplasty of the infarct related artery was performed in 47% of the patients and bypass surgery in 35%. In the conservative group, 55% underwent coronary angiography, 10% angioplasty and 30% bypass surgery within 6 months. The primary end-point (death/reinfarction) at 6 months occurred in 6.2% vs 22.3% (P<0.001). Six month mortality in the first day angiography/angioplasty group was 3.1% vs 13.4% in the conservative group (P<0.03). Non-fatal reinfarction occurred in 3.1% vs. 14.9% (P<0.02).\n First day coronary angiography followed by angioplasty whenever possible reduces mortality and reinfarction in evolving myocardial infarction without persistent ST-elevation, in comparison with an early conservative treatment strategy.\n Copyright 2001 The European Society of Cardiology.", "There is continued debate as to whether a routine, early invasive strategy is superior to a conservative strategy for the management of unstable angina and myocardial infarction without ST-segment elevation.\n We enrolled 2220 patients with unstable angina and myocardial infarction without ST-segment elevation who had electrocardiographic evidence of changes in the ST segment or T wave, elevated levels of cardiac markers, a history of coronary artery disease, or all three findings. All patients were treated with aspirin, heparin, and the glycoprotein IIb/IIIa inhibitor tirofiban. They were randomly assigned to an early invasive strategy, which included routine catheterization within 4 to 48 hours and revascularization as appropriate, or to a more conservative (selectively invasive) strategy, in which catheterization was performed only if the patient had objective evidence of recurrent ischemia or an abnormal stress test. The primary end point was a composite of death, nonfatal myocardial infarction, and rehospitalization for an acute coronary syndrome at six months.\n At six months, the rate of the primary end point was 15.9 percent with use of the early invasive strategy and 19.4 percent with use of the conservative strategy (odds ratio, 0.78; 95 percent confidence interval, 0.62 to 0.97; P=0.025). The rate of death or nonfatal myocardial infarction at six months was similarly reduced (7.3 percent vs. 9.5 percent; odds ratio, 0.74; 95 percent confidence interval, 0.54 to 1.00; P<0.05).\n In patients with unstable angina and myocardial infarction without ST-segment elevation who were treated with the glycoprotein IIb/IIIa inhibitor tirofiban, the use of an early invasive strategy significantly reduced the incidence of major cardiac events. These data support a policy involving broader use of the early inhibition of glycoprotein IIb/IIIa in combination with an early invasive strategy in such patients." ]

[ "17593956", "14985222", "9651405", "12052800", "16168782", "16310552" ]

[ "Zinc or multiple micronutrient supplementation to reduce diarrhea and respiratory disease in South African children: a randomized controlled trial.", "Randomized controlled trial of the effect of daily supplementation with zinc or multiple micronutrients on the morbidity, growth, and micronutrient status of young Peruvian children.", "Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and preschool children: a double-blind, controlled trial.", "Effect of routine zinc supplementation on pneumonia in children aged 6 months to 3 years: randomised controlled trial in an urban slum.", "Effect of weekly zinc supplements on incidence of pneumonia and diarrhoea in children younger than 2 years in an urban, low-income population in Bangladesh: randomised controlled trial.", "Safety and efficacy of zinc supplementation for children with HIV-1 infection in South Africa: a randomised double-blind placebo-controlled trial." ]

[ "Prophylactic zinc supplementation has been shown to reduce diarrhea and respiratory illness in children in many developing countries, but its efficacy in children in Africa is uncertain.\n To determine if zinc, or zinc plus multiple micronutrients, reduces diarrhea and respiratory disease prevalence.\n Randomized, double-blind, controlled trial.\n Rural community in South Africa.\n THREE COHORTS: 32 HIV-infected children; 154 HIV-uninfected children born to HIV-infected mothers; and 187 HIV-uninfected children born to HIV-uninfected mothers.\n Children received either 1250 IU of vitamin A; vitamin A and 10 mg of zinc; or vitamin A, zinc, vitamins B1, B2, B6, B12, C, D, E, and K and copper, iodine, iron, and niacin starting at 6 months and continuing to 24 months of age. Homes were visited weekly.\n Primary outcome was percentage of days of diarrhea per child by study arm within each of the three cohorts. Secondary outcomes were prevalence of upper respiratory symptoms and percentage of children who ever had pneumonia by maternal report, or confirmed by the field worker.\n Among HIV-uninfected children born to HIV-infected mothers, median percentage of days with diarrhea was 2.3% for 49 children allocated to vitamin A; 2.5% in 47 children allocated to receive vitamin A and zinc; and 2.2% for 46 children allocated to multiple micronutrients (P = 0.852). Among HIV-uninfected children born to HIV-uninfected mothers, median percentage of days of diarrhea was 2.4% in 56 children in the vitamin A group; 1.8% in 57 children in the vitamin A and zinc group; and 2.7% in 52 children in the multiple micronutrient group (P = 0.857). Only 32 HIV-infected children were enrolled, and there were no differences between treatment arms in the prevalence of diarrhea. The prevalence of upper respiratory symptoms or incidence of pneumonia did not differ by treatment arms in any of the cohorts.\n When compared with vitamin A alone, supplementation with zinc, or with zinc and multiple micronutrients, did not reduce diarrhea and respiratory morbidity in rural South African children.\n ClinicalTrials.gov NCT00156832.", "Zinc supplements reduce childhood morbidity in populations in whom zinc deficiency is common. In such populations, deficiencies in other micronutrients may also occur.\n The objective was to determine whether the administration of other micronutrients with zinc modifies the effect of zinc supplementation on children's morbidity and physical growth.\n Two hundred forty-six children aged 6-35 mo with persistent diarrhea were randomly assigned to 1 of 3 groups to receive a daily supplement of 10 mg Zn alone (Zn; n = 81), zinc plus vitamins and other minerals at 1-2 times recommended daily intakes (Zn+VM; n = 82), or placebo (n = 83) for approximately 6 mo after the diarrhea episode ended. Morbidity information was collected on weekdays. Weight, length, and other anthropometric indicators were measured monthly, and plasma zinc and other indicators of micronutrient status were measured at baseline and 6 mo.\n Supplement consumption was high ( approximately 90%) in all groups, although slightly more vomiting was reported in the Zn+VM group (P < 0.0001, analysis of variance). The change in plasma zinc from baseline to 6 mo was greater in the 2 zinc groups (6.1, 27.3, and 16.2 micro g/dL in the placebo, Zn, and Zn+VM groups, respectively; P < 0.0001, analysis of variance). The Zn group had fewer episodes of diarrhea, dysentery, and respiratory illness and a lower prevalence of fever and cough than did the Zn+VM group and a lower prevalence of cough than did the placebo group (P = 0.05). No significant effects of supplementation on growth were observed.\n Morbidity was greater after supplementation with zinc plus multivitamins and minerals than it was after supplementation with zinc alone.", "Increased acute lower respiratory infection incidence, severity, and mortality are associated with malnutrition, and reduced immunological competence may be a mechanism for this association. Because zinc deficiency results in impaired immunocompetence and zinc supplementation improves immune status, we hypothesized that zinc deficiency is associated with increased incidence and severity of acute lower respiratory infection.\n We evaluated the effect of daily supplementation with 10 mg of elemental zinc on the incidence and prevalence of acute lower respiratory infection in a double-blind, randomized, controlled trial in 609 children (zinc, n = 298; control, n = 311) 6 to 35 months of age. Supplementation and morbidity surveillance were done for 6 months.\n After 120 days of supplementation, the percentage of children with plasma zinc concentrations <60 microg/dL decreased from 35.6% to 11.6% in the zinc group, whereas in the control group it increased from 36.8% to 43.6%. Zinc-supplemented children had 0.19 acute lower respiratory infection episodes/child/year compared with 0.35 episodes/child/year in the control children. After correction for correlation of data using generalized estimating equation regression methods, there was a reduction of 45% (95% confidence interval, 10% to 67%) in the incidence of acute lower respiratory infections in zinc-supplemented children.\n A dietary zinc supplement resulted in a significant reduction in respiratory morbidity in preschool children. These findings suggest that interventions to improve zinc intake will improve the health and survival of children in developing countries.", "To evaluate the effect of daily zinc supplementation in children on the incidence of acute lower respiratory tract infections and pneumonia.\n Double masked, randomised placebo controlled trial.\n A slum community in New Delhi, India.\n 2482 children aged 6 to 30 months.\n Daily elemental zinc, 10 mg to infants and 20 mg to older children or placebo for four months. Both groups received single massive dose of vitamin A (100 000 IU for infants and 200 000 IU for older children) at enrollment.\n All households were visited weekly. Any children with cough and lower chest indrawing or respiratory rate 5 breaths per minute less than the World Health Organization criteria for fast breathing were brought to study physicians.\n At four months the mean plasma zinc concentration was higher in the zinc group (19.8 (SD 10.1) v 9.3 (2.1) micromol/l, P<0.001). The proportion of children who had acute lower respiratory tract infection during follow up was no different in the two groups (absolute risk reduction -0.2%, 95% confidence interval -3.9% to 3.6%). Zinc supplementation resulted in a lower incidence of pneumonia than placebo (absolute risk reduction 2.5%, 95% confidence interval 0.4% to 4.6%). After correction for multiple episodes in the same child by generalised estimating equations analysis the odds ratio was 0.74, 95% confidence interval 0.56 to 0.99.\n Zinc supplementation substantially reduced the incidence of pneumonia in children who had received vitamin A.", "Pneumonia and diarrhoea cause much morbidity and mortality in children younger than 5 years. Most deaths occur during infancy and in developing countries. Daily regimens of zinc have been reported to prevent acute lower respiratory tract infection and diarrhoea, and to reduce child mortality. We aimed to examine whether giving zinc weekly could prevent clinical pneumonia and diarrhoea in children younger than 2 years.\n 1665 poor, urban children aged 60 days to 12 months were randomly assigned zinc (70 mg) or placebo orally once weekly for 12 months. Children were assessed every week by field research assistants. Our primary outcomes were the rate of pneumonia and diarrhoea. The rates of other respiratory tract infections were the secondary outcomes. Growth, final serum copper, and final haemoglobin were also measured. Analysis was by intention to treat.\n 34 children were excluded before random assignment to treatment group because they had tuberculosis. 809 children were assigned zinc, and 812 placebo. After treatment assignment, 103 children in the treatment group and 44 in the control group withdrew. There were significantly fewer incidents of pneumonia in the zinc group than the control group (199 vs 286; relative risk 0.83, 95% CI 0.73-0.95), and a small but significant effect on incidence of diarrhoea (1881 cases vs 2407; 0.94, 0.88-0.99). There were two deaths in the zinc group and 14 in the placebo group (p=0.013). There were no pneumonia-related deaths in the zinc group, but ten in the placebo group (p=0.013). The zinc group had a small gain in height, but not weight at 10 months compared with the placebo group. Serum copper and haemoglobin concentrations were not adversely affected after 10 months of zinc supplementation.\n 70 mg of zinc weekly reduces pneumonia and mortality in young children. However, compliance with weekly intake might be problematic outside a research programme.", "Zinc deficiency is associated with impaired immune function and an increased risk of infection. Supplementation can decrease the incidence of diarrhoea and pneumonia in children in resource-poor countries. However, in children with HIV-1 infection, the safety of zinc supplementation is uncertain. We aimed to assess the role of zinc in HIV-1 replication before mass zinc supplementation is recommended in regions of high HIV-1 prevalence.\n We did a randomised double-blind placebo-controlled equivalence trial of zinc supplementation at Grey's Hospital in Pietermaritzburg, South Africa. 96 children with HIV-1 infection were randomly assigned to receive 10 mg of elemental zinc as sulphate or placebo daily for 6 months. Baseline measurements of plasma HIV-1 viral load and the percentage of CD4+ T lymphocytes were established at two study visits before randomisation, and measurements were repeated 3, 6, and 9 months after the start of supplementation. The primary outcome measure was plasma HIV-1 viral load. Analysis was per protocol.\n The mean log(10) HIV-1 viral load was 5.4 (SD 0.61) for the placebo group and 5.4 (SD 0.66) for the zinc-supplemented group 6 months after supplementation began (difference 0.0002, 95% CI -0.27 to 0.27). 3 months after supplementation ended, the corresponding values were 5.5 (SD 0.77) and 5.4 (SD 0.61), a difference of 0.05 (-0.24 to 0.35). The mean percentage of CD4+ T lymphocytes and median haemoglobin concentrations were also similar between the two groups after zinc supplementation. Two deaths occurred in the zinc supplementation group and seven in the placebo group (p=0.1). Children given zinc supplementation were less likely to get watery diarrhoea than those given placebo. Watery diarrhoea was diagnosed at 30 (7.4%) of 407 clinic visits in the zinc-supplemented group versus 65 (14.5%) of 447 visits in the placebo group (p=0.001).\n Zinc supplementation of HIV-1-infected children does not result in an increase in plasma HIV-1 viral load and could reduce morbidity caused by diarrhoea.\n Programmes to enhance zinc intake in deficient populations with a high prevalence of HIV-1 infection can be implemented without concern for adverse effects on HIV-1 replication. In view of the reductions in diarrhoea and pneumonia morbidity, zinc supplementation should be used as adjunct therapy for children with HIV-1 infection." ]

[ "9647153", "15511762", "2892739" ]

[ "Effective analgesia following perineal injury during childbirth: a placebo controlled trial of prophylactic rectal diclofenac.", "The prophylactic use of diclofenac (Voltarol) suppositories in perineal pain after episiotomy. A random allocation double-blind study.", "Effectiveness of indomethacin (indocid) suppositories as post-episiotomy analgesia." ]

[ "To determine if diclofenac suppositories administered prophylactically produce effective and lasting analgesia following perineal injury.\n A randomised double blind placebo controlled trial.\n York District Hospital.\n One hundred women sustaining objective perineal injury (second degree tear or episiotomy) during spontaneous vaginal delivery at term.\n Suppositories were administered at the time of repair and approximately 12 hours later. The suppositories were randomised prior to issue by the pharmacy department and contained either 100 mg diclofenac or placebo.\n Pain scores assessed at 12, 24, 48 and 72 hours after delivery using a six point numerical scoring system and the use of additional analgesia and local treatments to the perineum.\n The mean pain score was significantly reduced in the diclofenac group at 24, 48 and 72 hours after delivery (0.86, 0.7 and 0.59, respectively) compared with the control group (1.64, 1.31 and 1.5; P < 0.005). In addition there was less supplementary analgesia required (eight women only at 72 hours compared with 15 in the control group) and this was limited to paracetamol or topical treatments to the perineum.\n Prophylactic rectal diclofenac provides effective analgesia after perineal repair and its effect appears to be maintained into the second and third postpartum days.", "One hundred and ten patients who had episiotomies to aid normal vaginal delivery without epidural analgesia were = allocated at random to receive either diclofenac (n = 56) or = placebo (n = 54) suppositories. Pain after episiotomy was assessed at 24 and 48 hours using a combination of a visual analogue scale, a modified pain score and a review of additional analgesia required. All patients in both groups were allowed routine hospital analgesia on request. Our data suggests that very few patients suffered severe pain, even in the placebo group. However, the prophylactic use of diclofenac suppositories significantly reduced perineal pain in the first 24 hours, although the difference was less marked by 48 hours. Overall additional analgesia requirement was correspondingly less in the diclofenac group.", "A double-blind, randomised placebo-controlled study was carried out to assess the efficacy of indometacin suppositories as a post-episiotomy analgesic. Thirty patients received 2 X 100 mg indometacin suppositories, and 30 patients received placebo suppositories within 15 min of an episiotomy repair operation. Local infiltration of the episiotomy incision was performed using 20 ml of 0.5% lignocaine in every case. Subjective symptoms of pain were evaluated 15, 30, 60 and 90 min post-episiotomy repair. Average numbers of hours as lying in patients after delivery is 4 h. None of the patients who received indometacin complained of post-episiotomy pain; whereas the patients on placebo manifested varying degrees of pain." ]

[ "7930743", "15548314", "12812355", "9561593", "8560531", "1347854", "8131255" ]

[ "Treatment of multidrug-resistant Plasmodium falciparum malaria with 3-day artesunate-mefloquine combination.", "Comparison of chloroquine, sulfadoxine/pyrimethamine, mefloquine and mefloquine-artesunate for the treatment of falciparum malaria in Kachin State, North Myanmar.", "Efficacy of mefloquine and a mefloquine-artesunate combination therapy for the treatment of uncomplicated Plasmodium falciparum malaria in the Amazon Basin of Peru.", "A comparative study of artesunate and artemether in combination with mefloquine on multidrug resistant falciparum malaria in eastern Thailand.", "Artesunate versus artemether in combination with mefloquine for the treatment of multidrug-resistant falciparum malaria.", "Randomised trial of artesunate and mefloquine alone and in sequence for acute uncomplicated falciparum malaria.", "Pharmacokinetics of mefloquine alone or in combination with artesunate." ]

[ "Studies of 652 adults and children with acute uncomplicated falciparum malaria were done to determine the optimum treatment of multidrug-resistant Plasmodium falciparum malaria on the Thai-Burmese border. Single-dose artesunate (4 mg/kg) plus mefloquine (25 mg of base/kg) gave more rapid symptomatic and parasitologic responses than high-dose mefloquine alone but did not improve cure rates. Three days of artesunate (total dose, 10 mg/kg) plus mefloquine was 98% effective compared with a 28-day failure rate of 31% with high-dose mefloquine alone (relative risk [RR], 0.06; 95% confidence interval [CI], 0.02-0.2; P < .0001). By day 63, the reinfection adjusted failure rates were 2% and 44%, respectively (P < .0001). Artesunate also prevented high-grade failures. Both drugs were well tolerated. No adverse effects were attributable to artesunate. Vomiting was reduced significantly by giving mefloquine on day 2 of treatment (RR, 0.40; 95% CI, 0.20-0.79; P = .009. Artesunate (10 mg/kg over 3 days) plus mefloquine (25 mg/kg) is currently the most effective treatment for falciparum malaria in this area of increasing mefloquine resistance.", "Multi-drug resistant falciparum malaria is widespread in Asia. In Thailand, Cambodia and Vietnam the national protocols have changed largely to artesunate combined treatment regimens but elsewhere in East and South Asia chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) are still widely recommended by national malaria control programmes. In Kachin State, northern Myanmar, an area of low seasonal malaria transmission, the efficacy of CQ (25 mg base/kg) and SP (1.25/25 mg/kg), the nationally recommended treatments at the time, were compared with mefloquine alone (M; 15 mg base/kg) and mefloquine combined with artesunate (MA; 15:4 mg/kg). An open randomized controlled trial enrolled 316 patients with uncomplicated Plasmodium falciparum malaria, stratified prospectively into three age-groups. Early treatment failures (ETF) occurred in 41% (32/78) of CQ treated patients and in 24% of patients treated with SP (18/75). In young children the ETF rates were 87% after CQ and 35% after SP. Four children (two CQ, two SP) developed symptoms of cerebral malaria within 3 days after treatment. By day 42, failure rates (uncorrected for reinfections) had increased to 79% for CQ and 81% for SP. ETF rates were 2.5% after treatment with M and 3.9% after treatment with MA (P > 0.2). Overall uncorrected treatment failure rates at day 42 following M and MA were 23% and 21%, respectively. Chloroquine and SP are completely ineffective for the treatment of falciparum malaria in northern Myanmar. Mefloquine treatment is much more effective, but three day combination regimens with artesunate will be needed for optimum efficacy and protection against resistance.", "In the Amazon Basin of Peru, more than 50% of patients with uncomplicated Plasmodium falciparum malaria fail to respond to treatment with chloroquine or sulfadoxine-pyrimethamine. To assist the National Malaria Control Program in identifying an alternative first-line therapy for this region, we conducted a trial of the safety and efficacy of mefloquine (MQ) compared with mefloquine-artesunate (MQ-AS) combination therapy. Patients with uncomplicated P. falciparum infections between the ages of 5 and 50 years were randomly assigned to be treated with either MQ (15 mg/kg in a single oral dose) or MQ (15 mg/kg) plus AS (4 mg/kg/day for three days). A total of 98 patients were enrolled and followed for 28 days. None of the 47 patients who received MQ alone or the 51 patients who received MQ-AS combination therapy had recurrences of parasitemia during the 28-day follow-up period. Asexual parasite densities decreased significantly more rapidly and the proportion of patients with gametocytes was significantly lower on days 3-21 in the MQ-AS group than in patients treated with MQ alone. All patients tolerated the medication well. Based on the results of this study and with the objective of slowing the development of resistance, the Peruvian Ministry of Health has decided to revise its malaria treatment policy and recommend combination therapy with MO-AS as the new first-line treatment of uncomplicated P. falciparum malaria in the Amazon region.", "Plasmodium falciparum in Thailand is highly resistant to chloroquine, sulfadoxine-pyrimethamine and there is increasing resistance to quinine and mefloquine. The use of qinghaosu derivatives alone or in combination with mefloquine has been shown successfully effective against multidrug resistant P. falciparum in many clinical trials. However their applications with ambulatory treatment should be assessed. 394 uncomplicated falciparum malaria cases studied at Trat and Chanthaburi malaria clinics, eastern Thailand, were allocated at random to receive either one of the seven following regimens: A) artesunate 600 mg over 2 days and mefloquine 1,250 mg in divided doses. B) artemether 640 mg over 2 days and mefloquine 1,250 mg in divided doses. C) artesunate alone 700 mg over 5 days period. D) artemether alone 800 mg over 5 days period. E) quinine plus tetracycline for 7 days. F) mefloquine 1,250 mg in divided doses and G) artesunate 600 mg over 2 days period and mefloquine 750 mg. The follow-up was on Days 1, 2, 7, 14, 21 and 28. Patients tolerated all regimens very well and there was no serious side effects. The adverse effects did not differ among the seven regimens. The cure rates were 98.7, 97.1, 97.9, 96.7, 92.3, 100 and 95.2%, respectively. There was no significant difference of cure rates among various regimens. A total of 16 P. vivax and 1 P. malariae reinfections were reported among the study groups during the second half of the follow-up period, 14 of which were from the groups administered short action drugs (artesunate, artemether or quinine). The results suggested that either artesunate 600 mg or artemether 640 mg in combination with mefloquine 1,250 mg over a period of two days should be considered as alternative regimens for treating uncomplicated multi-drug resistant falciparum malaria.", "To compare the therapeutic efficacy of oral artesunate and artemether in combination with mefloquine for the treatment of multidrug resistant malaria, a trial was conducted in 540 adults and children on the Thai-Myanmar border. Three regimens were compared: artesunate (4 mg/kg/d for 3 d), artemether (4 mg/kg/d for 3 d), both in combination with mefloquine (25 mg/kg), and a single dose of mefloquine (25 mg/kg). The artesunate and artemether regimens gave very similar clinical and parasitological responses, and were both very well tolerated. There was no significant adverse effect attributable to the artemisinin derivatives. Fever and parasite clearance times with mefloquine alone were significantly longer (P < 0.001). After adjusting for reinfections the failure rates were 13.9% for the artesunate combination, 12.3% for the artemether combination and 49.2% for mefloquine alone (P < 0.0001; relative risk 3.8 [95% confidence interval 2.6-5.4]). Mefloquine should no longer be used alone for the treatment of multidrug resistant falciparum malaria in this area. Three-day combination regimens with artesunate or artemether are well tolerated and more effective.", "The increasing frequency of therapeutic failures in falciparum malaria in Thailand shows an urgent need for effective drugs or drug combinations. Artesunate, a qinghaosu derivative, is effective in clearing parasitaemia rapidly, but the recrudescence rate can be as high as 50%. We have compared artesunate followed by mefloquine with each drug alone in acute, uncomplicated falciparum malaria. 127 patients were randomly assigned treatment with artesunate (600 mg over 5 days), mefloquine (750 mg then 500 mg 6 h later), or artesunate followed by mefloquine. All patients were admitted to hospital for 28 days to exclude reinfection. Cure was defined as no recrudescence during the 28 days' follow-up. The cure rates for mefloquine and artesunate alone were 81% (30/37 patients) and 88% (35/40); the combination was effective in all of 39 patients. Fever and parasite clearance times were significantly shorter in the groups that received artesunate than in the mefloquine-only group. The frequency of nausea and vomiting was slightly, but not significantly, higher among patients who received both drugs than in the other groups. The combination of artesunate followed by mefloquine is highly effective and well tolerated in patients with acute, uncomplicated falciparum malaria in Thailand.", "A randomized comparative trial of the pharmacokinetics and pharmacodynamics of oral doses of mefloquine and of mefloquine in combination with artesunate was carried out on 20 Thai male patients with acute, uncomplicated falciparum malaria. The patients were randomized to receive either mefloquine alone (8 patients; 1250 mg of mefloquine--initial dose, 750 mg; followed 6 hours later by 500 mg), or in combination with oral artesunate (12 patients--initial dose, 200 mg of artesunate; followed by 750 mg and 500 mg of mefloquine 6 hours and 12 hours later, respectively). The patients who received mefloquine alone all showed initially good responses to the treatment, with mean +/- SD values for the fever clearance time (FCT) and parasite clearance time (PCT) of 44.7 +/- 43.1 hours and 82.3 +/- 52.3 hours, respectively. Two patients had recrudescences on day 20 and day 31 (RI response). The cure rate was 75%, and one patient had Plasmodium vivax in his peripheral blood on day 52. The patients who received the combination treatment were clinically markedly improved, with a relatively shorter FCT (31.2 +/- 12.4 hours) and significantly shorter PCT (47.5 +/- 19.6 hours). Four had recrudescences on days 12, 18, 26 and 33; the cure rate was 66%. Artesunate caused three significant changes in mefloquine pharmacokinetics: a decrease in the maximum concentration (Cmax: 1623 ng.ml-1 versus 2212 ng.ml-1); an increase in the clearance rate (Cl/f:2.9 ml.min-1.kg-1 versus 1.1 ml.min-1.kg-1); and an expansion of the volume of distribution (Vdz/f: 31.8 l.kg-1 versus 25.0 l.kg-1)." ]

[ "9145959", "8002642", "18474151", "6349944", "14636195", "12472345", "15355358", "8217756", "12889718", "12771472", "10561942", "15304189", "10417583", "17388924", "1816137", "18489266", "18616780" ]

[ "Glycolic acid peels in the treatment of melasma among Asian women.", "Topical retinoic acid (tretinoin) for melasma in black patients. A vehicle-controlled clinical trial.", "Comparison of 30% salicylic acid with Jessner's solution for superficial chemical peeling in epidermal melasma.", "The efficacy of a broad-spectrum sunscreen in the treatment of melasma.", "Safety and efficacy of 4% hydroquinone combined with 10% glycolic acid, antioxidants, and sunscreen in the treatment of melasma.", "Efficacy of glycolic acid peels in the treatment of melasma.", "Intense pulsed light for the treatment of refractory melasma in Asian persons.", "Topical tretinoin (retinoic acid) improves melasma. A vehicle-controlled, clinical trial.", "Efficacy and safety of a new triple-combination agent for the treatment of facial melasma.", "A randomized, double-blind, placebo-controlled trial of vitamin C iontophoresis in melasma.", "Topical isotretinoin for melasma in Thai patients: a vehicle-controlled clinical trial.", "A double-blind randomized trial of 5% ascorbic acid vs. 4% hydroquinone in melasma.", "Treatment of melasma using kojic acid in a gel containing hydroquinone and glycolic acid.", "Evaluation of efficacy and safety of rucinol serum in patients with melasma: a randomized controlled trial.", "The treatment of melasma. 20% azelaic acid versus 4% hydroquinone cream.", "Whitening effect of a dermocosmetic formulation: a randomized double-blind controlled study on melasma.", "A randomized controlled trial of the efficacy and safety of a fixed triple combination (fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%) compared with hydroquinone 4% cream in Asian patients with moderate to severe melasma." ]

[ "Melasma is a common disorder of facial hyperpigmentation among Asian women. Many modalities of treatment are available but none is satisfactory.\n This study was undertaken to see if glycolic acid peels are effective and safe in the treatment of melasma and fine facial wrinkling.\n Ten Asian women with moderate to severe melasma were recruited into the study. The women had twice daily applications of a cream containing 10% glycolic acid and 2% hydroquinone (Neostrata AHA Age Spot and Skin Lightening Gel) to both sides of the face, and glycolic acid peels every 3 weeks (20-70%) to one-half of the face using Neostrata Skin Rejuvenation System. All patients had to use a sunblock (SPF 15%). At regular intervals and at the end of 26 weeks (or after eight peels) the degree of improvement of pigmentation and fine facial wrinkling on each side of the face were assessed. Any skin irritation or side effects were also noted. Assessment was by an independent dermatologist, the patients themselves, and the use of the Munsell color chart and photographs. The nonparametric Wilcoxon Rank-Sum test was used for statistical analysis.\n The melasma and fine facial wrinkling improved on both sides of the face. The side that received glycolic acid peels did better but the results were not statistically significant (P > 0.059).\n A cream containing 10% glycolic acid and 2% hydroquinone (Neostrata AHA Age Spot and Skin Lightening Gel) improved melasma and fine facial wrinkling in Asian women. In combination with glycolic acid peels at 3-week intervals the lightening of melasma is subjectively much better. This improvement does not reach statistical significance and the sample size is small (n = 10).", "Melasma is an acquired, masklike, facial hyperpigmentation. The pathogenesis and treatment of melasma in black (African-American) patients is poorly understood. We investigated the efficacy of topical 0.1% all-trans-retinoic acid (tretinoin) in the treatment of melasma in black patients. Twenty-eight of 30 black patients with melasma completed a 10-month, randomized, vehicle-controlled clinical trial in which they applied either 0.1% tretinoin or vehicle cream daily to the entire face. They were evaluated clinically (using our Melasma Area and Severity Index), colorimetrically, and histologically.\n After 40 weeks, there was a 32% improvement in the Melasma Area and Severity Index score in the tretinoin treatment group compared with a 10% improvement in the vehicle group. Colorimetric measurements showed lightening of melasma after 40 weeks of tretinoin treatment vs vehicle. Lightening of melasma, as determined clinically, correlated well with colorimetric measurements. Histologic examination of involved skin revealed a significant decrease in epidermal pigmentation in the tretinoin group compared with the vehicle group. Side effects were limited to a mild \"retinoid dermatitis\" occurring in 67% of tretinoin-treated patients. Among the patients in this study in comparison with comparably recruited white patients, melasma was reported to have begun at a later age and was more likely to be in a malar distribution.\n This controlled study demonstrates that topical 0.1% tretinoin lightens melasma in black patients, with only mild side effects.", "To compare the efficacy and safety of Jessner's solution with 30% salicylic acid as superficial chemical peeling agents in treating epidermal melasma in Asian skin.\n Double blind, randomized, interventional comparative study.\n Department of Dermatology, Combined Military Hospital, Malir Cantt, Karachi, from January to December 2004.\n Sixty consenting patients with epidermal melasma were randomly divided into two groups. Group A was treated with Jessner's solution and Group B with 30% salicylic acid. Baseline Melasma Area Severity Index (MASI) score was noted and peeling started at 2-weekly intervals. Sunscreen in morning and moisturizer at night were prescribed in all patients. MASI score and adverse effects were recorded biweekly. Treatment was stopped at 12 weeks and patients were followed-up at 4 weekly intervals for further 12 weeks. Final MASI score and adverse effects were noted at the end of follow-up period. Mean MASI scores were compared using paired sample t-test and one-way ANOVA.\n Difference in baseline, treatment end and follow-up end MASI scores was not statistically significant between the two groups (p 0.54, 0.26, and 0.55 respectively). On the other hand, within group analysis of difference between pre and posttreatment MASI score was highly significant in both groups (p<0.0001). Adverse effects were mild and comparable in both groups.\n Jessner's solution and 30% salicylic acid are equally effective and safe peeling agents for use in epidermal melasma in Asian skin.", "A double-blind study comparing a broad-spectrum sunscreen agent with its vehicle in the treatment of melasma was performed in fifty-three patients who were concomitantly using a depigmentating solution. In this study, 96.2 percent of those who used the sunscreen agent showed improvement as compared with 80.7 percent of those who used placebo. These results confirm the positive role of sun protection in the treatment of melasma and also establish hydroquinone as a major therapeutic agent in pigmentary disorders.", "Melasma, also known as mask of pregnancy, is a common, acquired hypermelanosis seen in women with Fitzpatrick skin types II-V, and is often recalcitrant to treatment with depigmentation agents. Glycolic acid has been added to hydroquinone formulations in the past to enhance their depigmentation effects, but may cause irritation, leading to postinflammatory hyperpigmentation.\n To assess the safety and efficacy of a cream containing 4% hydroquinone, 10% buffered glycolic acid, vitamins C and E, and sunscreen (Glyquin, ICN Pharmaceuticals, Costa Mesa, USA) vs. a cream containing sunscreen alone in the depigmentation of epidermal melasma of the face.\n Thirty-nine Hispanic women, Fitzpatrick skin types III-V, with bilateral epidermal melasma were enrolled in a randomized controlled trial lasting 12 weeks. Patients underwent twice-daily full-face application with the study cream or with the cream containing sunscreen only. Changes in pigmentation were measured using a mexameter, the melasma area and severity index (MASI), and a global evaluation by the patient and blind investigator. Safety evaluations were performed at each follow-up visit.\n Thirty-five patients completed the trial. Irritation was more common with the study cream, but resolved with temporary cessation of cream application and the addition of moisturizers. Mexameter results demonstrated a significant decrease in the degree of pigmentation using the study cream compared with the cream containing sunscreen alone (P < 0.0001). Fifteen of 20 patients (75%) using the study cream improved, whereas only two of 15 patients (13%) improved using sunscreen alone.\n A cream containing 4% hydroquinone, 10% buffered glycolic acid, vitamins C and E, and sunscreen is safe and effective in the treatment of melasma.", "Melasma is an acquired hypermelanosis that is often recalcitrant to treatment with hypopigmenting agents.\n To assess the efficacy of 4% hydroquinone cream vs 4% hydroquinone cream combined with glycolic acid peels as treatment for melasma.\n Twenty-one Hispanic women with bilateral epidermal and mixed melasma were enrolled in a split-faced prospective trial lasting 8 weeks. Patients underwent 20% to 30% glycolic acid peels every 2 weeks to one side of the face only in addition to twice-daily full-face application of 4% hydroquinone cream and sun protective factor 25 UV-B sunscreen each morning. Pigmentation was measured objectively using a mexameter and the Melasma Area and Severity Index and subjectively using a linear analog scale and physician and patient global evaluation.\n Hydroquinone treatment alone and treatment with the combination of hydroquinone and glycolic acid had a significant effect in reducing skin pigmentation compared with baseline (P<.001). However, no significant difference was found using combination therapy compared with hydroquinone alone (P =.75).\n Use of 4% hydroquinone and a daily sunscreen is effective in the treatment of melasma; however, the addition of 4 glycolic acid peels did not enhance the hypopigmenting effect of hydroquinone treatment alone.", "Patients with dermal or mixed-type melasmas are often refractory to various treatments. Intense pulsed light has been used to treat melanocytic lesions with promising results.\n The purpose of this study was to clarify the effectiveness of intense pulsed light for refractory melasma in Asian persons.\n Seventeen patients were treated with intense pulsed light, during four sessions at 4-week intervals. The patients were also given 4% hydroquinone cream and broad-spectrum sunscreens to prevent and treat postinflammatory hyperpigmentation. Sixteen patients in the control group were treated with hydroquinone cream and sunscreens. The treatment efficacy was evaluated using reflectance spectrophotometer and patient satisfaction questionnaire.\n Patients in the intense pulsed light group achieved an average of 39.8% improvement in relative melanin index, compared to 11.6% improvement in the control group (p<0.05) at Week 16. Six (35%) patients in the intense pulsed light group had more than 50% improvement, compared to two (14%) patients in the control group. Two patients in the intense pulsed light group, however, experienced transient postinflammatory hyperpigmentation, and partial repigmentation was noted 24 weeks after the last treatment session.\n Intense pulsed light is a safe and effective treatment for refractory melasma in Asian persons, with minimal side effects. Further treatment sessions are required for maintenance therapy.", "Melasma is a common disorder of cutaneous hyperpigmentation predominantly affecting the faces of women. Little is known about the aetiology of melasma, and treatment is frequently disappointing. Topical tretinoin is of benefit in treating other forms of hyperpigmentation, for example liver spots, and we therefore investigated its effectiveness in melasma. Thirty-eight women completed a randomized, vehicle-controlled study, in which they applied 0.1% tretinoin (n = 19) or vehicle cream (n = 19) once daily to the face for 40 weeks. At the end of treatment 13 (68%) of 19 tretinoin-treated patients were clinically rated as improved or much improved, compared with 1 (5%) of 19 in the vehicle group (P = 0.0006). Significant improvement first occurred after 24 weeks of tretinoin treatment. Colorimetry (an objective measure of skin colour) demonstrated a 0.9 unit lightening of tretinoin-treated melasma and a 0.3 unit darkening with vehicle (P = 0.01); these results correlated with clinical lightening (r = 0.55, P = 0.0005). Histologically, epidermal pigment was reduced 36% following tretinoin treatment, compared with a 50% increase with vehicle (P = 0.002). Reduction in epidermal pigment also correlated with clinical lightening (r = -0.41, P = 0.01). Moderate cutaneous side-effects of erythema and desquamation occurred in 88% of tretinoin-treated and 29% of vehicle-treated patients. Topical 0.1% tretinoin produces significant clinical improvement of melasma, mainly due to reduction in epidermal pigment, but improvement is slow.", "Treatment of melasma, a hyperpigmentation disorder, remains a challenge. The primary objective of two 8-week, multicenter, randomized, investigator-blind studies was to compare the efficacy and safety of a hydrophilic cream formulation containing tretinoin 0.05%, hydroquinone 4.0%, and fluocinolone acetonide 0.01% (RA+HQ+FA) with the dual-combination agents tretinoin plus hydroquinone (RA+HQ), tretinoin plus fluocinolone acetonide (RA+FA), and hydroquinone plus fluocinolone acetonide (HQ+FA). All agents had the same drug concentration and vehicle. A total of 641 adult patients, predominantly female, with moderate to severe melasma and Fitzpatrick skin types I through IV, were randomized to the various treatment groups. Due to the similarity of the study designs, the results of the 2 studies were combined and are reported here. The primary efficacy analysis involved the proportion of intent-to-treat patients in each treatment group whose condition had completely cleared by week 8. The results of the combined clinical trials demonstrated that significantly more of the patients treated with RA+HQ+FA (26.1%) experienced complete clearing compared with the other treatment groups (4.6%) at the end of week 8 (P<.0001). In addition, at week 8, a 75% reduction in melasma/pigmentation was observed in more than 70% of patients treated with RA+HQ+FA compared with 30% in patients treated with the dual-combination agents. The most common adverse reactions seen with all treatment groups were erythema, skin peeling, burning, and/or stinging sensation. The majority of treatment-related adverse events were of mild severity.", "Vitamin C is known to both inhibit melanin formation and reduce oxidized melanin. However, vitamin C does not easily penetrate the skin. In this study, vitamin C iontophoresis was employed in order to enhance vitamin C penetration.\n The purpose of this study was to evaluate the efficacy of vitamin C iontophoresis for melasma patients.\n Twenty-nine females with melasma were enrolled. For iontophoresis, a vitamin C solution was applied to one side of the face, while distilled water was applied to the other side as a control. The L (luminance) value was measured by a colorimeter to obtain an objective pigmentation parameter.\n Twelve weeks after iontophoresis, the colorimeter of the treated site showed a significant decrease in the L value (from 4.60 to 2.78, p = 0.002), compared to that of the control site (from 4.45 to 3.87, p = 0.142).\n Vitamin C iontophoresis may be an effective treatment modality for melasma.\n Copyright 2003 S. Karger AG, Basel", "Melasma is an acquired hyperpigmentary disorder commonly seen in Orientals. Recently it has been demonstrated that tretinoin (all-trans-retinoic acid) can produce significant clinical improvement of melasma. However, moderate cutaneous side effects (retinoid dermatitis) occurred in a number of patients.\n To investigate the efficacy of topical 0.05 per cent isotretinoin gel (Isotrex) in the treatment of melasma in Thai patients.\n Thirty patients with moderate to severe melasma entered a 40-week, randomized, vehicle-controlled clinical trial in which they applied either 0.05 per cent isotretinoin gel, or its vehicle base together with a broad spectrum sunscreen (SPF 28) daily to the entire face. They were evaluated clinically (using Melasma Area and Severity Index), and colorimetrically (using our Melasma Area and Melanin Index).\n After 40 weeks, the average MASI and MAMI scores of the isotretinoin-treated group decreased by 68.2 per cent and 47 per cent respectively, while the corresponding control scores declined 60 per cent and 34 per cent. There was no statistically significant difference between the isotretinoin and vehicle groups. When the MASI and MAMI scores of each visit were compared to their baseline data, a statistically significant reduction of the score was first noted at weeks 4 and 12 respectively. Lightening of melasma, as determined clinically (MASI score), correlated well with pigmentation measurements (MAMI score). Side effects were limited to a mild transient \"retinoid dermatitis\" occurring in 27 per cent of isotretinoin-treated patients.\n Daily use of broad spectrum sunscreen has a significant lightening effect on melasma in Thai patients. However, there was no statistically significant difference between the isotretinoin and vehicle-treated group.", "Melasma is an acquired treatment-resistant hyperpigmentation of the skin.\n Sixteen women with idiopathic melasma were included in our trial. After randomization by another clinician, they were instructed to use, at night, 5% ascorbic acid cream on one side of the face and 4% hydroquinone cream on the other side, for 16 weeks. Sunscreen was applied daily throughout the period of observation. They were evaluated every month by colorimetry, digital photography, and regular color slides. Subjective evaluation by each patient was also taken into account.\n The best subjective improvement was observed on the hydroquinone side with 93% good and excellent results, compared with 62.5% on the ascorbic acid side (P < 0.05); however, colorimetric measures showed no statistical differences. Side-effects were present in 68.7% (11/16) with hydroquinone vs. 6.2% (1/16) with ascorbic acid.\n Although hydroquinone showed a better response, ascorbic acid may play a role in the therapy of melasma as it is almost devoid of side-effects; it could be used alone or in combination therapy.", "Melasma is difficult to clear. Many agents have been used, such as hydroquinone, and glycolic acid and glycolic acid peels, kojic acid, a tyrosinase inhibitor in the fungus Aspergilline oryzae.\n To see if the addition of 2% kojic acid in a gel containing 10% glycolic acid and 2% hydroquinone will improve melasma further.\n Forty Chinese women with epidermal melasma were treated with 2% kojic acid in a gel containing 10% glycolic acid and 2% hydroquinone on one half of the face. The other half was treated with the same application but without kojic acid. The side receiving the kojic acid was randomized. Determination of efficacy was based on clinical evaluation, photographs and self-assessment questionnaires at 4 weekly intervals until the end of the study at 12 weeks. The non-parametric Wilcoxon's rank sum test was used for statistical analysis.\n All patients showed improvement in melasma on both sides of the face. The side receiving the kojic acid did better. More than half of the melasma cleared in 24/40 (60%) patients receiving kojic acid compared to 19/40 (47.5%) patients receiving the gel without kojic acid. In 2 patients, there was complete clearance of melasma, and this was on the side where kojic acid was used. Side effects include redness, stinging, and exfoliation. These were seen on both sides of the face, and they settled by the third week.\n The addition of kojic acid to a gel containing 10% glycolic acid and 2% hydroquinone further improves melasma.", "Melasma is a hyperpigmentation disorder predominantly affecting sun-exposed areas in women, which is often refractory to treatment. Most commercially available treatments incorporate inhibitors of tyrosinase, a key enzyme in melanin production within the melanocyte. In general, however, the efficacy of these therapies is somewhat limited. Recent studies have identified other enzymes that play an important role in melanogenesis, including tyrosinase-related protein-1 (TRP-1), which catalyses the oxidation of the melanogenetic intermediate 5,6-dihydroxyindole-2-carbolylic acid. Rucinol (4-n-butylresorcinol) has been shown to inhibit the activity of both tyrosinase and TRP-1.\n To assess the efficacy of rucinol serum 0.3% vs. the corresponding vehicle as a treatment for melasma. Secondary objectives were to evaluate local and general tolerability and to assess the skin acceptability of rucinol serum in the target population.\n In this prospective, single-centre, double-blind, randomized, vehicle-controlled, bilateral (split-face) comparative trial, 32 women with melasma were provided with two identical tubes containing rucinol serum 0.3% or vehicle. The products were each applied to one-half of the face, according to the randomization scheme, twice daily for 12 weeks (phase 1). A broad-spectrum sunscreen (sun protection factor 60) was also applied daily. Assessments at baseline, 4, 8 and 12 weeks included clinical evaluations by a dermatologist, chromametry, ultraviolet and standard photography, and assessments of skin acceptability and tolerability. After 12 weeks, patients were given the option of an additional 3-month treatment period of open full-face rucinol treatment, with reviews at 16, 20 and 24 weeks (phase 2).\n Twenty-eight patients completed phase 1 and 26 patients completed phase 2. After 12 weeks, the clinical pigmentation score for rucinol-treated skin was significantly lower than for vehicle-treated skin (P = 0.027). During phase 2, rucinol induced a significant reduction in mean pigmentation score on the half of the face previously treated with vehicle. There was also a further, significant improvement on the rucinol-treated side of the face. Chromametry measurements showed that skin was significantly lighter and less yellow, with a strong trend towards reduced redness, following rucinol therapy compared with vehicle. Rucinol serum showed good tolerability and acceptability and was considered to have good or fair efficacy by 78% of the patient population.\n Rucinol serum was shown to have significant efficacy compared with vehicle alone in improving melasma after 3 months of treatment, according to clinical and objective assessments of skin colour.", "The efficacy of 20% azelaic acid cream and 4% hydroquinone cream, both used in conjunction with a broad-spectrum sunscreen, against melasma was investigated in a 24-week, double-blind study with 329 women. Over the treatment period the azelaic acid cream yielded 65% good or excellent results; no significant treatment differences were observed with regard to overall rating, reduction in lesion size, and pigmentary intensity. Severe side effects such as allergic sensitization or exogenous ochronosis were not observed with azelaic acid.", "Melasma is an endocrine-mediated facial hypermelanosis with epidermal and occasionally dermal components. We tested in a randomized double-blind design the effect of a whitening formulation (Thiospot intensive) on this skin disorder. The product containing ethyl linoleate, thioctic acid, octadecenedioic acid, lactic acid and ethylhexyl methoxycinnamate was applied twice daily for 3 months by 20 young women. Another control group of seven women received a non-skin lightening formulation. Clinical assessments were made at 1-month intervals. In addition, objective measurements of the hypermelanosis were performed using narrow-band reflectance spectrophotometry, image analysis of video-recorded ultraviolet light reflection (ULEV method) and photodensitometry of the corneomelametry test. A significant lightening effect was evidenced beginning the second month of treatment with the whitening formulation. No significant effect was observed with the control product.", "Melasma is an acquired, chronic hypermelanosis for which therapy remains a challenge.\n To compare the efficacy and safety of a triple combination [TC: fluocinolone acetonide 0.01%, hydroquinone (HQ) 4%, tretinoin 0.05%] vs. HQ 4% after 8 weeks of treatment of moderate to severe facial melasma in Asian patients.\n This was a multicentre, randomized, controlled, investigator-blinded, parallel comparison study. East and South-East Asian patients aged 18 years or older, with a clinical diagnosis of moderate to severe melasma, were enrolled in this study. Patients were enrolled at baseline and treated daily for 8 weeks with TC cream (one application at bedtime) or HQ cream (twice daily). There were four study visits: at baseline and weeks 2, 4 and 8. The primary efficacy variable was the melasma global severity score (GSS). Other outcome measures included Melasma Area and Severity Index, global improvement and patient satisfaction. Safety was assessed through the reporting of adverse events.\n TC had superior efficacy to HQ for the primary variable: 77/120 patients (64.2%) on TC had GSS 'none' or 'mild' at week 8 vs. 48/122 patients (39.4%) on HQ (P < 0.001). The secondary efficacy variables confirmed these results. Patient satisfaction was in favour of TC (90/127, 70.8%, vs. 64/129, 49.6%; P = 0.005). More patients had related adverse events on TC (63/129, 48.8%) than on HQ (18/131, 13.7%) but most were mild and none was severe.\n Efficacy in Asians and patient satisfaction were superior with the fixed TC than with HQ 4%." ]

[ "6282460", "11505405", "16022920", "1314632", "7833105", "1648142", "8106908", "16249353", "2820289", "12488411", "14662044", "2824710", "2547030", "1851339", "10470844", "1326734", "2153194", "6269770", "9106647", "3028596", "3022035", "1649265", "8052871", "1964073", "8410110" ]

[ "Phase II study of cisplatin, maytansine, and chlorozotocin in small cell lung carcinoma (EST 2578).", "Randomized phase II study of cyclophosphamide, doxorubicin, and vincristine compared with single-agent carboplatin in patients with poor prognosis small cell lung carcinoma.", "A randomised phase II study of the efficacy and safety of intravenous topotecan in combination with either cisplatin or etoposide in patients with untreated extensive disease small-cell lung cancer.", "Comparison of two carboplatin-containing regimens with standard chemotherapy for small cell lung cancer in a randomised phase II study. The EORTC Lung Cancer Cooperative group.", "Cisplatin and etoposide versus cyclophosphamide, epirubicin and vincristine in small cell lung cancer: a randomised study.", "Randomized trial of cyclophosphamide, doxorubicin, and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer.", "Cisplatin-VP16 alternating with cyclophosphamide-epirubicin versus cyclophosphamide-epirubicin-vincristine in small cell lung cancer.", "Paclitaxel/carboplatin/etoposide versus paclitaxel/topotecan for extensive-stage small cell lung cancer: a Minnie Pearl Cancer Research Network randomized, prospective phase II trial.", "Superiority of alternating non-cross-resistant chemotherapy in extensive small cell lung cancer. A multicenter, randomized clinical trial by the National Cancer Institute of Canada.", "Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up.", "Novel doublets in extensive-stage small-cell lung cancer: a randomized phase II study of topotecan plus cisplatin or paclitaxel (CALGB 9430).", "Cisplatin/etoposide versus ifosfamide/etoposide combination chemotherapy in small-cell lung cancer: a multicenter German randomized trial.", "A randomized trial of anticoagulation with warfarin and of alternating chemotherapy in extensive small-cell lung cancer by the Cancer and Leukemia Group B.", "Does the substitution of cisplatin in a standard four drug regimen improve survival in small cell carcinoma of the lung? A comparison of two chemotherapy regimens.", "Standard combination versus alternating chemotherapy in small cell lung cancer: a randomised clinical trial including 394 patients. 'Petites Cellules' Group.", "Randomized phase II trial of high-dose 4'-epi-doxorubicin + cyclophosphamide versus high-dose 4'-epi-doxorubicin + cisplatin in previously untreated patients with extensive small cell lung cancer.", "Treatment of limited small-cell lung cancer with etoposide and cisplatin alternating with vincristine, doxorubicin, and cyclophosphamide versus concurrent etoposide, vincristine, doxorubicin, and cyclophosphamide and chest radiotherapy: a Southwest Oncology Group Study.", "An evaluation of low-dose cisplatin as part of combined modality therapy of limited small cell lung cancer.", "Five-day oral etoposide treatment for advanced small-cell lung cancer: randomized comparison with intravenous chemotherapy.", "Alternating versus sequential chemotherapy in small cell lung cancer. A randomized German multicenter trial.", "Alternating non-cross resistant chemotherapy for small cell lung cancer.", "Comparison of cyclophosphamide, doxorubicin, and vincristine with an alternating regimen of methotrexate, etoposide, and cisplatin/cyclophosphamide, doxorubicin, and vincristine in the treatment of extensive-disease small-cell lung carcinoma: a Mid-Atlantic Oncology Program study.", "Etoposide/vincristine-based chemotherapy with or without carboplatin in extensive-stage small cell lung cancer: a prospective randomized phase III trial.", "A randomized study comparing etoposide and vindesine with or without cisplatin as induction therapy for small cell lung cancer. EORTC Lung Cancer Working Party.", "Multiple-drug weekly chemotherapy versus standard combination regimen in small-cell lung cancer: a phase III randomized study conducted by the European Lung Cancer Working Party." ]

[ "Seventy-three patients with small cell lung carcinoma refractory to standard chemotherapy were entered in this phase II randomized study of cisplatin, maytansine, and chlorozotocin. Of the 58 evaluable patients, only one partial response was observed among 21 patients given cisplatin, and no responses were seen among 19 given maytansine or 18 given chlorozotocin. One patient treated with chlorozotocin and two treated with cisplatin experienced life-threatening thrombocytopenia. One third of the maytansine-treated patients experienced moderate or severe neurologic toxicity. The overall median survival was 9.7 weeks. Chlorozotocin treatment was associated with inferior survival (7.7 weeks).", "Information on the effect of chemotherapy in a group of patients with poor prognosis, poor performance status small cell lung carcinoma (SCLC) is scarce. A randomized study comparing single-agent carboplatin with combination chemotherapy in this largely unreported population of SCLC patients was undertaken.\n One hundred nineteen patients were allocated to four cycles of either cyclophosphamide, doxorubicin, and vincristine (CAV) or single-agent carboplatin. Patients had either a Karnofsky performance score < or = 50 and/or a prognostic score indicative of a 1-year survival rate < or = 15%.\n Grade 3-4 neutropenia and intravenous antibiotic use were significantly more common with the CAV regimen (P < 0.005). Conversely, Grade 3-4 thrombocytopenia was more common (P < 0.0009) and platelet transfusion was more frequent (P < 0.05) with carboplatin therapy. Nonhematologic toxicity was similar in both treatment arms, except for alopecia with CAV therapy (P < 0.0007). Symptom relief occurred in 48% and 41% of patients in the CAV and carboplatin treatment arms, respectively. Dyspnea was improved in 66% and 41% of patients and cough was improved in 21% and 7% of patients in the CAV and carboplatin treatment arms, respectively. CAV therapy produced a higher response rate than carboplatin (38% vs. 25%), but this was not statistically significant (P = 0.15). The median overall survival for patients in the CAV and carboplatin treatment arms was 17 weeks and 15.9 weeks, respectively, with 1-year survival rates of 12% and 6%.\n Single-agent carboplatin is a feasible treatment in patients with poor prognosis SCLC and produces response rates, relief of tumor-related symptoms, and survival similar to what is seen in patients who receive CAV chemotherapy. The lower risk of life-threatening sepsis and less need for hospitalization or intravenous antibiotic courses is advantageous in this susceptible patient population.\n Copyright 2001 American Cancer Society.", "Topotecan (Hycamtin is active in small-cell lung cancer (SCLC). This phase II study investigated the efficacy and safety of topotecan in combination with either cisplatin or etoposide in untreated extensive disease SCLC (ED SCLC).\n Patients with untreated ED SCLC were randomised to treatment with T/C (topotecan 1.25mg/(m(2)day) IV days 1-5, cisplatin 50mg/m(2) IV day 5; 41 patients) or T/E (topotecan 0.75 mg/(m(2)day) IV days 1-- 5, etoposide 60 mg/(m(2)day) IV days 1-5; 41 patients) every 21 days. Response was evaluated by strict radiological criteria.\n Response rates were similar for T/C (63.4%, 95% CI: 48.7-78.2%) and T/E (61.0%, 95% CI: 46-76%) with one patient in each arm who underwent complete response. Median survival was 41.6 weeks (9.6 months) for the T/C group and 43.7 weeks (10.1 months) for the T/E group. Toxicity was primarily haematological in both groups. The proportion of patients with grades 3-4 anaemia was significantly higher in the T/C arm (46.4%) versus 20% with the T/E arm (p=0.018). The proportion of patients with grade 4 neutropenia was not significantly lower with T/C (56.1%) than with T/E (65.0%, p=0.41), as was the incidence of associated events such as sepsis (T/C: 0%; T/E: 9.8%, p=0.11). The overall deliverability of either regimen was similar. The most frequent non-haematological adverse experiences of all grades per patient were nausea (T/C: 43.9%; T/E: 36.6%), and alopecia (T/C: 39.0%; T/E: 56.1%). Topotecan did not appear to increase the frequency of adverse events specifically associated with cisplatin.\n This study showed T/C and T/E to be effective and well tolerated in patients with ED SCLC and further evaluation of topotecan in first line SCLC is warranted.", "The EORTC Lung Cancer Cooperative group performed a randomised phase II study in patients with small cell lung cancer comparing the standard cyclophosphamide/doxorubicin/etoposide (CDE) regimen with two regimens containing the new and active cisplatin derivative, carboplatin, 400 mg/m2 in combination with ifosfamide, a drug without important myelotoxicity, at a dose of 5 g/m2 (IMP) or the non-myelotoxic drug vincristine twice 2 mg (VP). Of 178 evaluable patients, 63 received CDE [30 limited disease (LD), 33 extensive disease (ED)], 55 received IMP (22 LD, 33 ED) and 60 (26 LD, 34 ED) were treated with VP. The response duration was not statistically different: CDE 31 weeks, IMP 29 weeks and VP 21 weeks. The time to progression after CEE was 28 weeks, IMP 24 weeks and VP 17 weeks. This was significantly shorter after VP than after CDE (P = 0.017). The 60% response rate of the VP combination was low compared with CDE (83%) and IMP (77%). Toxicity of all three regimens was acceptable, and dose reduction for myelosuppression was necessary in only a minority of the patients. We conclude from this study that the combination of carboplatin, at the maximally tolerated dose of 400 mg/m2, in combination with ifosfamide 5 g/m2, is an active regimen with efficacy comparable with the standard CDE regimen.", "From September 1986 until December 1991, 139 patients with histologically-proven small cell lung cancer, age < 75 years, performance status > 40, absence of brain metastases and no previous treatment, were randomised to receive either CEV cyclophosphamide 1000 mg/m2 intravenous (i.v.), epirubicin 70 mg/m2 i.v., vincristine 1.2 mg/m2 i.v., every 3 weeks or PE (cisplatin 20 mg/m2 i.v. and etoposide 75 mg/m2 i.v. for 5 consecutive days, every 3 weeks) for six cycles. After three cycles, responding patients received radiotherapy to the chest (45 Gy/15 sessions) and to the brain (30 Gy/10 sessions--only in patients with limited disease achieving complete remission). 3 patients were ineligible. Patient characteristics included (CEV/PE) total number 66/70, median age 60/61 years, median performance status 80/80, extended disease 33/48 cases (P = 0.04). In evaluable patients, 42/62 (67.7%) responded to CEV while 42/58 (72.4%) responded to PE (P = non-significant); respective complete response rates were 16.1 and 29.3% (P = non-significant) and respective complete response rates in patients with extended disease were 9.4 and 28.9% (P = 0.03). Median survival was 10.5 months, without significant differences in the two treatment arms, even after adjustment for stage. PE was less well tolerated than CEV. Although PE is more active than CEV in certain subsets of patients, its apparent inability to improve survival in this and in other studies questions its routine use in small cell lung cancer.", "Between April 1985 and May 1988, we conducted a randomized study comparing two standard chemotherapy regimens with the same regimens given on an alternating basis in patients with small-cell lung cancer. The patients were randomly assigned to receive cyclophosphamide at a dose of 800 mg/m2 intravenously (IV) on day 1, doxorubicin at 50 mg/m2 IV on day 1, and vincristine at 1.4 mg/m2 IV on day 1 (CAV); cisplatin at 80 mg/m2 IV on day 1 and etoposide at 100 mg/m2 IV on days 1, 3, and 5 (PE); or CAV alternating with PE (CAV/PE). Each regimen was repeated every 3-4 weeks. Three hundred patients were entered in the study, and 288 of them were eligible for analysis (97 for CAV, 97 for PE, and 94 for CAV/PE). The response rates for PE (78%) and CAV/PE (76%) were significantly higher than the rate for CAV (55%), while the complete response rates were similar (14%, 16%, and 15%, respectively). Nine (23%) of 39 patients who failed to respond to the initial CAV regimen responded to PE when they were crossed over. In contrast, only one (8%) of 13 patients responded to CAV after failing to respond to the PE regimen, suggesting that these two regimens were partially non-cross-resistant. The response duration on CAV/PE was significantly longer than that with CAV (P = .004). The survival time with CAV/PE (11.8 months) was superior to that with CAV (9.9 months) (P = .027) or that with PE (9.9 months) (P = .056). In patients with limited disease, the survival in the alternating arm was significantly superior to the survival in the CAV arm (P = .014) or the survival in the PE arm (P = .023). The toxic effects were acceptable in all three chemotherapy regimens. These results favor the alternating chemotherapy over either standard chemotherapy, such as CAV and PE, although the differences are not dramatic.", "In the hope of increasing the incidence of objective remissions and the survival time of patients with small cell lung cancer, we conducted a randomized study designed to compare a treatment scheme of alternating chemotherapy featuring cisplatin+etoposide followed by cyclophosphamide+epirubicin versus conventional chemotherapy with cyclophosphamide+epirubicin+vincristine, in a total of 113 patients (56 treated with the alternating regime and 57 treated conventionally). Patients receiving the alternating drug regimen showed some increase in objective remission rates, and above all increased mean survival time (297 days versus 232). The higher incidence of side effects encountered was effectively controlled by the usual medical therapy.", "To compare the combination of paclitaxel (Taxol; Bristol-Myers Squibb, Princeton, NJ, http://www.bms.com) and topotecan (Hycamtin; Glaxo SmithKline, Philadelphia, http://www.gsk.com) with paclitaxel, carboplatin (Paraplatin; Bristol-Myers Squibb), and etoposide (Etopophos, VePesid; Bristol-Myers Squibb) in patients with previously untreated extensive-stage small cell lung cancer.\n In this phase II trial, 120 patients were randomly allocated to receive either topotecan (1.5 mg/m(2) i.v. days 1, 2, and 3) and paclitaxel (175 mg/m(2) i.v. day 1) every 21 days orpaclitaxe l (200 mg/m(2) i.v. day 1), carboplatin (area under the concentration-time curve 6 i.v. day 1), and etoposide (50 mg/100 mg alternating daily by mouth days 1-10) every 21 days, each regimen for a maximum of eight cycles. The primary end points were objective response rate and time to progression.\n The paclitaxel-carboplatin-etoposide combination produced a significantly higher overall response rate (78% versus 48%), longer median time to progression (7.6 months versus 5.5 months), and greater number of patients free from progression at 1 year (14% versus 8%) compared with paclitaxel plus topotecan. There was no difference in overall survival. Toxicities were similar in the two treatment arms.\n The paclitaxel-carboplatin-etoposide combination produced a superior overall response rate and time to progression in patients with extensive-stage small cell lung cancer compared with paclitaxel plus topotecan. The platinum compounds continue to be a necessary component of the initial therapy for these patients.", "The National Cancer Institute of Canada Clinical Trials Group conducted a prospective randomized study comparing standard chemotherapy with alternating chemotherapy in patients with extensive small cell lung cancer. \"Standard\" treatment consisted of cyclophosphamide (1000 mg/m2 body surface area); doxorubicin (50 mg/m2), and vincristine (2 mg) every 3 weeks for six courses. Alternating chemotherapy was cyclophosphamide, doxorubicin, and vincristine alternating with etoposide (100 mg/m2 on days 1 to 3) and cisplatin (25 mg/m2 on days 1 to 3) every 3 weeks for six treatment cycles. Two hundred eighty-nine patients were eligible and evaluable for response to therapy and survival. Best response was higher in patients on alternating chemotherapy (complete plus partial response, 80% compared with 63.2%; p less than 0.002). Progression-free survival for patients on alternating chemotherapy was superior (p less than 0.0001) as was overall survival (p = 0.03). Major toxicities were equally frequent in both treatment groups. These results show a modest superiority of alternating chemotherapy over standard therapy in extensive small cell lung cancer.", "To investigate whether chemotherapy with etoposide and cisplatin (EP) is superior to cyclophosphamide, epirubicin, and vincristine (CEV) in small-cell lung cancer (SCLC).\n A total of 436 eligible patients were randomized to chemotherapy with EP (n = 218) or CEV (n = 218). Patients were stratified according to extent of disease (limited disease [LD], n = 214; extensive disease [ED], n = 222). The EP group received five courses of etoposide 100 mg/m(2) intravenously (IV) and cisplatin 75 mg/m(2) IV on day 1, followed by oral etoposide 200 mg/m(2) daily on days 2 to 4. The CEV group received five courses of epirubicin 50 mg/m(2), cyclophosphamide 1,000 mg/m(2), and vincristine 2 mg, all IV on day 1. In addition, LD patients received thoracic radiotherapy concurrent with chemotherapy cycle 3, and those achieving complete remission during the treatment period received prophylactic cranial irradiation.\n The treatment groups were well balanced with regard to age, sex, and prognostic factors such as weight loss, and performance status. The 2- and 5-year survival rates in the EP arm (14% and 5%, P =.0004) were significantly higher compared with those in the CEV arm (6% and 2%). Among LD patients, median survival time was 14.5 months versus 9.7 months in the EP and CEV arms, respectively (P =.001). The 2- and 5-year survival rates of 25% and 10% in the EP arm compared with 8% and 3% in the CEV arm (P =.0001). For ED patients, there was no significant survival difference between the treatment arms. Quality-of-life assessments revealed no major differences between the randomized groups.\n EP is superior to CEV in LD-SCLC patients. In ED-SCLC patients, the benefits of EP and CEV chemotherapy seem equivalent, with similar survival time and quality of life.", "Chemotherapy for extensive-stage small-cell lung cancer (E-SCLC) produces high response rates and improved survival but few cures. We tested three new regimens for E-SCLC that might merit further investigation in a subsequent phase III trial. Cancer and Leukemia Group B 9430 was a randomized phase II study evaluating 4 treatment arms in 57 evaluable, previously untreated E-SCLC patients. Each arm consisted of the following: Arm 1: cisplatin plus topotecan; Arm 2: cisplatin plus paclitaxel; Arm 3: paclitaxel 230 mg/m2 plus topotecan; and Arm 4: paclitaxel 175 mg/m2 plus topotecan. Because of an accrual time difference, Arm 2 will not be discussed in this manuscript. Arm 1 (12 patients) produced 1 complete response (CR, 8%) and an overall response rate (ORR) of 42%. Toxicity was excessive, with 3 deaths (25%). Arm 3 (13 patients) produced no CRs, 7 partial responses (PRs, 54%), median survival of 13.8 months, and failure-free survival (FFS) of 7.41 months, with 3 toxic deaths (25%). Among 32 evaluable patients on Arm 4, there were 2 CRs (6%) and 20 PRs (63%) for an ORR of 69%, median survival of 9.9 months, FFS of 5.21 months, and 1-year survival of 40%. There was 1 possible treatment-related death (3%). Topotecan plus cisplatin, in the doses and schedule employed, produced excessive toxicity and modest efficacy in E-SCLC patients. Paclitaxel (230 mg/m2 on day 1) plus topotecan (1 mg/m2 on days 1-5) produced excessive toxicity that was ameliorated with an attenuated paclitaxel dose (175 mg/m2). With the latter regimen (Arm 4) in patients with a performance status of 0/1, CR rates, FFS, overall survival, and 1-year survival were similar to standard etoposide plus cisplatin chemotherapy. Further exploration of topoisomerase inhibitors and taxanes in SCLC patients is warranted.", "A total of 144 patients with small-cell lung cancer (SCLC) were randomized to receive cisplatin/etoposide (PE) or ifosfamide/etoposide (IE) combination chemotherapy. PE consisted of cisplatin, 80 mg/m2, intravenously (IV) on day 1, and etoposide, 150 mg/m2, IV on days 3 through 5. IE consisted of ifosfamide, 1,500 mg/m2, IV on days 1 through 5, and etoposide, 120 mg/m2, IV on days 3 through 5. Six cycles were administered in 3-week intervals. Nonresponders were switched immediately to CAV, consisting of cyclophosphamide, 600 mg/m2, IV on days 1 and 2, Adriamycin (Adria Laboratories, Columbus, OH), 50 mg/m2, IV on day 1, and vincristine, 2 mg, IV on day 1. Patients obtaining complete remission (CR) received prophylactic cranial irradiation with 30 Gy. After completion of chemotherapy, patients with limited disease received chest irradiation with 45 Gy. No maintenance therapy was given to patients in CR. Minimum follow-up was 2 years. Of the 141 patients evaluable, the overall response rate was 65% in PE therapy and 68% in IE therapy. The CR rate was 32% v 20% for all patients, 50% v 24% for limited disease, and 22% v 18% for extensive disease, all in favor of PE therapy. Median survival for all patients was 11.6 months v 9.4 months, for limited disease 14.8 months v 11.0 months, and for extensive disease 8.9 months v 7.5 months, all preferring PE therapy. The 2-year survival rate was higher in PE therapy than in IE therapy for all patients (12% v 9%) and for limited disease (23% v 10%), but not for extensive disease (5% v 9%). Median progression-free survival was 7.5 months v 6.0 months for all patients, 12.2 months v 8.8 months for limited disease, and 5.9 months v 4.4 months for extensive disease, all in favor of PE. Relapse in the area of the primary tumor was found less often after PE than after IE therapy (25% v 38%). Response to second-line CAV was seen in 30% of patients with prior PE and 43% with prior IE therapy, but was usually short lasting, and only one patient achieved CR. Toxicity included three lethal complications. Nausea, vomiting, diarrhea, and skin lesions occurred more often after PE than after IE therapy. These results suggest that PE is superior to IE chemotherapy in limited-stage, but not in extensive-stage SCLC, and that CAV is cross-resistant to PE, as well as to IE in the majority of patients.", "The Cancer and Leukemia Group B (CALGB) conducted a prospective randomized trial to evaluate the role of warfarin and alternating chemotherapy in extensive small-cell lung cancer (SCCL). After stratification for sex and performance status, patients were randomly assigned to receive chemotherapy with methotrexate, doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH), cyclophosphamide, and lomustine (CCNU) (MACC), or MACC plus warfarin (MACC + W), or mitomycin, etoposide, cisplatin, and hexamethylmelamine alternating with MACC (MEPH/MACC). Warfarin was given continuously to maintain a prothrombin time of one and one half to twice the control values. A total of 328 patients were enrolled, and 294 were evaluable. There was a statistically significant advantage in objective response rates (complete [CR] and partial responses [PR], respectively) for MACC + W (17% and 50%) as compared with MACC alone (8% and 43%) or MEPH/MACC (10% and 38%) (P = .012). Both failure-free survival (P = .054 Wilcoxon test) and overall survival (P = .098 Wilcoxon test) were higher on MACC + W (median, 6.6 months and 9.3 months, respectively), as compared with MACC (5.0 months and 7.9 months) and MEPH/MACC (5.0 months and 7.9 months). Toxicity was comparable among the three arms, except for increased hemorrhagic events on MACC + W, which were life-threatening in four patients (4%), and lethal in two others (2%). These data support the role of warfarin in the treatment of SCCL, but do not establish its mechanism of action. Warfarin deserves further studies in SCCL, particularly in patients with limited disease.", "Ninety five patients with small cell carcinoma of the lung were randomly assigned to one of two chemotherapy regimens (VACE or CVACE), each consisting of six cycles at three week intervals. The VACE regimen consisted of six cycles of vincristine 1.2 mg/m2, doxorubicin 40 mg/m2, and cyclophosphamide 700 mg/m2 on day 1 plus etoposide 110 mg/m2 daily for three days. The CVACE regimen was identical to the VACE regimen for cycles 3 and 4; cycles 1, 2, 4, and 6 consisted of etoposide 110 mg/m2 for three days plus cisplatin 100 mg/m2 with mannitol diuresis on the second day. Forty eight patients received VACE and 47 CVACE. Side effects resulted in withdrawal of four patients receiving VACE and six receiving CVACE. Three deaths were attributed to VACE and one to CVACE. Median survival did not differ between the two treatments overall, though there was a small increase in median survival in partial responders receiving CVACE. It is concluded that replacing four of the six cycles of VACE (vincristine, doxorubicin, cyclophosphamide, and etoposide) with etoposide and cisplatin conferred no overall advantage.", "to compare standard and alternating administration of chemotherapy combinations in small cell lung cancer (SCLC) patients.\n in a multicenter clinical trial, 394 previously untreated SCLC patients were randomised to receive, every 4 weeks, eight courses of either a standard regimen with CCNU, cyclophosphamide, adriamycin (CCA) and VP16 or an alternating regimen (CCA regimen alternating with cisplatin-vindesine-VP16).\n overall response rate was higher in the standard group (78%) than in the alternating group (64%) (P = 0.0001). Complete response rate was also higher in the standard group (32%) than in the alternating group (18%) (P = 0.004). The median survival in the overall SCLC population was 306 days in the standard group and 272 days in the alternating group (P = 0.08). In limited SCLC patients, median survival was higher in the standard group (421 days) than in the alternating group (328 days) (P = 0.01). Grade III/IV haematological toxicity was lower in patients in the alternating group (25 versus 47%) (P < 0.001).\n the standard regimen was better than the alternating regimen for patients with limited forms of SCLC. The alternating regimen, associated with better haematological safety and ensuring a fairly similar survival, may be considered in patients with extensive SCLC. Pleiomorphic resistance mechanisms to chemotherapy make it difficult to define a non-cross-resistant chemotherapy regimen.", "One hundred and eleven previously untreated patients with extensive small cell lung cancer were included in a prospective randomized study with the aim to assess the efficacy and tolerance of high-dose epirubicin (120 mg/m2) in combination with either cyclophosphamide (800 mg/m2; arm 1) or cisplatin (60 mg/m2; arm 2). Ninety-six patients were evaluable for response and toxicity and additional 12 patients for toxicity only. The overall response rate (CR+PR) in arm 1 and 2 were 61.4 (27/44) and 67.3% (35/52), respectively. The mean duration of remission was 4.4 months (arm 1) and 4.9 months (arm 2). The mean survival time was 6.6 months in arm 1 and 7.7 months in arm 2. WHO grade 4 toxicity was encountered in 25.5 and 15.8% of patients in arm 1 and 2, respectively. One case of cardiotoxicity resulting in the patient's death was observed in arm 1. Both combinations showed considerable antitumor activity. Toxicity was acceptable.", "The Goldie-Coldman model explaining the kinetics of tumor cell kill and drug resistance has a potential application in designing chemotherapy regimes. In this Southwest Oncology Group (SWOG) trial we tested the alternation of two potentially noncrossresistant drug combinations with a concurrent drug combination in patients with limited small-cell lung cancer. The concurrent drug combination consisted of etoposide (VP-16), 75 mg/m2/intravenously (IV), days 1, 2, and 3; vincristine, 1.0 mg/m2/IV, days 1 and 8; Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), 40 mg/m2/IV, day 1; and cyclophosphamide, 750 mg/m2/IV, day 1 (EVAC). The alternating combination consisted of VP-16, 100 mg/m2/IV, days 1, 2, and 3; and cisplatin (CDDP), 100 mg/m2/IV, day 1, alternating with vincristine, 1.0 mg/m2/IV, days 1 and 8; Adriamycin, 50 mg/m2/IV, day 1; and cyclophosphamide, 750 mg/m2/IV, day 1 (VP-16/CDDP-VAC). Chemotherapy was administered at 3-week intervals for six cycles both before and after chest (5,000 rads/5 weeks) and whole brain radiotherapy (3,000 rads/2 weeks). One hundred ninety-nine patients received EVAC and 201 received the alternating combination. There was no significant difference in the response rate to the initial six cycles of treatment with EVAC (CR, 40%) versus the alternating combination (CR, 38%). There was no significant difference between the best response, EVAC (CR, 48%) and VP-16/CDDP-VAC (CR, 51%). Median survival for all randomized patients on EVAC is 15.1 months versus 16.5 months on the alternating combination (P = .58). Toxicities consisted primarily of bone marrow suppression, anorexia, nausea and vomiting, peripheral neuropathies, and alopecia. As in previous trials, the chest was the most common site of relapse (33%). There were no differences in the incidence and sites of relapse between the two treatment arms. These treatments appear equally effective at inducing remission and prolonging survival in patients with small-cell lung cancer.", "Sixty-two patients with previously untreated limited stage small cell lung cancer were treated in a prospectively randomized trial comparing thoracic irradiation plus combination chemotherapy with VP-16-213, vincristine (Oncovin), cyclophosphamide, and Adriamycin (VOCA) or those same four drugs plus low-dose (40 mg/m2) cisplatin (VOCAP). The addition of the cisplatin in eight courses of planned chemotherapy did not significantly improve either time to tumor progression of survival or alter sites of disease progression. It did, however, worsen the degree and frequency of nausea, vomiting, and myelosuppression. We did not identify any benefit from the usage of low-dose cisplatin as employed in this study.", "Oral etoposide is an active single agent in small-cell lung cancer (SCLC) and is widely prescribed as first-line treatment as an alternative to intravenous combination chemotherapy in patients with extensive disease.\n The intention of this study was to determine if the effects of oral etoposide therapy on survival and quality of life are equivalent to those of intravenous chemotherapy.\n In a randomized trial of palliative treatment in advanced SCLC, oral etoposide (100 mg given twice daily for 5 days) was compared with intravenous chemotherapy consisting of alternating cycles of cisplatin and etoposide (PE) and cyclophosphamide, doxorubicin, and vincristine (CAV). Six cycles of chemotherapy were administered every 21 days in both regimens. Symptom control and quality of life were measured with the Rotterdam Symptom Checklist and a daily diary card. In January 1996, after 155 patients had been randomly assigned from a projected intake of 365 patients, an independent Data Monitoring Committee examined the interim results. Survival was determined by the Kaplan-Meier method, and the logrank test was used to compare treatments. For quality-of-life comparisons, average scores were calculated for each time point. The Mann-Whitney U test was used to determine any significant overall differences between treatments. For the Rotterdam Symptom Checklist, separate analyses were done for each subset (psychological well-being, physical symptoms, lung cancer symptoms, treatment symptoms, activity, and quality of life). Response rates and toxicity scores were compared by using chi2. All statistical tests were two-sided.\n Survival was inferior at 1 year in the oral etoposide group compared with intravenous therapy (9.8% for oral versus 19.3% for intravenous; difference = 9.5%; 95% confidence interval of difference = 0.3%-18.7%; P<.05), and there was a trend toward inferior overall survival. Median survival was 4.8 months for oral treatment and 5.9 months for intravenous therapy. Progression-free survival was worse in the oral etoposide arm (median = 3.6 months versus 5.6 months; P<.001), as well as overall response rate (32.9% versus 46.3%; P<.01). With the exception of acute nausea and vomiting associated with intravenous chemotherapy, all aspects of symptom control and quality of life were either the same or worse in the oral etoposide group. Study closure was recommended.\n These interim results show that this schedule of oral etoposide is inferior to intravenous chemotherapy in the treatment of advanced SCLC and should not be used as first-line treatment of this disease.", "A total of 306 patients with small cell lung cancer (SCLC) were randomized to receive chemotherapy in a sequential or alternating mode. Sequential chemotherapy consisted of eight cycles of cyclophosphamide, Adriamycin (doxorubicin), and vincristine (CAV) and alternating chemotherapy consisted of three cycles (1, 3, 5) of etoposide, vindesine, and ifosfamide (EVI); three cycles (2, 4, 6) of cisplatin, Adriamycin, and vincristine (PAV); and two cycles (7, 8) of cyclophosphamide, methotrexate, and CCNU (CMC). Responsive patients received prophylactic cranial irradiation after three cycles and chest irradiation after eight cycles of chemotherapy. No maintenance therapy was applied to patients achieving complete remission. Minimum follow-up was 2 years. Of the 302 patients evaluable, overall response rate was 59% in the sequential arm and 70% in the alternating arm. Patients treated with CAV had a complete response rate of 21% in contrast to 36% for those receiving alternating therapy. The median survival for all patients was 9.8 versus 11.3 months, for limited disease 11.1 versus 13.4 months, and for extensive disease 8.9 versus 9.9 months, all in favor of the alternating treatment. Two-year survival rate for all patients was 6% versus 9%, for limited disease 11% versus 14%, and for extensive disease 3% versus 6%, all preferring the alternating treatment mode. Progression-free survival demonstrated a strong correlation to the extent of response irrespective of the treatment regimen applied. Toxicity included 11 lethal and 8 life-threatening complications with a higher frequency in the alternating treatment arm. These results suggest that alternating treatment of SCLC with different drug combinations is more effective than sequential application of CAV.", "After stratification for the extent of disease, previously untreated patients with small cell lung cancer randomized to receive therapy with the four-drug combination of cyclophosphamide, oncovin, nimustine hydrochloride (ACNU), and procarbazine (CONP) every four weeks (continuous regimen) or to receive CONP alternating with the three-drug combination of etoposide (VP-16), adriamycin and cisplatin (VAD) at four-week intervals (alternating regimen). Sixty-nine patients were entered in the study. Of 34 evaluable patients receiving the continuous regimen, six (17.6%) achieved complete response (CR) and 16 (47.1%) achieved partial response (PR). Of 31 evaluable patients receiving the alternating regimen, 10 (32.3%) achieved CR, and 16 (51.6%) achieved PR. There was a tendency in favor of the alternating regimen in CR and over-all response rates (0.05 less than p less than 0.1). There were no significant differences between the regimens in response duration or survival. The projected median survival times were 9.2 months and 9.4 months for the continuous and alternating regimens, respectively. One patient receiving the continuous regimen and three receiving the alternating regimen have been living for more than two years. The major toxicity was myelosuppression in both regimens. One patient died of hemorrhage due to thrombocytopenia during induction with CONP, and one patient died of cisplatin-induced renal failure. We conclude that alternating non-cross resistant chemotherapy leads to improved CR and response rates, but does not improve survival.", "An alternating regimen for the treatment of extensive-disease small-cell lung cancer (SCLC) was compared with standard treatment with cyclophosphamide, doxorubicin, and vincristine (CAV) in 170 patients. Overall severity of toxicity was similar in both arms, with four toxic deaths in each arm (4.7%). Response results were also similar, with 54% complete and partial responses with the standard regimen and 53% complete and partial responses with the alternating regimen. Median survival time was 6.9 months with the standard regimen and 9.2 months with the alternating regimen (P = .078). The 2-year survival rate was 1.2% for the standard regimen and 4.7% for the alternating regimen. Survival benefit for treatment with the alternating regimen reached statistical significance only in those subsets of patients with poorer prognosis (male sex, performance status 3, liver metastases, bone marrow metastases, and oat cell histologic subtype).", "In the treatment of small cell lung cancer, carboplatin/etoposide/vincristine (CEV) is one of the most active regimens. In contrast, the etoposide/vincristine (EV) combination also has produced acceptable results in patients with extensive disease. To evaluate the efficacy and survival of patients treated with EV in comparison to those treated with more intensive CEV chemotherapy, a prospective, randomized, phase III trial was performed. The protocol for the treatment groups was as follows: treatment A (156 patients): carboplatin 300 mg/m2 day I, etoposide 140 mg/m2 days 1 through 3, and vincristine 1.4 mg/m2 days 1, 8, and 15; and treatment B (161 patients): etoposide 200 mg/m2 days 1 through 3 and vincristine 1.4 mg/m2 days 1 and 8. Chemotherapy cycles in each treatment arm were repeated every 4 weeks. Doses were reduced by 20% when hematologic or nonhematologic toxicity (grade 4) occurred. In all, 317 evaluable patients were treated. The overall response rate for patients treated with CEV was 79.8% compared with 59.8% for those treated with EV (P < .001). The median length of survival was 10 months for CEV-treated patients compared with 9 months for EV-treated patients (P = .19). Based on long-term survival rates, there was an advantage for the CEV-treated patients if they had good performance status, were younger than 60 years, had no distant metastases, and achieved a complete response to first-line therapy. We conclude that patients with poor prognostic factors (ie, poor performance status, multiple distant metastases, and less than partial response to the first cycle of chemotherapy) should appropriately be treated with the less aggressive two-drug combination chemotherapy. On the other hand, patients with good prognostic factors should be treated as aggressively as possible, and they will benefit from the more aggressive induction chemotherapy.", "We conducted a randomized trial testing etoposide (120 mg/m2 d1-3) + vindesine (3 mg/m2 d1) with or without cisplatin (60 mg/m2 d1) in patients with SCLC. A total of 8 courses were given at 3-week intervals. 221 patients were registered and 201, 95 in the CEV arm and 106 in the EV arm, were eligible for survival analysis. 183 patients were evaluable for response: 74% had an objective response (OR) with CEV versus 55% with EV (p = 0.01). Complete response rates were, respectively, 21% and 13% (NS). In patients with limited disease (LD), OR rates were 72% and 61% (NS), and 76% and 48% in extensive disease (ED) (p = 0.01). There was no statistically significant difference in survival between the two regimens (p = 0.745, log rank test). Median survival for EV and CEV were, respectively, 40 and 45 weeks, and two-year survivals were 11% and 9%; in patients with LD, the corresponding figures were 14% and 16% (NS) and in those with ED, 8% and 3% (NS). Disease extent (LD vs ED), Karnofsky performance status and loss of body weight were significant prognostic factors for survival; age, sex, type of treatment and type of lesion were not. The CEV regimen was not significantly more myelotoxic than EV but was associated with more severe nausea, vomiting and alopecia. In conclusion, the addition of cisplatin to the EV regimen, a combination reported to be easily manageable, was associated with a significantly higher OR rate but survival was not significantly improved.", "A randomized trial was conducted in patients with small-cell lung cancer (SCLC) to determine if survival can be improved by a weekly chemotherapy regimen combining various drugs.\n Two hundred twenty-three patients were randomized to receive either six courses of a multiple-drug combination (MDC) regimen (Adriamycin [ADR; doxorubicin; Farmitalia Carlo Erba, Milan, Italy] 25 mg/m2 intravenously [i.v.] on day 1; etoposide [VP16] 120 mg/m2 i.v. on day 1; cyclophosphamide [CPA] 500 mg/m2 i.v. on day 1; cisplatin 60 mg/m2 i.v. on day 8; vindesine [VDS] 3 mg/m2 i.v. on day 8; vincristine [VCR] 2 mg i.v. on day 15; methotrexate [MTX] 100 mg/m2 i.v. on day 15), or a standard chemotherapy (SC) regimen (ADR 50 mg/m2 i.v. on day 1; CPA 1 g/m2 i.v. on day 1; VP16 80 mg/m2 i.v. on days 1 to 3).\n In 98 MDC-treated and 101 SC-treated assessable patients, we observed 69% and 62% objective responses rates, respectively. There was no significant difference in survival, with median durations and 2-year overall survival rates of 49 and 43 weeks and 8.5% and 7.9%, respectively. There was a significant increase in response rate in favor of MDC patients with limited disease (84% v 62%). Toxicity was tolerable, although SC was more hematotoxic, with 76% (v 59%) experiencing leukopenia and 17% (v 7%) experiencing thrombocytopenia (grades III and IV). If the cumulative doses received were nearly equal to the scheduled cumulative doses in both arms, the total relative dose-intensity (RDI) was significantly higher in the SC arm. The difference was due to increased treatment delays in the MDC arm.\n Weekly MDC failed to improve survival rates in patients with SCLC." ]

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[ "Psychiatric rehabilitation in a Chinese psychiatric hospital.", "An intervention study to prevent relapse in patients with schizophrenia.", "London-East Anglia randomised controlled trial of cognitive-behavioural therapy for psychosis. I: effects of the treatment phase.", "Psychoeducational psychotherapy for schizophrenic patients and their key relatives or care-givers: results of a 2-year follow-up.", "Skills training versus psychosocial occupational therapy for persons with persistent schizophrenia.", "An evaluation of a stress management program for individuals with schizophrenia.", "Outcomes of an effectiveness trial of cognitive-behavioural intervention by mental health nurses in schizophrenia.", "Multiple-family group treatment of outpatients with schizophrenia: impact on service utilization.", "Three-year trials of personal therapy among schizophrenic patients living with or independent of family, II: Effects on adjustment of patients.", "Disease management in Latinos with schizophrenia: a family-assisted, skills training approach.", "Multiple-family group treatment for English- and Vietnamese-speaking families living with schizophrenia.", "Family-based intervention for schizophrenic patients in China. A randomised controlled trial.", "One-year follow-up of a multiple-family-group intervention for Chinese families of patients with schizophrenia.", "Efficacy of the team solutions program for educating patients about illness management and treatment.", "Psychoeducation in schizophrenia: 7-year follow-up concerning rehospitalization and days in hospital in the Munich Psychosis Information Project Study.", "TRIP: a psycho-educational programme in Hong Kong for people with schizophrenia.", "A program for relapse prevention in schizophrenia: a controlled study.", "An evaluation of a medication management training programme for community mental health professionals; service user level outcomes: a cluster randomised controlled trial.", "Patient and relative education in community psychiatry: a randomized controlled trial regarding its effectiveness.", "Cognitive therapy and recovery from acute psychosis: a controlled trial. I. Impact on psychotic symptoms.", "Early intervention for relapse in schizophrenia: results of a 12-month randomized controlled trial of cognitive behavioural therapy.", "Teaching psychiatric inpatients to re-enter the community: a brief method of improving the continuity of care.", "Effects of psychoeducation for Korean Americans with chronic mental illness.", "Cognitive--behavioural therapy and family intervention for relapse prevention and symptom reduction in psychosis: randomised controlled trial.", "Medication and symptom management education program for the rehabilitation of psychiatric patients in Korea: the effects of promoting schedule on self-efficacy theory.", "A randomized, controlled trial of cognitive behavioral social skills training for middle-aged and older outpatients with chronic schizophrenia.", "Training persons with schizophrenia in illness self-management: a randomized controlled trial in Japan.", "Social cognitive skills training in schizophrenia: an initial efficacy study of stabilized outpatients." ]

[ "nan", "To determine whether the use of relapse prevention plans (RPPs) in nursing practice is an effective intervention in reducing relapse rates among patients with schizophrenia.\n Experimental design. Patients with schizophrenia (or a related psychotic disorder) and nurses from three mental health organizations were randomly assigned to either an experimental (RPP) or control condition (care as usual). The primary outcome measure was the psychotic relapses in the research groups.\n The relapse rates in the experimental and control groups after 1-year follow-up were 12.5% and 26.2%, respectively (p=. 12, ns). The relative risk of a relapse in the experimental versus the control group was 0.48 (ns).\n In this study no statistically significant effects of the intervention were found. Effectiveness research in this area should be continued with larger sample sizes and longer follow-up periods.", "A series of small, mainly uncontrolled, studies have suggested that techniques adapted from cognitive-behavioural therapy (CBT) for depression can improve outcome in psychosis, but no large randomised controlled trial of intensive treatment for medication-resistant symptoms of psychosis has previously been published.\n Sixty participants who each had at least one positive and distressing symptom of psychosis that was medication-resistant were randomly allocated between a CBT and standard care condition (n = 28) and a standard care only control condition (n = 32). Therapy was individualised, and lasted for nine months. Multiple assessments of outcome were used.\n Over nine months, improvement was significant only in the treatment group, who showed a 25% reduction on the BPRS. No other clinical, symptomatic or functioning measure changed significantly. Participants had a low drop-out rate from therapy (11%), and expressed high levels of satisfaction with treatment (80%). Fifty per cent of the CBT group were treatment responders (one person became worse), compared with 31% of the control group (three people became worse and another committed suicide).\n CBT for psychosis can improve overall symptomatology. The findings provide evidence that even a refractory group of clients with a long history of psychosis can engage in talking about psychotic symptoms and their meaning, and this can improve outcome.", "Psychoeducational medication management training (PMT), cognitive psychotherapy (CP) and key-person counselling (KC) were carried out in various combinations in this randomized, controlled intervention study of schizophrenic out-patients (according to DSM-III-R). Special design characteristics of the study were a control group consisting of non-specifically treated patients and a 2-year follow-up after completion of treatment in order to evaluate medium-term effects. A total of 132 patients underwent a follow-up examination 2 years after completion of treatment and were evaluated with an intention-to-treat approach. In the second follow-up year, all treatment groups had lower but not significantly different relapse rates compared to the control group. The most intensive treatment (PMT+CP+KC) produces a clinically relevant reduction in rehospitalization rate (a 26% reduction compared to the control group). In comparison with the non-specifically treated control group, whose original effect decreased, at least a medium-term therapeutic effect was recorded in the treatment groups.", "The authors compared the community functioning of outpatients with persistent forms of schizophrenia after treatment with psychosocial occupational therapy or social skills training, with the latter conducted by paraprofessionals.\n Eighty outpatients with persistent forms of schizophrenia were randomly assigned to receive either psychosocial occupational therapy or skills training for 12 hours weekly for 6 months, followed by 18 months of follow-up with case management in the community. Antipsychotic medication was prescribed through \"doctor's choice\" by psychiatrists who were blind to the psychosocial treatment assignments.\n Patients who received skills training showed significantly greater independent living skills during a 2-year follow-up of everyday community functioning.\n Skills training can be effectively conducted by paraprofessionals, with durability and generalization of the skills greater than that achieved by occupational therapists who provide their patients with psychosocial occupational therapy.", "Vulnerability-stress models suggest that training in specific stress management techniques should yield benefits to those suffering from schizophrenia and related disorders. In this paper, we describe an evaluation of the impact of adding a stress management program to other medical and psychosocial interventions for such patients. Outcomes were compared for 121 patients randomly assigned to receive either a 12-week stress management program with follow-up sessions or participation in a social activities group. The two treatment conditions did not differ in levels of symptoms, perceived stress or life skills immediately after completion of treatment or at 1-year follow-up. Patients who received the stress management program did have fewer hospital admissions in the year following treatment. This effect of stress management was most apparent for those who showed high levels of attendance for treatment sessions. It was concluded that training in stress management may provide patients with skills for coping with acute stressors and reduce the likelihood of subsequent acute exacerbation of symptoms with need for hospitalization.", "Little is known about the medium-term durability of cognitive-behavioural therapy (CBT) in a community sample of people with schizophrenia.\n To investigate whether brief CBT produces clinically important outcomes in relation to recovery, symptom burden and readmission to hospital in people with schizophrenia at 1-year follow-up.\n Participants (336 of 422 randomised at baseline) were followed up at a mean of 388 days (s.d. = 53) by raters masked to treatment allocation (CBT or usual care).\n At 1-year follow-up, participants who received CBT had significantly more insight (P = 0.021) and significantly fewer negative symptoms (P = 0.002). Brief therapy protected against depression with improving insight and against relapse; significantly reduced time spent in hospital for those who did relapse and delayed time to admission. It did not improve psychotic symptoms or occupational recovery, nor have a lasting effect on overall symptoms or depression at follow-up.\n Mental health nurses should be trained in brief CBT for schizophrenia to supplement case management, family interventions and expert therapy for treatment resistance.", "The impact of multiple-family group treatment (MFGT) on outpatient and inpatient mental health service utilization of 97 persons with schizophrenia was investigated. Participants were randomly assigned to standard care (n = 44) or standard care plus MFGT (n = 53). Service use for a year prior to randomization, the 2-year study period, and a 1-year follow-up were examined. Relative to standard care participants, the MFGT group had reduced community hospitalization during year 1 of the intervention and reduced state hospitalization at follow-up. During the intervention period, MFGT participants demonstrated a significant increase in outpatient utilization as a direct consequence of the intervention. However, when service use was summed across 3 years post-randomization, no group differences were observed. Results suggest that implementation of MFGT in a community mental health setting reduces inpatient service at specific time periods, without significantly increasing outpatient service utilization. These findings add to other outcomes from this study that demonstrate decreased psychiatric symptoms and caregiver distress.", "Previous analyses of the personal and social adjustment of outpatients with schizophrenia have either relied on the assessment of unrepresentative patients who survived without relapse or used analyses that included relapse assessments, a potential confound when different rates of relapse existed among treatment conditions. The authors' goal was to conduct a study of the effects of personal therapy on outcome that was designed to take into consideration the effects of relapse.\n They evaluated the effectiveness of personal therapy over 3 years after hospital discharge among 151 patients with schizophrenia or schizoaffective disorder. The patients were randomly assigned to receive personal therapy or contrasting therapies in one of two concurrent trials. One trial included patients who were living with family (N = 97); the other included patients who were living independent of family (N = 54). Patients were assessed at 6-month intervals over 3 years of treatment on measures of personal and social adjustment; patients who relapsed and restabilized and those who did not relapse were included.\n Personal therapy had positive effects on broad components of social adjustment (role performance) but had few differential effects on symptoms, and patients receiving personal therapy remained more anxious than patients who received family or supportive therapy. For patients who were living with family, personal therapy led to better outcomes in overall performance than did the other treatments. Although family therapy had only one positive effect on patients' social adjustment, the personal adjustment (residual symptoms) of patients who received family therapy appeared to improve more than that of patients receiving personal or supportive therapy. For patients not living with family, personal therapy was more successful than supportive therapy in improving work performance and relationships out of the home. Longitudinal effects of personal therapy on symptoms were similar to those of family and supportive therapies, particularly in the first 2 years, but personal therapy effect sizes increased over time on measures of social adjustment.\n Personal therapy has pervasive effects on the social adjustment of patients with schizophrenia that are independent of relapse prevention. Supportive therapy, with or without family intervention, produces adjustment effects that peak at 12 months after discharge and plateau thereafter. However, personal therapy, a definitive psychosocial intervention, continues to improve the social adjustment of patients in the second and third years after discharge. Brief treatment would appear to be less effective than a long-term, disorder-relevant intervention for schizophrenia.", "This study evaluated the effectiveness of a skills training program designed to teach disease management to Latinos with schizophrenia treated at a community mental health center. Ninety-two Latino outpatients with schizophrenia and their designated relatives were randomly assigned to 3 months of skills training (ST) versus customary outpatient care (CC) and followed for a total of 9 months. The skills training approach was culturally adapted mainly by including the active participation of key relatives to facilitate acquisition and generalization of disease management skills into the patients' natural environment. There was a significant advantage for the ST group over the CC group on several symptom measures, skill acquisition and generalization, level of functioning, and rates of rehospitalization. There were no significant differences between the groups on quality of life or caregiver burden. Skills training had a direct effect on skill acquisition and generalization, and utilization of disease management skills led to decreased rates of rehospitalization. Incorporating an intensive, culturally relevant generalization effort into skills training for Latinos with schizophrenia appeared to be effective in teaching disease management and viable in a community mental health center.", "This study, which was the first evaluation in Australia of multiple-family group treatment, explored the effectiveness of this approach for a newly arrived non-English speaking migrant group, first-generation Vietnamese families, and for English-speaking families.\n Thirty-four pairs of English-speaking consumers and family members and 25 Vietnamese-speaking pairs were randomly assigned to a multiple-family group or a control group. All consumers had a diagnosis of schizophrenia. The multiple-family group intervention (26 sessions over 12 months) was delivered as an adjunct to case management services, which all consumers received. Outcomes, which were measured immediately after treatment and 18 months later, included the number of relapse episodes; the presence and severity of symptoms, as measured by the Brief Psychiatric Rating Scale (BPRS) and the Scale for the Assessment of Negative Symptoms; and social functioning, as measured by the Family Burden Scale, the Health of the Nation Outcome Scale, and the Quality of Life Scale.\n Relapse rates immediately after treatment were significantly lower for the multiple-family group than for the control group (12 and 36 percent), and relapse rates were also lower during the follow-up period (25 and 63 percent). BPRS ratings were significantly lower for participants in the multiple-family group, and vocational outcomes also improved. The reductions in relapse and symptoms were similar for the English-speaking and the Vietnamese-speaking family groups; sample size precluded statistical analysis of differences.\n Multiple-family group treatment is an effective cognitive-behavioral intervention in the treatment of schizophrenia. The findings suggest continued application of and research on family interventions for non-English speaking migrant populations.", "We developed and evaluated a comprehensive, ongoing intervention for families of schizophrenic patients appropriate for China's complex family relationships and unique social environment.\n Sixty-three DSM-III-R schizophrenic patients living with family members were enrolled when admitted to hospital and randomly assigned to receive standard care or a family-based intervention that included monthly 45-minute counselling sessions focused on the management of social and occupational problems, medication management, family education, family group meetings, and crisis intervention.\n At 6, 12, and 18-month follow-ups by blind evaluators, the proportion of subjects rehospitalised was lower, the duration of rehospitalisation was shorter, and the duration of employment was longer in the experimental group than in the control group; these differences were statistically significant at the 12 and 18-month follow-ups and were not explained by differences in drug compliance. Family intervention was associated with significantly lower levels of family burden.\n This intervention is less costly than standard treatment, is suitable for urban families of schizophrenic patients in China and feasible given the constraints of the Chinese mental health system.", "This study tested the effectiveness of a mutual support multiple-family-group intervention for schizophrenia in terms of improvements in patients' psychosocial functioning, use of mental health services, and rehospitalization compared with a psychoeducation intervention and standard care.\n A controlled trial was conducted in a sample of 96 Chinese families who were caring for a relative with schizophrenia in Hong Kong. The families were randomly assigned to one of three groups: mutual support (N=32), psychoeducation (N=33), and standard care (N=31). The interventions were delivered at two psychiatric outpatient clinics over a six-month period. The mutual support and psychoeducation interventions consisted of 12 group sessions every two weeks, each lasting about two hours. The mutual support group was a peer-led group designed to provide information, emotional support, and coping skills for caregiving in stages. The psychoeducation group was a professional-led group designed to educate families about the biological basis of schizophrenia and treatment and to improve illness management and coping skills. The standard care group and the other two groups received routine psychiatric outpatient care during the intervention. Data analyses of multiple outcomes over one-year follow-up were conducted on an intention-to-treat basis.\n Multivariate analyses of variance showed that the mutual support intervention was associated with consistently greater improvements in patients' functioning and rehospitalization and stable use of mental health services over the follow-up period compared with the other two interventions.\n The study provides evidence that mutual support groups can be an effective family intervention for Chinese persons with mental illness in terms of improving patients' functioning and hospitalization without increasing their use of mental health services.", "Despite the demonstrated efficacy of psychosocial approaches to schizophrenia treatment that include a psychoeducational component, such as illness management, the implementation of these approaches into routine mental health treatment has been slow. The authors sought to examine the efficacy of a comprehensive, modularized, psychoeducational program called Team Solutions, which was designed to educate patients with major mental illnesses about their illness and how to manage it. Team Solutions was chosen for study because it is available over the Internet and other venues at no cost and is used by mental health agencies across the United States and Canada.\n Seventy-one persons with schizophrenia or schizoaffective disorder from three day treatment settings participated in this randomized, single-blind study. Participants were randomly assigned to attend one of two interventions: the Team Solutions intervention, which consisted of participating in a 24-week psychoeducational group focused on illness management, or treatment as usual.\n For participants who attended the experimental group, significant improvement was observed in knowledge about schizophrenia. In addition, client satisfaction was high. However, no changes were observed in symptoms or functioning.\n Results indicated that participation in the Team Solutions psychoeducational group improved participants' knowledge. However, participation in the program did not demonstrate superiority over treatment as usual with respect to secondary and tertiary outcomes, such as symptom severity, treatment adherence, and global functioning.", "According to most of the relevant guidelines, psychoeducation is considered a basic part of routine therapy for patients with schizophrenia; scientific proofs of its efficacy are based mainly on the results of 1- and 2-year follow-ups. Therefore, the long-term effects of psychoeducation over a period of 7 years were investigated in regard to rehospitalization rates and hospital days.\n Of 101 patients with DSM-III-R or ICD-9 schizophrenia randomly allocated to either an intervention group or a control group between 1990 and 1994, 48 patients were available for follow-up after 7 years. During their index stay, the 24 patients of the intervention group and their key relatives each received a separate psychoeducational group therapy. The 24 patients of the control group received the usual treatment. After index discharge, all 48 patients received a comparable outpatient treatment. Main outcome measures were rehospitalization rate, number of intervening hospital days, compliance, and mean number of consumed chlorpromazine (CPZ) units.\n Seven years after index discharge, the rate of rehospitalization was 54% in the intervention group and 88% in the control group. The rate of rehospitalization per patient was 1.5 in the intervention group and 2.9 in the control group (p < .05). In the intervening period, the mean number of hospital days spent in a psychiatric hospital was 75 in the intervention group and 225 days in the control group. (p < .05). The mean number of consumed CPZ units after 7 years was 354 in the intervention and 267 in the control group.\n Seven years after psychoeducational group therapy, significant effects on the long-term course of the illness can be found. Therefore, the integration of psychoeducation into standard therapy for schizophrenia should become obligatory.", "'TRIP' (Transforming Relapse and Instilling Prosperity) is a ward-based illness management programme that aims to decrease treatment non-compliance and relapse rate by improving the insight and health of acute psychiatric patients with schizophrenia. Eighty-one stable male acute psychiatric patients with schizophrenia were randomized to receive the TRIP programme (n = 44) or the comparison group of traditional ward occupational therapy (WOT) programme (n = 37). Participants' insights and health were assessed by the Unawareness of Mental Disorder Scale and the Hong Kong version of the Short Form-36 (SF-36) health survey, respectively. Each group was then followed up for a 12-month period. One-way analysis of covariance (ANCOVA) showed that participants in the TRIP programme had significantly better insight and health than a comparison group during post-study measurement. Participants in the TRIP programme had significantly fewer re-admissions in the 12-month follow-up period than those who attended the WOT programme. In summary the TRIP programme, as led by an occupational therapist, was effective in improving insight, awareness of health and in having a lower re-admission rate than a traditional occupational therapy programme.", "This study examined whether a program for relapse prevention (PRP) is more effective than treatment as usual (TAU) in reducing relapse and rehospitalization rates among outpatients with schizophrenia.\n Eighty-two outpatients with DSM-III-R schizophrenia or schizoaffective disorder were randomly assigned to receive either PRP (experimental group, n = 41) or TAU (control group, n = 41) and were followed up for an 18-month prospective controlled study. Patients in both groups were prescribed standard doses of maintenance antipsychotic medication. Treatment with PRP consisted of a combination of psychoeducation, active monitoring for prodromal symptoms with clinical intervention when such symptoms occurred, weekly group therapy for patients, and multifamily groups. The TAU consisted of biweekly individual supportive therapy and medication management.\n Outcome rates over 18 months were 17% for relapse (7 patients) and 22% for rehospitalization (9 patients) in the PRP group, compared with 34% for relapse (14 patients) and 39% for rehospitalization (16 patients) in the TAU group (P = .01 and P = .03, respectively). Addition of age, sex, baseline Global Assessment Scale score, Positive and Negative Syndrome Scale scores (3 measures), and substance abuse to the proportional hazards regression models all yielded nonsignificant effects. The PRP teams were much more likely than the TAU psychiatrists to identify prodromal episodes before patients met objective relapse criteria or needed hospitalization.\n The PRP was effective in detecting prodromal symptoms of relapse early in an episode. Crisis intervention including increased antipsychotic medication use during the prodromal phase reduced relapse and rehospitalization rates.", "Antipsychotic treatment is important in reducing symptomatology and relapse in schizophrenia. Community mental health professionals (CMHPs) have a significant role in this treatment; however, evidence suggests that many are ineffective in medication management.\n To develop and evaluate a medication management training programme whose aims are to increase the effectiveness of pharmacological treatment and increase services users' involvement in treatment decisions.\n Twenty-eight pairs of CMHPs were recruited from mental health Trusts in England. For each practitioner an average of 3.4 service users were randomly selected for their 'study caseload'.\n A pragmatic cluster randomised trial assessed the service users of CMHPs allocated to medication management training or waiting list controls.\n All practitioner participants were taught to use a variety of assessment measures and undertook baseline assessments with their service users. The experimental practitioners then attended the training programme. At the 9-month endpoint the service users were re-assessed.\n After the outcome data was adjusted for clustering the trained practitioners made significant improvements in global psychopathology and service user involvement in treatment when compared to controls at 9 months.\n Training CMHPs in medication management has a positive impact on clinical outcomes and service user involvement in treatment.", "Family psychoeducation has a well-documented effect on the short-term prognosis in schizophrenia. Less is known about the effectiveness of shorter programmes with the main focus on information for patients (patient education) or for patients and relatives (family education).\n A randomized study of the effectiveness of an eight-session psychoeducational programme for patients with schizophrenia and for their relatives was conducted in two community mental health centres, in Arhus and Viborg (Denmark). Patient outcome measures were knowledge, relapse, compliance, insight and satisfaction, and relative outcome measures were knowledge and satisfaction. Post-intervention outcome and follow-up evaluation 1 year after the start of the intervention are presented.\n A statistically significant increase in knowledge of schizophrenia in both relatives and patients was demonstrated at postintervention and a non-significant trend at 1-year follow-up. Statistically significant changes in the Verona Service Satisfaction Scale Scores in the subdimension of satisfaction with Relatives involvement were demonstrated both for patients and relatives postintervention and for patients at 1-year follow-up. There was a tendency that time-to-relapse increased in the intervention group at postintervention and that the schizophrenia subscore of the Brief Psychiatric Rating Scale was reduced in the intervention group at 1-year follow-up. No differences were found between the groups regarding compliance, insight into psychosis, psychosocial function (General Assessment of Function) or in relatives' expressed emotion scores postintervention or at 1-year follow-up.\n A short patient and relative education programme seems to be able to influence knowledge and some aspects of satisfaction, but does not seem to be sufficient to influence important variables such as relapse, compliance, psychopathology, insight or psychosocial functioning.", "The application of cognitive therapy (CT) to psychosis is currently being developed in the UK. This paper reports a trial of CT in acute psychosis with the objective of hastening the resolution of positive symptoms and reducing residual symptoms.\n Of 117 patients with acute non-affective psychosis, 69 satisfied inclusion criteria and 40 proceeded to stratified randomisation. The experimental intervention involving individual and group CT was compared with a group receiving matched hours of therapist input providing structured activities and informal support; routine pharmacotherapy was provided by clinicians blind to group allocation. Patients were monitored weekly using self-report and mental state assessments during admission and over the subsequent nine months.\n Both groups showed a decline in positive symptoms but this was more marked in the CT group (P < 0.001). At 9 months 5% of the CT group, v.56% of the control group, showed moderate or severe residual symptoms.\n CT appears to be a potent adjunct to pharmacotherapy and standard care for acute psychosis. Issues concerning internal and external validity of the study and opportunities for further research are discussed.", "The paper describes a randomized controlled trial of targeting cognitive behavioural therapy (CBT) during prodromal or early signs of relapse in schizophrenia. We hypothesized that CBT would result in reduced admission and relapse, reduced positive and negative symptoms, and improved social functioning.\n A total of 144 participants with schizophrenia or a related disorder were randomized to receive either treatment as usual (TAU) (N = 72) or CBT+TAU (N = 72). Participants were prospectively followed up between entry and 12 months.\n At 12 months, 11 (15.3%) participants in the CBT group were admitted to hospital compared to 19 (26.4%) of the TAU group (hazard ratio = 0.53, P = 0.10, 95% CI 0.25, 1.10). A total of 13 (18.1%) participants in CBT relapsed compared to 25 (34.7%) in TAU (hazard ratio = 0.47, P < 0O05, 95% CI 0.24, 0.92). In addition, the CBT group showed significantly greater improvement in positive symptoms, negative symptoms, global psychopathology, performance of independent functions and prosocial activities.\n The study provides evidence for the feasibility and effectiveness for targeting CBT on the appearance of early signs of relapse in schizophrenia. The results are discussed in context of the study's methodological limitations.", "The study evaluated the effects of a brief manualized treatment program that taught patients skills to re-enter the community and actively follow through with their own care.\n A total of 59 recently admitted inpatients with schizophrenia or schizoaffective disorder were randomly assigned to either the community re-entry program or an equally intensive regimen of occupational therapy. The community re-entry program consisted of eight 45-minute sessions conducted with groups of six to eight patients on a continuous, twice-a-day, four-day-a-week schedule. The effects were measured by a review of the records of aftercare services that patients received in the month after discharge from the inpatient facility. Patients' knowledge and performance of the specific material taught in the community reentry program was ascertained through assessments conducted before and after training.\n Results indicated that patients in the community re-entry program significantly improved their knowledge and performance of the skills taught in the sessions, compared with patients in the occupational therapy group. Community re-entry participants were also significantly more likely to attend their first aftercare appointment than were occupational therapy participants (85 percent versus 37 percent).\n Not only can patients learn relatively complex material during a brief typical inpatient stay despite the acuteness of their illnesses, but they can also meaningfully improve the continuity of their own care by participating in a brief and highly structured training program. The program fits well within the time and staffing constraints of typical inpatient facilities.", "Korean Americans' access to mental health services may be limited because of differences in their views of mental illness compared with Westerners, unfamiliarity with treatment methods, and cultural associations of social stigma with mental problems. This study used data from an urban outpatient clinic to assess the effects of a ten-week psychoeducational intervention for Korean Americans with chronic mental illness.\n Forty-eight Korean-American adults with a diagnosis of schizophrenia were randomly assigned to either an experimental group that provided a culturally sensitive psychoeducational group program in addition to individual supportive therapy or a control group that offered only individual supportive therapy. The two groups were compared on pre- and posttreatment measures of psychiatric symptoms, attitudes about and understanding of mental illness, and coping skills. The experimental psychoeducational treatment group was expected to show lower symptom severity, greater understanding of mental illness leading to a decreased perception of stigma, and greater coping skills after the intervention than the control group. Comparisons were made with repeated-measures analysis of covariance with the effects of gender and education controlled for.\n Compared with the control group, the psychoeducational group showed significantly reduced symptom severity and perception of stigma and greater coping skills immediately after treatment.\n These findings suggest that a culturally sensitive psychoeducational intervention is a useful short-term treatment modality for Korean Americans with a diagnosis of schizophrenia.", "Family intervention reduces relapse rates in psychosis. Cognitive-behavioural therapy (CBT) improves positive symptoms but effects on relapse rates are not established.\n To test the effectiveness of CBT and family intervention in reducing relapse, and in improving symptoms and functioning in patients who had recently relapsed with non-affective psychosis.\n A multicentre randomised controlled trial (ISRCTN83557988) with two pathways: those without carers were allocated to treatment as usual or CBT plus treatment as usual, those with carers to treatment as usual, CBT plus treatment as usual or family intervention plus treatment as usual. The CBT and family intervention were focused on relapse prevention for 20 sessions over 9 months.\n A total of 301 patients and 83 carers participated. Primary outcome data were available on 96% of the total sample. The CBT and family intervention had no effects on rates of remission and relapse or on days in hospital at 12 or 24 months. For secondary outcomes, CBT showed a beneficial effect on depression at 24 months and there were no effects for family intervention. In people with carers, CBT significantly improved delusional distress and social functioning. Therapy did not change key psychological processes.\n Generic CBT for psychosis is not indicated for routine relapse prevention in people recovering from a recent relapse of psychosis and should currently be reserved for those with distressing medication-unresponsive positive symptoms. Any CBT targeted at this acute population requires development. The lack of effect of family intervention on relapse may be attributable to the low overall relapse rate in those with carers.", "An effective rehabilitation program was developed for psychiatric patients' self-management of medication and symptoms. The rehabilitation program was designed to allow the patients to understand their illness, cope with their medical regimen, and prevent a relapse by recognizing any of the symptoms when they recur. This study consisted of three phases. The first phase was to explore the extent and the specific mental health needs of psychiatric patients. Data was obtained from 82 subjects who had symptoms of a mental illness including schizophrenia, bipolar disorders, and delusional disorder. They had received medication instruction during their hospitalization. The subjects were at the time outpatients in a psychiatric hospital. In the second phase, the researchers developed an educational program focused on coping with the residual and relapse warning signs, managing the drug side effects, medication compliance, and daily routines, according to the information acquired in the first step. The developed program includes the self-efficacy method reported by Bandura, including manuals and videotapes focusing on real life situations, small group discussions, and telephone coaching. Finally, the researchers investigated the effects of this program. Thirty-eight patients were selected for this study, 18 in the experimental program and 20 as controls. The diagnoses were same as those with the first step. The results showed that the subjects who attended this educational program reported significantly more improvement in self-efficacy (p=0.014) and medication compliance (p= 0.005), and significantly less relapse warning symptom scores (p=0.000) than the controls. In conclusion, these instructional materials will be beneficial for medication and symptom management in rehabilitating psychiatric patients in Korea. In addition, the materials may be a useful psychoeducational resource for professionals in the field of clinical psychiatry.", "The number of older patients with chronic schizophrenia is increasing. There is a need for empirically validated psychotherapy interventions for these patients. Cognitive behavioral social skills training teaches cognitive and behavioral coping techniques, social functioning skills, problem solving, and compensatory aids for neurocognitive impairments. The authors compared treatment as usual with the combination of treatment as usual plus cognitive behavioral social skills training.\n The randomized, controlled trial included 76 middle-aged and older outpatients with chronic schizophrenia, who were assigned to either treatment as usual or combined treatment. Cognitive behavioral social skills training was administered over 24 weekly group sessions. Blind raters assessed social functioning, psychotic and depressive symptoms, cognitive insight, and skill mastery.\n After treatment, the patients receiving combined treatment performed social functioning activities significantly more frequently than the patients in treatment as usual, although general skill at social functioning activities did not differ significantly. Patients receiving cognitive behavioral social skills training achieved significantly greater cognitive insight, indicating more objectivity in reappraising psychotic symptoms, and demonstrated greater skill mastery. The overall group effect was not significant for symptoms, but the greater increase in cognitive insight with combined treatment was significantly correlated with greater reduction in positive symptoms.\n With cognitive behavioral social skills training, middle-aged and older outpatients with chronic schizophrenia learned coping skills, evaluated anomalous experiences with more objectivity (achieved greater cognitive insight), and improved social functioning. Additional research is needed to determine whether cognitive insight mediates psychotic symptom change in cognitive behavior therapy for psychosis.", "Despite the worldwide shift from inpatient to community-based treatment for individuals with severe mental illness, Japanese psychiatric services remain hospital based. In 1998, Japan had 29 psychiatric beds per 10,000 persons, twice as many as in most European countries and five times as many as in the United States (1). The reasons for Japan's slow transition to a community-based mental health system are both economic and cultural. For instance, 90 percent of psychiatric beds are in private for-profit hospitals. There is little incentive for inpatient facilities to discharge patients promptly, because the Japanese health care system provides universal coverage with virtually unlimited reimbursement for inpatient services, and the government does not have a mechanism for financing the relocation of resources from hospitals to communities (2). In addition, the stigma associated with mental illness in Japanese families is high (3). Thus a patient's primary residence is the psychiatric hospital, and opportunities are provided for periodic visits from the family.However, psychiatric rehabilitation principles and practices are beginning to take root in Japan. Anzai and his colleagues at the Matsuzawa Psychiatric Hospital in Tokyo have adapted an empirically validated skills training program to prepare patients with schizophrenia for life in the community after discharge from the hospital. In this column, they report the results of a randomized controlled trial of this approach in an inpatient facility serving a large urban center.", "Social cognitive deficits are promising treatment targets for new interventions to improve functional outcome in schizophrenia. A few preliminary studies of inpatients support the feasibility of improving social cognition through psychosocial interventions. This clinical trial evaluated a new 12-session social cognitive skills training program designed to address four aspects of social cognition (affect perception, social perception, attributional style, Theory of Mind) in outpatients with psychosis, a population for whom such interventions will likely be very useful. Thirty-one clinically stabilized outpatients were randomly assigned to a social cognition skills training intervention or a time-matched control condition (illness self-management and relapse prevention skills training), and completed pre- and post-treatment assessments of social cognition, neurocognition, and symptoms. The social cognition group demonstrated a large, significant improvement in facial affect perception, which was not present in the control group. This improvement was independent of changes in basic neurocognitive functioning or symptoms. Results support the efficacy of a social cognitive intervention for community-dwelling outpatients and encourage further development of this treatment approach to achieve broader improvements in social cognition and generalization of treatment gains." ]

[ "6374057", "6398121", "6432353", "7026074", "3655855", "3896353", "367574", "6344982", "2649221", "338136", "2731120", "1419290", "7037152", "6685644", "7074523", "667798" ]

[ "Randomized trial of cyclophosphamide, doxorubicin, and 5-fluorouracil alone or alternating with a \"cycle active\" non-cross-resistant combination in women with visceral metastatic breast cancer: a Southeastern Cancer Study Group project.", "A new six-drug antiblastic regimen (R 14) at low doses (micropolychemotherapy) compared to CMF in the treatment of metastatic breast cancer: phase III study.", "A randomized trial of adriamycin, cyclophosphamide, ftorafur (ACF) and adriamycin, cyclophosphamide, ftorafur, methotrexate (ACFM) in patients with advanced breast cancer.", "Adriamycin plus vincristine alone or with dibromodulcitol or ICRF-159 in metastatic breast cancer.", "Chemotherapy versus chemoimmunotherapy (CAF v CAFVP v CMF each +/- MER) for metastatic carcinoma of the breast: a CALGB study. Cancer and Leukemia Group B.", "An evaluation of the effect of vincristine added to cyclophosphamide, 5-fluorouracil, methotrexate, and prednisone in advanced breast cancer.", "Low dose chemotherapy of metastatic breast cancer with cyclophosphamide, adriamycin, methotrexate, 5-fluorouracil (CAMF) versus sequential cyclophosphamide, methotrexate, 5-fluorouracil (CMF) and adriamycin.", "Doxorubicin and CCNU with or without vincristine in patients with advanced refractory breast cancer. A randomized trial.", "Randomized clinical trial of CFP versus CMFP in women with metastatic breast cancer.", "Adriamycin plus alkylating agents in the treatment of metastatic breast cancer.", "Differential response to chemotherapy in metastatic breast cancer in relation to estrogen receptor level. Results of a prospective randomized study.", "Mitozantrone and methotrexate chemotherapy with and without mitomycin C in the treatment of advanced breast cancer: a randomised clinical trial.", "Adriamycin combinations in advanced breast cancer. A Southwest Oncology Group Study.", "Randomized trial of 3 different regimens of combination chemotherapy in patients receiving simultaneously a hormonal treatment for advanced breast cancer.", "Comparison of four-combination chemotherapy programs in metastatic breast cancer: comparison of multiple drug therapy with cytoxan, 5-FU and prednisone versus cytoxan and adriamycin, versus cytoxan, 5-FU and adriamycin, versus cytoxan, 5-FU and prednisone alternating with cytoxan and adriamycin.", "Combination chemotherapy for advanced breast cancer: two regimens containing adriamycin." ]

[ "Patients with visceral patterns of metastatic breast cancer were stratified according to dominant metastatic site and performance status and then randomized to therapy with cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) or CAF alternating with a \"cell-cycle active\" regimen including cytosine arabinoside, methotrexate with leucovorin rescue, and oncovin ( CAMELEON ). One hundred eighty-seven patients were randomized; response rate for CAF was 44% and for CAF + CAMELEON , 40%. Durations of disease control and survival were not significantly different. Toxicity of CAF was as anticipated with predominant granulocytopenia, vomiting, and alopecia. Toxicity of CAMELEON was less severe than that of CAF, and CAF toxicity was not worsened by preceding courses of CAMELEON ; however, the CAF- CAMELEON regimen was cumbersome and complex leading to both physician and patient noncompliance. Contrary to the preliminary results of a pilot study, and preliminary reports of the present trial suggesting benefit for the CAF- CAMELEON regimen the present randomized trial does not confirm any significant benefit of CAF- CAMELEON over CAF alone in patients with visceral metastatic breast cancer although this conclusion must be viewed in light of the high inevaluability rate due to patient and physician noncompliance.", "Two groups of 23 patients each, having advanced breast cancer, entered this prospective and randomized study. One group was treated with the conventional schedule of CMF (cyclophosphamide 100 mg/m2/po from the first to the 14th day, methotrexate 40 mg/m2/iv the first and the 8th day, 5-fluorouracil 600 mg/m2/iv the first and the 8th day), and the other was treated with a new six-drug regimen, administered at low doses (R 14: cyclophosphamide 2 mg/kg/iv, vincristine 0.01 mg/kg/iv, vinblastine 0.1 mg/kg/iv, the first day and 5-fluorouracil 5 mg/kg/iv, methotrexate 0.7 mg/kg/iv, adriamycin 0.5 mg/kg/iv the 2nd day every 21 days). The remission rate was 35% (8/23) and 39% (9/23) for CMF and R 14 respectively. The median duration of objective remission was 6 months for CMF and 5 months for R 14 regimen. The median survival time of responding patients was 18 months for CMF and 14 months for R 14. This study shows that the new six-drug regimen at low doses is effective (regarding subjective, objective response and survival rate), and its toxicity is no higher than that of CMF (the incidence of leukopenia was significantly lower during the first course). Therefore, R 14 should be considered an alternative regimen to CMF in the treatment of advanced and, possibly, early breast cancer. The advantages for using R 14 are: 1) it is less toxic (a single dose is a very small amount of medicine compared to what is usually administered), 2) an iv administration always follows a therapeutic program (while in a CMF schedule cyclophosphamide is self-administered by the patient).", "A prospective randomized trial was conducted comparing the clinical response of 60 patients with advanced breast cancer to a combination of adriamycin, cyclophosphamide, and oral ftorafur (ACF), or to a combination of ACF plus methotrexate (ACFM). The response rate was 12 of 28 (43%) in ACF and 18 of 30 (60%) in ACFM. Responses were seen more frequently in patients in whom fewer than two organs were involved, and responses at dominant metastatic sites were equal for the two arms. The response duration was 21 + (3.5-49.5+) months with ACF, as against 6.9 (1.9-30.8+) months with ACFM (P less than 0.05). The median survival time from start of therapy was 20.8+ months for ACF, while that for ACFM was 13+ months (statistically not significant). The major toxicities were hair loss, GI toxicity, and leukopenia. The response rate with ACFM was higher than that with ACF, but the addition of methotrexate to ACF did not increase the complete response rate or prolong response duration.", "A total of 268 patients with metastatic breast cancer were prospectively randomized to receive Adriamycin-vincristine (AV) alone, AV plus dibromodulcitol (AVD), or AV plus ICRF-159 (AVI). Two hundred thirty were eligible and had received prior chemotherapy. The objective response rates were 27%, 23%, and 16% for AV, AVD and AVI, respectively, and an additional 44% had stabilization of disease. Duration of responses ranged from 4.1 to 4.6 months and the times to treatment failure from 2.9 to 3.8 months. Median survivals ranged from 7.1 to 8.3 months. Performance status and the presence of liver or brain metastases were significant prognostic variables for outcome. These studies show that AVI is inferior to AV with respect to survival when prognostic variables are taken into account in a multivariate model, whereas AVD which utilizes a lower dose of Adriamycin appears to have comparable antitumor activity to AV. This does not appear to offer any benefit to patients previously treated with chemotherapy, as in this trial, but it may be an advantage to previously untreated patients since Adriamycin can be administered to responding patients over a longer period of time before an unacceptable total cumulative dose is reached.", "Three combination chemotherapy regimens each with or without the methanol-extracted residue of bacillus Calmette-Guérin (BCG) (MER) were compared for efficacy. After stratification for disease-free interval and dominant sites of disease, patients were randomized to either CMF (cyclophosphamide [CYC], 100 mg/m2 orally, days 1 through 14; methotrexate [MTX], 40 mg intravenously [IV], days 1 and 8; 5-fluorouracil [5-FU], 500 mg/m2 IV, days 1 and 8), or CAF (CYC, 100 mg/m2 orally, days 1 through 14; doxorubicin [DOX], 25 mg/m2 IV, days 1 and 8; 5-FU, 500 mg/m2 IV, days 1 and 8), or CAFVP (CAF as above plus vincristine [VCR], 1.0 mg/m2 IV, days 1 and 8; and prednisone [PRED], 40 mg/m2 orally, days 1 through 14). Nonspecific immunotherapy with MER was administered in five sites at 100 micrograms or at the lowest tenfold dilution that produced a 1-cm indurated lesion. A total of 432 patients were entered, but 37 were disqualified, leaving 395 evaluable for treatment results and toxicities. One hundred thirty-five evaluable patients were randomized to chemoimmunotherapy until October 28, 1978. One hundred twenty-six evaluable patients were randomized to chemotherapy alone in the same time period. For the entire study, a total of 260 evaluable patients were randomized to chemotherapy. Chemoimmunotherapy patients were compared with the initial 126 chemotherapy patients. Chemotherapy regimens were compared among all 260 patients. Patient characteristics were similar between regimens and between chemotherapy and chemoimmunotherapy treatment groups. For patients on chemotherapy plus MER, there was no significant differences between the regimens for response frequencies: 43%, 41%, and 32%, respectively for CMF, CAF, and CAFVP. The comparable chemotherapy alone group had 36%, 58%, and 63% response, respectively. The response rates, adjusted for chemotherapy regimen, were 52% and 38% (P = .02) for chemotherapy and chemoimmunotherapy, respectively. MER was associated with painful ulcers and fevers. Thus, MER produced toxicity without response or survival benefit and further randomization after October 28, 1978 was to chemotherapy alone. For 260 evaluable patients on chemotherapy alone, the complete (CR) and partial responses (PR) were 37%, 55%, and 58%, respectively for CMF, CAF, and CAFVP. These response rates for CAF and CAFVP were significantly better than CMF (P = .01 and P less than .01, respectively). These comparisons were consistent within subgroupings such as dominant sites of disease.(ABSTRACT TRUNCATED AT 400 WORDS)", "A multi-institutional randomized clinical trial was carried out to evaluate the effect of vincristine (V) added to cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP) for the treatment of metastatic breast cancer. There were 427 patients entered into the study and randomly assigned to one of the two treatments, i.e. the five drug therapy CMFPV or the four drug therapy CMFP. The differences in patient survival and tumor response between the two treatment groups were not statistically significant. The data were also analyzed using multivariate procedures to determine those factors ascertained at entry into the study which were predictors of survival or predictors of response to therapy. The one factor that predicted both response and survival was performance status. An additional important predictor of survival was sites of metastatic involvement. Other significant predictors of response were menopausal age, BUN, and hematocrit.", "Seventy-eight advanced breast cancer patients with hormone-resistant disease or visceral metastases were randomized to receive either of two low dose regimens consisting of cyclophosphamide (C), methotrexate (M), 5-fluorouracil (F), and Adriamycin (A) as their initial chemotherapy. One group was treated with CAMF, and the other with CMF until progression, followed by A (CMF leads to A). C was given at 50 mg/m2, po, days 1-14; M at 20 mg/m2, F at 300 mg/m2, and A at 20 mg/m2, iv, days 1 and 8 of each 28-day cycle. The response rates for CAMF vs. CMF did not differ significantly (complete and partial responses-62% vs. 49%; stabilizations-23% vs. 31%). Responses by site of metasis, median times to progression and median survivals were similar for both groups. Poor and good risk partial responders had similar survivals. Twelve percent of CMF patients treated with Adriamycin at the time of progression had partial responses with an associated improved survival. Since CMF is as effective as CAMF, but has less toxicity, low dose therapy with CMF is more acceptable than CAMF as an initial chemotherapy regimen for metastatic breast cancer. Adriamycin may be reserved for subsequent regression induction.", "Thirty-five patients with advanced breast cancer refractory to initial chemotherapy were randomized to receive two-drug doxorubicin-CCNU or three-drug doxorubicin-CCNU-vincristine (VCR) treatment. Doxorubicin (25-40 mg/m2) and VCR (1.4 mg/m2) were given intravenously every 21 days; CCNU (65-90 mg/m2) was given orally every 42 days. Patients with liver or bone marrow metastases initially received the lower range doses. All patients failed prior chemotherapy with cyclophosphamide and 5-FU with or without methotrexate and prednisone; 67% received prior hormonal therapy. Pretreatment patient characteristics were comparable in both groups. Objective responses (greater than 50% reduction in tumor size) were seen in 7 of 18 patients (39%) on the VCR containing arm and in 8 of 17 patients (46%) on the doxorubicin-CCNU arm. Survival was not improved by VCR addition with overall survival on the doxorubicin-CCNU arm, approximately 10% greater at all intervals (median 9.1 versus 7.0 months; not statistically significant). However, neurotoxicity was significantly greater in the VCR arm (36% versus 0%; P less than 0.05). In advanced breast cancer, no benefit to VCR addition was seen in prior randomized studies of first-line combinations where VCR was the treatment variable. Such results, combined with our experience with VCR in a salvage regimen, question the value of VCR addition to combination regimens in advanced breast cancer.", "A randomized trial was performed to determine relative efficacy and toxicity of two first-line combination chemotherapy regimens in women with metastatic breast cancer: CFP (cyclophosphamide, 5-fluorouracil, prednisone) and CMFP (cyclophosphamide, 5-fluorouracil, methotrexate, prednisone). Both regimens have reported efficacy in this setting but differ in dosages and scheduling of the agents they have in common. Three hundred thirty-six women with no prior chemotherapy for metastatic disease were eligible and evaluable, and 309 had either measurable or evaluable disease and were assessable for objective response. Responses were seen in 65 of 153 (42%) on CFP and 83 of 156 (53%) on CMFP (two-sided P = 0.06). Median durations of response were 7.1 months for CFP and 8.5 months for CMFP (log-rank, two-sided P = 0.67). Considering all 336 patients, the median times to disease progression were 4.7 months for CFP and 6.2 months for CMFP (log-rank P = 0.31) and median survivals were 15.2 and 14.9 months, respectively (log-rank P = 0.88). Covariate analysis did not alter these findings. Median leukocyte nadirs were 1800 for CFP and 1500 for CMFP, with 22% and 21%, respectively, having nadirs less than 1000/microliters. Emesis was more frequent on CFP (49%) than on CMFP (26%) but was severe in only 7% and 5%, respectively. It is concluded that despite a higher response rate on CMFP and some differences in toxicities including a higher reported incidence of emesis on CFP, there was no substantial difference in efficacy or tolerability between the two regimens.", "A randomized trial of Adriamycin (A) in combination with melphalan (M), (MA therapy), and in combination with M plus cyclophosphamide (C) (MAC therapy), was initiated in 40 evaluable patients with metastatic breast cancer. Twenty-two patients demonstrated an objective response to therapy: 9/20 to the MA regimen, and 13/20 to the MAC regimen. For the 22 responders, median duration of response is not yet achieved for either complete or partial responders, at 10 and 9 months, respectively. The addition of the two alkylating agents to Adriamycin was superior to the single alkylating agent addition, both in total response rate and in completeness of response. Maintenance therapy, after achieving the maximum cumulative dose of Adriamycin, was provided by cyclophosphamide plus methotrexate and 5-fluorouracil (CMF). In 19 patients completing induction and entering maintenance therapy, only one relapse has developed with maximun follow-up at 15 months.", "The predictive value of estrogen receptor (ER) level for response to chemotherapy was studied in 182 patients with metastatic breast cancer in a prospective study. Patients were stratified according to ER status and dominant site of disease and randomized to one of three regimens: cyclophosphamide, 5-Fluorouracil, and prednisone (CFP) versus CFP, methotrexate, and vincristine (CFPMV) versus doxorubicin and cyclophosphamide (AC). There was no significant differences in all response categories (P = 0.21), was taken as a predictor for response to chemotherapy, there was no significant difference in overall response (P = 0.61) between ER+ (62/108, 57%) and ER- patients (31/49, 63%). However, there was a significant trend toward a higher degree of response in ER- patients (more complete response [CR] nine of 49, 18%, and fewer failures six of 49, 12%) than in ER+ (less CR seven of 108, 7%, and more failures 37/108, 34%) (P = 0.006). Patients with higher measured levels of ER showed worse response (Kendall's tau C, P = 0.026). This trend for ER- patients to have better response than ER+ patients was generally consistent, regardless of the predominant site of metastases or chemotherapy regimen (P = 0.04 for CFP; P = 0.08 for CFPMV; and P = 0.20 for AC). The advantage of a better response for ER- patients was nullified by an earlier relapse which was reflected in longer duration of remission, time to treatment failure, and survival in favor of ER+ patients (12.3 months versus 7.3 months remission duration, 18.7 months versus 13.6 months survival in partial responders). These data suggest that ER- patients respond to a higher extent to chemotherapy but relapse sooner than ER+ patients, suggesting a more rapid growth for ER- tumors. In patients with ER- tumors and poorer prognosis on conventional chemotherapy, new trials of intensive consolidation after response should be considered.", "Patients with advanced breast cancer were randomised to 3M (mitozantrone 6.5 mg/m2q 21 days, methotrexate 30 mg/m2q 21 days, mitomycin C 6.5 mg/m2q 42 days) or 2M (as 3M but without mitomycin C). The objective response rates of 30% in 51 evaluable patients receiving 3M and 26% of 54 patients receiving 2M were not significantly different. 4/16 patients not responding to 2M responded to 3M on crossover. Both regimes were well tolerated but there was significantly less haematological toxicity and fewer dose reductions and delays with 2M. We conclude that patients should initially be treated with 2M and that non-responding patients should be crossed to 3M.", "nan", "We report the results of a randomized trial carried out by the Swiss Group for Clinical Cancer Research (SAKK) and in which 230 patients with advanced breast cancer receiving concurrently a hormonal treatment (oophorectomy for pre- and tamoxifen for postmenopausal women) were randomly allocated to three different regimens of combination chemotherapy. The therapeutic results registered with the two more intensive combinations (LMP/FVP and LMFP/ADM) were similar with regard to response rates, time to progression and survival. The patients receiving the low-dose chemotherapy lmfp showed a statistically significant lower response rate (32%, P less than 0.001) and a shorter survival (P = 0.03) than the results observed in patients treated with the two other regimens. This difference was particularly pronounced, at least regarding survival, in the following subgroups: postmenopausal women, patients with a poor performance status, dominant visceral lesions, two sites of disease and a disease-free interval longer than 12 months. Patients with bony metastases as dominant lesion fared similarly with all three regimens of chemotherapy. This latter subset of advanced breast cancer patients should probably be spared too intensive cytotoxic treatment. This is, to our knowledge, the first report of a randomized trial showing an evident correlation between response rate and survival in various subgroups of patients with advanced breast cancer treated with different chemotherapeutic regimens.", "In 126 postmenopausal women with metastatic breast cancer, four chemotherapeutic combination programs were tested. Patients were stratified and randomized to one of the four programs: (1) fluorouracil, cytoxan and prednisone (CFP): (2) fluorouracil, cytoxan and Adriamycin (CAF); (3) cytoxan and Adriamycin (CA); or (4) alternating combinations of CFP-CA. Objective response rates were 17% for 18 patients on CFP, 25% for 40 patients on CAF, 42% for 41 patients on CA and 63% for 19 patients on CFP-CA. CFP-CA provided a significantly higher response rate than either CFP or CAF. The response rate of CA was intermediate. The duration of remission and survival were similar for all four groups. When progression or relapse following remission was demonstrated, patients were rerandomized to either adrenalectomy or tamoxifen. There were no responders either in the 15 patients undergoing adrenalectomy or the 11 patients receiving tamoxifen. In a crossover study, nine adrenalectomized patients received tamoxifen and four tamoxifen-treated patients underwent adrenalectomy. None responded. It appears that response rates to hormonal modalities are reduced in patients previously treated by combination chemotherapy.", "Forty-eight women with advanced metastatic carcinoma of the breast were treated with one of two combination chemotherapy regimens: 1) adriamycin and cyclophosphamide or 2) adriamycin, cyclophosphamide, methotrexate and 5-fluorouracil. The response rate in the two-drug treatment group was 50% and in the four-drug treatment group, 55%. The median duration of response was ten months in both treatment groups. Dramatic responses were seen in patients with visceral metastases. Patients who responded to chemotherapy had a significantly longer survival than nonresponders (p less than 0.01). The long interval between adriamycin doses (six weeks) in the four drug regimen did not adversely effect the response rate--an important finding in view of the dose-related cardiac toxicity of this agent." ]

[ "16446892", "16878246", "15235364", "16178407", "21859055", "15011204", "19410397", "15179204", "16702565", "8683652", "15285773" ]

[ "Posture restrictions do not interfere in the results of canalith repositioning maneuver.", "Is it important to restrict head movement after Epley maneuver?", "Effect of mastoid oscillation on the outcome of the canalith repositioning procedure.", "Treatment of benign paroxysmal positional vertigo: necessity of postmaneuver patient restrictions.", "Are postural restrictions necessary for management of posterior canal benign paroxysmal positional vertigo?", "Treatment variations on the Epley maneuver for benign paroxysmal positional vertigo.", "Are postural restrictions after an Epley maneuver unnecessary? First results of a controlled study and review of the literature.", "Vibration with the canalith repositioning maneuver: a prospective randomized study to determine efficacy.", "Efficacy of postural restriction in treating benign paroxysmal positional vertigo.", "Post-treatment instructions in the nonsurgical management of benign paroxysmal positional vertigo.", "Repeated vs single physical maneuver in benign paroxysmal positional vertigo." ]

[ "Benign Paroxysmal Positional Vertigo (BPPV) is a frequent cause of dizziness and despite of the excellent results with its treatment, there is some controversy about management.\n To assess the efficacy of Epley Maneuver with and without post-maneuver restrictions.\n Prospective randomized.\n Fifty patients presenting BPPV of the posterior semicircular canal, treated with Epley Maneuver and divided into two groups: study group--23 patients--with post-maneuver restrictions, and control group--27 patients--without post-maneuver restrictions.\n No significant difference was found between the studied and the control group.\n Post-maneuver restrictions do not influence the efficacy of Epley Maneuver for BPPV management.", "The effectiveness of postmaneuver postural restrictions is controversial in patients with benign paroxysmal positional vertigo.\n To verify the role of postural restrictions in patients with benign paroxysmal positional vertigo of posterior canal, submitted to a single Epley maneuver.\n clinical prospective.\n Fifty eight patients with benign paroxysmal positional vertigo of posterior canal were randomly divided in two groups following the application of a unique Epley maneuver. The patients from group 1 were informed to restrict their head movements and to use a cervical collar and group 2 patients were not informed about these postmaneuver restrictions. The patients from both groups were reevaluated one week after Epley maneuver, regarding the presence of symptoms and positional nystagmus.\n One week after Epley maneuver 82.1% of the patients from group 1 and 73.3% from group 2 didn't present positional nystagmus (p=0.421). There was a clinical improvement in 96.0% of the patients from group 1 and in 94.0% from group 2 (p=0.781).\n The use of postural restrictions in patients with benign paroxysmal positional vertigo of posterior canal didn't interfere in their clinical evaluation, one week after a unique Epley maneuver.", "The canalith repositioning procedure (CRP), as described by Epley, is a well-established method of treatment for benign paroxysmal positional vertigo (BPPV). Debate exists as to whether simultaneous application of a mastoid oscillator confers any added benefit. The aim of this study was to examine this question.\n Prospective randomized study.\n Eighty-four subjects with unilateral posterior canal BPPV were randomized into two groups. The oscillator group was treated by CRP with mastoid oscillation and the nonoscillator group was treated by CRP alone. Positive outcome was regarded as complete resolution of symptoms and a negative Dix-Hallpike's test after a 4 to 6 week follow-up period.\n Five patients were lost to follow-up. Twenty-eight (72%) patients from the oscillator group and 26 (65%) patients from the nonoscillator group had a positive outcome. This difference was not significant (chi = 0.17, P =.68)\n For the treatment of posterior canal BPPV, concurrent mastoid oscillation with CRP does not significantly alter the short-term outcome.", "Benign paroxysmal positional vertigo (BPPV) is the most common cause of vertigo, resulting from migration of otoconia into the semicircular canals. Several treatment methods involving positioning maneuvers that return the otoconia to the utricle have been described. Following treatment, most patients are provided with a variety of activity restrictions. Previous studies suggest that, overall, BPPV treatment may be successful without these restrictions. The purpose of this study was to determine the necessity of postmaneuver restrictions using an experimental and control group with participants matched for age, gender, involved ear, and symptoms. A canalith repositioning maneuver was used to treat the BPPV. During postmaneuver instruction, the 21 participants assigned to the restricted group were provided with typical activity restrictions. Twenty-one participants assigned to the nonrestricted group were given no postmaneuver restrictions. Only one participant in the restricted group and two participants in the nonrestricted group were not clear at the one-week follow-up appointment. Results indicated that postmaneuver restrictions do not improve treatment efficacy.", "An important component of management of benign paroxysmal positional vertigo (BPPV) has been the application of postural restrictions after use of a canalith repositioning maneuver (CRM) to prevent the return of otolithic debris into the posterior semicircular canal (PSC). This study was designed to explore the effectiveness of postural restrictions in patients with BPPV caused by otolithic debris in the PSC.\n Seventy-four adult patients with unilateral PSC BPPV were enrolled into this study. All patients were managed with a CRM--either the modified Epley maneuver or the Semont maneuver. The patients were divided randomly into 2 groups: group A, with postural restrictions, and group B, without postural restrictions. The statistical analysis was performed with X2 tests and t-tests.\n No patients in either group showed positional nystagmus in the posttreatment evaluation under infrared videonystagmoscopy. No patients had symptoms of vertigo after the therapy. The results of follow-up vestibular tests were normal in both groups.\n In our experience, postural restrictions do not enhance the beneficial effect of the CRMs. They do not seem to have any protective role and therefore should not be recommended as an adjunct to the treatment of PSC BPPV.", "To determine if using more head rotation during the Epley maneuver or specific posttreatment instructions for sleeping position would affect treatment effectiveness, compared with the usual maneuver without extra instructions.\n Patients with unilateral benign paroxysmal positional vertigo of the posterior semicircular canal were randomized to a standard Epley maneuver group, a group that received an additional 45 degrees head rotation during the maneuver (Augmented Epley), and a group that received instructions about sleeping position after treatment.\n Posttests from 1 week to 6 months showed no differences in vertigo intensity or frequency or responses to the Dix-Hallpike maneuver. All groups showed significant decreases in vertigo and Dix-Hallpike responses. Some subjects in each group had abnormal pretreatment scores on computerized dynamic posturography. Those subjects in the Augmented Epley group who had abnormal pretreatment posturography scores had significantly better posttreatment scores than those subjects in the Home Instruction group who had abnormal pretreatment scores. All subjects with abnormal responses, however, showed improvement.\n Although clinicians continue to give patients home instructions and to use additional head rotation during the maneuver, these variations are not essential for achieving improvement in symptoms.", "Postural restrictions after canalith repositioning maneuvers (CRM) for benign paroxysmal positional vertigo of the posterior semicircular canal (p-BPPV) have no proven value and therefore most physicians regard them as unnecessary. The aim of this study was to assess the short-term efficacy of head and body movement limitations after a single Epley maneuver. A review of the literature was performed to assess the current level of evidence for the efficacy of postural restrictions.\n Sixty-four patients, median age 59 years (range 37-82 years), with p-BPPV, were allocated either to instructions for movement restrictions or free movements for 48 h after a single Epley maneuver. The minimization method was used for allocation to treatment. This procedure 'minimizes' the differences in the distribution of pre-specified prognostic factors (e.g. sex and age) between the two groups of treatment. Minimization was preferred over randomization which is not as effective in balancing baseline characteristics when the number of participants is small. Outcome was assessed by physician and patient reported measures (Dix-Hallpike test, subjective vertigo intensity in a 10-point scale, patient's assessment of improvement) within 1 week after treatment by an independent investigator. The level of statistical significance was 0.05.\n More patients with movement restrictions reported a subjective improvement after treatment (p=0.007). Ninety percent of patients with movement restrictions and 74.2% of patients with free movements had a negative follow up Dix-Hallpike test but the difference was not significant (p=0.108). The mean pre-treatment vertigo intensity was reduced from 6.07 and 5.97 to 1.18 and 2.86, respectively but the difference was not significant (p=0.122).\n Postural restrictions do not increase the efficacy of the canal-repositioning maneuver despite the fact that patients report a subjective improvement after post-procedural instructions. In the review of the literature, all studies except one conclude that postural restrictions are unnecessary. However, a number of methodological issues such as inadequate sample size are not addressed and more conclusive evidence is required. Based on current evidence, the use of postural restrictions after the canal-repositioning maneuver is unjustified.", "The objective was to determine whether the inclusion of vibration and additional treatment cycles has an effect on short- and long-term success rates in the treatment of benign paroxysmal positional vertigo with the canalith repositioning maneuver.\n Prospective randomized study of patients treated at a tertiary vestibular rehabilitation center.\n Variables identified for statistical analysis included patient age, gender, vibration used, and canalith repositioning cycles. Analysis using Student t test, chi2 test, Kaplan-Meier curves with log rank test, and Cox proportional hazards regression was performed.\n One hundred two patients with benign paroxysmal positional vertigo treated over a 1-year period (August 2001-August 2002) were randomly assigned to receive the canalith repositioning maneuver with or without vibration. Average duration of follow-up was 9.44 months. The single treatment success rate was 93.1%. To relieve symptoms, 29.4% of patients required more than one canalith repositioning cycle. The relapse rate was 30.5%. Thirty-nine patients were assigned to the canalith repositioning group with vibration, and 63 to the canalith repositioning group without vibration. There was no statistical difference in age, gender, initial success rates, or relapse rates between the canalith repositioning groups with and without vibration. On average, patients required 1.38 canalith repositioning cycles for successful treatment. Vibration did not affect the number of canalith repositioning cycles required to convert the Dix-Hallpike test result to normal. The need for additional canalith repositioning cycles had no statistical effect on initial treatment success or relapse rates.\n Vibration provided no additional benefit in initial treatment success or in reducing long-term relapse rates when included in the canalith repositioning maneuver. Many patients with benign paroxysmal positional vertigo require more than one canalith repositioning cycle at the time of initial treatment to relieve symptoms, but this does not indicate a higher likelihood for recurrence. No variable predicted a higher rate of recurrence.", "To investigate the efficacy of postural restriction after canalith repositioning in treating benign paroxysmal positional vertigo (BPPV).\n Prospective trial of patients with postural restriction vs those without postural restriction after treatment.\n Patients with classic BPPV and with BPPV without nystagmus were treated using the modified Epley canalith repositioning procedure. Patients were randomly separated into 2 groups. The first group was instructed to wear a cervical collar and to maintain an upright head position for 2 days. The second group had no motion restriction. After 5 days, the patients were followed up and evaluated using the Dix-Hallpike test.\n In the first group, 56 of 62 ears healed after the first maneuver, and the remaining ears healed after the second. In the second group, 45 of 57 ears healed after the first maneuver, 6 after the second, and 5 (with subsequent postural restriction) after the third (1 ear did not improve). Five patients in the first group and 3 patients in the second group had BPPV without nystagmus; all of these patients healed after a single maneuver. The difference between the 2 groups in the number of maneuvers required for treatment was statistically significant (P<.05). The number of patients who required a third maneuver was significantly higher in the second group (P<.05).\n Postural restriction enhances the therapeutic effect of canalith repositioning in the treatment of posterior semicircular canal BPPV. The long-term efficacy of postural restriction in preventing BPPV recurrence has not been demonstrated.", "Benign paroxysmal positional vertigo (BPPV) is the commonest peripheral vestibular disorder seen in dizziness clinics. It was long believed that the condition was caused by inorganic particles in the cupula of the posterior semicircular canal (PSC). More recently it has been suggested that BPPV may result from free-floating densities in the endolymph of the long arm of the PSC. Among the various treatment modalities used, two maneuvers, each based on a different theory of pathogenesis, have reported equally high success in the control of this disorder. These maneuvers are customarily followed by strict post-treatment instructions. We studied patients with BPPV prospectively by comparing the therapeutic effectiveness of these two modalities and studying the importance of post-treatment instructions in affecting the final outcome in each modality. We showed that both maneuvers were equally successful in controlling the symptoms and that post-treatment instructions were not necessary.", "To evaluate the effectiveness and possible side effects of a single session of repeated particle repositioning maneuver (PRM) to treat posterior canal benign paroxysmal positional vertigo (BPPV) and the usefulness of post-treatment restrictions.\n A total of 125 consecutive patients with idiopathic BPPV participated in the study. Fifty patients received a single session of repeated PRM only (group I). Results were compared with those of 50 patients with BPPV who received a single PRM (group IIb), and 25 patients who received a single PRM followed by the use of a neck collar and keeping the head upright for 48 h (group IIa).\n Forty-six patients (92%) of group I, 40 patients (80%) of group IIb, and 21 patients (84%) of group IIa were completely free of signs and symptoms when re-examined 1 week after treatment. Transient nausea and disequilibrium following treatment were reported equally in all subgroups and well tolerated. Nearly all patients of group IIa considered the post-treatment restrictions very inconvenient.\n A single session of repeated physical procedure seems to be clinically superior to one single maneuver and well tolerated. Additional post-treatment measurements are inconvenient and should be abandoned." ]

[ "1605959" ]

[ "[The incorporation of acyclovir into the treatment of peripheral paralysis. A study of 45 cases]." ]

[ "The relation between use of acyclovir and facial nerve palsy prognosis was studied. In a randomised study, steroids or steroids + acyclovir (oral doses for Bell's palsy, and intravenous doses for Ramsay Hunt's syndrome) were given to 45 patients with facial palsy. There was a significant reduction of sequelae in patients treated with acyclovir in the group of Ramsay Hunt's syndrome (n = 15) (p less than 0.05). There were no significant differences in the group of Bell's palsy (n = 30) (p greater than 0.05), treated with acyclovir compared with steroids." ]

[ "19208440", "14702509", "15625351" ]

[ "Management of diabetic neuropathy by sodium valproate and glyceryl trinitrate spray: a prospective double-blind randomized placebo-controlled study.", "Sodium valproate for painful diabetic neuropathy: a randomized double-blind placebo-controlled study.", "Divalproex sodium in the management of post-herpetic neuralgia: a randomized double-blind placebo-controlled study." ]

[ "Combination of drugs with different mechanisms of action helps in achieving synergistic analgesic effect in neuropathic pain. Keeping this point in view, the effect and safety aspects of sodium valproate and GTN were assessed alone as well as in combination in this study.\n Prospective double-blind randomized placebo-controlled study.\n Eighty-seven type 2 diabetics with painful neuropathy were enrolled. Four were excluded: three with HbA1c>11 while one withdrew consent. The remaining 83 were given either sodium valproate and GTN spray (group A) or placebo drug and GTN spray (group B) or sodium valproate and placebo spray (group C) or placebo drug and placebo spray (group D). Quantitative assessment of pain was done by McGill pain questionnaire, visual analogue score (VAS) and present pain intensity (PPI) at the beginning of the study and after 3 months along with motor and sensory nerve conduction velocities measurements.\n All the three treatment groups experienced significant improvement in pain score in their drug phase of trial (p<0.001/<0.05) along with some of the electrophysiological parameters. The assessment of the magnitude of therapeutic effect of sodium valproate, GTN and their combination gave numbers needed to treat (NNT) of 7, 5 and 4, respectively.\n Sodium valproate and GTN are well tolerated and provide significant improvement in pain scores as well as in electrophysiological parameters.", "Various drugs are effective in the management of painful diabetic neuropathy, but none is completely satisfactory. We previously found sodium valproate to be effective and safe in a short-term study.\n To test the effectiveness and safety of sodium valproate in the management of painful diabetic neuropathy over 3 months.\n Randomized double-blind placebo-controlled study.\n Consecutive attending patients with type 2 diabetes mellitus with painful neuropathy were asked to participate in the trial: 48 agreed. Five were excluded: three with HbA(1c) > 11, one with too low a pain level and one who withdrew consent. The remaining 43 were given either drug (group A) or placebo (group B). Each patient was assessed clinically. Quantitative assessment of pain was done by McGill Pain Questionnaire, Visual Analogue Score and Present Pain Intensity, at the beginning of the study, after 1 month and after 3 months. Motor and sensory nerve conduction velocities were measured initially and after 3 months. Liver function tests and other adverse drug-related effects were assessed periodically.\n Of the 43 patients, four dropped out: one in group A and three in group B. There was significant improvement in pain score in group A, compared to group B, at 3 months (p < 0.001). Changes in electrophysiological data were not significant. The drug was well-tolerated by all patients, except one, who had raised serum AST and ALT levels after 1 month of treatment, and whose treatment was discontinued.\n Sodium valproate is well-tolerated, and provides significant subjective improvement in painful diabetic neuropathy.", "Post-herpetic neuralgia is difficult to treat. Divalproex sodium (valproic acid and sodium valproate in molar ratio 1:1) has been used successfully in the management of various painful neuropathies.\n To study the effectiveness and safety of divalproex sodium in the management of post-herpetic neuralgia.\n Randomized double-blind placebo-controlled trial.\n We enrolled 48 consecutively attending out-patients with post-herpetic neuralgia, out of whom three were excluded (two had insufficient pain, one withdrew consent). Quantification of pain was by Short Form-McGill pain questionnaire (SF-MPQ), visual analogue scale (VAS), present pain intensity score (PPI) and 11 point Likert scale (11 PLS) at the beginning of the study, after 2 weeks, 4 weeks and at the end of the study (8 weeks). We also assessed patients' global impression of change by questionnaire at the end of the study.\n After 8 weeks treatment with 1000 mg/day divalproex sodium, there was significant reduction in pain: SF-MPQ, 20.47 +/- 2.29 to 11.90 +/- 6.52 (p < 0.0001); PPI 4.0 +/- 0.52 to 1.95 +/- 1.29 (p < 0.0001); VAS 70.17 +/- 9.21 to 31.27 +/- 29.74 (p < 0.0001) and 11 PLS 6.97 +/- 0.73 to 3.63 +/- 2.34 (p < 0.0001) in comparison to placebo (means +/- SEM). The 'global impression of change' questionnaire showed much or moderate improvement in pain in 58.2% of patients receiving divalproex vs. 14.8% of those receiving placebo. The drug was well tolerated by all patients, except one who developed severe vertigo after 10 days of treatment.\n Divalproex sodium provides significant pain relief in patients of post-herpetic neuralgia, with very little incidence of adverse reactions. These data provide a basis for longer trials in a larger group of patients." ]

[ "19033573", "19070889" ]

[ "Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial.", "Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study." ]

[ "Pelvic lymph nodes are the most common site of extrauterine tumor spread in early-stage endometrial cancer, but the clinical impact of lymphadenectomy has not been addressed in randomized studies. We conducted a randomized clinical trial to determine whether the addition of pelvic systematic lymphadenectomy to standard hysterectomy with bilateral salpingo-oophorectomy improves overall and disease-free survival.\n From October 1, 1996, through March 31, 2006, 514 eligible patients with preoperative International Federation of Gynecology and Obstetrics stage I endometrial carcinoma were randomly assigned to undergo pelvic systematic lymphadenectomy (n = 264) or no lymphadenectomy (n = 250). Patients' clinical data, pathological tumor characteristics, and operative and early postoperative data were recorded at discharge from hospital. Late postoperative complications, adjuvant therapy, and follow-up data were collected 6 months after surgery. Survival was analyzed by use of the log-rank test and a Cox multivariable regression analysis. All statistical tests were two-sided.\n The median number of lymph nodes removed was 30 (interquartile range = 22-42) in the pelvic systematic lymphadenectomy arm and 0 (interquartile range = 0-0) in the no-lymphadenectomy arm (P < .001). Both early and late postoperative complications occurred statistically significantly more frequently in patients who had received pelvic systematic lymphadenectomy (81 patients in the lymphadenectomy arm and 34 patients in the no-lymphadenectomy arm, P = .001). Pelvic systematic lymphadenectomy improved surgical staging as statistically significantly more patients with lymph node metastases were found in the lymphadenectomy arm than in the no-lymphadenectomy arm (13.3% vs 3.2%, difference = 10.1%, 95% confidence interval [CI] = 5.3% to 14.9%, P < .001). At a median follow-up of 49 months, 78 events (ie, recurrence or death) had been observed and 53 patients had died. The unadjusted risks for first event and death were similar between the two arms (hazard ratio [HR] for first event = 1.10, 95% CI = 0.70 to 1.71, P = .68, and HR for death = 1.20, 95% CI = 0.70 to 2.07, P = .50). The 5-year disease-free and overall survival rates in an intention-to-treat analysis were similar between arms (81.0% and 85.9% in the lymphadenectomy arm and 81.7% and 90.0% in the no-lymphadenectomy arm, respectively).\n Although systematic pelvic lymphadenectomy statistically significantly improved surgical staging, it did not improve disease-free or overall survival.", "Hysterectomy and bilateral salpingo-oophorectomy (BSO) is the standard surgery for stage I endometrial cancer. Systematic pelvic lymphadenectomy has been used to establish whether there is extra-uterine disease and as a therapeutic procedure; however, randomised trials need to be done to assess therapeutic efficacy. The ASTEC surgical trial investigated whether pelvic lymphadenectomy could improve survival of women with endometrial cancer.\n From 85 centres in four countries, 1408 women with histologically proven endometrial carcinoma thought preoperatively to be confined to the corpus were randomly allocated by a minimisation method to standard surgery (hysterectomy and BSO, peritoneal washings, and palpation of para-aortic nodes; n=704) or standard surgery plus lymphadenectomy (n=704). The primary outcome measure was overall survival. To control for postsurgical treatment, women with early-stage disease at intermediate or high risk of recurrence were randomised (independent of lymph-node status) into the ASTEC radiotherapy trial. Analysis was by intention to treat. This study is registered, number ISRCTN 16571884.\n After a median follow-up of 37 months (IQR 24-58), 191 women (88 standard surgery group, 103 lymphadenectomy group) had died, with a hazard ratio (HR) of 1.16 (95% CI 0.87-1.54; p=0.31) in favour of standard surgery and an absolute difference in 5-year overall survival of 1% (95% CI -4 to 6). 251 women died or had recurrent disease (107 standard surgery group, 144 lymphadenectomy group), with an HR of 1.35 (1.06-1.73; p=0.017) in favour of standard surgery and an absolute difference in 5-year recurrence-free survival of 6% (1-12). With adjustment for baseline characteristics and pathology details, the HR for overall survival was 1.04 (0.74-1.45; p=0.83) and for recurrence-free survival was 1.25 (0.93-1.66; p=0.14).\n Our results show no evidence of benefit in terms of overall or recurrence-free survival for pelvic lymphadenectomy in women with early endometrial cancer. Pelvic lymphadenectomy cannot be recommended as routine procedure for therapeutic purposes outside of clinical trials." ]

[ "3664330", "3056555", "6308441", "3879598", "4067613", "7773582", "2191444", "6122057", "356523", "2771374", "8442620", "3535491", "3892729", "10560360", "311410", "6365008", "1437036", "10671332", "8142675", "8360134", "1588260", "8172437", "1965007", "2037541", "10064240" ]

[ "A randomized trial comparing ketoconazole and nystatin prophylactic therapy in neutropenic patients.", "Control of oral mucositis and candidiasis in marrow transplantation: a prospective, double-blind trial of chlorhexidine digluconate oral rinse.", "Prevention of mycosis in granulocytopenic patients with prophylactic ketoconazole treatment.", "Nystatin prophylaxis of fungal colonization and infection in granulocytopenic patients: correlation of colonization and clinical outcome.", "Prophylaxis of oropharyngeal candidiasis with clotrimazole.", "Comparison of fluconazole with oral polyenes in the prevention of fungal infections in neutropenic patients. A prospective, randomized, single-center study.", "Prophylaxis of candidiasis in cancer patients.", "Ketoconazole versus nystatin plus amphotericin B for fungal prophylaxis in severely immunocompromised patients.", "Prophylactic treatment with miconazole in patients highly predisposed to fungal infection. A placebo-controlled double-blind study.", "Effects of chlorhexidine mouthrinse on oral health in patients with acute leukemia.", "Fluconazole prophylaxis of fungal infections in patients with acute leukemia. Results of a randomized placebo-controlled, double-blind, multicenter trial.", "Clotrimazole treatment for prevention of oral candidiasis in patients with acute leukemia undergoing chemotherapy. Results of a double-blind study.", "Ketoconazole prophylaxis in patients with solid tumours receiving aggressive immunosuppressive therapy. An open randomized comparison between 200 mg/d and 400 mg/d doses.", "Fluconazole versus itraconazole for the prevention of fungal infections in haemato-oncology.", "Oral anticandidal prophylaxis in patients undergoing chemotherapy for acut- leukemia.", "Prophylaxis of oral candidiasis with clotrimazole troches.", "Efficacy of chlorhexidine and nystatin rinses in prevention of oral complications in leukemia and bone marrow transplantation.", "A double-blind, randomized, placebo-controlled trial of itraconazole capsules as antifungal prophylaxis for neutropenic patients.", "Prevention of bacterial and fungal infections in acute leukemia patients: a new and potent combination of oral norfloxacin and amphotericin B.", "Randomized comparison of oral fluconazole versus oral polyenes for the prevention of fungal infection in patients at risk of neutropenia. Multicentre Study Group.", "Oral ketoconazole prophylaxis for Candida infections during induction therapy for acute leukaemia in adults: more bacteraemias.", "Preventing fungal infection in neutropenic patients with acute leukemia: fluconazole compared with oral amphotericin B.", "Antifungal chemoprophylaxis in cancer children: a prospective randomized controlled study.", "A randomized study to compare oral fluconazole to amphotericin B in the prevention of fungal infections in patients with acute leukaemia.", "Itraconazole oral solution as prophylaxis for fungal infections in neutropenic patients with hematologic malignancies: a randomized, placebo-controlled, double-blind, multicenter trial. GIMEMA Infection Program. Gruppo Italiano Malattie Ematologiche dell' Adulto." ]

[ "A randomized trial was conducted comparing ketoconazole and nystatin in the prevention of oral candidiasis and appearance of invasive fungal infections in 51 neutropenic leukemic patients undergoing induction chemotherapy. Ketoconazole was administered in a 200 mg dose twice daily. Nystatin oral suspension was given in doses of 500,000 units four times daily. Surveillance cultures of the throat and urine were obtained prior to treatment and conducted weekly. Patients were enrolled in the study if the absolute granulocyte count was less than 1500/microliter, if physical examination revealed no evidence of oral candidiasis, no evidence of urinary tract infection, and there was no pulmonary infiltrate on chest x-ray. Patients were continued on study until the absolute granulocyte count reached 1500/microliter, evidence of oral candidiasis appeared, or presumed or proven invasive fungal infections appeared. Of the 46 evaluable patients, 22 received ketoconazole, 3 (14%) developed oral candidiasis, and 5 developed suspected systemic fungal infections (23%). Of 24 patients who received nystatin, 4 (17%) developed oral candidiasis and 8 (33%) developed systemic fungal infections, 4 proven and 4 suspected. Significantly more patients on the nystatin arm progressed to invasive fungal infections. Ketoconazole was not superior to nystatin in reducing the frequency of oral candidiasis but possibly reduced the frequency of invasive fungal infections.", "Conditioning chemoradiotherapy damages the mucosal barrier of the mouth and throat and often produces severe oral inflammation and infection. In a prospective, double-blind, randomized study, we examined the use of a chlorhexidine digluconate mouthrinse for prophylaxis against oral mucosal complications in 51 bone marrow transplant patients. Use of chlorhexidine mouthrinse produced significant reductions in the incidence and severity of oral mucositis. Mucositis also resolved more quickly in patients receiving chlorhexidine. Concomitant reductions in total oral streptococci (p less than 0.02-p less than 0.001) and oral candida (p less than 0.004) were seen in patients using chlorhexidine. Persistent clinical oral candidiasis (thrush) was observed in 15 to 27 control group patients (56%), but only transiently in two (8%) of 24 patients who used chlorhexidine rinse (p less than 0.001). Five of 27 control group patients (19%) had candidemia, while no candidemia was observed in the chlorhexidine group (p less than 0.03). Three deaths from disseminated candidiasis occurred in the placebo group; none occurred in patients who received chlorhexidine. Prophylactic use of chlorhexidine mouthrinse produces reductions in oral soft tissue disease and oral microbial burden in patients undergoing bone marrow transplantation. The reductions in mucositis and in oral candida infections observed with prophylactic chlorhexidine mouthrinse represent a significant advantage for patients undergoing marrow transplantation.", "nan", "Nystatin, one million units every four hours, was prospectively studied as a prophylactic antifungal agent in 164 neutropenic patients who were not initially colonized by fungi: 104 received nystatin and 60 served as controls. Fungal colonization occurred in 68/104 (65%) nystatin recipients and in 43/60 (71%) controls. However, nystatin significantly reduced multiple body site colonization and persistent oropharyngeal colonization. Despite these alterations in colonization profile, 16/104 (15%) nystatin recipients developed disseminated fungal infections, as compared to 5/60 (8%) control patients (0.5 greater than p greater than 0.1, N.S). Differences in the clinical course of colonized and non-colonized patients were observed. Eighteen of 111 (16%) colonized patients had afebrile clinical courses as compared to 16/53 (30%) non-colonized patients (p less than 0.05). Twenty-nine of 93 (31%) febrile episodes in colonized patients failed to respond to empiric antibiotic therapy as compared to 3/37 (8%) episodes in non-colonized patients (p less than 0.01). Disseminated fungal infections were diagnosed in 19/111 (17%) of colonized patients, as compared to 1/53 (2%) non-colonized patients (p less than 0.02). We conclude that colonized patients are more likely to develop febrile clinical courses, to fail to respond to empiric antibiotic therapy, and to develop disseminated fungal infection. Nystatin altered colonization patterns but did not prevent disseminated fungal infection.", "A total of 202 evaluable cancer patients were randomly assigned to receive or not receive oral clotrimazole as antifungal prophylaxis during hospitalization. Oropharyngeal candidiasis occurred in 1% of the former patients and 27% of the latter patients (P less than .00001). Candida sp were cultured from the initial throat specimens of 53 control patients and 55 patients who received prophylaxis. Oropharyngeal candidiasis subsequently developed in 2% of the former patients and 38% of the latter patients (P = less than .00001). Oral clotrimazole is an effective agent for prophylaxis of oropharyngeal candidiasis in susceptible cancer patients.", "The goal of this prospective randomized single-center study was the comparison of safety and efficacy of high-dose oral/intravenous fluconazole (400 mg daily) (group A) with oral nystatin plus miconazole inhalations (group B) in the prevention of fungal infections on a hemato-oncological isolation Ward. Of 157 patients admitted to the isolation ward during the study period only 90 (57%) were eligible for randomization; 22 (14%) had a fungal infection at admission. Of the 90 randomized patients, 89 were evaluable, 43 in group A and 46 in group B. The age, sex, diagnosis, planned therapy and risk factors for fungal infections at admission as well as the duration of neutropenia were in the same proportions in both groups. Oral thrush and mucocutaneous candidiasis were prevented in all patients of both groups, and 29 patients (32%: 17 in group A, 12 in group B) were discharged after successful prophylaxis (NS). Empiric amphotericin B was given according to predetermined criteria to 45 patients (51%: 23 group A, 22 group B; NS). Fluconazole significantly delayed the time before the start of intravenous amphotericin B. It was begun after a median of 10 days (0-45 days, range) of neutropenia below 0.5 x 10(9) granulocytes/l in group A and 7.5 days (0-26, range) in group B (P < 0.05). The duration of successful prophylaxis was significantly longer in group A (26 days median) than in group B (21 days, median) (P < 0.05). Systematic fungal infection was documented in 3 patients (1 group A, 2 group B; NS).", "Patients undergoing therapy for metastatic malignancies were randomly assigned to receive fluconazole or placebo as antifungal prophylaxis. Oropharyngeal candidiasis developed in 28% of 54 evaluable patients receiving placebo but in only 2% of 58 evaluable patients receiving fluconazole (P = .0003). Among patients receiving placebo, oropharyngeal candidiasis (thrush) occurred in 30% of those receiving antibiotic therapy and in 44% of those receiving adrenal corticosteroid therapy. Oropharyngeal candidiasis developed in 54% of the placebo patients who were colonized by Candida sp at the onset of prophylaxis. Fluconazole proved to be effective for prophylaxis of oropharyngeal candidiasis in susceptible patients and was well tolerated.", "72 patients severely immunocompromised by their underlying disease (marrow aplasia, acute leukaemia, or solid tumour) or by the treatment they were receiving, or both, were randomised to receive antifungal prophylaxis with either oral ketoconazole or conventional doses of oral amphotericin B and nystatin. All patients also had gut decontamination with non-absorbable antibiotics, skin antisepsis, sterile food, and oral cotrimoxazole. Protection against fungal infection was significantly superior with ketaconazole. When patients who had received allogeneic bone-marrow transplant were studied separately, there was no significant difference between the two treatments, probably because there was a fall-off in ketoconazole absorption from the end of the third week after the transplant. However, ketoconazole greatly reduced the likelihood of fungal infection in non-transplant patients.", "In a placebo-controlled double-blind study the prophylactic value of oral systemic treatment with the antimycotic agent miconazole was assessed in 30 highly predisposed patients receiving intensive cytostatic chemotherapy because of haematological malignancies. Patients colonized with Candida before treatment were not freed from this micro-organism by miconazole treatment. However, only 3 out of 6 initially non-colonized miconazole-treated patients became colonized during the study, against 10 out of 10 placebo-treated patients (p = 0.036). Seven out of 15 patients in the placebo group developed clinical mycosis, against only two out of 15 in the miconazole group. The miconazole-treated patients remained clinically free of mycosis for 252 out of 264 treatment days, while the placebo-treated patients remained free of mycosis for only 263 out or 338 treatment days (p = 0.0001). The results indicate that systemic miconazole treatment protects highly predisposed patients from colonization with Candida and prevents or postpones clinically established candidosis.", "The effects of chlorhexidine mouthrinses, used as a supplement to mechanical oral hygiene measures, were studied in patients receiving treatment for acute leukemia. Twenty-eight patients were randomly divided into two groups. During two periods, when the patients were taking medication for the leukemia, one group rinsed with a 0.2% chlorhexidine solution twice daily and the other group did not. Chlorhexidine had no effects of any clinical significance on parameters such as number of days with fever, number of oral lesions, plaque score, gingival bleeding score, or occurrence of candidiasis. There was, however, an increased number of patients who had a burning sensation in the mouth, and a tendency toward increased numbers of salivary enterococci, enterobacteria, and/or Pseudomonas in patients who rinsed with chlorhexidine. The results of the present study do not support the use of chlorhexidine mouthrinses in patients who are able to maintain good oral hygiene by mechanical means during their illness.", "To evaluate the efficacy and safety of fluconazole for prevention of fungal infections.\n A randomized, placebo-controlled, double-blind, multicenter trial.\n Adults (257) undergoing chemotherapy for acute leukemia.\n Patients were randomly assigned to receive either fluconazole (400 mg orally once daily or 200 mg intravenously every 12 hours) or placebo. The study drug was started at initiation of chemotherapy and continued until recovery of neutrophil count, development of proven or suspected invasive fungal infection, or the occurrence of a drug-related toxicity.\n Fungal colonization, proven superficial or invasive fungal infection, empiric antifungal therapy with amphotericin B, drug-related side effects, and mortality.\n Fluconazole decreased fungal colonization (83 of 122 [68%] placebo patients compared with 34 of 119 [29%] fluconazole patients colonized at end of prophylaxis, P < 0.001) and proven fungal infections (27 of 132 [21%] placebo patients compared with 11 of 123 [9%] fluconazole patients infected, P = 0.02). Superficial fungal infections occurred in 20 of 132 (15%) placebo patients but in only 7 of 123 (6%) fluconazole patients (P = 0.01), whereas invasive fungal infections developed in 10 of 132 (8%) placebo patients and in 5 of 123 (4%) fluconazole patients (P = 0.3). Fluconazole was especially effective in eliminating colonization and infection by Candida species other than Candida krusei (66 of 122 [64%] placebo patients colonized at end of prophylaxis compared with 11 of 119 [9%] fluconazole patients, P < 0.001; 22 of 132 [17%] placebo patients infected compared with 7 of 123 [6%] fluconazole patients, P = 0.005). Aspergillus infections were infrequent in both fluconazole (3 cases) and placebo groups (3 cases). The use of amphotericin B, the incidence of drug-related side effects, and overall mortality were similar in both study groups.\n Prophylactic fluconazole prevents colonization and superficial infections by Candida species other than Candida krusei in patients undergoing chemotherapy for acute leukemia and is well tolerated. Fluconazole could not be clearly shown to be effective for preventing invasive fungal infections, reducing the use of amphotericin B, or decreasing the number of deaths.", "Fungal infections have become an increasing cause of morbidity in patients with acute leukemia undergoing chemotherapy. Oral candidiasis is prone to develop in these patients, and there is also a risk of the development of esophageal Candida infection. Clotrimazole troches have been previously reported to be effective in the treatment of documented oral Candida infection. This report documents a double-blind controlled study in 30 patients with acute leukemia in which the effectiveness of clotrimazole troches in preventing oropharyngeal candidiasis was assessed. Patients were randomly assigned to receive 10 mg troches of clotrimazole or a placebo three times per day. Mucosal scrapings were obtained weekly and examined directly by smear and culture. There were 28 evaluable patients. Of 12 patients with oral Candida infection, 11 were taking placebo and one received clotrimazole (p = 0.0002). Clotrimazole is effective in preventing oropharyngeal candidiasis.", "Forty-three patients, most with solid tumours, were included in a study comparing the antifungal prophylactic effect of ketoconazole (Nizoral; Janssen) 200 mg/d and 400 mg/d during the period of immunosuppressive therapy. Seven patients were not seen for follow-up and 6 died of their underlying disease without clinical evidence of mycosis. Twelve of the patients who could be evaluated received ketoconazole 200 mg/d and 18 received 400 mg/d. No infections occurred during the period of prophylactic treatment. In the group receiving 200 mg/d 10 of 36 cultures (28%) were positive for Candida albicans before prophylaxis. During prophylaxis 5 of 18 cultures (28%) were positive and at the end of the prophylactic regimen 1 out of 37 cultures (3%) was positive. In the 400 mg/d group, 13 of 47 cultures (28%) were positive at the start, 2 out of 20 (10%) were positive during prophylaxis and 1 out of 45 (2%) was still positive at the end. The drug was clinically well tolerated. Twenty of the 30 evaluable patients had no significant biochemical abnormalities, 5 had an increased serum transaminase level, 2 had an increased alkaline phosphatase level, and 3 had combined increases of serum transaminase and alkaline phosphatase levels. These abnormalities are regularly seen in patients with metastatic malignant disease, and are not necessarily related to the ketoconazole prophylaxis.", "To compare the efficacy of and tolerance to oral fluconazole and intraconazole in preventing fungal infection in neutropenic patients with haematological malignancies.\n 213 consecutive, afebrile adult patients treated with or without autologous stem cell transplantation for haematological malignancies.\n A randomised, double blind, single centre study. Patients were randomly assigned to receive fluconazole 50 mg or itraconazole 100 mg, both twice daily in identical capsules. An intention to treat analysis was performed on 202 patients, 101 in each group.\n Microbiologically documented systemic fungal infections occurred in four patients in each group. Clinical fungal infection was thought to be present in seven recipients of fluconazole and four of itraconazole. In all 202 patients, 29 proceeded to intravenous amphotericin (amphotericin B), 16 in the fluconazole group and 13 in the itraconazole group. Superficial fungal infection was seen only in three non-compliant patients in the fluconazole group. All these infections were oral. No major differences were noted in the isolates of fungi in mouth washes and fecal samples. Overall mortality was 8.9% (18 deaths; seven in the fluconazole group, 11 in the itraconazole group). Mortality from microbiologically and clinically documented fungal infection was 4.5% (nine deaths; three in the fluconazole group, six in the itraconazole group). Median time to suspected or proven fungal infection was 16 days in both groups. None of these comparisons reached statistical significance (p < 0.05). No major clinical toxicity was noted and compliance was excellent.\n In neutropenic patients treated for haematological malignancies with or without autologous stem cell transplantation, fluconazole and itraconazole in low doses result in a similar low frequency of fungal disease. Fluconazole may be the preferable drug because of the smaller number of capsules and lack of need for timing relative to meals.", "Fifty-six untreated patients with acute leukemia (38 acute myelogenous leukemia, 16 acute lymphoblastic leukemia, and 2 blast crisis of chronic granulocytic leukemia) were randomized on admission to one of three groups--one to receive oral anticandidal prophylaxis through the period of remission induction chemotherapy with nystatin, another to receive natamycin, and the third to receive no anticandidal prophylaxis. Neither of the first two groups show any advantage over the last and it is concluded that provided gut sterilization regimes are not employed, prophylactic oral anticandidal treatment is of no value in these patients and should be reserved until there is clinical evidence of infection.", "Oropharyngeal candidiasis is frequently a complication of patients with altered immune states. Clotrimazole troches are effective in the treatment of Candida and were evaluated in this study in a prophylaxis regimen. Patients with malignant neoplasms who were receiving chemotherapy and renal transplant recipients who were receiving immunosuppressives were randomized to receive either clotrimazole (10 mg) or placebo troches three times a day in a prospective, double-blinded study. Eighty-four patients were randomized into the study, 18 patients with leukemia, 19 patients with malignant neoplasms, and 47 patients with renal transplants. Among all patients, thrush developed in 57% while receiving placebo compared with 13% while receiving clotrimazole prophylaxis. Prophylaxis showed significant benefit for the renal transplant recipients and for patients with solid malignant neoplasms, but not for the leukemic patients. Clotrimazole troches are effective in preventing oral candidiasis in a select group of patients.", "The goal of reducing oral complications during chemotherapy and bone marrow transplantation has received attention at several centers. The current randomized study of 86 adults with leukemia treated with chemotherapy or bone marrow transplantation assessed the potential role of chlorhexidine, nystatin, and saline solution rinses to reduce the findings of oral mucositis, gingivitis, and oral infection. The results of this study did not show a reduction in mucositis with the use of these rinses. However, potential bacterial and fungal pathogens were identified less frequently in the patients using chlorhexidine rinse.", "To evaluate the efficacy of itraconazole capsules in prophylaxis for fungal infections in neutropenic patients, we conducted a prospective, double-blind, placebo-controlled, randomized trial. Patients with hematologic malignancies or those who received autologous bone marrow transplants were assigned either a regimen of itraconazole (100 mg orally twice daily; n=104) or of placebo (n=106). Overall, fungal infections (superficial or systemic) occurred more frequently in the placebo group (15% vs. 6%; P=.03). There were no differences in the empirical use of amphotericin B or systemic fungal infections. Among patients with neutropenia that was profound (<100 neutrophils/mm3) and prolonged (for at least 7 days), those receiving itraconazole used less empirical amphotericin B (22% vs. 61%; P=.0001) and developed fewer systemic fungal infections (6% vs. 19%; P=.04). For patients with profound and prolonged neutropenia, itraconazole capsules at the dosage of 100 mg every 12 h reduce the frequency of systemic fungal infections and the use of empirical amphotericin B.", "The effect of a combination regimen using norfloxacin (NFLX) and amphotericin B (AMPH-B) for prevention of infections in patients with acute leukemia being treated by remission-induction chemotherapy in a randomized, controlled trial was studied. One hundred and six consecutive, evaluable patients were randomly assigned to receive orally 200 mg of norfloxacin two or four times daily and 200 mg of amphotericin B four times daily, or amphotericin B only. A smaller percentage of patients with bacteriologically-documented infections was observed in the study group compared with the control group (34.6% vs 56.9%; P < 0.05). The mean number of days that the patients received empirical antibiotic therapy was shorter in the study group (23 days vs 30 days; P < 0.05). The percentage of patients with a gram-negative bacterial infection (9.6% vs 27.5%; P < 0.05) or a fungal infection (17.3% vs 37.3%; P < 0.05) was decreased in the study group. This new combination antimicrobial regimen is safe and effective for prevention of gram-negative bacterial as well as fungal infections in patients with acute leukemia being treated with cytotoxic remission-induction chemotherapy.", "An open, randomized study was performed at 18 European centres to compare the efficacy, safety and tolerance of oral fluconazole with oral polyenes for the prophylaxis of fungal colonization and infection in adults at high risk of developing neutropenia. Five hundred and thirty-six hospitalized patients with malignant disease, about to receive chemotherapy, radiotherapy, or bone marrow transplantation, and who were already neutropenic or were expected to develop neutropenia were included in the study. Before therapy or transplantation, patients commenced either oral fluconazole therapy (50 mg/day as a single dose) or oral polyenes therapy (amphotericin B 2 g/day and/or nystatin 4 x 10(6) units/day in four or more divided doses), for a mean of 29.3 days and 31.3 days, respectively. After baseline clinical and mycological testing, patients were re-evaluated at least weekly during prophylaxis, at the end of prophylaxis and two to six weeks later to identify proven or suspected fungal infection and to determine rates of colonization with fungi. Fungal infection was diagnosed in 41 of 511 evaluable patients, 10 (3.9%) of 256 in the fluconazole group and 31 (12.2%) of 255 in the polyene group (P = 0.001). This total included four patients (1.6%) in the fluconazole group who developed oropharyngeal candidiasis compared with 22 (8.6%) in the polyene group (P < 0.001). Systemic infections comprised 6 (2.3%) in the fluconazole group and 9 (3.5%) in the polyene group (P = not significant), and included three Candida krusei infections in each group. Parenteral amphotericin B therapy was given empirically for persistent fevers in an additional 62 (24.2%) patients receiving fluconazole and 59 (23.1%) receiving polyenes (P = not significant). Colonization with fungi was generally similar in each treatment group, although an increased proportion of patients receiving fluconazole developed colonization of the faeces (P < 0.01). Adverse reactions, possibly related to treatment, were recorded in 15 (5.6%) of 269 patients in the fluconazole group and 14 (5.2%) of 267 in the polyene group; these necessitated discontinuation of therapy in seven patients in each group. Once-a-day fluconazole was therefore more effective than oral polyenes for the prevention of oropharyngeal fungal infection and as effective for the prevention of infections at other sites in patients with neutropenia.", "We determined whether ketoconazole prophylaxis might reduce Candida colonization and infections in adult patients with acute leukaemia. During first-remission induction therapy 50 patients were treated with 200 mg ketoconazole administered orally daily, while 57 patients received placebo in a double-blind, randomized trial. The duration of severe neutropenia (granulocytes less than 0.1 x 10(9) l-1) represented 36% of the study period in the ketoconazole group and 26% in the placebo group (P = 0.043). Although fewer patients presented with positive Candida surveillance cultures and serological evidence of Candida infection in the ketoconazole group compared to the placebo group, two candidaemias and one Trichosporum fungaemia were observed in the ketoconazole group. Moreover, significantly more bacteraemias were noted in the ketoconazole group (n = 37) than in the placebo group (n = 21) (P = 0.004). Thus, although oral ketoconazole prophylaxis might be associated with less Candida colonization and fewer seroconversions, it also resulted in more bacteraemias and longer duration of severe neutropenia, suggesting that caution should be exercised when ketoconazole (or related drugs) is given to this group of immunocompromised hosts.", "To compare the efficacy and tolerability of fluconazole and oral amphotericin B in preventing fungal infection in neutropenic patients with acute leukemia.\n A randomized, controlled, multicenter trial.\n 30 hematologic units in tertiary care or university hospitals.\n 820 consecutive, afebrile, adult patients with acute leukemia and chemotherapy-induced neutropenia.\n Patients were randomly assigned to receive fluconazole, 150 mg, as a once-daily capsule, or amphotericin B suspension, 500 mg every 6 hours.\n An intention-to-treat analysis was done for 820 patients: 420 treated with fluconazole and 400 treated with oral amphotericin B.\n Definite systemic fungal infection occurred in 2.6% of fluconazole recipients and 2.5% of amphotericin B recipients; suspected systemic fungal infection requiring the empiric use of intravenous amphotericin B occurred in 16% of fluconazole recipients and 21% of oral amphotericin B recipients, a difference of 5 percentage points (95% CI for difference, -0.02% to 10%; P = 0.07). Superficial fungal infection was documented in 1.7% of fluconazole recipients compared with 2.7% of amphotericin B recipients, a difference of one percentage point (CI of difference, -0.9% to 3%; P > 0.2). The distribution of fungal isolates in systemic and superficial fungal infection was similar in both groups. The overall mortality rate accounted for 10% in both groups. An excellent compliance was documented for 90% of patients treated with fluconazole compared with 72% of those treated with amphotericin B suspension, a difference of 18 percentage points (CI for difference, 13% to 23%). Side effects were documented less frequently in fluconazole than in amphotericin B recipients (1.4% compared with 7%, a difference of 5.6 percentage points; CI for difference, 2% to 8%; P < 0.01).\n Fluconazole was at least as effective as oral amphotericin B in preventing systemic and superficial fungal infection and the empiric use of amphotericin B in neutropenic patients with acute leukemia but was better tolerated.", "We report a prospective, randomized, controlled study of antifungal chemoprophylaxis in forty immunocompromised children with hematologic malignancies, receiving respectively itraconazole, ketoconazole, amphotericin-B and no prophylaxis. Fungal isolates from patients' saliva or stools were obtained from 19/40 patients (Candida albicans from 15 patients). Disseminated infection was never observed. Fungal isolates were significantly less frequent in the ketoconazole group of patients vs any other group. Systemic antifungal chemoprophylaxis with ketoconazole appears more effective even than the recently introduced itraconazole.", "In a prospective randomized study the efficacy of fluconazole (50 mg in one single daily dose) was compared with oral amphotericin B in suspension and tablets (each 200 mg four times daily) for prevention of colonization and subsequent infection by yeasts in 50 patients undergoing remission induction treatment for acute leukaemia. All patients received ciprofloxacin for prevention of bacterial infections. Fluconazole was as effective as amphotericin B in preventing severe local and disseminated fungal disease (one documented and one highly suspected infection in each group of patients). Fluconazole effectively prevented yeast colonization of the oropharynx but was less effective than amphotericin B in preventing colonization of the lower alimentary tract. Fifty-two percent of patients receiving fluconazole had persistent positive stool cultures as compared to 4% in the amphotericin B group (P less than 0.01). Fluconazole was better tolerated than amphotericin B. One patient developed an extended rash leading to the termination of fluconazole.", "To evaluate the efficacy and safety of itraconazole oral solution for preventing fungal infections, a randomized, placebo-controlled, double-blind, multicenter trial was conducted: 405 neutropenic patients with hematologic malignancies were randomly assigned to receive either itraconazole, 2.5 mg/kg every 12 hours (201 patients), or placebo (204 patients). Proven and suspected deep fungal infection occurred in 24% of itraconazole recipients and in 33% of placebo recipients, a difference of 9 percentage points (95% confidence interval [CI], 0.6% to 22.5%; P = .035). Fungemia due to Candida species was documented in 0.5% of itraconazole recipients and in 4% of placebo recipients, a difference of 3.5 percentage points (95% CI, 0.5% to 6%; P = .01). Deaths due to candidemia occurred in none of the itraconazole recipients compared with 4 placebo recipients, a difference of 2 percentage points (95% CI, 0.05% to 4%; P = .06). Aspergillus infection was documented in four itraconazole recipients (one death) and one placebo recipient (one death). Side effects causing drug interruption occurred in 18% of itraconazole recipients and 13% of placebo recipients. Itraconazole oral solution was well-tolerated and effectively prevented proven and suspected deep fungal infection as well as systemic infection and death due to Candida species." ]

[ "15958805" ]

[ "Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin." ]

[ "Selective blockade of interactions between leukocytes and vascular endothelium in the gut is a promising strategy for the treatment of inflammatory bowel diseases.\n We conducted a multicenter, double-blind, placebo-controlled trial of MLN02, a humanized antibody to the alpha4beta7 integrin, in patients with active ulcerative colitis. We randomly assigned 181 patients to receive 0.5 mg of MLN02 per kilogram of body weight, 2.0 mg per kilogram, or an identical-appearing placebo intravenously on day 1 and day 29. Eligible patients also received concomitant mesalamine or no other treatment for colitis. Ulcerative colitis clinical scores and sigmoidoscopic assessments were evaluated six weeks after randomization.\n Clinical remission rates at week 6 were 33 percent, 32 percent, and 14 percent for the group receiving 0.5 mg of MLN02 per kilogram, the group receiving 2.0 mg per kilogram, and the placebo group, respectively (P=0.03). The corresponding proportions of patients who improved by at least 3 points on the ulcerative colitis clinical score were 66 percent, 53 percent, and 33 percent (P=0.002). Twenty-eight percent of patients receiving 0.5 mg per kilogram and 12 percent of those receiving 2.0 mg per kilogram had endoscopically evident remission, as compared with 8 percent of those receiving placebo (P=0.007). For the minority of patients in whom an MLN02 antibody titer greater than 1:125 developed, incomplete saturation of the alpha4beta7 receptor on circulating lymphocytes was observed and no benefit of treatment was identifiable.\n In this short-term study, MLN02 was more effective than placebo for the induction of clinical and endoscopic remission in patients with active ulcerative colitis." ]

[ "10770980", "7473832", "7730878", "9162305", "11073017" ]

[ "Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas. Phoenix Colon Cancer Prevention Physicians' Network.", "Randomized trial of intake of fat, fiber, and beta carotene to prevent colorectal adenomas.", "A randomized trial of a low fat high fibre diet in the recurrence of colorectal polyps. Toronto Polyp Prevention Group.", "The polyp prevention trial II: dietary intervention program and participant baseline dietary characteristics.", "Calcium and fibre supplementation in prevention of colorectal adenoma recurrence: a randomised intervention trial. European Cancer Prevention Organisation Study Group." ]

[ "The risks of colorectal cancer and adenoma, the precursor lesion, are believed to be influenced by dietary factors. Epidemiologic evidence that cereal fiber protects against colorectal cancer is equivocal. We conducted a randomized trial to determine whether dietary supplementation with wheat-bran fiber reduces the rate of recurrence of colorectal adenomas.\n We randomly assigned 1429 men and women who were 40 to 80 years of age and who had had one or more histologically confirmed colorectal adenomas removed within three months before recruitment began to a supervised program of dietary supplementation with either high amounts (13.5 g per day) or low amounts (2 g per day) of wheat-bran fiber. The primary end point was the presence or absence of new adenomas at the time of follow-up colonoscopy. Subjects and physicians, including colonoscopists, were unaware of the group assignments.\n Of the 1303 subjects who completed the study, 719 had been randomly assigned to the high-fiber group and 584 to the low-fiber group. The median times from randomization to the last follow-up colonoscopy were 34 months in the high-fiber group and 36 months in the low-fiber group. By the time of the last follow-up colonoscopy, at least one adenoma had been identified in 338 subjects in the high-fiber group (47.0 percent) and in 299 subjects in the low-fiber group (51.2 percent). The multivariate adjusted odds ratio for recurrent adenoma in tile high-fiber group, as compared with the low-fiber group, was 0.88 (95 percent confidence interval, 0.70 to 1.11; P=0.28), and the relative risk of recurrence according to the number of adenomas, in the high-fiber group as compared with the low-fiber group, was 0.99 (95 percent confidence interval, 0.71 to 1.36; P=0.93).\n As used in this study, a dietary supplement of wheat-bran fiber does not protect against recurrent colorectal adenomas.", "Epidemiologic evidence of associations between the high intake of fat and low intake of dietary fiber, beta carotene, and other dietary constituents and the risk of colorectal neoplasia has been inconsistent and has not provided a sufficient basis for recommendations concerning the dietary prevention of large-bowel cancer in humans.\n We conducted a clinical trial to assess the effects on the incidence of adenomas of reducing dietary fat to 25% of total calories and supplementing the diet with 25 g of wheat bran daily and a capsule of beta carotene (20 mg daily).\n We performed a randomized, partially double-blinded, placebo-controlled factorial trial in which half the patients were assigned to each intervention, resulting in seven intervention groups and one control group. Eligibility criteria included histologic confirmation of at least one colorectal adenoma and confidence expressed by the colonoscopist that all polyps had been removed. Dietary changes were individually initiated and monitored by dietitians and research nurses. At surveillance colonoscopy, the size and location of all polyps were recorded, and their histology was later centrally reviewed. Among 424 patients who were randomly assigned in the trial, 13 were found to be ineligible upon histologic review. Among the remaining 411, complete outcome data were collected from 390 at 24 months and from 306 at 48 months. All P values are from two-sided tests of statistical significance.\n There was no statistically significant prevention of total new adenomas with any of the interventions. We found a statistically non-significant reduced risk of large adenomas (> or = 10 mm) with the low-fat intervention: At 24 months, the odds ratio (OR) adjusted for potential confounders = 0.4 and 95% confidence interval (CI) = 0.1-1.1; at 48 months, OR = 0.3 and 95% CI = 0.1-1.0. Less and statistically nonsignificant reductions in the risk of large adenomas were found with wheat bran: At 24 months, OR = 0.8 and 95% CI = 0.3-2.2; at 48 months, OR = 0.8 and 95% CI = 0.3-2.5. Patients on the combined intervention of low fat and added wheat bran had zero large adenomas at both 24 and 48 months, a statistically significant finding (P = .03).\n Because only small numbers of patients were studied, our finding that the combination of fat reduction and a supplement of wheat bran reduced the incidence of large adenomas in this randomized, controlled trial must be treated with caution. The results do suggest, however, that these interventions may reduce the transition from smaller to larger adenomas, a step that may critically define those adenomas most likely to progress to malignancy.", "After polypectomy for adenomatous colorectal polyps, 201 persons were randomized to receive counselling on a diet low in fat (the lesser of 50 g/day or 20% of energy) and high in fibre (50 g/day) (LFHF), or to follow a normal western diet (ND), high in fat and low in fibre. After 12 months of counselling, fat consumption was about 25% of energy in the LFHF group and 33% in the ND group; fibre consumption was 35 g and 16 g respectively. After an average of two years of follow-up, an intention to treat analysis led to a ratio of cumulative incidence rates of 1.2 (95% CL 0.6-2.2) for recurrence of neoplastic polyps, a finding which suggests no significant difference between dietary groups over the period of observation. An exploratory analysis conducted among 142 persons with substantial diet counselling indicated a reduced risk of neoplastic polyp recurrence in women (RR = 0.5), associated with reduced concentrations of faecal bile acids while on the LFHF diet, but indicated an increased risk of recurrence in men (RR = 2.1), associated with increased faecal bile acids. Although a larger study would be needed to rule out the role of chance, these findings of gender-specific associations between diet counselling and both faecal bile acid concentrations and recurrence of colorectal neoplasia are consistent with recently published evidence of differences between genders.", "The Polyp Prevention Trial (PPT) is a multicenter randomized controlled trial to evaluate whether a low-fat, high-dietary fiber, high-fruit and -vegetable eating pattern will reduce the recurrence of adenomatous polyps of the large bowel. Men and women who had one or more adenomas removed recently were randomized into either the intervention (n = 1037) or control (n = 1042) arms. Food frequency questionnaire data indicate that PPT participants at the beginning of the trial consumed 36.8% of total energy from fat, 9.7 g of dietary fiber/1000 kcal, and 3.8 daily servings of fruits and vegetables. Baseline dietary characteristics, including intake of fat, fiber, and fruits and vegetables, as well as other macro- and micronutrients, were similar in the two study groups. The intervention participants receive extensive dietary and behavioral counseling to achieve the PPT dietary goals of 20% of total energy from fat, 18 g/1000 kcal of dietary fiber, and 5-8 daily servings (depending on total caloric intake) of fruits and vegetables. Control participants do not receive such counseling and are expected to continue their usual intake. Dietary intake in both groups is mentioned annually using a 4-day food record (also completed at 6 months by intervention participants only) and a food frequency questionnaire, with a 10% random sample of participants completing an annual unscheduled 24-h telephone recall. Blood specimens are drawn and analyzed annually for lipids and carotenoids. This article provides details on the rationale and design of the PPT dietary intervention program and describes the participant baseline dietary intake data characteristics.", "Some epidemiological studies have suggested that high dietary intake of calcium and fibre reduces colorectal carcinogenesis. Available data are not sufficient to serve as a basis for firm dietary advice. We undertook a multicentre randomised trial to test the effect of diet supplementation with calcium and fibre on adenoma recurrence.\n We randomly assigned 665 patients with a history of colorectal adenomas to three treatment groups, in a parallel design: calcium gluconolactate and carbonate (2 g elemental calcium daily), fibre (3.5 g ispaghula husk), or placebo. Participants had colonoscopy after 3 years of follow-up. The primary endpoint was adenoma recurrence. Analyses were by intention to treat.\n 23 patients died, 15 were lost to follow-up, 45 refused repeat colonoscopy, and five developed severe contraindications to colonoscopy. Among the 552 participants who completed the follow-up examination, 94 stopped treatment early. At least one adenoma developed in 28 (15.9%) of 176 patients in the calcium group, 58 (29.3%) of 198 in the fibre group, and 36 (20.2%) of 178 in the placebo group. The adjusted odds ratio for recurrence was 0.66 (95% CI 0.38-1.17; p=0.16) for calcium treatment and 1.67 (1.01-2.76, p=0.042) for the fibre treatment. The odds ratio associated with the fibre treatment was significantly higher in participants with baseline dietary calcium intake above the median than in those with intake below the median (interaction test, p=0.028)\n Supplementation with fibre as ispaghula husk may have adverse effects on colorectal adenoma recurrence, especially in patients with high dietary calcium intake. Calcium supplementation was associated with a modest but not significant reduction in the risk of adenoma recurrence." ]

[ "9848888", "11063952", "9715861", "11951094", "9510281", "10510990" ]

[ "Effect of the novel antiplatelet agent cilostazol on plasma lipoproteins in patients with intermittent claudication.", "A comparison of cilostazol and pentoxifylline for treating intermittent claudication.", "Cilostazol has beneficial effects in treatment of intermittent claudication: results from a multicenter, randomized, prospective, double-blind trial.", "Effect of cilostazol in patients with intermittent claudication: a randomized, double-blind, placebo-controlled study.", "Effect of cilostazol on walking distances in patients with intermittent claudication caused by peripheral vascular disease.", "A new pharmacological treatment for intermittent claudication: results of a randomized, multicenter trial." ]

[ "Cilostazol is an antiplatelet agent and vasodilator marketed in Japan for treatment of ischemic symptoms of peripheral vascular disease. It is currently being evaluated in the United States for treatment of symptomatic intermittent claudication (IC). Cilostazol has been shown to improve walking distance in patients with IC. In addition to its reported vasodilator and antiplatelet effects, cilostazol has been proposed to have beneficial effects on plasma lipoproteins. We examined the effect of cilostazol versus placebo on plasma lipoproteins in 189 patients with IC. After 12 weeks of therapy with 100 mg cilostazol BID, plasma triglycerides decreased 15% (P<0.001). Cilostazol also increased plasma high density lipoprotein cholesterol (HDL-C) (10%) and apolipoprotein (apo) A1 (5.7%) significantly (P<0.001 and P<0.01, respectively). Both HDL3 and HDL2 subfractions were increased by cilostazol; however, the greatest percentage increase was observed in HDL2. Individuals with baseline hypertriglyceridemia (>140 mg/dL) experienced the greatest changes in both HDL-C and triglycerides with cilostazol treatment. In that subset of patients, HDL-C was increased 12.2% and triglycerides were decreased 23%. With cilostazol, there was a trend (3%) toward decreased apoB as well as increased apoA1, resulting in a significant (9.8%, P<0.002) increase in the apoA1 to apoB ratio. Low density lipoprotein cholesterol and lipoprotein(a) concentrations were unaffected. Cilostazol treatment resulted in a 35% increase in treadmill walking time (P=0.0015) and a 9.03% increase in ankle-brachial index (P<0.001). These results indicate that in addition to improving the symptoms of IC, cilostazol also favorably modifies plasma lipoproteins in patients with peripheral arterial disease. The mechanism of this effect is currently unknown.", "We performed a randomized, double-blind, placebo-controlled, multicenter trial to evaluate the relative efficacy and safety of cilostazol and pentoxifylline.\n We enrolled patients with moderate-to-severe claudication from 54 outpatient vascular clinics, including sites at Air Force, Veterans Affairs, tertiary care, and university medical centers in the United States. Of 922 consenting patients, 698 met the inclusion criteria and were randomly assigned to blinded treatment with either cilostazol (100 mg orally twice a day), pentoxifylline (400 mg orally 3 times a day), or placebo. We measured maximal walking distance with constant-speed, variable-grade treadmill testing at baseline and at 4, 8, 12, 16, 20, and 24 weeks.\n Mean maximal walking distance of cilostazol-treated patients (n = 227) was significantly greater at every postbaseline visit compared with patients who received pentoxifylline (n = 232) or placebo (n = 239). After 24 weeks of treatment, mean maximal walking distance increased by a mean of 107 m (a mean percent increase of 54% from baseline) in the cilostazol group, significantly more than the 64-m improvement (a 30% mean percent increase) with pentoxifylline (P <0.001). The improvement with pentoxifylline was similar (P = 0.82) to that in the placebo group (65 m, a 34% mean percent increase). Deaths and serious adverse event rates were similar in each group. Side effects (including headache, palpitations, and diarrhea) were more common in the cilostazol-treated patients, but withdrawal rates were similar in the cilostazol (16%) and pentoxifylline (19%) groups.\n Cilostazol was significantly better than pentoxifylline or placebo for increasing walking distances in patients with intermittent claudication, but was associated with a greater frequency of minor side effects. Pentoxifylline and placebo had similar effects.", "Cilostazol is a new phosphodiesterase inhibitor that suppresses platelet aggregation and also acts as a direct arterial vasodilator. This prospective, randomized, placebo-controlled, parallel-group clinical trial evaluated the efficacy of cilostazol for treatment of stable, moderately severe intermittent claudication.\n Study inclusion criteria included age > or =40 years, initial claudication distance (ICD) on treadmill (12.5% incline, 3.2 km/h) between 30 and 200 m, and confirmation of diagnosis of chronic lower-extremity arterial occlusive disease. After stabilization and single-blind placebo lead-in, 81 subjects (62 male, 19 female) from 3 centers were randomized unequally (2:1) to 12 weeks of treatment with cilostazol 100 mg PO BID or placebo. Primary outcome measures included ICD and maximum distance walked (absolute claudication distance, or ACD). Secondary outcome measures included ankle pressures, subjective assessments of benefit by patients and physicians, and safety. Treatment and control groups were similar with respect to age, severity of symptoms, ankle pressures, and smoking status. Statistical analyses used intention-to-treat analyses for each of 77 subjects who had > or =1 treadmill test after initiation of therapy. Comparisons between groups were based on logarithms of ratios of ICD and ACD changes from baseline using ANOVA test at last treatment visit. The estimated treatment effect showed a 35% increase in ICD (P<0.01) and a 41% increase in ACD (P<0.01). There was no significant change in resting or postexercise ankle/brachial indexes. Patients' and physicians' subjective assessments corroborated the measured improvements in walking performance observed in the cilostazol-treated group.\n Cilostazol improved walking distances, significantly increasing ICD and ACD. The data suggest cilostazol is safe and well tolerated for the treatment of intermittent claudication.", "A multicenter, double-blind, randomized, placebo-controlled, parallel study was conducted to compare the efficacy and safety of cilostazol 100 mg and 50 mg, both administered twice daily, with that of placebo in patients with moderately severe intermittent claudication (IC) secondary to peripheral arterial disease.A total of 394 subjects 40 years of age or older with chronic, stable, symptomatic IC received cilostazol 100 mg twice daily, 50 mg twice daily, or placebo for 24 weeks. Subjects receiving cilostazol 100 mg twice daily experienced a 21% net improvement in maximal walking distance (MWD)compared with placebo subjects (p = 0.0003) and a 22% net improvement in distance walked to the onset of symptoms (PFWD) (p = 0.0015). Subjects who received cilostazol 50 mg twice daily also benefited from therapy, but not to a statistically significant degree (7% and 11% improvement in MWD and PFWD, respectively). Quality-of-life and functional status assessments corroborated these objective results. Cilostazol, in particular 100 mg twice daily, significantly improves symptoms in patients with IC.", "This study evaluated the effects of cilostazol on walking distances in patients with intermittent claudication (IC) caused by peripheral arterial occlusive disease.\n The study was a multicenter, randomized, double-blind, placebo-controlled trial. Two hundred thirty-nine patients with IC were randomly assigned to receive cilostazol (100 mg b.i.d.) or a placebo for 16 weeks. All patients underwent serial, variable-grade, constant-speed treadmill testing. Absolute claudication distance (ACD), assessed at the end of the 12-hour dosing interval (trough), was the primary end point. Secondary end points included ACD assessed 3 to 4 hours after dosing (peak) and initial claudication distances (trough and peak). Functional status measures, including the Medical Outcomes Scale (SF-36) and Walking Impairment Questionnaire, were used to assess subjective changes over the 16-week treatment period. Ankle-brachial indexes were calculated from Doppler-measured systolic pressures at every visit with treadmill testing.\n Patients treated with cilostazol demonstrated significant improvements over the placebo patients in ACD at all three time points tested after baseline (weeks 8, 12, and 16). Peak treadmill testing at weeks 8 and 12 also showed significant improvement in walking distances for cilostazol-treated patients over placebo-treated patients. At week 16, patients in the cilostazol group had a 96.4-meter (47%) increase in ACD compared with 31.4 meters (12.9%) for the placebo group (p < 0.001). In the SF-36, significant improvement was observed in the physical component subscale and the composite physical component score. In the Walking Impairment Questionnaire, improvements were significant in patient reports of walking speed and specific measures of walking difficulty. Ankle-brachial indexes improved in the cilostazol group (0.64 +/- 0.02 to 0.70 +/- 0.02) compared with the placebo group (0.68 +/- 0.02 to 0.69 +/- 0.02) (p < 0.0125). The most frequent adverse events were headache, abnormal stools (e.g. loose stools), diarrhea, and dizziness.\n Cilostazol significantly increased ACD at all measured time points and initial claudication distances at most time points. This agent may represent a new treatment option for patients with intermittent claudication.", "Effective medication is limited for the relief of intermittent claudication, a common manifestation of arterial occlusive disease. Cilostazol is a potent inhibitor of platelet aggregation with vasodilation effects.\n To evaluate the safety and efficacy of cilostazol for the treatment of intermittent claudication.\n Thirty-seven outpatient vascular medicine clinics at regional tertiary and university hospitals in the United States participated in this multicenter, randomized, double-blind, placebo-controlled, parallel trial. Of the 663 screened volunteer patients with leg discomfort, a total of 516 men and women 40 years or older with a diagnosis of moderately severe chronic, stable, symptomatic intermittent claudication were randomized to receive cilostazol, 100 mg, cilostazol, 50 mg, or placebo twice a day orally for 24 weeks. Outcome measures included pain-free and maximal walking distances via treadmill testing, patient-based quality-of-life measures, global assessments by patient and physician, and cardiovascular morbidity and all-cause mortality survival analysis.\n The clinical and statistical superiority of active treatment over placebo was evident as early as week 4, with continued improvement at all subsequent time points. After 24 weeks, patients who received cilostazol, 100 mg, twice a day had a 51% geometric mean improvement in maximal walking distance (P<.001 vs placebo); those who received cilostazol, 50 mg, twice a day had a 38% geometric mean improvement in maximal walking distance (P<.001 vs placebo). These percentages translate into an arithmetic mean increase in distance walked, from 129.7 m at baseline to 258.8 m at week 24 for the cilostazol, 100 mg, group, and from 131.5 to 198.8 m for the cilostazol, 50 mg, group. Geometric mean change for pain-free walking distance increased by 59% (P<.001) and 48% (P<.001), respectively, in the cilostazol, 100 mg, and cilostazol, 50 mg, groups. These results were corroborated by the results of subjective quality-of-life assessments, functional status, and global evaluations. Headache, abnormal stool samples or diarrhea, dizziness, and palpitations were the most commonly reported potentially drug-related adverse events and were self-limited. A total of 75 patients (14.5%) withdrew because of any adverse event, which was equally distributed between all 3 treatment groups. Similarly, there were no differences between groups in the incidence of combined cardiovascular morbidity or all-cause mortality.\n Compared with placebo, long-term use of cilostazol, 100 mg or 50 mg, twice a day significantly improves walking distances in patients with intermittent claudication." ]

[ "3688150" ]

[ "The benefits of group occupational therapy for patients with Parkinson's disease." ]

[ "The medical treatment of idiopathic Parkinson's disease has improved the quality of life and increased survival of patients with Parkinson's disease. However, as the illness progresses, impairments in daily living activities occur. A clinical trial for a group rehabilitation program was initiated to maintain the functional status of these patients. The research protocol consisted of a pretreatment evaluation, random assignment to experimental or control groups, and posttreatment evaluations after therapy, at 6 months and at 1 year. The results showed that the subjects of the treated experimental group maintained their functional status after 1 year, demonstrated a significant decrease of bradykinesia, and perceived a significant improvement in their psychological well-being. This study confirms the value of an occupational therapy group approach and its benefits to the functional independence, to the improvement of physical and motor symptoms, and to the quality of life of persons with Parkinson's disease." ]

[ "3052065", "3513567", "3513568", "3513569", "1481832" ]

[ "Folic acid treatment of fragile X males: a further study.", "Oral folic acid versus placebo in the treatment of males with the fragile X syndrome.", "High dose folic acid treatment of fragile (X) males.", "Folic acid treatment in males and females with fragile-(X)-syndrome.", "Double-blind, placebo-controlled crossover study of folinic acid (Leucovorin for the treatment of fragile X syndrome." ]

[ "Investigations of the effect of high dose folic acid treatment of fragile X syndrome in males has produced mixed results. However, no study had examined the possible drug effects of folic acid on non-fragile X control males. Therefore, we examined the effect of folic acid on fragile X males using non-fragile X control males. Subjects were assigned randomly to an ABA or BAB design. Duration of either folic acid or placebo condition was 4 months. Folic acid or placebo was given in a double-blind fashion. At the end of each condition, the subjects' behavior was assessed. At the end of the study, parents were asked to complete a questionnaire. Using parents' responses, we examined 22 items on the Autistic Descriptors Checklist and two subscales from the Vineland Adaptive Behavior Scale which corresponded to areas of behavior parents' noted to have shown improvement. We did not find significant differences between fragile X males and control males, within subjects, nor across folic acid and placebo conditions. Thus, our follow-up study confirms and extends our original findings, as well as those of other researchers: namely, that no dramatic changes in behavior result from high dose folic acid. Moreover, subtle improvements observed in earlier investigations were not confirmed.", "A double-blind, crossover study of a 10 mg folic acid per day (vs. placebo) treatment was carried out in 25 fra(X) males (ages 1-31 years). Each treatment period lasted 6 months. Before, during and after the study, the patients were assessed blindly with psychological, language and behavioral evaluations, and parent or caretaker reports were collected. Standardized testing did not show statistically significant changes in the group as a whole; psychological testing demonstrated a statistically significant improvement on folic acid in the prepubertal males. After uncoding, caretaker or parent reports also demonstrated behavioral improvements in the prepubertal males while being treated with folic acid.", "We conducted an experimental trial of high-dose folic acid given to five males, ages 8 to 26 years, with the fra(X) syndrome. In this double blind study, each subject received 250 mg per day of folic acid for 3 months, followed by placebo for 3 months, and folic acid again for an additional three months. Based on IQ tests, behavior ratings, the Autistic Descriptors Checklist, and parental ratings, there was little evidence to suggest any positive effects seen during the administration of high-dose folic acid. Therefore, this study has provided little support for a hypothesis of benefit of high-dose folic acid in the treatment of the fra(X) syndrome.", "Ten males with the fragile X (fra(X] syndrome were treated with folic acid (10 mg/day) for 4 months in a double-blind design study. To eight heterozygotes with mental impairment and fra(X), folic acid was given for 4 months (10 mg/day) in an effort to study possible beneficial effects of folic acid. Psychological and cytogenetic testing were carried out during the trial. There was no improvement in concentration, fine motor co-ordination, or comprehension in the adult male and female patients of the study. One patient showed improvement under a control medications. In the females, improvement was seen only in the youngest patient, a 5-year-old girl. Folate treatment does not seem to be effective in fra(X) adults, but may have some effect in children of both sexes with the disorder. Cytogenetic studies using peripheral lymphocytes showed that the fra(X) frequency decreased significantly (t = 0.00856; 1% level) only in cells cultured in a folic acid-free medium but not in cells cultured in a medium with added antifolate (methotrexate). This shows a \"contamination effect\" of folate-free culture medium after oral folic acid treatment of these patients. The decrease of fra(X) involves primarily the early-replicating X when culturing with folic acid-free medium. A synergistic suppression effect of \"external folate\" and BrdU is the most likely explanation of this phenomenon.", "We conducted a randomized, double-blind, placebo-controlled crossover study of folinic acid therapy (dl-Leucovorin, 15 mg/day) or placebo for males with Fragile X (fra(x)) syndrome. Twenty-one patients were enrolled in the study. The treatment periods were 3 months in length. Patients were followed with chemistry panels and complete blood counts. No differences between placebo and treatment phases were noted in any laboratory parameter. Instruments to measure functioning were the Vineland Adaptive Behavioral Scales, Peabody Picture Vocabulary Test-Revised, Conners Parent and Teaching Rating Scales, the ADD-H: Comprehensive Teacher's Rating Scales (ACTeRS), and a questionnaire designed by the investigators. At the crossover point, 2 parents requested to withdraw from the study because they felt their children had made dramatic gains during the first half of the study and had lost those gains after the crossover point. Both parents had accurately predicted that their sons were receiving folinic acid during the first half of the study. However, no statistically significant differences could be demonstrated between the treatment and placebo phases of the study with any instrument when the results were averaged over the entire cohort. After the conclusion of the study, approximately one-half of the parents believed that their children had benefitted from the folinic acid therapy and elected to continue treatment. Thus far, no significant side effects have been noted from long-term folinic acid therapy so we are offering all Fragile X patients a 3-month trial of medication." ]

[ "4868835", "5331043", "12681025", "12502668", "9702435", "9822940", "14770192", "10440592", "1338388", "994969", "788327", "380178", "12087008", "10971792", "12406041", "7648804", "11874427", "1317828", "11220553", "8181239", "12941710", "813947", "5940969", "14597860", "14199468", "11837755", "12032111", "361463", "11220522", "14693963", "329259", "11679464", "13906420" ]

[ "Trial of a long-acting preparation of diethylpropion in obese diabetics.", "Obesity in diabetes. Some considerations on treatment.", "Latin-American trial of orlistat for weight loss and improvement in glycaemic profile in obese diabetic patients.", "A randomized trial of sibutramine in the management of obese type 2 diabetic patients treated with metformin.", "Role of orlistat in the treatment of obese patients with type 2 diabetes. A 1-year randomized double-blind study.", "Cimetidine reduces weight and improves metabolic control in overweight patients with type 2 diabetes.", "Health-related quality of life in a randomised placebo-controlled trial of sibutramine in obese patients with type II diabetes.", "Absence of cardiac valve dysfunction in obese patients treated with sibutramine.", "Fluoxetine therapy in obese diabetic and glucose intolerant patients.", "The effect of an anorectic agent (Mazindol) on control of obese diabetics.", "[Mazindol in the treatment of obese diabetic patients].", "[Weight reduction in obese diabetics: a double-blind study of diethylpropionate (author's transl)].", "Effect of orlistat in overweight and obese patients with type 2 diabetes treated with metformin.", "The effect of orlistat on body weight and coronary heart disease risk profile in obese patients: the Swedish Multimorbidity Study.", "The effects of orlistat on body weight and glycaemic control in overweight patients with type 2 diabetes: a randomized, placebo-controlled trial.", "A study of fluoxetine in obese elderly patients with type 2 diabetes.", "Role of sibutramine in the treatment of obese Type 2 diabetic patients receiving sulphonylurea therapy.", "Fluoxetine treatment of the obese diabetic.", "Weight loss with sibutramine improves glycaemic control and other metabolic parameters in obese patients with type 2 diabetes mellitus.", "Fluoxetine in the treatment of obese type 2 diabetic patients.", "One-year outcome of a combination of weight loss therapies for subjects with type 2 diabetes: a randomized trial.", "Double-blind clinical evaluation of mazindol (42-548) in obese diabetics.", "Weight control in obese diabetics. A comparative trial of Filon and phenmetrazine.", "Orlistat in hypertensive overweight/obese patients: results of a randomized clinical trial.", "[EXPERIENCES WITH THE THERAPEUTIC USE OF AN ANOREXIC SUBSTANCE ON DIABETES OF THE OBESE].", "Clinical evaluation of sibutramine in obese type 2 diabetic patients refractory to dietary management.", "Clinical efficacy of orlistat therapy in overweight and obese patients with insulin-treated type 2 diabetes: A 1-year randomized controlled trial.", "Double blind clinical trial of mazindol on weight loss blood glucose, plasma insulin and serum lipids in overweight diabetic patients.", "Sibutramine is effective for weight loss and diabetic control in obesity with type 2 diabetes: a randomised, double-blind, placebo-controlled study.", "Effects of moderate weight loss and orlistat on insulin resistance, regional adiposity, and fatty acids in type 2 diabetes.", "A controlled trial of phentermine in obese diabetic patients.", "Effects of sibutramine in obese female subjects with type 2 diabetes and poor blood glucose control.", "Use of diethylpropion in obese diabetic patients." ]

[ "nan", "nan", "To determine if obese non-insulin-dependent diabetic patients lose more weight when treated for 24 weeks (6 months) with orlistat (120 mg t.i.d.), in conjunction with a hypocaloric diet plus behavioural counselling, than when treated by placebo (t.i.d.) plus similar instructions. The secondary objectives were to evaluate the effects on glucose profile and to determine the tolerability and safety of orlistat.\n Double-blind, parallel, randomized, placebo-controlled, multicentre study.\n Obese, non-insulin-dependent diabetic patients, aged 18-70 years old, with BMI > 27 kg/m2, evaluated at 10 Latin-American centres, in five countries. EFFICACY AND TOLERABILITY MEASUREMENTS: After screened, eligible patients passed by a 2-week placebo run-in period receiving a hypocaloric diet. On day 0, patients were randomized to orlistat or placebo for 24 weeks. At each visit, body weight, blood pressure and waist circumference were measured. At the screening visit, baseline visit (week 0), and at weeks 8, 16 and 24, a central laboratory was in charge of measuring fasting glucose and insulin, HbA1c, postprandial glucose and insulin, fasting total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and postprandial triglycerides. Other safety laboratory assessments were measured locally at the screening visit, baseline visit and at the end of the study. Adverse events were assessed at each visit from baseline.\n After 24 weeks of treatment, the orlistat group lost an average of 4.7% of initial body weight vs. 3.0% in the placebo group (p = 0.0003). A greater weight loss was achieved in the orlistat compared with the placebo group (4.24 +/- 0.23 vs. 2.58 +/- 1.46 kg, p = 0.0003). Almost twice as many patients receiving orlistat (30% vs. 17%) lost > or = 5% of initial body weight (p = 0.003). Orlistat treatment plus diet compared to placebo plus diet was associated with significant improvement in glycaemic control, as reflected in decreases in HbA1c (p = 0.04), fasting plasma glucose (p = 0.036) and postprandial glucose (p = 0.05). Orlistat-treated patients had a mean decrease in glucose levels of 1.00 +/- 0.34 mmol/l [3.7%] vs. 0.01 +/- 0.30 mmol/l for placebo group, at week 24 and an absolute decrease of HbA1c of 0.61 +/- 0.15 vs. a decrease of 0.22 +/- 0.14% in the placebo group. Orlistat therapy also resulted in significantly greater improvements than placebo in lipid profile, with reductions in total cholesterol (p = 0.0001) and LDL-cholesterol (p = 0.002). Mild to moderate transient gastrointestinal events were reported, mainly with orlistat treatment, but their association with withdrawal from the study was low.\n Orlistat is a useful and an effective therapy in obese diabetic patients, promoting clinically significant weight loss and improved glycaemic control and lipid profile.", "To evaluate the effects of sibutramine (15 and 20 mg/day) on weight, metabolic control, and blood pressure in metformin-treated obese subjects with type 2 diabetes.\n A 12-month randomized prospective placebo-controlled double-blind study was performed. It included 21 primary and secondary care centers in England, Canada, France, and Belgium. A total of 195 subjects (44% male) with type 2 diabetes and a BMI >27 kg/m(2) were studied. Changes were assessed in weight, blood pressure and resting heart rate, HbA(1c), fasting glucose, and lipids.\n Sibutramine induced significant weight loss (P < 0.001) with both 15 mg/day (5.5 +/- 0.6 kg at 12 months) and 20 mg/day (8.0 +/- 0.9 kg), whereas placebo did not (0.2 +/- 0.5 kg). Weight loss > or = 10% was achieved by 14 and 27% of subjects receiving 15 and 20 mg, respectively, but by none given placebo. Glycemic control improved in parallel with weight loss, and subjects who lost > or = 10% weight showed significant decreases in both HbA(1c) (1.2 +/- 0.4%, P < 0.0001) and fasting plasma glucose (1.8 mmol/l, P < 0.001). HDL cholesterol increased slightly with the higher dose, whereas plasma triglycerides fell with both doses, especially in subjects with weight loss of > or = 10% (a 29% decrease, P < 0.01). Treatment was generally well tolerated. Sibutramine treatment raised sitting diastolic blood pressure by > or = 5 mmHg in a higher proportion of patients than did placebo (43% with 15 mg/day vs. 25% with placebo, P < 0.05), but this effect was less evident in subjects who had a weight loss of > or = 10% weight. Pulse rate increased significantly more with sibutramine, being > or = 10 bpm higher in 42% of treated patients versus 17% with placebo (P < 0.01).\n Sibutramine can be an effective adjunct to metformin treatment in selected obese type 2 diabetic subjects and improves metabolic control in individuals who lose weight.", "Obesity is an important risk factor for type 2 diabetes. Weight loss in patients with type 2 diabetes is associated with improved glycemic control and reduced cardiovascular disease risk factors, but weight loss is notably difficult to achieve and sustain with caloric restriction and exercise. The purpose of this study was to assess the impact of treatment with orlistat, a pancreatic lipase inhibitor, on weight loss, glycemic control, and serum lipid levels in obese patients with type 2 diabetes on sulfonylurea medications.\n In a multicenter 57-week randomized double-blind placebo-controlled study, 120 mg orlistat or placebo was administered orally three times a day with a mildly hypocaloric diet to 391 obese men and women with type 2 diabetes who were aged > 18 years, had a BMI of 28-40 kg/m2, and were clinically stable on oral sulfonylureas. Changes in body weight, glycemic control, lipid levels, and drug tolerability were measured.\n After 1 year of treatment, the orlistat group lost 6.2 +/- 0.45% (mean +/- SEM) of initial body weight vs. 4.3 +/- 0.49% in the placebo group (P < 0.001). Twice as many patients receiving orlistat (49 vs. 23%) lost > or = 5% of initial body weight (P < 0.001). Orlistat treatment plus diet compared with placebo plus diet was associated with significant improvement in glycemic control, as reflected in decreases in HbA1c (P < 0.001) and fasting plasma glucose (P < 0.001) and in dosage reductions of oral sulfonylurea medication (P < 0.01). Orlistat therapy also resulted in significantly greater improvements than placebo in several lipid parameters, namely, greater reductions in total cholesterol, (P < 0.001), LDL cholesterol (P < 0.001), triglycerides (P < 0.05), apolipoprotein B (P < 0.001), and the LDL-to-HDL cholesterol ratio (P < 0.001). Mild to moderate and transient gastrointestinal events were reported with orlistat therapy, although their association with study withdrawal was low. Fat-soluble vitamin levels generally remained within the reference range, and vitamin supplementation was required in only a few patients.\n Orlistat is an effective treatment modality in obese patients with type 2 diabetes with respect to clinically meaningful weight loss and maintenance of weight loss, improved glycemic control, and improved lipid profile.", "To investigate the weight-reducing effect of cimetidine in overweight patients with Type 2 diabetes.\n A 12-week clinical intervention study of 400 mg cimetidine prescribed three times daily in a randomised, double-blind, placebo-controlled design.\n Forty-three overweight patients with Type 2 diabetes (age 18-65 y, body mass index (BMI) 27.2-48.2 kg/m2).\n Body weight, BMI, body fat, waist and hip circumference, waist/hip ratio, blood pressure, fasting blood glucose, HbA1c, plasma concentrations of insulin, insulin/glucose ratio and lipids at the start and after 12 weeks, and daily recordings of appetite.\n Subjects given cimetidine (n = 19) and placebo (n = 24) lost 5.0 +/- 2.2 kg (mean +/- s.d.) and 1.3 +/- 1.1 kg, respectively. Significant reductions were observed in appetite, body fat (29.9 +/- 6.6% to 25.3 +/- 7.4%), waist circumference (111.5 +/- 10.3 cm to 107.4 +/- 10.6 cm), waist/hip ratio (0.96 +/- 0.08 to 0.94 +/- 0.08), and systolic and diastolic blood pressure (reductions of 6.9 +/- 11.4 mm Hg and 6.0 +/- 6.6 mm Hg, respectively) in cimetidine group only. Significant decreases in fasting concentrations of blood glucose, HbA1c, plasma insulin, insulin/glucose ratio, plasma triglycerides and a significant increase in plasma high-density lipoprotein cholesterol were observed in the cimetidine group only.\n Cimetidine reduces appetite and body weight, and improves metabolic control in overweight subjects with Type 2 diabetes.", "We evaluated the effects of 12-month treatment with sibutramine 15 mg daily compared with placebo on health-related quality of life (HRQL) in obese type II diabetes patients. We examined the associations between the changes in HRQL and in weight, glycaemic control, and haemodynamic variables. We also explored the predictive value of HRQL and its changes early during treatment.\n A randomised clinical trial. The subjects were enrolled in a 2-week single-blind run-in period with a modestly hypocaloric diet (700 kcal daily deficit) and then randomised to receive either sibutramine 15 mg (n=114, 60% female) or placebo (n=122, 58% female) once daily with the hypocaloric diet for 12 months.\n Obese (mean BMI 36 kg/m(2) and age 54 y) type II diabetes patients untreated with antidiabetic medications.\n The main outcome measures included body weight and HRQL (the RAND 36-Item Health Survey 1.0).\n The mean weight loss was greater in the sibutramine group (-7.1 kg) than in the placebo group (-2.6 kg, P<0.001). The baseline HRQL was relatively high. There were no significant differences between the treatment groups in glycaemic control or in any of the RAND-36 scales during the study. The scores on physical functioning (PF) and health change (HC) since last year improved in both groups and this improvement was related to weight loss. When HRQL changes were examined in categories of weight loss, the scores on PF and HC increased with >/=5% weight loss, but the scores on vitality (V) and general health (GH) increased only after >/=15% weight loss. Decrease in HbA1c was associated with increases in the scores of PF, GH, V, mental health, and HC. In the sibutramine group, the increase in diastolic blood pressure was associated with the decrease in the scores of PF, physical role functioning, emotional role functioning (ERF), social functioning (SF), and bodily pain. High baseline scores on ERF and SF, and low scores on V predicted weight loss at 12 months. Also, increasing scores on PF and V during the first 3 months predicted weight loss at 12 months. The sum of four dichotomised HRQL variables (baseline ERF >/=75=1 and <75=0; baseline SF>/=80=1 and <80=0; 3-month change in PF>0=1 and </=0=0; 3-month change in V>0=1 and </=0=0) predicted weight loss: In the group with sum 0, the mean(s.d.) weight change at 12 months was 0.0(2.6)% and with sum 4 it was -9.0(8.1)% of baseline weight.\n Despite the superior weight loss, sibutramine 15 mg daily did not produce HRQL benefits over placebo when measured with the generic RAND-36 in obese type II diabetes patients. PF and HC since last year improved with >/=5% weight loss, but >/=15% weight loss was needed to achieve a cluster of HRQL improvements. The decrease in HbA1c was associated with many HRQL benefits. Poor baseline HRQL and the improvement observed in the first months of treatment may prove to be useful in predicting success in long-term weight loss.", "Serotonin-releasing agents prescribed as weight-loss medications have been implicated as a cause of acquired aortic and mitral valve abnormalities. Sibutramine hydrochloride (MERIDIA) is a serotonin and norepinephrine reuptake inhibitor with proven efficacy of weight reduction. The purpose of this study was to determine the incidence of cardiac valve disease in sibutraminetreated patients.\n Obese patients with type 2 diabetes mellitus enrolled in an ongoing double-blind, placebo-controlled, parallel-arm, 12-month study of sibutramine (followed by a 12-month open label extension) underwent transthoracic echocardiographic imaging and color Doppler interrogation for assessment of cardiac valve anatomy and function.\n A total of 210 patients were evaluated. Of these, 133 were receiving sibutramine (72 in the double-blind period), and 77 were receiving placebo. The mean+/-Standard Deviation age was 54+/-9 years, and the mean duration of treatment was 229+/-117 days (approximately 7.6 months). The prevalence of left-sided cardiac valve dysfunction was low and similar for the two treatment groups (sibutramine 3/133, or 2.3%; placebo 2/77, or 2.6%). All five cases were cases of aortic insufficiency; four were mild, one was severe (in a placebo patient). All three sibutramine cases were patients over age 50; two had a history of systemic hypertension.\n The prevalence of left-sided cardiac valve dysfunction was not higher than background in obese patients treated with sibutramine for an average of 7.6 months.", "A double-blind placebo-controlled trial was conducted, involving 97 obese diabetic and glucose intolerant patients receiving either 60 mg fluoxetine daily (47 patients) or a placebo (50 patients); a similar calorie-restricted diet was prescribed to all patients. Weight loss was significantly higher in the fluoxetine-treated patients, whose diabetic status improved. Drop-out rate was not significantly different for both groups of patients.", "The use of an anorectic drug (mazindol) did not significantly interfere with the therapy needed to maintain control in obese diabetics. In two of four insulin-requiring patients, a reduction of the insulin requirement occurred when weight was lost. No change was needed in oral hypoglycaemic therapy in the six weeks of the trial.", "nan", "In a double-blind study 40 overweight maturity-onset diabetics on a weight-reducing diet were randomly assigned to treatment with either the appetite-suppressant diethylpropion hydrochloride (Tenuate), or placebo. After treatment for 8 weeks the mean weight loss achieved by each group was 4.9 and 3.3%, respectively. This approximately equal weight loss was too slight to exert any significant effect on glucose tolerance. Thus, an additional effect of this anorexiant in comparison with diet restriction alone, as described in obese non-diabetic subjects, is not evident in the case of obese diabetic patients.", "The purpose of this study was to assess the effect of orlistat, a gastrointestinal lipase inhibitor, on body weight, glycemic control, and cardiovascular risk factors in metformin-treated type 2 diabetic patients.\n A 1-year multicenter, randomized, double-blind, placebo-controlled trial of 120 mg orlistat t.i.d. (n = 249) or placebo (n = 254) combined with a reduced-calorie diet was conducted in overweight and obese patients with suboptimal control of type 2 diabetes.\n After 1 year of treatment, mean (+/-SE) weight loss was greater in the orlistat than in the placebo group (-4.6 +/- 0.3% vs. -1.7 +/- 0.3% of baseline wt, P < 0.001). Orlistat treatment caused a greater improvement in glycemic control than placebo, as evidenced by a greater reduction in serum HbA(1c), adjusted for changes in metformin and sulfonylurea therapy (-0.90 +/- 0.08 vs. -0.61 +/- 0.08, P = 0.014); a greater proportion of patients achieving decreases in HbA(1c) of > or = 0.5 and > or = 1.0% (both P < 0.01); and a greater reduction in fasting serum glucose (-2.0 +/- 0.2 vs. -0.7 +/- 0.2 mmol/l, P = 0.001). Compared with the placebo group, patients treated with orlistat also had greater decreases in total cholesterol, LDL cholesterol, and systolic blood pressure (all P < 0.05). Although more subjects treated with orlistat experienced gastrointestinal side effects than placebo (83 vs. 62%, P < 0.05), more subjects in the placebo group withdrew prematurely from the study than in the orlistat group (44 vs. 35%, P < 0.05).\n Orlistat is a useful adjunctive treatment for producing weight loss and improving glycemic control, serum lipid levels, and blood pressure in obese patients with type 2 diabetes who are being treated with metformin.", "To assess the effect of orlistat on body weight and cardiovascular risk amongst obese patients at high coronary risk.\n After screening, patients entered a two-week single-blind placebo lead-in period, during which they followed a mildly hypocaloric diet, before being randomized to double-blind treatment with either orlistat 120 mg or placebo three times daily, in conjunction with dietary intervention for 1 years.\n The study was conducted at 33 primary care centres in Sweden.\n A total of 382 obese adults (body mass index 28-38 kg m-2) with type 2 diabetes, hypercholesterolaemia and/or hypertension were recruited, of whom 376 were randomized to orlistat (n = 190) or placebo (n = 186).\n Change in body weight, waist and hip circumferences, blood pressure, serum lipid profile, fasting glucose and HbA1c.\n After 1 years, mean weight loss was significantly greater with orlistat compared with placebo (5.9% vs. 4.6%; P < 0.05). Moreover, significantly more orlistat-treated patients than placebo recipients maintained weight loss of > or = 5% (54.2% vs. 40.9%; P < 0.001). Orlistat was also associated with significantly greater improvements than placebo in total serum cholesterol (- 3.3% vs. -0.5%; P < 0.05), LDL-cholesterol (- 7.0% vs. -1.1%; P < 0.05), fasting glucose (5.1% vs. -0.1%; P < 0.01) and HbA1c (- 2.7% vs. -0.5%; P < 0.05). Similar results were reported for the subgroup of patients with type 2 diabetes. Orlistat was well tolerated.\n Treatment with orlistat in conjunction with diet promotes significantly greater weight loss and cardiovascular risk factor reduction than diet alone amongst obese patients at high risk of future coronary events.", "To assess the long-term effects of orlistat on body weight, glycaemic control and cardiovascular risk factors in overweight patients with type 2 diabetes.\n This was a multicentre, randomized, placebo-controlled study with a 4-week placebo plus diet lead-in period and a 48-week, double-blind treatment period. Overweight or obese adults [body mass index (BMI) >or= 28 kg/m2] with HbA1c of 6.5-11% and clinical type 2 diabetes were randomized to orlistat (120 mg t.i.d. n = 189) or placebo (n = 180) in conjunction with a low-calorie diet. Patients had either received sulphonylurea therapy for at least 2 months before the study or were not receiving any antidiabetic medication (the majority of which were drug-naïve).\n After 1 year, patients in the orlistat group lost significantly more weight than patients in the placebo group (-5.4% vs. -3.6%; p = 0.006). Moreover, significantly more patients achieved weight loss of >or= 5% with orlistat compared with placebo (51.3% vs. 31.6%; p = 0.0001). Patients treated with orlistat also had significantly greater improvements than placebo-treated patients in HbA1c (-0.9% vs. -0.4%; p < 0.001), fasting glucose (-1.6 vs.-0.7 mmol/l; p = 0.004) and post-prandial glucose (-1.8 vs. -0.5 mmol/l; p = 0.003). In addition, orlistat-treated patients had a significantly greater reduction in LDL cholesterol compared with placebo. Overall, orlistat had a similar safety profile to placebo, with the exception of a higher incidence of generally mild and transient gastrointestinal events known to be associated with the mode of action of orlistat.\n Treatment with orlistat plus diet resulted in significant weight loss, improved glycaemic control and cardiovascular risk factor profile in overweight patients with type 2 diabetes.", "In order to establish the safety and efficacy of fluoxetine in subjects over 60 years of age with Type 2 diabetes, a randomized, double-blind, parallel study of 30 obese subjects was undertaken, comparing the use of fluoxetine 60 mg daily with placebo. Subjects were diet controlled with an HbA1 < 14% (reference range 6-9%) and BMI > 29 kg m2. Those taking fluoxetine had a median weight loss of 2.6 kg at 3 months (p < 0.001) and 3.9 kg at 6 months (p < 0.02), compared with weight loss in the placebo group of 0.1 kg and 0.0 kg at 3 and 6 months, respectively. Improved glycaemic control was also demonstrated in the fluoxetine group compared with placebo, initial HbA1 levels of 8.0% vs 8.7% (NS) falling at 4 months by 0.9% (p < 0.02) and at six months by 0.9% (p < 0.02). No sustained improvement in fasting blood glucose levels was demonstrated. Reporting of adverse events was similar in both groups. Fluoxetine in the short term aids weight loss and improves glycaemic control without a significant increase in adverse events in elderly Type 2 diabetic subjects.", "To investigate whether the satiety-inducing agent sibutramine affected body weight and associated anthropometry in overweight and obese (body mass index (BMI) > 27) Type 2 diabetic patients on sulphonylurea therapy.\n A randomized, placebo-controlled trial was undertaken in 134 patients with stable metabolic control on chronic sulphonylurea therapy. Patients were placed on moderate caloric restriction and received treatment with either sibutramine (15 mg/day) or placebo for 6 months.\n Fifty-three of 69 sibutramine-treated and 57/65 placebo-treated patients completed the study. Both groups showed progressive weight loss. At the end of the trial weight loss was two times greater in the sibutramine group (mean +/- SEM; -4.5 +/- 0.5 kg) than placebo (-1.7 plus minus 0.5 kg, P < 0.001 vs. sibutramine). There was a trend for more patients to lose > 5% of initial body weight in the sibutramine group than placebo. BMI (P < 0.001) and waist circumference (P < 0.001) were also decreased to a greater extent by sibutramine. Mean reductions in HbA(1c) were commensurate with weight loss in both the sibutramine and placebo (- 0.78 +/- 0.17% and -0.73 +/- 0.23%; P = 0.84). Sibutramine was well tolerated with only two patients withdrawn due to potentially drug-related serious adverse events (palpitations).\n Sibutramine, in conjunction with moderate caloric restriction, enhances weight loss and reduces waist circumference in overweight and obese Type 2 diabetic patients receiving sulphonylurea therapy. This is associated with additional improvements in glycaemic control in a limited number of patients losing > or = 10% of their baseline body weight.", "Fluoxetine, an inhibitor of serotonin re-uptake, has been shown to cause weight loss in humans and animals. In order to determine the effects in diabetic subjects, 48 male and female, obese, type 2 non-insulin dependent diabetics being treated with insulin were randomized to receive fluoxetine 60 mg or placebo once daily in double blind fashion for 24 weeks. In all subjects, this treatment was preceded by four weeks and followed by six weeks of single blind placebo washout treatment. Subjects performed daily home glucose monitoring and were given instruction in a 1200 kcal American Diabetes Association diet. Fluoxetine treated subjects who completed the trial (n = 16) lost more weight than placebo treated subjects (n = 20) (9.3 +/- 2.4 vs. 1.9 +/- 2.9 kg +/- s.e.m, P less than 0.05). Subjects in the fluoxetine group also showed a greater percentage decrease in insulin dose than those in the placebo group (46.9 +/- 7.6% vs. 19.3 +/- 7.6%, P less than 0.01). During active treatment, the change in serum glucose levels did not differ between the two groups, while glycohemoglobin fell more in fluoxetine treated subjects than in placebo treated subjects at two of four follow-up visits. These results suggest that fluoxetine may be of benefit in the treatment of obese patients with type 2 non-insulin dependent diabetes mellitus.", "To determine the efficacy and tolerability of sibutramine hydrochloride in obese patients whose type 2 diabetes was poorly controlled on diet alone or with an oral antidiabetic agent.\n This study was a 24-week, double-blind, multicentre trial following a 5-week placebo run-in period. One hundred and seventy-five obese (body mass index (b.m.i.) > or =27 kg/m2) patients with poorly controlled type 2 diabetes mellitus were randomized either to sibutramine (n = 89; mean age 53.5 years; mean weight 99.3 kg) or placebo (n = 86; mean age 55 years; mean weight 98.2 kg) at 16 participating centres. To achieve moderate calorie restriction (deficit > or = 250-500 kcal/day), individual dietary counselling was accompanied by either placebo or sibutramine (initial dosage of 5 mg/day titrated up by 5 mg biweekly through week 6, and maintained at 20 mg through week 24). The main outcome measures included changes in weight, b.m.i., waist and hip circumference, glycaemic control, lipid profile, and quality of life, and evaluation of reported adverse events.\n Sixty-seven per cent of sibutramine patients and 71% of placebo patients completed the study. At week 24 when comparing those who completed the course, sibutramine compared with placebo patients showed significantly greater (p < 0.001) absolute (-4.3 vs. -0.4 kg) and percentage (-4.5% vs. -0.5%) weight loss. Weight loss > or =5% or 10% was achieved by 33% and 8% of sibutramine patients, respectively, but no placebo patients (p < 0.03 or better). Improvement in glycaemic control was correlated with weight loss (p < 0.001). In 5% and 10% weight-loss responders, mean treatment differences were -0.53% and -1.65% (p < or = 0.05), respectively, for HbA1c, and -1.4 mmol/l (p < or =0.05) and -3.8 (p < or =0.05) mmol/l for fasting plasma glucose. Sibutramine patients also showed improvements in fasting insulin, triglycerides, HDL cholesterol, and quality-of-life assessments. Overall, sibutramine was well tolerated compared with the placebo. Sibutramine treatment was associated with small mean increases in blood pressure (BP) and pulse, although an increase in BP was not seen in sibutramine-treated patients who lost > or = 5% of their weight.\n Sibutramine produced statistically and clinically significant weight loss when used in combination with recommendations for moderate caloric restriction. This weight loss was associated with improvements in metabolic control and quality of life, and sibutramine was generally well tolerated in obese patients with type 2 diabetes.", "In a 12-month randomly allocated double-blind trial in 19 obese Type 2 diabetic patients, fluoxetine 60 mg daily compared to placebo produced a significant fall in median body weight after 3 months (3.8 kg), 6 months (6.5 kg), 9 months (7.1 kg) and at 1 year (5.8 kg). Median fasting blood glucose and HbA1c levels fell significantly after 3 months (1.9 mmol l-1) and 1.7%, respectively) and 6 months (1.8 mmol l-1 and 1.7%) but neither showed a significant difference to placebo after 9 or 12 months therapy with fluoxetine. There were no significant changes in serum cholesterol levels in the year but patients on fluoxetine showed a significant fall in serum triglyceride level (0.5 mmol l-1) after 3 months therapy but not thereafter. Compared to placebo there was a significant fall in median energy intake on fluoxetine after 3 months (257 kcal day-1) and 6 months (199 kcal day-1) but this difference was not significant at 9 or 12 months. There was also a significant fall in carbohydrate intake after 3 months (30 g day-1) and 6 months (23 g day-1) on fluoxetine as well as a significant fall in carbohydrate intake expressed as a percentage of the total daily energy intake; 5.9% at 3 months, 6.1% at 6 months, and 4.0% at 9 months. There were no significant effects on protein or fat intake except a significant increase in the intake of fat expressed as a percentage of daily energy intake, 5.9% after 6 months. Two of the nine patients on fluoxetine dropped out of the study due to gastrointestinal side-effects. Fluoxetine might prove to be a useful adjunct therapy in obese Type 2 diabetic patients where short-term weight loss and fall in carbohydrate intake and an improvement in glycaemia are indicated.", "The purpose of this study was to evaluate the effects of a combination weight loss program using intermittent low-calorie diets, energy-controlled meal replacement products, and sibutramine on weight loss, diabetes control, and cardiovascular risk factors in overweight or obese subjects with type 2 diabetes.\n Overweight or obese individuals with type 2 diabetes treated with diet or oral medication were randomly assigned to either a standard therapy or combination therapy group. Both groups received a standardized program to facilitate weight loss. The combination therapy group also received 10-15 mg sibutramine daily, low-calorie diets using meal replacement products for 1 week every 2 months, and between low-calorie diet weeks, once daily use of meal replacement product and snack bars to replace one usual meal and snack. Primary outcome measures were changes in body weight, glycemic control, plasma lipids, blood pressure, pulse, and body composition at 1 year.\n At 1 year, combination therapy, compared with standard therapy, resulted in significantly more weight loss (-7.3 +/- 1.3 kg vs. -0.8 +/- 0.9 kg, P < 0.001) and reduction in HbA(1c) (-0.6 +/- 0.3 vs. 0.0 +/- 0.2%, P = 0.05). Combination therapy resulted in reduced requirement for diabetes medications and decreased fat mass and lean body mass. A 5-kg decrease in weight at 1 year was associated with a decrease of 0.4% in HbA(1c) (P = 0.006). Changes in fasting glucose, lipids, pulse, and blood pressure did not differ between groups.\n This combination weight loss program resulted in greater weight loss and improved diabetes control compared with a standard weight loss program in overweight or obese subjects with type 2 diabetes.", "nan", "nan", "To assess the effect of orlistat plus diet compared with diet alone in promoting weight loss and blood pressure reduction in hypertensive, overweight/obese patients.\n A pragmatic randomized, controlled trial.\n Hypertension clinic of a university hospital.\n Hypertensive patients aged 18-75 years with a body mass index greater than 25 kg/m(2).\n Orlistat 360 mg/day combined with a hypocaloric diet (treatment group), or a calorie-restricted diet alone (control group).\n Primary outcomes were reductions in weight and blood pressure. Secondary outcomes were decreases in lipid and glucose concentrations. A subgroup analysis of the main outcomes among diabetic and non-diabetic patients was also performed.\n A total of 204 patients were included in the intention-to-treat analysis. After 12 weeks the orlistat group lost, on average, 3.7 kg and the control group lost 2.0 kg in weight (P < 0.001). Systolic (SBP) and diastolic (DBP) blood pressures decreased by 15.3 and 11.4 mmHg, respectively, in the group given orlistat plus a hypocaloric diet and by 11.6 and 5.2 mmHg, respectively, in the control group given the calorie-restricted diet alone (P = 0.25 and P = 0.0004, respectively). Fasting glucose (0.82 and 0.17 mmol/l, P = 0.01) and total cholesterol (0.85 and 0.56 mmol/l, P = 0.05) were reduced to a greater extent with orlistat than with diet alone. The mean reduction in triglycerides with orlistat plus the hypocaloric diet was 0.75 mmol/l and that in the control group was 0.30 mmol/l (P = 0.28); the increases in high-density lipoprotein cholesterol were 0.05 and 0.00 mmol/l, respectively, in the two groups (P = 0.17). Treatment improved blood pressure and glucose control in the individuals with diabetes, but not in those without diabetes.\n In both groups there was a reduction in weight, blood pressure and metabolic parameters. The orlistat group performed better in reducing weight, DBP, glucose and cholesterol. Results show that even a small reduction in weight helps to control blood pressure and glucose. The cost-benefit of the use of orlistat should be evaluated for hypertensive obese patients.", "nan", "An open, non-comparative study was carried out to assess the efficacy and toleration profile of sibutramine, a new antiobesity drug, in promoting weight loss in obese type 2 diabetes mellitus subject who failed to reduce weight after strict dietary control. Twenty seven patients completed the study. Sibutramine was started as a single morning dose of 10 mg and was subsequently increased to 15 mg daily if weight loss was not satisfactory. The total duration of the study was twelve weeks with followup at every four weeks. Effect of drug was monitored in terms of weight reduction, changes in body mass index, waist circumference, hip circumference, waist/hip ratio and other metabolic parameters. A fixed dietary prescription and concomitant therapy with drugs, if required and not likely to interfere with the trial therapy, was permitted but was not changed during the study period.\n At the end of 12 week, mean weight reduction in study subjects was 4.16 kg (p < 0.001), the corresponding BMI decreased by 1.6 (p < 0.0001) and hip circumference by 3.68 (p < 0.001). However, there was no significant change in fasting blood glucose and Hb(A1c) values.\n The study indicates sibutramine to be an effective and well tolerated agent leading to significant reduction in parameter of obesity in obese type 2 diabetic subjects.", "OBJECTIVE; Weight loss improves glycemic control, lipid profiles, and blood pressure in patients with type 2 diabetes. However, successful long-term weight loss is difficult for these patients, particularly those treated with insulin. The aim of this study was to assess the effect of orlistat, a gastrointestinal lipase inhibitor, on weight loss, glycemic control, and cardiovascular risk factors in overweight or obese insulin-treated type 2 diabetic patients.\n This study was a 1-year multicenter, randomized, double-blind, placebo-controlled trial of orlistat (120 mg three times a day) or placebo combined with a reduced-calorie diet in overweight or obese adults (BMI 28-40 kg/m(2)) with type 2 diabetes treated with insulin alone or combined with oral agents, but with suboptimal metabolic control (HbA(1c) 7.5-12.0%). Outcome measurements included changes in body weight, glycemic control, blood pressure, and serum lipids. RESULTS; After 1 year, the orlistat group lost significantly more weight (-3.89 +/- 0.3% of baseline body weight, means +/- SE) than the placebo group (-1.27 +/- 0.3%, P < 0.001). Orlistat treatment, compared with placebo, produced greater decreases in HbA(1c) (-0.62 +/- 0.08 vs. -0.27 +/- 0.08%, P = 0.002), fasting serum glucose (-1.63 +/- 0.3 vs. -1.08 +/- 0.3 mmol/l, P = 0.02), and the required doses of insulin and other diabetic medications. Orlistat also produced greater improvements than placebo in serum total cholesterol (P = 0.0002) and LDL cholesterol concentrations (P = 0.001) and LDL/HDL ratio (P = 0.01). CONCLUSIONS; Orlistat therapy produces clinically significant weight loss, with improvements in glycemic control and cardiovascular disease risk factors, in overweight or obese patients with type 2 diabetes who have suboptimal metabolic control with insulin therapy.", "Mazindol, a drug with tricyclic structure unrelated to amphetamine and other anorectic drugs, has been used as an anorectic agent in a double blind clinical trial at a dose of 2 mg/day for 12 week (mazindol v. s. placebo), associated with a 1000 calorie diet on 46 obese diabetic patients. Thirty seven patients completed the trial with no significant difference between the two groups in the drop-out population; mazindol was well tolerated. In the mazindol-treated group the mean weight loss was 13.5 kg (22.3%) which was significantly greater (p less than 0.001) than in the placebo treated group where the mean weight loss was 4.2 kg (9.8%). Comparing the two groups after the 12 week trial, decrease in fasting blood glucose, serum insulin and triglycerides was not significant. In the mazindol-treated group a significant decrease of serum cholesterol, triglycerides and of the mean area under the curve of insulinemia during the OGTT has been observed. In the placebo treated group only serum triglycerides decreased significantly. The variations of plasma insulin and serum cholesterol were found to be correlated to the magnitude of weight loss. In conclusion mazindol is an effective drug for weight loss on the whole well tolerated but without specific properties on metabolism.", "To assess the efficacy and tolerability of sibutramine 15 mg once daily as a weight reduction agent in overweight and obese patients (body mass index (b.m.i.) > 26 kg/m2) with type 2 diabetes when given with a customised, reduced-calorie diet, and to evaluate the influence of weight loss on diabetic control.\n Randomised, placebo-controlled, double-blind, parallel-group, 12-week study conducted at two hospital-based obesity/diabetes clinics. Patients were men and women aged 30-65 years, with b.m.i. > 26 kg/m2 and < or = 35 kg/m2 and treated or untreated type 2 diabetes diagnosed > or = 6 months previously. Each patient was given sibutramine 15 mg or placebo once daily and advised to follow a customised diet of 500 kcal/day less than the individual's energy needs. The principal measure of efficacy was change in body weight (b.w.). Additional efficacy measurements were changes in b.m.i., body composition as measured by dual-energy X-ray absorptiometry, and change in waist and hip measurements. Changes in diabetic control were assessed by blood glucose levels fasting and after a standard test meal, fasting insulin level, and glycosylated haemoglobin level. Adverse events (AEs) were monitored at each visit, and routine laboratory safety tests were done at 4-week intervals.\n Ninety-one patients were randomised into the study, 44 to placebo and 47 to sibutramine 15 mg once daily. Eighty-three patients (91%) completed the study, 40 (91%) on placebo and 43 (91%) on sibutramine. Mean weight reduction from baseline was statistically significantly greater with sibutramine than with placebo at every measurement and at the end of the study (2.4 vs. 0.1 kg at week 12; p < 0.001; intent-to-treat). The proportion of patients who lost > 5% of their baseline b.w. was 19% in the sibutramine group and 0% in the placebo group (p < 0.001; 95% confidence interval: 9, 30). Patients receiving sibutramine lost significantly more fat mass compared with those receiving placebo, as a percentage (1.0% vs. 0.1%; p < 0.05) and in absolute terms (1.8 vs. 0.2 kg, p < 0.001). Loss of lean mass was not significantly different between the groups. Mean peak blood glucose concentration after a standard test meal decreased by 1.1 mmol/l in the sibutramine treatment group but increased by 0.5 mmol/l in the placebo group (p = 0.04; difference in means, 1.6, 95% confidence interval: -3.3, -0.1). Mean fasting blood glucose decreased by 0.3 mmol/l with sibutramine and increased by 1.4 mmol/l with placebo. Mean glycosylated haemoglobin levels decreased by 0.3% units with sibutramine treatment, and were unchanged with placebo. However, more sibutramine-treated patients (33%) than placebo-treated patients (5%) achieved decreases in glycosylated haemoglobin of 1% unit or more (p < 0.05). Sibutramine 15 mg was safe and well tolerated, and AEs were mostly mild or moderate in severity. No significant differences were found between treatment groups in blood pressure. No clinically significant conduction or rhythm abnormalities were observed on ECG.\n Sibutramine 15 mg once daily with a customised, reduced-calorie diet significantly reduced weight compared with placebo in overweight and obese patients (b.m.i. > 26 kg/m2) with type 2 diabetes. Sibutramine was well tolerated, and significant improvement in diabetic control was seen in conjunction with weight reduction on sibutramine treatment.", "Moderate weight loss is recommended for overweight and obese patients with type 2 diabetes, and conjunctive use of weight loss medication has been advocated. The current study examined weight loss-dependent and -independent effects of the intestinal lipase inhibitor orlistat at 6 months of treatment, using behavioral intervention (Int) combined with randomized, double-blinded, placebo (P)-controlled treatment with orlistat (O).\n Metabolic control, insulin sensitivity (IS), regional fat distribution, and fat content in liver and muscle were measured in 39 volunteers with type 2 diabetes in whom all antidiabetic medication was withdrawn 1 month preceding randomization. Weight loss was equivalent in the Int+O and Int+P groups, respectively (-10.3 +/- 1.3 vs. -8.9 +/- 1.1%), and there were identical decreases in visceral adipose tissue (VAT), fat mass (FM), thigh adiposity, and hepatic steatosis.\n Weight loss resulted in substantial improvement (P < 0.001) in HbA(1c) (-1.6 +/- 0.3 vs. -1.0 +/- 0.4%; NS between groups). IS improved significantly more with orlistat (Delta2.2 +/- 0.4 vs. Delta1.2 +/- 0.4 mg. min(-1). kg(-1) fat-free mass [FFM]; P < 0.05), and plasma free fatty acid (FFA) levels were strongly correlated with IS (r = 0.56; P < 0.001). Orlistat caused greater reductions in fasting plasma FFA (Delta-154 +/- 22 vs. Delta-51 +/- 33 micro mol/l; P < 0.05), insulin-suppressed FFA (Delta-119 +/- 23 vs. Delta-87 +/- 34 micro mol/l; P < 0.05), and fasting plasma glucose (FPG; -62 +/- 9 vs. -32 +/- 8 mg/dl; P = 0.02). Changes in HbA(1c) were correlated with DeltaIS (r = -0.41; P < 0.01) but not with weight loss per se.\n At equivalent weight loss, conjunctive use of orlistat resulted in greater improvement in FFA levels and IS.", "nan", "In this study, we evaluated the efficacy of sibutramine in combination with hypoglycemic drugs in obese type 2 diabetic women whose glucose levels were poorly regulated.\n Female patients with type 2 diabetes, poorly controlled glucose levels, and HbA(1c) >8% were randomly assigned to one of two groups. In addition to their prescribed hypoglycemic agents (maximum doses of sulfonylureas and metformin), one group (n = 30) received a placebo twice daily for 6 months and the other (n = 30) received sibutramine 10 mg b.i.d. for the same period.\n One patient in the sibutramine group was excluded during the study period because of hypertension; thus, a total of 29 data sets were analyzed for this group. In the placebo group, five patients had to be excluded because of low treatment efficacy, leaving a total of 25 who completed the study. Comparing the changes that occurred over 6 months in the sibutramine and placebo groups, the former showed significantly greater reductions in fasting blood glucose (P < 0.0001), second-hour postprandial blood glucose (P < 0.0001), insulin resistance (P < 0.0001), waist circumference (P < 0.0001), BMI (P < 0.0001), HbA(1c) (P < 0.0001), diastolic blood pressure, pulse rate, uric acid levels, and all elements of the lipid profile except HDL cholesterol and apolipoprotein A1.\n The addition of sibutramine to oral hypoglycemic therapy resulted in significant weight loss and improvement in metabolic parameters in this patient group. Sibutramine is an effective adjunct to oral hypoglycemic therapy in obese women with type 2 diabetes.", "nan" ]

[ "2529659", "2009067", "8198723", "10490109", "11207693", "1448534", "8113473", "16837136", "8905040", "11493295", "11442615", "7591421", "16711171", "9810992" ]

[ "Topical silicone gel: a new treatment for hypertrophic scars.", "Topical silicone gel for the prevention and treatment of hypertrophic scar.", "Cica-Care gel sheeting in the management of hypertrophic scarring.", "Prospective, single-blind, randomized, controlled study to assess the efficacy of the 585-nm flashlamp-pumped pulsed-dye laser and silicone gel sheeting in hypertrophic scar treatment.", "Effect of the 585 nm flashlamp-pumped pulsed dye laser for the treatment of keloids.", "Hypertrophic sternal scars: silicone gel sheet versus Kenalog injection treatment.", "A controlled clinical trial of topical silicone gel sheeting in the treatment of hypertrophic scars and keloids.", "A prospective randomized clinical trial to investigate the effect of silicone gel sheeting (Cica-Care) on post-traumatic hypertrophic scar among the Chinese population.", "Effectiveness of silicone sheets in the prevention of hypertrophic breast scars.", "Silicone versus nonsilicone gel dressings: a controlled trial.", "Prevention of hypertrophic scars and keloids by the prophylactic use of topical silicone gel sheets following a surgical procedure in an office setting.", "Vitamin E added silicone gel sheets for treatment of hypertrophic scars and keloids.", "Evaluation of a self-adherent soft silicone dressing for the treatment of hypertrophic postoperative scars.", "The use of silicone occlusive sheeting (Sil-K) and silicone occlusive gel (Epiderm) in the prevention of hypertrophic scar formation." ]

[ "A prospective, controlled clinical trial was designed to assess the efficacy of a new treatment of hypertrophic scars. Silicone gel sheeting was applied to 14 hypertrophic scars in 10 adults for 8 weeks. The treated scars and untreated, mirror-image or adjacent control scars were photographed, biopsy specimens were taken, and they were measured elastometrically before and after treatment. Photography and elastometry were repeated 4 weeks after treatment was discontinued. All the scars that had been treated for at least 12 hours a day were improved clinically after 4 weeks. There was further clinical improvement during the second 4 weeks of treatment. Elastometrically, the treated scars were improved significantly at 4, 8, and 12 weeks, compared with both their own treatment value and the control scars (p less than 0.05). Control scars were unchanged elastometrically. Clinical improvement persisted for at least 4 weeks after treatment was discontinued. The silicone gel sheeting was well tolerated, except for occasional transient rashes or superficial maceration--both of which resolved promptly when treatment was withdrawn. There was no histologic evidence of inflammation or foreign body reaction suggesting that silicone had entered the treated tissues. We conclude that this simple method of treating hypertrophic scar is efficacious, even in relatively chronic cases. The mechanism of action of silicone gel, which is apparently not related to compression, remains to be determined.", "We studied the effects of a silicone gel bandage that was worn for at least 12 hours daily on the resolution of hypertrophic burn scar. In a second cohort, the prevention of hypertrophic scar formation in fresh surgical incisions by this bandage was also evaluated. In 19 patients with hypertrophic burn scars, elasticity of the scars was quantitated serially with the use of an elastometer. An adjacent or mirror-image hypertrophic burn scar served as a control. Scar elasticity was increased after both 1 and 2 months compared with that in controls. There was corresponding improvement clinically that persisted for at least 6 months. In the other cohort, scar volume changes in 21 surgical incisions were measured before and after 1 and 2 months. Gel-treated incisions gained less volume than control incisions after both intervals. Clinical assessment corroborated this quantitative demonstration of a decrement in scar volume. We concluded that topical silicone gel is efficacious, both in the prevention and in the treatment of hypertrophic scar.", "A prospective, controlled clinical trial was undertaken to assess the efficacy and safety of two types of silicone gel, Silastic Gel Sheeting (SGS) and Cica-Care (CC), in the management of hypertrophic scars. Forty-two patients were randomly assigned to SGS and CC groups and their hypertrophic scars were divided into treated and control areas. Extensometric measurements were made at monthly intervals for 6 months and significant improvement of the treated areas relative to the control areas was observed. The two gels were not significantly different in efficacy or safety, but CC, being more adhesive and more comfortable than SGS, has advantages in ease of use and patient acceptability.", "To determine the efficacy of the 585-nm flashlamp-pumped pulsed-dye laser and silicone gel sheeting in the treatment of hypertrophic scars in lighter- and darker-skinned patients.\n Prospective, single-blind, randomized, internally controlled, comparison investigation.\n Large academic dermatology department.\n Twenty patients with hypertrophic scars (19 completed the laser treatments and 18 completed the silicone gel sheeting treatments).\n Clinical measurements included hypertrophic scar blood flow, elasticity, and volume. Patients' subjective complaints of pruritus, pain, and burning were also monitored. Histological assessment of fibrosis, number of telangiectasias, and number of mast cells was performed. Statistically significant improvements in clinical measurements and patients' subjective complaints determined treatment success.\n Mean scar duration was 32 months (range, 4 months to 20 years). There was an overall reduction in blood flow, volume, and pruritus over time (P = .001, .02, and .005, respectively). However, no differences were detected among treatment and control groups. There was no reduction in pain or burning (0-40 weeks), elasticity (8-40 weeks), or fibrosis (0-40 weeks, n = 5 biopsies) in the treated or control sections of the scars. Unlike in a previous study, the number of mast cells in the scars was similar to the number of mast cells in healthy skin.\n Clinical results demonstrate that the improvements in scar sections treated with silicone gel sheeting and pulsed-dye laser were no different than in control sections.", "Due to its potential effects on skin microcirculation and collagen metabolism, the 585 nm flashlamp-pumped pulsed dye laser has been proposed for treating abnormal scars. Indeed, one of the main problems with keloidal scars is their disfiguring erythematous color.\n To assess the efficacy of the 585 nm pulsed dye laser on the appearance of keloids.\n Eleven patients with skin phototypes II-IV and keloids were treated with the 585 nm pulsed dye laser. After one to three treatment sessions, clinical assessments of the scars were performed in combination with remittance spectroscopy measurements of the redness and melanin pigmentation. A group of nine keloids covered by silicone gel sheeting served as controls. Data were compared statistically.\n During laser treatments, a discrete decrease in redness of the scars was clinically reported. However, this improvement was not confirmed by the objective spectrophotometric data. No side effects, especially hyperpigmentation, were disclosed. The keloids redness was not improved in the control group.\n The 585 nm pulsed dye laser yields only minimal effects, if any, on the erythema of keloids. Similarly silicone gel sheeting does not modify the keloids redness.", "A prospective, randomized trial was designed to compare the standard Kenalog injection of established hypertrophic sternal scars with topical silicone gel sheets (Spenco). Fourteen poststernotomy cardiac patients with symptomatic scars were randomized to treatment in one-half of the scar with Kenalog injection. Simultaneously, the other half of the scar received the silicone gel sheet. The standard Kenalog injection used was 40 mg/ml x 1 cc, mixed with 1 cc of 1% Xylocaine with epinephrine. The gel sheets were worn continuously for 12 hours for 12 weeks. Pretreatment and posttreatment photographs were compared for color and appearance by blindfolded observers. Scar measurements (length, width, and height) were taken weekly in each area, and the patients were asked to rank their symptoms within each half as worse, the same, or better. The primary outcome of patient preference was analyzed sequentially, and the recruitment was terminated after 11 patients had completed the study, 10 of whom favored the silicone gel treatment (p < 0.05). Three patients remained in the treatment phase at the time of termination and completed the study subsequently. For the total sample of 14 subjects, 11 preferred the silicone gel, 1 expressed no preference, and 2 preferred the injection. The average time to improvement was 3.9 +/- 0.62 days (gel) versus 6.8 +/- 1.86 days (Kenalog). This study demonstrates that silicone gel sheets provide earlier symptomatic relief and a more aesthetic scar and are the preferred treatment of patients with symptomatic hypertrophic sternal scars.", "nan", "This study aimed to determine the efficacy of silicone gel (Cica-Care) on severe post-traumatic hypertophic scars among the Chinese population.\n A randomized clinical trial (RCT) was conducted on 45 Chinese patients with post-traumatic hypertrophic scars. Twenty-two subjects were placed in the experimental group with silicone gel sheeting (SGS) applied 24h per day for 6 months while all subjects were taught to massage the scar daily for 15 min serving as the control intervention. Scar assessments were conducted regularly to measure the changes in thickness, pigmentation, vascularity, pliability, itchiness and pain.\n Two-way repeated ANOVA showed a significant difference between MT group and SGS group on scar thickness. The post hoc comparison analysis showed that the difference was significant at the post-2-month (p=0.008) and post-6-month (p<0.001) intervention. The SGS group also showed changes in pigmentation which resembled normal skin but no statistical significance was found. Pain, itchiness and pliability were also improved after intervention.\n This study indicated that silicone gel sheeting (Cica-Care) was effective to reduce thickness, pain, itchiness and pliability of the severe hypertrophic scar among the Chinese population. The moisturization effect of the tough and hard scar might contribute to the reduction of the skin thickness after 6 month's intervention.", "A clinical study was designed in which 20 women who were to undergo bilateral McKissock reduction mammaplasties were requested to use a precut silicone elastomer sheet over the scars of one breast, starting at the time of suture removal. The patients were instructed to use the silicone sheet for 12 hours each day for 2 months. Evaluation of the scars at 2 months revealed that 60% of the nontreated scars were hypertrophic and only 25% of the treated scars were hypertrophic. The difference was found to be statistically significant (p < 0.05). The use of the sheets was discontinued after 2 months and the beneficial effect remained at the 6-month evaluation.", "Silicone gel dressings decrease scar volume and soften hypertrophic tissue, allowing it to be more easily controlled by other methods. Although silicone does not appear to be an essential component of the treatment, nonsilicone dressings have been reported to cause no change in physical parameters during a 2-month treatment period.\n To compare silicone and nonsilicone gel dressings in the treatment of keloids and hypertrophic scars, including a control group, and to evaluate the effectiveness of these treatments using two new assessment techniques.\n Patients were randomly chosen to receive silicone or nonsilicone gel dressings in a 4.5-month controlled prospective study. Scar size, induration, and symptoms were evaluated before and after the treatment. Scar color was visually measured using a color palette catalog, and a new device was developed to measure intracicatricial pressure.\n All of the measured parameters were significantly reduced in both silicone- and nonsilicone-treated groups, as compared to the control, with no significant differences between them.\n Silicone and nonsilicone gel dressings are equally effective in the treatment of keloids and hypertrophic scars.", "Topical silicone gel sheeting has been used for more than 20 years to help reduce the size of hypertrophic scars and keloids. Its clinical efficacy and safety is well established.\n To determine whether topical silicone gel sheeting can be used to prevent hypertrophic scars and keloids from forming following dermatologic skin surgery.\n Patients undergoing skin surgery were stratified into two groups: those with no history of abnormal scarring (low-risk group) and those with a history of abnormal scarring (high-risk group). Following the procedure, patients within each group were randomized to receive either routine postoperative care or topical silicone gel sheeting (48 hours after surgery). Patients were followed for 6 months.\n In the low-risk group, there were no statistical differences between individuals using routine postoperative care or using topical silicone gel sheets. In the high-risk group, there was a statistical difference (39% versus 71%) between patients who did not develop abnormal scars and used topical silicone gel sheeting and patients who developed abnormal scars after routine postoperative treatment. Those individuals having a scar revision procedure also showed a statistical difference if topical silicone gel sheeting was used following surgery.\n Topical silicone gel sheeting, with a 20-year history of satisfaction in dermatology, now appears to be useful in the prevention of hypertrophic scars and keloids in patients undergoing scar revision.", "Trauma of various origins can induce a connective tissue disorder that leads to keloids. This condition has yet not been clearly distinguished from scars and hypertrophic scars. Only electronmicroscopic and biochemical data can help to do this. Among some more or less therapeutic approaches, the use of silicon (polydimethylsiloxane) plates, wrapped on the keloid surface, has been reported effective by some authors. These authors also demonstrated that it is not the mechanical pressure that is the mechanism of action, but a direct action on fibroblasts and a hyperhydration of subcutaneous tissue. The authors of this study conceived that the silicon plate may be able to improve the transdermal penetration of a compound such as vitamin E. This vitamin is capable of preserving some important morphologic and functional features of biological membranes by means of its phytilside chain of the molecule acting as a stabilizer of lysosomal membranes.\n Eighty patients of both sexes, aged between 18 and 63 years, who had hypertrophic scars and keloids, were admitted to the trial. The patients were randomized to two groups in a simple-blinded study. Group A: Forty patients whose scars have been covered with silicon plates with added vitamin E. Group B: Forty patients treated with simple silicone gel sheets. No pressure bandages were used, only tape fixing the sheet for 10 hours overnight. The trial lasted for 2 months. The results were recorded at 4 and 8 weeks, evaluating the improvement according to a Scott-Husskinson scale. For objective assessment photos were taken. The results were analyzed by the chi-square test.\n At the end of the first month, group A had improved by more than 50% in 85% of cases, whereas the improvement in group B was 55% (P < 0.01). At the end of the second month, 95% of patients in group A had improved by 50%, whereas 75% had improved by 50% in group B (P < 0.05).\n Vitamin E added to the silicon plate scored better than the simple silicon plate at the end of both periods. We have reported the successful combined action of vitamin E and silicone gel sheets in scar treatment, especially in the short-term prophylaxis of hypertrophic scars or keloids.", "The primary objective was to compare the efficacy of a self-adherent soft silicone dressing (Mepiform) with 'left-alone' management of hypertrophic scars using theVancouver Scar Scale. Secondary objectives were to follow photographs of the scars, patients' opinions of the scars, and doctors' and patients' assessments of the overall dressing performance, safety and tolerance.\n An exploratory open randomised controlled clinical investigation was undertaken on 11 female patients aged 21-43 years with postoperative scars (nine following breast surgery, two following lower abdominal-glutealplasty). Treatment was initiated between two weeks and two months (mean 4.7 weeks) after surgery. Ten patients completed the 12-month investigation; one patient in the treatment group discontinued for personal reasons.\n All parameters in the Vancouver Scar Scale improved in both groups, although patients treated with the soft silicone dressing showed greater and more rapid improvements compared with the non-treated patients, while their assessments of the condition of the scar were more favourable. Medical staff rated the overall dressing performance as 'very good' or'good'. One adverse event was reported--local skin irritation at the site of the scar.\n The results suggest that patients treated with the soft silicone dressing experienced greater and more rapid improvements compared with non-treated patients. These results concur with those of previous studies. The fact that Mepiform is self-adhesive and causes limited damage to the stratum corneum on removal gives it an added value compared with non-adhesive silicone gel dressings.", "The development of hypertrophic scars and keloids is an unsolved problem in the process of wound healing. For this reason, a successful treatment to prevent excessive scar formation still has not been found. Over the last decade, however, a promising new treatment has been introduced. Silicone materials have proved to reduce the amount of scar tissue and are believed even to prevent hypertrophic scar and keloid formation. In this study, the prophylactic effect of a silicone occlusive sheeting (Sil-K, Degania, Israel) and a silicone occlusive gel (Epiderm, Inamed B.V., The Netherlands) was investigated in a bilateral breast-reduction scar model in which the nontreated scars were supported by nonocclusive Micropore (3M, The Netherlands). The inframammary scars of 129 female patients with a mean age of 31 years ( 14 to 69 years) were studied up to 1 year after the operation. The width and height were measured, and B-scan ultrasound, laser-Doppler flowmetry, and color measurements were used as objective indicators to distinguish between normal and exuberant scars. Three months following the operation, 64.3 percent of the patients developed a hypertrophic scar, which was reduced to 56.6 percent after 6 months and down to 35.3 percent after 1 year. No keloids were seen. Patients with an easily tanning skin, nonsmokers, and patients with an allergy showed more hypertrophic scar formation. Neither Sil-K, used in 68 patients, nor Epiderm, used in 61 patients, could prevent the formation of hypertrophic scars. If both groups were taken together, the scars treated with silicone materials even developed significantly more hypertrophy compared with the Micropore-applicated scars." ]

[ "18572993", "21057736", "19225417", "12771395", "19148765", "16675365", "20363809", "17549228" ]

[ "Individual and group cognitive-behavioral treatment for work-related stress complaints and sickness absence: a randomized controlled trial.", "Effects of a stress management intervention on absenteeism and return to work--results from a randomized wait-list controlled trial.", "Guideline-based care of common mental disorders by occupational physicians (CO-OP study): a randomized controlled trial.", "Reducing long term sickness absence by an activating intervention in adjustment disorders: a cluster randomised controlled design.", "Cognitively oriented behavioral rehabilitation in combination with Qigong for patients on long-term sick leave because of burnout: REST--a randomized clinical trial.", "Effectiveness of an intervention to reduce sickness absence in patients with emotional distress or minor mental disorders: a randomized controlled effectiveness trial.", "A workplace intervention for sick-listed employees with distress: results of a randomised controlled trial.", "A cluster-randomised trial evaluating an intervention for patients with stress-related mental disorders and sick leave in primary care." ]

[ "Work-related stress is widespread and can lead to long-term absenteeism and work disability. Cognitive-behavioral treatment (CBT) has demonstrated effectiveness in treating psychopathology but has only rarely been tested in clinical samples with work-related stress. A randomized controlled trial was conducted to investigate the efficacy of CBT-based stress management training (SMT). Eighty-two patients on sickness leave with work-related stress were randomly assigned to (a) individual SMT, (b) group SMT, or (c) care as usual (CAU). The SMT comprised 12 sessions conducted by a psychologist. Complaints of burnout and distress were measured at baseline, and at 4, 7, and 10 months. Absenteeism was measured during the whole research period. Across treatment conditions, complaints and sickness absence reduced considerably between baseline and 4 months. Thereafter, complaints remained approximately stable, whereas sickness absence further reduced. Hardly any significant group difference emerged, and no consistent pattern could be discerned in favor of any treatment condition. In subgroups with low depressive complaints, though, individual SMT resulted in larger reductions of some complaints than CAU. In conclusion, this study adds to the evidence that CBT-based interventions as currently practiced are not successful in treating patients with clinical levels of work-related stress.\n Copyright (c) 2008 APA, all rights reserved.", "High levels of work-related stress are associated with increased absenteeism from work and reduced work ability. In this study, we investigated the effects of a stress management intervention on absenteeism and return to work.\n We randomized 102 participants into either the intervention or wait-list control (WLC) group. The intervention group received the intervention in weeks 1-16 from baseline, and the WLC group received the intervention in weeks 17-32. Self-reported data on absenteeism (number of days full- or part-time absent from work within the previous three months) were obtained at 16, 32, and 48 weeks follow-up. Register-based data on long-term absence from work were drawn from the Danish public transfer payments (DREAM) database from baseline and 48 weeks onwards. The DREAM database contains weekly information on long-term sickness absence compensation. The threshold to enter DREAM is sick leave for two consecutive weeks.\n At follow-up in week 16, self-reported absenteeism in the intervention group [median 11 days (range 3-25)] was lower (P=0.02) than in the WLC group [median 45 days (range 19-60)], corresponding to a 29% [95% confidence interval (95% CI) 5-52] reduction. On register-based data (cumulated weeks in DREAM, weeks 1-16), the intervention group median [6 weeks (range 0-11)] was lower than that of the WLC group [median 12 weeks (range 8-16)], though not significantly (P=0.06), corresponding to a 21% (95% CI 0-42) reduction. For return to work, a hazard ratio of 1.58 (95% CI 0.89-2.81) favoring the intervention group was found (P=0.12).\n The intervention reduces self-reported absenteeism from work. A similar trend was found from register-based records. No conclusive evidence was found for return to work.", "To evaluate the effectiveness of guideline-based care (GBC) of workers with mental health problems, which promotes counseling by the occupational physician (OP) facilitating return to work (RTW).\n In a randomized controlled trial with police workers on sick leave due to mental health problems (n = 240), trained OPs delivered GBC in the intervention group. Time to RTW and recurrences during 1-year follow-up, analyzed using Cox proportional hazards models, were compared with usual care (UC) with easy access to a psychologist.\n GBC by OPs did not result in earlier RTW than UC. Subgroup analysis showed a small effect in favor of GBC for workers with administrative functions and/or \"minor\" stress-related symptoms.\n GBC did not differ in RTW compared with UC, but may be beneficial for the majority of workers with minor stress-related disorders.", "To compare an innovative activating intervention with \"care as usual\" (control group) for the guidance of employees on sickness leave because of an adjustment disorder. It was hypothesised that the intervention would be more effective than care as usual in lowering the intensity of symptoms, increasing psychological resources, and decreasing sickness leave duration.\n A prospective, cluster randomised controlled trial was carried out with 192 patients on first sickness leave for an adjustment disorder. Symptom intensity, sickness duration, and return to work rates were measured at 3 months and 12 months. Analyses were performed on an intention to treat basis.\n At 3 months, significantly more patients in the intervention group had returned to work compared with the control group. At 12 months all patients had returned to work, but sickness leave was shorter in the intervention group than in the control group. The recurrence rate was lower in the intervention group. There were no differences between the two study groups with regard to the decrease of symptoms. At baseline, symptom intensity was higher in the patients than in a normal reference population, but decreased over time in a similar manner in both groups to approximately normal levels.\n The experimental intervention for adjustment disorders was successful in shortening sick leave duration, mainly by decreasing long term absenteeism.", "Despite an increase in the occurrence of burnout, there is no agreement on what kind of rehabilitation these patients should be offered.\n Primary aim of this study was to evaluate effects on psychological variables and sick leave rates by two different group rehabilitation programs for patients on long-term sick leave because of burnout. Rehabilitation program A (Cognitively oriented Behavioral Rehabilitation (CBR) and Qigong) was compared with rehabilitation program B (Qigong only).\n In a randomized clinical trial, 96 women and 40 men with a mean age of 41.6 +/- 7.4 years were allocated to one of the two rehabilitation programs.\n A per-protocol analysis showed no significant difference in treatment efficacy between the groups. Both groups improved significantly over time with reduced levels of burnout, self-rated stress behavior, fatigue, depression, anxiety, obsessive-compulsive symptoms, and sick leave rates. In an intention-to-treat analysis, patients in program A had fewer obsessive-compulsive symptoms and larger effect sizes in self-rated stress behavior and obsessive-compulsive symptoms compared to patients in program B.\n This study showed no differences in effect between CBR and Qigong compared with Qigong only in a per-protocol analysis. Both rehabilitation programs showed positive effect for patients with burnout.", "The purpose of this study was to evaluate the effectiveness of an activating intervention designed to reduce sick leave duration in patients with emotional distress or minor mental disorders.\n In a 1.5-year randomized controlled trial, 194 patients with minor mental disorders received either an experimental intervention by social workers or general practitioners' usual care. The intervention focused on understanding causes, developing and implementing problem-solving strategies and promoting early work resumption. Outcome measures were sick leave duration, mental health and physical health (questionnaires included the Hospital Anxiety and Depression Scale, the Four-Dimensional Symptom Questionnaire and SF-36), all measured at baseline at and 3, 6 and 18 months later. Multilevel analyses were used to evaluate differences between groups.\n The groups did not differ significantly on any of the outcome measures, except that the experimental group reported higher satisfaction with treatment.\n Although the intervention has benefits, it was not successful at its primary goal (i.e., to reduce sick leave duration in patients with emotional distress or minor mental disorders). Programs aimed at the reduction of sick leave duration may yield better results if targeted at patients with more severe emotional problems than at those with exclusively emotional distress or minor mental disorders, or if delivered by caregivers who are closer to the work environment than are social workers, such as occupational physicians.", "To evaluate the effectiveness of a participatory workplace intervention compared with usual care for sick-listed employees with distress, with regard to return to work (RTW) within the 12-month follow-up.\n Employees with distress and sick-listed for 2-8 weeks were randomised to a workplace intervention (n=73) or to usual care (n=72). The participatory workplace intervention is a stepwise process involving the sick-listed employee and their supervisor, aimed at reducing obstacles for RTW by reaching consensus about an action plan for RTW. Outcome variables were lasting RTW, cumulative sickness absence and stress-related symptoms.\n Overall, an HR of 0.99 (95% CI 0.70 to 1.39) indicated no effect of the workplace intervention on lasting RTW. However, the workplace intervention significantly reduced the time until lasting RTW for employees who at baseline intended to return to work despite symptoms with an HR of 2.05 (95% CI 1.22 to 3.45). Employees who intended to return to work despite symptoms returned to work after 55 days in the workplace intervention group and 120 days in the usual care group. No such effect of the intervention was found for employees without baseline intentions to return to work despite symptoms (HR=0.78, 95% CI 0.47 to 1.28).\n No overall effect of the participatory workplace intervention on lasting RTW was found. The workplace intervention appeared effective on lasting RTW for employees who at baseline intended to return to work despite symptoms. For employees who showed no baseline intention to return to work, the intervention did not have any effect. Other approaches are needed for this subgroup. This trial has been registered at the Dutch National Trial Register ISRCTN92307123.", "Mental health problems often affect functioning to such an extent that they result in sick leave. The worldwide reported prevalence of mental health problems in the working population is 10%-18%. In developed countries, mental health problems are one of the main grounds for receiving disability benefits. In up to 90% of cases the cause is stress-related, and health-care utilisation is mainly restricted to primary care. The aim of this study was to assess the effectiveness of our Minimal Intervention for Stress-related mental disorders with Sick leave (MISS) in primary care, which is intended to reduce sick leave and prevent chronicity of symptoms.\n Cluster-randomised controlled educational trial.\n Primary health-care practices in the Amsterdam area, The Netherlands.\n A total of 433 patients (MISS n = 227, usual care [UC] n = 206) with sick leave and self-reported elevated level of distress.\n Forty-six primary care physicians were randomised to either receive training in the MISS or to provide UC. Eligible patients were screened by mail.\n The primary outcome measure was duration of sick leave until lasting full return to work. The secondary outcomes were levels of self-reported distress, depression, anxiety, and somatisation.\n No superior effect of the MISS was found on duration of sick leave (hazard ratio 1.06, 95% confidence interval 0.87-1.29) nor on severity of self-reported symptoms.\n We found no evidence that the MISS is more effective than UC in our study sample of distressed patients. Continuing research should focus on the potential beneficial effects of the MISS; we need to investigate which elements of the intervention might be useful and which elements should be adjusted to make the MISS effective." ]

[ "14569109", "9808483", "11423583", "12826169", "14514747", "12039990", "11119979", "10812111", "10676721", "15714177", "12270333", "6368958", "10652047", "15265162", "8962355", "14717945", "12631097" ]

[ "Preventing bone loss in renal transplant recipients with vitamin D.", "Treatment of osteopenia and osteoporosis after kidney transplantation.", "Effect of ibandronate on bone loss and renal function after kidney transplantation.", "Alendronate for treatment of renal transplant patients with osteoporosis.", "Prevention of bone loss in renal transplant recipients: a prospective, randomized trial of intravenous pamidronate.", "Treatment with vitamin D and calcium reduces bone loss after renal transplantation: a randomized study.", "Pamidronate and calcitriol trial for the prevention of early bone loss after renal transplantation.", "Efficiency of preventive treatment for osteoporosis after renal transplantation.", "Effect of 1,25-dihydroxyvitamin D3 and calcium carbonate on bone loss associated with long-term renal transplantation.", "A controlled study of vitamin D3 to prevent bone loss in renal-transplant patients receiving low doses of steroids.", "Alendronate increases bone mineral density in long-term renal transplant recipients.", "Bone mineral content after renal transplantation. Placebo-controlled prospective study with 1,25-dihydroxy vitamin D3.", "Pamidronate therapy as prevention of bone loss following renal transplantation.", "Treatment of osteopenia and osteoporosis in renal transplant children and adolescents.", "Efficiency of preventive treatment of glucocorticoid-induced osteoporosis with 25-hydroxyvitamin D3 and calcium in kidney transplant patients.", "Treatment with intermittent calcitriol and calcium reduces bone loss after renal transplantation.", "Zoledronic acid to prevent bone loss in the first 6 months after renal transplantation." ]

[ "Very rapid bone loss, osteopenia, and osteoporosis have been documented in the first 6 to 12 mo after renal transplantation. Investigated was the effect of treatment with active vitamin D on the prevention of posttransplantation bone loss. Forty adult men who were recent renal transplant recipients were enrolled onto the study. Patients were randomized into two groups: group 1 received daily alfacalcidol 0.5 micro g by mouth, and group 2 (control) received placebo. Every patient in both groups received daily 500-mg calcium carbonate supplements. Parameters of bone metabolism and bone mineral density measured at three sites were assessed before and after the study period. Bone mineral density was increased by 2.1%, 1.8%, and 3.2% at lumbar spine, femoral neck, and forearm, respectively, in group 1, whereas it decreased by 3.2%, 3.8%, and 1.8% at the same sites in the control group (P < 0.05). Serum intact parathyroid hormone level decreased significantly in group 1 compared with the control group (P = 0.003). Early bone loss that occurs during the first 1 yr after renal transplantation could be prevented by alfacalcidol. Use of alfacalcidol early after transplantation is safe and well tolerated.", "Osteopenia and osteoporosis are frequent complications after kidney transplantation. Data for the treatment of low bone mass after kidney transplantation are not available.\n To test the efficacy of antiresorptive treatment, 46 patients with osteopenia or osteoporosis after kidney transplantation (bone mineral density < or =1.5 SD below normal) were randomly assigned to three groups cyclically treated as follows: group 1 with daily oral clodronate (800 mg) and group 2 with daily intranasal calcitonin (200 IU) for 2 weeks every 3 months. These two groups were compared with a control group (group 3). Every patient was supplemented with 500 mg of calcium per day. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DEXA) at the lumbar spine and femoral neck before and after the 12-month treatment period.\n BMD at the lumbar spine was increased by 4.6% in the clodronate group (n=15, P=0.005), by 3.2% in the calcitonin group (n=16, P=0.034), and by 1.8% in the control group (n=15, P=0.265). However, the differences in BMD changes among the groups were not statistically significant. During therapy, serum calcium decreased slightly in all groups by 4.6%; however, parathyroid hormone values increased significantly in the treatment groups by 116%. Therapy was well tolerated without impact on graft function.\n Cyclical therapy with clodronate or calcitonin appears to induce a gain in BMD at the lumbar spine in patients with low bone mass after kidney transplantation. This treatment had no adverse impact on graft function but may aggravate preexisting secondary hyperparathyroidism.", "Severe osteoporosis frequently is observed after organ transplantation. In kidney transplantation, it adds to pre-existing renal bone disease and strategies to prevent osteoporosis are not established. Eighty kidney recipients were included in a randomized controlled prospective intervention trial. Treated patients (n = 40) received an injection of ibandronate, a bisphosphonate, immediately before and at 3, 6, and 9 mo after transplantation. The primary outcome measured was the change in bone mineral density. Secondary measures included graft outcome, spinal deformities, fracture rate, body height, and hormonal and metabolic data. Loss of spongy and cortical bone after transplantation was prevented by ibandronate. Changes of bone mineral density (ibandronate versus controls) were as follows: lumbar spine, -0.9 +/- 6.1% versus -6.5 +/- 5.4% (P < 0.0001); femoral neck, +0.5 +/- 5.2% versus -7.7 +/- 6.5% (P < 0.0001); and midfemoral shaft, +2.7 +/- 12.2% versus -4.0 +/- 10.9% (P = 0.024). Fewer spinal deformities developed with ibandronate (7 patients with 7 deformities versus 12 patients with 23 deformities; P = 0.047). Loss of body height was 0.5 +/- 1.0 cm versus 1.1 +/- 1.0 cm in control subjects (P = 0.040). Two bone fractures occurred in each group. There were fewer acute rejection episodes with ibandronate (11 versus 22; P = 0.009). Graft function after 1 yr was comparable. Bone loss, spinal deformation, and loss of body height during the first year after kidney transplantation are prevented by injection of ibandronate at intervals of 3 mo. The smaller number of rejection episodes of the ibandronate-treated group should be confirmed and its mechanism should be explored in additional studies.", "Osteoporosis is a frequent complication after renal transplantation. Some workers have shown that bisphosphonates may be effective to prevent and treat corticosteroid-induced osteoporosis in these patients. In this study we report our experience with administration of the biphosphonate alendronate to treat renal transplanted patients with established osteoporosis.\n Twelve to 24 months after transplantation (9 women, 5 men) 14 renal transplant patient were treated with alendronate and 12 patients (7 women, 5 men) were untreated. All patients displayed an iPTH <240 pg/mL and a bone mineral density (BMD) t-score <-2.5. All patients received cyclosporine and prednisone therapy. Biochemical measurements, BMD, and X-rays of the lumbar spine were measured during study. Patients in the treatment group received alendronate 10 mg/d (po) and vitamin D plus calcium (800 UI cholecalciferol and 2.5 g of CaCO(3)) per day while those in the control group only received vitamin D plus calcium, at the same dose.\n There was no difference in mean age, weight, time after transplantation, or immunosuppression between the treatment and control groups. There were no significant differences in the biochemical parameters during the study period. Over the 1-year study period, patients receiving alendronate displayed a greater increase in BMD. Lumbar spine BMD increased 4.3 +/- 6.1% in the treatment group versus 0.55 +/- 5.30% in controls. Femoral neck BMD increased 10.3 +/- 11.9% and 2.2 +/- 5.7%, respectively, in the treatment and control groups. Patients receiving alendronate frequently experienced intestinal disconfort.\n The bisphosphonate alendronate is effective to treat renal transplant patients suffering from established osteporosis.", "Renal transplant recipients are at risk of developing bone abnormalities that result in bone loss and bone fractures. These are related to underlying renal osteodystrophy, hypophosphatemia, and immunosuppressive treatment regimen. Although bisphosphonates are useful in ameliorating bone mineral loss after transplantation, it is not known whether their use in renal transplant patients leads to excessive suppression of bone turnover and increased incidence of adynamic bone disease. A randomized, prospective, controlled, clinical trial was conducted using the bisphosphonate pamidronate intravenously in patients with new renal transplants. Treatment subjects (PAM) received pamidronate with vitamin D and calcium at baseline and at months 1, 2, 3, and 6. Control (CON) subjects received vitamin D and calcium only. During months 6 to 12, the subjects were observed without pamidronate treatment. Biochemical parameters of bone turnover were obtained monthly and, bone mineral density (BMD) was obtained at baseline and months 6 and 12. Bone biopsies for mineralized bone histology were obtained at baseline and at 6 mo in a subgroup of subjects who underwent scheduled living donor transplantation. PAM preserved bone mass at 6 and 12 mo as measured by bone densitometry and histomorphometry. CON had decreased vertebral BMD at 6 and 12 mo (4.8 +/- 0.08 and 6.1 +/- 0.09%, respectively). Biochemical parameters of bone turnover were similar in both groups at 6 and 12 mo. Bone histology revealed low turnover bone disease in 50% of the patients at baseline. At 6 mo, all of PAM had adynamic bone disease, whereas 50% of CON continued to have or developed decreased bone turnover. Pamidronate preserved vertebral BMD during treatment and 6 mo after cessation of treatment. Pamidronate treatment was associated with development of adynamic bone histology. Whether an improved BMD with adynamic bone histology is useful in maintaining long-term bone health in renal transplant recipients requires further study.", "A decrease in bone mineral density (BMD) is a major complication of renal transplantation (RTx), predominantly occurring within the first 6 mo after RTx. The most important causative factor is the use of corticosteroids, but persisting hyperparathyroidism and abnormalities in vitamin D metabolism play a role too. This study examines the effect of treatment with calcium and active vitamin D on the loss of BMD in the first 6 mo after RTx. A total of 111 renal transplant recipients (65 men, 46 women; age, 47 +/- 13 yr) were randomized to either treatment with active vitamin D (0.25 microg/d) plus calcium (1000 mg/d) (CaD group), or to no treatment (NoT group). Immunosuppressive therapy consisted of cyclosporine, prednisone, and mycophenolate mofetil. Laboratory parameters and BMD (lumbar spine and hip) were measured at 0, 1 (laboratory only), 3, and 6 mo after RTx. Lumbar BMD was nearly normal at the time of RTx. In both groups, a significant decrease in lumbar BMD was observed during the first 3 mo (CaD, -3.3 +/- 4.3%; P < 0.0001; NoT, -4.1 +/- 4.8%; P < 0.0001). Between the third day and sixth month, lumbar BMD slightly recovered in the CaD group, but it decreased further in the NoT group (total loss 0 to 6 mo: CaD, -2.6 +/- 5.0% [P < 0.001]; NoT, -5.0 +/- 4.7% [P < 0.0001]). As a result, the amount of bone loss at 6 mo was significantly lower in the CaD group (P = 0.02). Loss of BMD at the different femoral sites was also significantly reduced in the CaD group. Apart from a trend toward more frequent hypercalcemia in the CaD group, no clinical or biochemical differences existed between the groups. Treatment with a low dose of active vitamin D and calcium partially prevents bone loss at the lumbar spine and proximal femur during the first 6 mo after RTx.", "nan", "nan", "To investigate the effect of calcitriol plus calcium carbonate on the bone loss associated with long-term renal transplantation, 30 patients with serum creatinine levels less than 2.0 mg/dL were randomly allocated to a control (n = 14) or treatment group (n = 16) and studied with bone biopsy and densitometry at baseline and after 1 year of follow-up. Calcitriol (0.25 microg/d) plus calcium carbonate (500 mg/d of elemental calcium) were administered to patients in the treatment group. Comparing the baseline and final data of each group at a time, no change in bone mineral density (BMD) z score was observed at the distal radius (control, -0.8 +/- 0.8 versus -0.6 +/- 0.9; treatment, -1.0 +/- 1.0 versus -1.0 +/- 1.1). However, a significant increase (P < 0.05) was found at the lumbar spine in both groups (control, 0.1 +/- 1.6 versus 0.4 +/- 1.6; treatment, -0.1 +/- 1.5 versus 0.3 +/- 1.5) and only in the treatment group at the femoral neck (control, -0.9 +/- 1.0 versus -0.8 +/- 1.0; treatment, -0.5 +/- 0.9 versus -0.3 +/- 1.1). When BMD was compared between groups, no significant differences were observed at the evaluated anatomic sites at baseline or after 1 year of follow-up. After 1 year of follow-up, adjusting for age and sex (z score), the control group showed a trend to reduce the value of several histomorphometric parameters, including osteoblast surface (-2.2 +/- 6.1 versus -3.4 +/- 3.9), osteoid surface (-2.3 +/- 3.5 versus -3.1 +/- 3.9), and osteoclast surface (0.2 +/- 5.0 versus -1.3 +/- 3.3). Consequently, there was a significant reduction (P < 0.05) in mineralizing surface (-9.8 +/- 11.0 versus -15.8 +/- 12.3) and appositional rate (-5.8 +/- 2.7 versus -7.6 +/- 2.2). In the treatment group, a significant reduction (P < 0.05) in osteoclast surface was observed at the end of the study (3.9 +/- 6.8 versus -1.2 +/- 4.1), and although a trend to reduce osteoblast surface (-2.5 +/- 2.6 versus -3.2 +/- 5.7) and osteoid surface (-2.1 +/- 2.5 versus -3.2 +/- 2.8) was also found, patients maintained approximately the same level of wall thickness (-5.2 +/- 5.3 versus -5.3 +/- 3.3) and bone volume (-2.7 +/- 1.8 versus -2.5 +/- 1.7). However, there was no improvement in mineralizing surface (-4.2 +/- 2.9 versus -10.4 +/- 3.6) or appositional rate (-5.8 +/- 3.1 versus -8.1 +/- 2.6). No significant differences in bone histomorphometric variables were observed between groups after 1 year of follow-up. In conclusion, 1,25-dihydroxyvitamin D3 and calcium carbonate did not significantly improve bone loss in long-term renal transplant recipients. However, significant osteoclast suppression and a trend to maintain trabecular bone volume and wall thickness as well as improve the axial BMD were observed in the treatment group.", "New and potent immunosuppressive regimens allow for reduced doses of corticosteroids after renal transplantation. The aims of our study were to investigate whether the use of low-dose corticosteroids is associated with a reduction in posttransplant bone loss and to assess the ability of cholecalciferol supplementation to further decrease bone loss in this setting.\n Ninety patients admitted for renal transplantation and scheduled to be treated per protocol with low doses of prednisolone were randomized to receive either 400 mg daily oral calcium (Ca group, n=44) or the same dose of calcium in association with a monthly dose of 25,000 IU of vitamin D3 (CaVitD group, n=46). Bone mineral density (BMD) was measured by dual energy absorptiometry at baseline and at 1 year.\n The overall population experienced a moderate but significant -2.3+/-0.9% loss of lumbar spine BMD (P<0.01) but no bone loss at the femoral neck and shaft during the first posttransplant year. Bone loss tended to be slightly higher in the CaVitD group, but the difference did not reach statistical significance. Patients in the CaVitD group had significantly higher 25(OH) but not 1,25(OH)2 vitamin D levels. We observed a highly significant negative correlation between 25(OH) vitamin D and intact parathyroid hormone (iPTH) serum levels.\n Kidney-transplant recipients receiving modern immunosuppressive regimens with low doses of corticosteroids experience only minimal loss of BMD during the first posttransplant year. Cholecalciferol supplementation did not prevent posttransplant bone loss but contributed to the normalization of iPTH levels after renal transplantation.", "nan", "Forearm bone mineral content (BMC), as evaluated by photonabsorption densitometry, was measured in 28 cadaver kidney donor recipients who entered the study 8 weeks postoperatively and were followed up for 18 months. BMC decreased significantly (p less than 0.05) but marginally in placebo-treated patients (n = 14) (initial BMC 1.09 +/- 0.25 g/cm; final BMC 1.05 +/- 0.24). Fourteen patients were prophylactically given 1,25(OH)2 vitamin D3 in a dose which avoided hypercalcemia and hypercalciuria (approximately 0.25 microgram/day); under 1,25(OH)2 vitamin D3 prophylaxis a significant decrease of forearm BMC was observed no longer (initial BMC 0.94 +/- 0.21 g/cm; final BMC 0.95 +/- 0.21), but the difference between placebo and 1,25(OH)2 vitamin D3 narrowly missed statistical significance (p = 0.066). It is concluded that the decrease of forearm BMC is negligible in transplant recipients with low steroid regimens. The data suggest a trend for prophylaxis with 1,25(OH)2 vitamin D3 to slightly ameliorate forearm (cortical) BMC loss.", "Very rapid bone loss, osteopenia and skeletal morbidity after renal transplantation have been well documented and found to occur in a sex dependent fashion. Glucocorticoids, cyclosporine and pre-existing uremic osteodystrophy have been implicated in the pathogenesis of the skeletal lesions. Glucocorticoid induced osteopenia is also a serious clinical problem in patients with various nonrenal diseases and can be prevented, or at least attenuated, by pamidronate and other bisphosphonates.\n We prospectively studied 26 male patients undergoing renal transplantation, and randomized them to receive either placebo or intravenous pamidronate (0.5 mg/kg) at the time of transplantation and again one month later. All patients received immunosuppression comprising prednisolone, cyclosporine and azathioprine. The bone mineral density (BMD) of the second, third and fourth lumbar vertebrae and of the femoral neck was measured at the time of transplantation and at three months and 12 months after transplantation using dual energy X-ray absorptiometry (DXA).\n Twelve months after transplantation, the mean (+/- SEM) BMD of the lumbar vertebrae in patients who received placebo had decreased 6.4% (P < 0.05). In contrast, patients who received pamidronate experienced no significant reduction of BMD at the lumbar vertebrae. At the femoral neck, placebo-treated patients showed a reduction of BMD of 9% (P < 0.005), whereas there was no significant change in the pamidronate treated group. The two study groups had similar patient profiles, serum parathyroid hormone (PTH) and aluminium concentrations. After transplantation, comparable falls in the serum creatinine and PTH concentration were found in the two groups. Apart from transient hypocalcemia in two patients, no significant adverse effects of pamidronate were noted.\n This study has shown that the early rapid bone loss that occurs in men during the first 12 months after renal transplantation can be prevented by two intravenous doses of pamidronate given at transplantation and one month later. The regimen was simple to administer, well tolerated and potentially applicable to other clinical groups of glucocorticoid treatment patients.", "Successful renal transplantation corrects many of the metabolic abnormalities associated with the development of renal osteodystrophy, but despite a well-functioning graft osteopenia, growth failure, spontaneous fractures, and avascular necrosis remain prevalent in adult and pediatric kidney recipients. A paucity of information exists regarding the effects of different therapies to prevent and treat bone loss in the renal transplant recipients. We constructed a design to study the effect of different modalities of treatment on bone mass in our renal transplant children. Among 93 patients who underwent renal transplantation at the age of 17 yr or less and were subjected to dual-energy X-ray absorptiometry (DEXA), we blindly randomized 60 patients who had osteopenia or osteoporosis (T-score = -1 by DEXA) in a prospective study. Their mean age at time of transplantation was 13.4 +/- 4.3 yr. The mean duration after transplantation was 48 +/- 34 months. The patients were classified randomly into four groups. Each group consisted of 15 patients: group 1 was the control group, group 2 received oral alfacalcidol 0.25 microg daily, group 3 received oral alendronate 5 mg daily, and group 4 received 200 IU/day nasal spray calcitonin. Parameters of bone turnover, calcium metabolism, and DEXA were measured before and after 12 months of treatment duration. The characteristics of all groups were comparable at the beginning of the study. At the lumber spine, bone mass density decreased from -2.4 to -2.8 in group 1, increased from -2.3 to -0.5 in group 2, from -2.3 to -1.9 in group 3, and from -2.3 to -1.0 in group 4. The four groups had similar patient profiles, serum creatinine, intact parathyroid hormone, osteocalcin, and deoxypyridinoline. This study confirmed the value of alfacalcidol and antiresorptive agents in the treatment of osteopenia and osteoporosis in young renal transplant recipients.These therapies were safe, tolerable, simple to administer and potentially applicable to other renal transplant patients.\n Copyright 2004 Blackwell Munksgaard", "nan", "Bone loss occurs during the first 6 months after renal transplantation (RT), and corticosteroid therapy plays an important role. Although calcium plus vitamin D administration prevents corticosteroid-induced osteoporosis, its use in RT recipients is limited by the risk of hypercalcemia.\n This double-blind, randomized, and controlled prospective intervention trial examined the effect of intermittent calcitriol (0.5 microg/48 h) during the first 3 months after RT, plus oral calcium supplementation (0.5 g/day) during 1 year with calcium supplementation alone. The primary outcome measure was the change in bone mineral density (BMD) at 3 and 12 months after RT; we also explored whether the effect of calcitriol on BMD was different among vitamin D receptor (VDR) genotypes (BsmI). Forty-five recipients were randomized to calcitriol therapy (CT) and 41 were randomized to placebo (PL).\n Both groups had a similar degree of pre-existing hyperparathyroidism (197 +/- 229 vs. 191 +/- 183 pg/mL), but a more pronounced decrease of parathyroid hormone (PTH) levels after RT was observed in CT patients (at 3 months: 61.4 +/- 42.2 vs. 85.7 +/- 53.1 pg/mL, P= 0.02; at 12 months: 67.3 +/- 33.7 vs. 82.6 +/- 37 pg/mL; P= 0.08). CT patients preserved their BMD at the total hip significantly better than those on PL (3 months: 0.04 +/- 3.3 vs. -1.93 +/- 3.2%, P= 0.01; 12 months: 0.32 +/- 4.8 vs. -2.17 +/- 4.4%, P= 0.03); significant differences were noted at the intertrochanter, trochanter, and Ward's triangle. Differences did not reach significance at the femoral neck. Two CT patients (4.4%) and 4 PL patients (9.8%) developed a hypercalcemic episode during the first 3 months after RT. The effect of CT on BMD at 3 months was more prominent in recipients with the at-risk allele of the VDR gene (P= 0.03).\n Therapy with low-dose calcium supplements during 1 year, plus intermittent calcitriol for 3 months after RT, is safe, decreases PTH levels more rapidly, and prevents bone loss at the proximal femur; a more pronounced effect is seen in recipients with at least one at-risk allele of the VDR genotype.", "Bisphosphonates can prevent bone mineral density loss after renal transplantation, but their effect on trabecular mineralization and bone morphology, two key factors of bone stability, remains unknown.\n In a 6-month, randomized, placebo-controlled study, 20 kidney transplant recipients received either 4 mg zoledronic acid or placebo twice within 3 months after engraftment. At transplantation and after 6 months, mean trabecular calcium concentration and trabecular morphometry were measured in bone biopsies. Bone mineral density (BMD) of the femoral neck and the lumbar spine were evaluated by dual-energy x-ray absorptiometry, and serum biochemical markers of bone metabolism were determined monthly.\n Trabecular calcium content increased significantly in the zoledronic acid group, but remained unchanged in the placebo group. BMD at femoral neck showed no change in the zoledronic acid group, but decreased in the placebo group. BMD of the lumbar spine was increased in the zoledronic acid group without change in the placebo group. High-turnover bone disease resolved similarly in both groups, as evidenced by a significant decrease of eroded bone surface, osteoclast and osteoblast surface. Serologic markers of bone formation and resorption were significantly lower in zoledronic acid-treated patients throughout the study. Kidney transplant function was stable after zoledronic acid therapy.\n Our results show that administration of zoledronic acid improves the calcium content of cancellous bone after kidney transplantation. The beneficial effect of bisphosphonate therapy is further evidenced by an increase of lumbar spine BMD, and stabilization of femur BMD." ]

[ "3096460", "7943128", "12162601", "12621096", "11865270", "15060235" ]

[ "Effect of night and day on preterm infants in a newborn nursery: randomised trial.", "A controlled clinical trial of light and retinopathy of prematurity.", "Randomized controlled study of the effects of different durations of light exposure on weight gain by preterm infants in a neonatal intensive care unit.", "Circadian and sleep development in preterm infants occurs independently from the influences of environmental lighting.", "Preterm infants born at less than 31 weeks' gestation have improved growth in cycled light compared with continuous near darkness.", "Rest-activity patterns of premature infants are regulated by cycled lighting." ]

[ "The effect of alternating night and day on sleep, feeding, and weight gain in 41 healthy preterm infants was examined in a randomised controlled trial. Twenty infants from a night and day nursery, where the intensity of light and noise was reduced between 7 pm and 7 am, spent longer sleeping and less time feeding and gained more weight than 21 infants from a control nursery, where the intensity of light and noise was not reduced. Differences were significant and became apparent only after discharge home; they were still present three months after the expected date of delivery, when infants from the night and day nursery were an average of 0.5 kg heavier (p less than 0.02). These findings suggest that physical environment has an effect (either direct or indirect) on the subsequent behaviour of preterm infants and that exposure to night and day is beneficial.", "Bright continuous light has been implicated in the pathogenesis of retinopathy of prematurity. To investigate the influence of light on the incidence and severity of retinopathy of prematurity, we enrolled 127 preterm infants (birth weight < or = 1,500 g; gestational age < or = 32 weeks) in a controlled clinical study. Randomization was done separately for three birth-weight groups (< 1,000 g; 1,000 to 1,249 g; 1,250 to 1,500 g). The babies' eyes were patched all day and night from birth to a gestational age of 35 weeks. The infants in the control group were exposed to cycled lighting conditions (that is, reduced light level during the night). Of 62 infants with patched eyes, 26 (42%) developed retinopathy of prematurity. In the control group, 25 of 65 infants (39%) showed retinopathy of prematurity (P = .596). There were also no statistically significant differences in the incidences of retinopathy of prematurity in the birth-weight subgroups or in the severity of retinopathy of prematurity. Thus, patching of the eyes from birth to 35 weeks of postconceptional age does not decrease the risk of retinopathy of prematurity in preterm infants when compared to a control group exposed to cycled lighting conditions.", "A randomized controlled study was carried out on 96 preterm infants (< 37 wk) with birthweight less than 2000 g admitted to a neonatal intensive care unit. The aim was to compare the weight gain between preterm infants exposed to 12 h cyclical lighting (intensity of light: 78.4 +/- 24.7 lux, mean +/- SD) and those exposed to a continuously dim environment (5.9 +/- 1.9 lux). The exclusion criteria were infants with major congenital malformations or who needed continuous lighting for treatment procedure and care. From day 7 of life until discharge, 50 infants were randomized to receive 12 h cyclical lighting and 46 infants to a continuously dim environment. There was no significant difference in the mean birthweight (12 h lighting vs continuously dim: 1482 vs 1465 g, p = 0.8), mean gestational age (31.6 vs 31.4 wk, p = 0.6), median duration of hospital stay (28.5 vs 28.5 d, p = 0.8), mean age to regain birthweight (13.0 vs 12.9 d, p = 0.3), mean weight gained by day 14 (27.6 vs 36.2 g, p = 1.0), median weight gain per day (11.9 vs 12.2 g, p = 0.9) or median body weight on discharge (1800 vs 1800 g, p = 0.4) between the two groups of infants.\n Exposing preterm infants to either 12 h cyglical lighting or continuously dim environment did not have any significant effect on their weight gain during the neonatal period.", "This study investigated the effect of intermediate nursery illumination on circadian rhythm and sleep development of preterm infants. Preterm infants were randomly assigned to one of two intermediate nursery rooms: a dimly lighted room, the dim (control) group, or a day-night lighted room, the cycled (intervention) group. Continuous rectal temperature and sleep were recorded at 36 wk postconceptional age (before discharge) and at 1 and 3 mo corrected age at home. Forty infants, 21 in the dim group and 19 in the cycled group, were recorded. The clinical demographic data and neonatal scores were similar between groups before the intervention. Circadian rhythms and sleep showed significant development with age, but there was no environmental lighting effect. Circadian and sleep organization seems to develop endogenously in preterm infants.", "Our purpose was to evaluate the benefits of cycled light (CL) versus near darkness (ND) on health in preterm infants born at <31 weeks' gestational age.\n Randomized, interventional study comparing infants receiving (1) CL from birth, (2) CL at 32 weeks' postconceptional age (PCA), and (3) CL at 36 weeks' PCA in transition for discharge home. Statistical significance was assessed with segmented mixed general linear models, analysis of covariance, general estimating equations, chi(2), and Fisher's exact procedure.\n Infants receiving CL at birth and 32 weeks' PCA gained weight faster than infants not receiving CL until 36 weeks' PCA. There were no differences among the groups in length of hospitalization stay or number of ventilator days, but the power was low for these variables.\n These findings suggest that CL has significant weight gain benefits over ND, and there are no short-term advantages of ND over cycled light for health in preterm infants.", "Many hospitalized premature infants are exposed to continuous dim lighting rather than to cycled lighting. However, we do not know whether dim lighting or low-intensity cycled lighting is more conducive to the development of rest-activity patterns that are in phase with the solar light-dark cycle. Thus, we examined the effects of nursery lighting conditions on the development of activity patterns in premature infants.\n Premature infants who were born at <32 weeks' postmenstrual age and were medically stable in neonatal intensive care unit rooms were randomly assigned between 32 and 34 weeks' postmenstrual age to either continuous dim lighting (<25 lux; duration 24 days; control group; n = 29) or cycled lighting (239 +/- 29 lux, 7:00 AM to 7:00 PM; <25 lux, 7:00 PM to 7:00 AM; duration: 25 days; experimental group; n = 33). Activity was continuously monitored from enrollment until approximately 1 month after discharge from the hospital. Weight and head circumference were also assessed up to 6 months after discharge from the hospital.\n Over the first 10 days at home, distinct day-night differences in activity were not seen in control subjects (D day-night: N 1.07 +/- 0.02), but experimental group infants were more active during the day than at night (day-night: 1.25 +/- 0.03). It was not until 21 to 30 days after discharge that day-night activity ratios in control infants matched those seen in experimental group infants shortly after discharge, yet even at this age, experimental group infants (day-night: 2.13 +/- 0.19) were considerably more active during the day than at night as compared with control subjects (day-night: 1.43 +/- 0.09).\n Exposure of premature infants to low-intensity cycled lighting in the hospital nursery induces distinct patterns of rest-activity that are apparent within 1 week after discharge. In comparison, the appearance of distinct patterns of rest and activity are delayed in infants who are exposed to continuous dim lighting in the hospital. These observations show that day-night rhythms in activity patterns can be detected shortly after discharge to home in premature infants and that the circadian clock of developing infants is entrained by cycled lighting." ]

[ "9077617" ]

[ "The effect of magnesium sulfate therapy on the duration of labor in women with mild preeclampsia at term: a randomized, double-blind, placebo-controlled trial." ]

[ "The primary outcome was to determine whether magnesium sulfate therapy prolongs the duration of labor in women with mild preeclampsia. Secondary outcomes were to assess the side effects associated with magnesium sulfate therapy: hours and maximum dose of oxytocin, incidence of progression to severe preeclampsia, incidence of cesarean delivery, change in maternal hematocrit, incidence of postpartum hemorrhage, incidence of maternal infection, and Apgar scores.\n Women with a diagnosis of mild preeclampsia at term were randomized to receive standard therapy during labor and for 12 hours post partum with either magnesium sulfate (n = 67) or a matching placebo solution (n = 68).\n There was no difference between magnesium sulfate and placebo with respect to the primary outcome variables: total length of labor (median 17.8 hours vs 16.5 hours, p = 0.7) and length of the active phase of labor (median 5.4 hours vs 6.0 hours, p = 0.5). In addition, no difference was observed in the secondary outcome variables: hours of oxytocin use, change in hematocrit, frequency of maternal infection, progression to severe preeclampsia, incidence of cesarean delivery, and Apgar scores. Although not statistically significant, the incidence of postpartum hemorrhage was approximately fourfold greater in the magnesium sulfate group (relative risk 4.1, 95% confidence interval 0.5 to 35.4). There was a significant difference in the maximum dose of oxytocin used (13.9 +/- 8.6 mU/min with magnesium sulfate vs 11.0 +/- 7.6 mU/min with placebo, p = 0.036).\n The use of magnesium sulfate during labor in women with mild preeclampsia at term does not affect any component of labor but did necessitate a higher dose of oxytocin." ]

[ "3925335", "1671434", "8504794", "8603630", "8601999", "7823066", "3098555", "4207990" ]

[ "Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures.", "Comprehensive primary health care antiepileptic drug treatment programme in rural and semi-urban Kenya. ICBERG (International Community-based Epilepsy Research Group)", "Antiepileptic drug treatment in a community health care setting in northern Ecuador: a prospective 12-month assessment.", "Comparison of antiepileptic drugs on cognitive function in newly diagnosed epileptic children: a psychometric and neurophysiological study.", "Randomised comparative monotherapy trial of phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed childhood epilepsy.", "Phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed adult epilepsy: a randomised comparative monotherapy trial.", "Carbamazepine versus phenobarbital for partial onset seizures in children.", "Carbamazepine for epilepsy. A controlled prospective evaluation." ]

[ "We conducted a 10-center, double-blind trial to compare the efficacy and toxicity of four antiepileptic drugs in the treatment of partial and secondarily generalized tonic-clonic seizures in 622 adults. Patients were randomly assigned to treatment with carbamazepine, phenobarbital, phenytoin, or primidone and were followed for two years or until the drug failed to control seizures or caused unacceptable side effects. Overall treatment success was highest with carbamazepine or phenytoin, intermediate with phenobarbital, and lowest with primidone (P less than 0.002). Differences in failure rates of the drugs were explained primarily by the fact that primidone caused more intolerable acute toxic effects, such as nausea, vomiting, dizziness, and sedation. Decreased libido and impotence were more common in patients given primidone. Phenytoin caused more dysmorphic effects and hypersensitivity. Control of tonic-clonic seizures did not differ significantly with the various drugs. Carbamazepine provided complete control of partial seizures more often than primidone or phenobarbital (P less than 0.03). Overall, carbamazepine and phenytoin are recommended drugs of first choice for single-drug therapy of adults with partial or generalized tonic-clonic seizures or with both.", "A programme of antiepileptic treatment in a rural and semi-urban region in Kenya was assessed. Patients with generalised tonic-clonic seizures were treated according to one of two simple drug protocols. Health workers screened cases reported by key informants in the community. From the 529 patients identified by health workers as having active seizures 302 patients aged 6-65 years were recruited by a psychiatrist for therapy with carbamazepine or phenobarbitone. Treatment was supervised largely by primary health workers, and the programme was monitored by a research team, which assessed the effectiveness of treatment. Of the 249 patients who completed the study, 53% became seizure-free in the second 6 months of therapy, and another 26% had substantially (50% or more reduction) fewer seizures than in the 6 months before therapy. The similarity of these findings to those obtained in newly diagnosed patients in the developed world, the low drop-out rate, the low rate of withdrawal due to adverse effects, and the acceptable compliance with therapy indicate that health workers can monitor therapy adequately. Most patients had had several years of delay before starting therapy for their epilepsy, yet they responded well--a finding that does not support the suggestion that the disorder becomes intractable if not treated early.", "The results of a prospective assessment of antiepileptic drug treatment carried out over a 12-month period, in the context of existing community health care in a rural area of a developing country (a highland region of northern Ecuador), are reported. A house to house survey defined all patients in the area with a history of epileptic seizures, and 192 patients with active epilepsy were recruited into the programme. These patients were randomised to treatment with carbamazepine or phenobarbital, and 139 completed the assessment. Treatment was carried out by health visitors and rural doctors, monitored by a team of neurologists, and standard treatment regimens were used. Treatment was effective in controlling seizures, 53% of the patients were rendered entirely seizure free in the second 6 months of therapy, and a further 14% had a 50% or more reduction in seizures. These results were similar to those reported in hospital based studies in developed countries. No significant differences were found between the efficacy and safety of phenobarbital or carbamazepine. Antiepileptic drug levels were monitored during the study, and ranges similar to those found in developed countries were recorded. Compliance was good. In view of the successful treatment in this community control programme, we would recommend that community programmes for the control of epilepsy in rural settings should be given a higher priority in the planning of health care provision than is commonly the case. Finally, the programme afforded the opportunity to study the efficacy of treatment in patients with chronic long-standing epilepsy, who had not been previously treated, and the results of this treatment were good.", "Using a randomized parallel group study design, we compared the cognit ive effects of carbamazepine (CBZ), phenobarbital (PB), and valproate (VPA) in children with epilepsy. Seventy-three children with newly diagnosed epilepsy were tested with the Wechsler Intelligence Scale for Children-Revised (WISC-R), Bender-Gestalt test, and auditory event-related potentials (P 300) before and 6 and 12 months after antiepileptic drug (AED) treatment. There were no significant differences in WISC-R IQs and Bender-Gestalt scores for children in any group at any of the three sessions. P 300 latencies were increased in the children receiving PB but not in children receiving CBZ and VPA. P 300 amplitudes were significantly reduced in treated children in all three groups, but amplitudes were not significantly different among the three groups. These findings suggest that PB may affect cognitive function of epileptic children and that the P 300 may be a sensitive additional procedure that can be used to assess the cognitive effect of AEDs.", "The medical treatment of childhood epilepsy is largely influenced by clinical trials in adult patients. We know of only one randomised comparative trial (of two drugs) in newly diagnosed childhood epilepsy. We have undertaken a long-term, prospective, randomised, unmasked, pragmatic trial of the comparative efficacy and toxicity of four standard antiepileptic drugs used as monotherapy in children with newly diagnosed epilepsy.\n Between 1981 and 1987, 167 children aged 3-16 years, who had had at least two previously untreated tonic-clonic or partial seizures, with or without secondary generalisation, were randomly allocated treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform to standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to achieving 1-year remission.\n The overall outcome with all four drugs was good. 20% of children remained free of seizures and 73% had achieved 1-year remission by 3 years of follow-up. We found no significant differences between the drugs for either measure of efficacy at 1, 2, or 3 years of follow-up. The overall frequency of unacceptable side-effects necessitating withdrawal of the randomised drug was 9%. This total included six of the first ten children assigned phenobarbitone; no further children were allocated this drug. Of the other three drugs, phenytoin (9%) was more likely to be withdrawn than carbamazepine (4%) or sodium valproate (4%). INTERPRETATION Our data will inform choice of drug and outcome with four of the standard drugs available for newly diagnosed tonic-clonic or partial seizures with or without secondary generalisation in children.", "Recent studies have shown that most newly diagnosed epileptic patients can be satisfactorily treated with a single antiepileptic drug. We therefore undertook a prospective randomised pragmatic trial of the comparative efficacy and toxicity of four major antiepileptic drugs, utilised as monotherapy in newly diagnosed epileptic patients. Between 1981 and 1987 243 adult patients aged 16 years or over, newly referred to two district general hospitals with a minimum of two previously untreated tonic-clonic or partial with or without secondary generalised seizures were randomly allocated to treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform with standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to enter one year remission. The overall outcome with all of the four drugs was good with 27% remaining seizure free and 75% entering one year of remission by three years of follow up. No significant differences between the four drugs were found for either measure of efficacy at one, two, or three years of follow up. The overall incidence of unacceptable side effects, necessitating withdrawal of the randomised drug, was 10%. For the individual drugs phenobarbitone (22%) was more likely to be withdrawn than phenytoin (3%), carbamazepine (11%), and sodium valproate (5%). In patients with newly diagnosed tonic-clonic or partial with or without secondary generalised seizures, the choice of drug will be more influenced by considerations of toxicity and costs.", "Thirty-nine children were treated with either phenobarbital (PB) or carbamazepine (CBZ) for newly diagnosed partial onset seizures. Drug selection was randomized in 33 subjects. Parents and the psychologist evaluating the child were blind to drug identity. Psychometric and behavioral evaluations were done at intake and at 6- and 12-month follow-ups. There were no significant differences between drugs in effect on behavior or cognitive function. CBZ caused more systemic problems. There was a trend toward better seizure control with CBZ, but this was not statistically significant. Although individual children in each group had changes in behavior or cognitive status, neither group changed significantly, in either acute or chronic follow-up.", "nan" ]

[ "7603807", "21334262", "17968821", "17921553" ]

[ "Oral glycerol and intravenous dexamethasone in preventing neurologic and audiologic sequelae of childhood bacterial meningitis. The Finnish Study Group.", "Glycerol adjuvant therapy in adults with bacterial meningitis in a high HIV seroprevalence setting in Malawi: a double-blind, randomised controlled trial.", "Adjuvant glycerol and/or dexamethasone to improve the outcomes of childhood bacterial meningitis: a prospective, randomized, double-blind, placebo-controlled trial.", "Role of dexamethasone and oral glycerol in reducing hearing and neurological sequelae in children with bacterial meningitis." ]

[ "To assess the value of adjunctive intravenous dexamethasone (DXM) and oral glycerol (GLY) for the treatment of bacteriologically proved bacterial meningitis, 122 infants and children with bacterial meningitis were randomly assigned to receive DXM intravenously (n = 32), GLY orally (n = 30), DXM plus GLY (n = 34) or neither (n = 26) of these drugs. All patients were treated with the same antimicrobial agent, ceftriaxone. The patients were followed neurologically for as long as 6 months. A thorough hearing evaluation was performed routinely 2 months or more after discharge from hospital. Overall 4 (7%) of the GLY-treated patients, compared with 11 (19%) of those not given GLY, developed audiologic or neurologic sequelae (P = 0.052), the relative risk of sequelae being 2.94 (95% confidence interval, 0.99 to 8.72). The patients who had received GLY showed less severe or profound bilateral hearing impairment than those not given GLY (0 vs. 7%, P = 0.049), and none of them had other neurologic abnormalities 3 or 6 months after discharge, compared with 5 (9%) of those not treated with GLY (P = 0.024). The DXM recipients showed only a tendency to less severe hearing impairment than those not given DXM. In conclusion oral GLY prevented neurologic sequelae in infants and children with bacterial meningitis more effectively than intravenous DXM.", "Southern Africa has a high incidence of bacterial meningitis in adults, often associated with HIV co-infection. Mortality exceeds 50%, even with appropriate antibiotic therapy, and is not improved with corticosteroids. Glycerol adjuvant therapy reduces long-term morbidity in bacterial meningitis in children, and its use is being promoted. We aimed to assess the effectiveness of glycerol as an adjuvant therapy for adults with bacterial meningitis in Africa.\n The study was done in two phases. First, in an open-label dose-finding study, 45 adult patients with symptoms, signs, and cerebrospinal fluid findings consistent with bacterial meningitis received either 50 mL, 75 mL, or 100 mL of glycerol four times a day for 4 days. We then did a randomised, double-blind, placebo-controlled trial of oral glycerol in adults with bacterial meningitis. Patients with clinical and cerebrospinal fluid findings suggestive of bacterial meningitis were randomly assigned in blocks of 12 by use of a random number list produced by an independent statistician to receive either glycerol or an equivalent volume of sugar solution. Glycerol and placebo were indistinguishable by colour or taste. The primary outcome was mortality at 40 days, with secondary outcomes including disability and mortality restricted to pneumococcal disease. All patients were analysed for the primary outcome excluding those who were lost to follow-up. This trial is registered at controlled-trials.com, number ISRCTN70121840.\n 75 mL glycerol four times a day was the highest tolerated dose, and was used for the main study. 265 patients were assigned treatment: 137 glycerol and 128 placebo. The trial was stopped early on the advice of the data and safety monitoring board after a planned interim analysis. By day 40, 61 (49%) of 125 patients in the placebo group and 86 (63%) of 136 in the glycerol group had died (adjusted odds ratio 2.4, 95% CI 1.3-4.2, p=0.003). There was no benefit from glycerol for death and disability by day 40, and glycerol did not improve death and disability by day 40 or death at day 40 in patients with proven bacterial disease or pneumococcal disease. Two serious adverse events occurred that were possibly due to the study drug.\n Oral glycerol therapy cannot be recommended as an adjuvant therapy in adults with bacterial meningitis in resource-poor settings with a high HIV prevalence.\n Meningitis Research Foundation.\n Copyright © 2011 Elsevier Ltd. All rights reserved.", "Despite favorable meta-analyses, no study involving third-generation cephalosporins for the treatment of childhood bacterial meningitis has documented a benefit of adjuvant dexamethasone therapy if the outcomes are examined individually.\n We conducted a prospective, randomized, double-blind trial comparing adjuvant dexamethasone or glycerol with placebo in children aged from 2 months through 16 years in Latin America. Ceftriaxone was administered to all children; children were randomized to also receive dexamethasone intravenously, glycerol orally, both agents, or neither agent. Primary end points were death, severe neurological sequelae, or deafness, with the first 2 end points forming a composite end point. A subgroup analysis for Haemophilus influenzae type b meningitis was undertaken. Intention-to-treat analysis was performed using binary logistic regression models.\n H. influenzae type b, pneumococci, and meningococci were the main agents found among 654 patients; dexamethasone was given to 166, dexamethasone and glycerol were given to 159, glycerol was given to 166, and placebo was given to 163. No adjuvant therapy significantly affected death or deafness. In contrast, glycerol and dexamethasone plus glycerol reduced severe neurological sequelae, compared with placebo; the odds ratios were 0.31 (95% confidence interval [95% CI], 0.13-0.76; P=.010) and 0.39 (95% CI, 0.17-0.93; P=.033), respectively. For neurological sequelae and death, the odds ratios were 0.44 (95% CI, 0.25-0.76; P=.003) and 0.55 (95% CI, 0.32-0.93; P=.027), respectively. Dexamethasone therapy prevented deafness in patients with H. influenzae type b meningitis only if patients were divided grossly into dexamethasone recipients and nonrecipients and if timing between dexamethasone and ceftriaxone administration was not taken into account (odds ratio, 0.27; 95% CI, 0.09-0.77; P=.014).\n Oral glycerol therapy prevents severe neurological sequelae in patients with childhood meningitis. Safety, availability, low cost, and oral administration also add to its usefulness, especially in resource-limited settings.", "To investigate the efficacy of dexamethasone and oral glycerol in reducing hearing and neurological sequelae in children with acute bacterial meningitis (ABM).\n Prospective double blind, placebo controlled randomized study.\n Pediatric services of a tertiary care teaching and referral hospital.\n Children 2 months to 12 years with a diagnosis of acute bacterial meningitis admitted between June 2002 to September 2003.\n Subjects were assigned randomly to receive dexamethasone, glycerol, dexamethasone+glycerol or placebo. Neurological and hearing impairment was assessed at discharge and after 1 month.\n 58 children (48 boys, 10 girls), mean age 50.2 +/- 41.0 months, were studied. Twelve patients received dexamethasone, 13 glycerol, 20 dexamethasone + glycerol and 13 placebo. Bacterial etiology was ascertained in 24 patients: Streptococcus pneumoniae-10, H influenzae b-7, Staph. aureus-5 and others-2. Three (5.2%) children died during hospital stay and 55 survived. Seven (12%) patients had neurological sequelae (3 in glycerol, 3 in dexamethasone+glycerol, 1 in placebo group, P = 0.29), and 10 patients (17%) had hearing sequelae (2 in glycerol, 3 in dexamethasone, 2 dexamethasone + glycerol and 3 in placebo group, P = 0.68).\n No significant difference was seen in neurological or hearing outcome with use of either glycerol or dexamethasone in children with acute bacterial meningitis." ]

[ "18399862", "18245143" ]

[ "Effects of pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis.", "Short term improvement in exercise capacity and symptoms following exercise training in interstitial lung disease." ]

[ "Although pulmonary rehabilitation is effective for patients with COPD, its efficacy in patients with IPF is unknown. The purpose of this study was to evaluate the effects of pulmonary rehabilitation in IPF.\n Thirty patients diagnosed with IPF, according to the consensus statement, were randomly assigned to the rehabilitation group or the control group. The pulmonary rehabilitation mainly consisted of a 10-week programme of exercise training. Pulmonary function, blood gas analysis, 6MWD, dyspnoea rating with the baseline dyspnoea index and health-related quality of life score on the St George's Respiratory Questionnaire were evaluated at baseline and after the programme.\n Assessment of efficacy was carried out on 13 patients who completed the programme and 15 patients in the control group. There were no significant effects of the programme on measures of pulmonary function, values of arterial blood gas analysis or dyspnoea rating. Although there were some differences in the baseline 6MWD and total health-related quality of life score which were not statistically significant, marked improvements were observed in the 6MWD (mean difference 46.3 m (95% CI: 8.3-84.4), P < 0.05) and the total health-related quality of life score (-6.1 (95% CI: -11.7 to -0.5), P < 0.05).\n Pulmonary rehabilitation improves both exercise capacity and health-related quality of life in patients with IPF.", "Interstitial lung disease (ILD) is characterised by exertional dyspnoea, exercise limitation and reduced quality of life. The role of exercise training in this diverse patient group is unclear. The aims of this study were to establish the safety of exercise training in ILD; its effects on exercise capacity, dyspnoea and quality of life; and whether patients with idiopathic pulmonary fibrosis (IPF) had similar responses to those with other types of ILD.\n 57 subjects with ILD (34 IPF) were randomised to receive 8 weeks of supervised exercise training or weekly telephone support. The 6 min walk distance (6MWD), incremental exercise test, modified Medical Research Council (MRC) dyspnoea score and Chronic Respiratory Disease Questionnaire (CRDQ) were performed at baseline, following intervention and at 6 months.\n 80% of subjects completed the exercise programme and no adverse events were recorded. The 6MWD increased following training (mean difference to control 35 m, 95% CI 6 to 64 m). A significant reduction in MRC score was observed (0.7 points, 95% CI 0.1 to 1.3) along with improvements in dyspnoea (p = 0.04) and fatigue (p<0.01) on the CRDQ. There was no change in peak oxygen uptake; however, exercise training reduced heart rate at maximum isoworkload (p = 0.01). There were no significant differences in response between those with and without IPF. After 6 months there were no differences between the training and control group for any outcome variable.\n Exercise training improves exercise capacity and symptoms in patients with ILD, but these benefits are not sustained 6 months following intervention." ]

[ "18048059" ]

[ "A pilot study to evaluate the effects of Cerebrolysin on cognition and qEEG in vascular dementia: cognitive improvement correlates with qEEG acceleration." ]

[ "The effects of the neurotrophic compound Cerebrolysin (Cere) on cognitive performance, evaluated with the ADAS-cog, and on qEEG activity were investigated in forty one patients with mild to moderate severe probable vascular dementia (VaD) according to NINDS-AIREN criteria, included in a placebo-controlled pilot study. Patients received i.v. infusions of Cere (10 or 30 ml) or placebo (normal saline) 5 days/week for 4 weeks. Mean score of change from baseline in the ADAS-cog and percent change from baseline in slow to fast EEG power ratio (PR) scores were the two primary endpoints. Correlations between cognition and qEEG were also evaluated for both baseline scores and for scores of change from baseline in ADAS-cog and in qEEG parameters, including EEG power ratio (PR) as an index of EEG slowing. Baseline ADAS-cog scores showed significant positive correlations with delta power, theta power and PR scores, and correlated negatively with alpha activity. These correlations indicating that an increased EEG slowing is associated with a worst cognitive performance in VaD patients. Cere treatment improved cognitive performance significantly at the 10 ml dose and reduced EEG slowing with both 10 and 30 ml dosages. A significant positive correlation between PR and ADAS-cog scores of change from baseline was observed in Cere-treated patients. According to results of this pilot study, it is concluded that Cere improves cognitive performance and reduces EEG slowing in patients with VaD, and that there is a positive relationship between changes in cognition and qEEG activity induced by Cere. The conduction of further regular clinical trials is required to confirm the potential utility of Cere in the treatment of VaD suggested by the present results." ]

[ "17223873", "19138010", "17310011", "16785375", "11069454", "8977678", "16713457", "14732656" ]

[ "Treatment of post-transplant premalignant skin disease: a randomized intrapatient comparative study of 5-fluorouracil cream and topical photodynamic therapy.", "Fractionated illumination improves the outcome in the treatment of precancerous lesions with photodynamic therapy.", "Response of Bowen disease to ALA-PDT using a single and a 2-fold illumination scheme.", "Comparison of topical methyl aminolevulinate photodynamic therapy with cryotherapy or Fluorouracil for treatment of squamous cell carcinoma in situ: Results of a multicenter randomized trial.", "Comparison of red and green light in the treatment of Bowen's disease by photodynamic therapy.", "Comparison of photodynamic therapy with cryotherapy in the treatment of Bowen's disease.", "Imiquimod 5% cream monotherapy for cutaneous squamous cell carcinoma in situ (Bowen's disease): a randomized, double-blind, placebo-controlled trial.", "Photodynamic therapy of multiple nonmelanoma skin cancers with verteporfin and red light-emitting diodes: two-year results evaluating tumor response and cosmetic outcomes." ]

[ "Organ transplant recipients (OTR) are at high risk of developing nonmelanoma skin cancer and premalignant epidermal dysplasia (carcinoma in situ/ Bowen's disease and actinic keratoses). Epidermal dysplasia is often widespread and there are few comparative studies of available treatments.\n To compare topical methylaminolaevulinate (MAL) photodynamic therapy (PDT) with topical 5% fluorouracil (5-FU) cream in the treatment of post-transplant epidermal dysplasia.\n Eight OTRs with epidermal dysplasia were recruited to an open-label, single-centre, randomized, intrapatient comparative study. Treatment with two cycles of topical MAL PDT 1 week apart was randomly assigned to one area of epidermal dysplasia, and 5-FU cream was applied twice daily for 3 weeks to a clinically and histologically comparable area. Patients were reviewed at 1, 3 and 6 months after treatment. The main outcome measures were complete resolution rate (CRR), overall reduction in lesional area, treatment-associated pain and erythema, cosmetic outcome and global patient preference.\n At all time points evaluated after completion of treatment, PDT was more effective than 5-FU in achieving complete resolution: eight of nine lesional areas cleared with PDT (CRR 89%, 95% CI: 0.52-0.99), compared with one of nine lesional areas treated with 5-FU (CRR 11%, 95% CI: 0.003-0.48) (P = 0.02). The mean lesional area reduction was also proportionately greater with PDT than with 5-FU (100% vs. 79% respectively). Cosmetic outcome and patient preference were also superior in the PDT-treated group.\n Compared with topical 5-FU, MAL PDT was a more effective and cosmetically acceptable treatment for epidermal dysplasia in OTRs and was preferred by patients. Further studies are now required to confirm these results and to examine the effect of treating epidermal dysplasia with PDT on subsequent development of squamous cell carcinoma in this high risk population.", "Photodynamic therapy (PDT) is a noninvasive therapy for non-melanoma skin cancer. The aim of this study was comparison of efficacy between fractioned versus single dose illumination in photodynamic therapy (PDT) of actinic keratosis (AK) and Bowen's disease (BD). Fifty-one patients (36 AK and 15 BD) were treated with PDT They were randomly arranged in two treatment groups. Group one included 26 patients (20 AK and 6 BD) that, after five hours of incubation with 20% 5-ALA, were treated with a single illumination of 100 Jcm(-2) at fluence rate of 30 mWcm(-2). Group two included 25 patients (16 AK and 9 BD) that, after 16 hours of incubation with 20% 5-ALA, were treated with two light fractions (50 plus 50 Jcm(-2)) at same fluence rate with dark interval of two hours between fractions. Twenty-four weeks later, a treated area was incubated for four hours again with 5-ALA in order to detect occult areas of abnormal skin with possible remaining tumor tissue. In case of fluorescence, histological examination was performed. In the group one, fluorescence at the end of the session was absent in 19 (73%) or very weak in 7 (27%). Residual tumor was found in 15 (75%) AK and in 4 (66.6%) BD. In the group two, fluorescence at the end of second session was more intense; in one patient (4%) was absent, very weak in 5 (20%) and weak in 19 (76%) of patients. In this group histology revealed remaining tumor tissue in only 2 (12.5%) AK and 2 (22.2%) BD. Among the patients in the first group, the remaining tumor tissue was significantly bigger (p=0.005). The treatment response with clearing of tumor tissue was significantly higher in fractionated illumination than in a single dose illumination group. Fractionated illumination scheme with 16 hours of incubation separated by two hours dark interval significantly improves the therapeutic outcome in tumor eradication.", "nan", "To compare the efficacy, tolerability, and cosmetic outcome of photodynamic therapy (PDT) using topical methyl aminolevulinate with cryotherapy or topical fluorouracil for treatment of squamous cell carcinoma in situ.\n Randomized, placebo-controlled study, with follow-up at 3 and 12 months after last treatment.\n Forty outpatient dermatology centers in 11 European countries.\n Random sample of 225 patients with histologically confirmed squamous cell carcinoma in situ (lesion size, 6-40 mm) and no evidence of progression.\n Treatment with PDT with methyl aminolevulinate (160 mg/g; n = 96) or matching placebo cream (n = 17), cryotherapy (n = 82), or topical fluorouracil (5% cream; n = 30). Methyl aminolevulinate or placebo cream was applied for 3 hours before illumination with broadband red light (75 J/cm2, 570-670 nm). Treatment was repeated 1 week later. Cryotherapy was performed with liquid nitrogen spray. Fluorouracil was applied for 4 weeks. Lesions with a partial response at 3 months were re-treated.\n Clinically verified complete response of lesions; blinded and on-site assessment of cosmetic outcome (4-point rating scale).\n At 12 months, the estimated sustained lesion complete response rate with methyl aminolevulinate PDT was superior to that with cryotherapy (80% vs 67%; odds ratio, 1.77; 95% confidence interval, 1.01-3.12; P = .047), and better than that with fluorouracil (80% vs 69%; odds ratio, 1.64; 95% confidence interval, 0.78-3.45; P = .19). Cosmetic outcome at 3 months was good or excellent in 94% of patients treated with methyl aminolevulinate PDT vs 66% with cryotherapy and 76% with fluorouracil, and was maintained at 12 months.\n Methyl aminolevulinate PDT is an effective treatment option for squamous cell carcinoma in situ, with excellent cosmesis.", "A variety of protocols exist for the treatment of Bowen's disease by photodynamic therapy (PDT) using topical 5-aminolaevulinic acid (5-ALA).\n To determine the optimal wavelength (red or green light) for this treatment.\n A randomized comparison study of ALA-PDT using red (630 +/- 15 nm) or green (540 +/- 15 nm) light in the treatment of Bowen's disease.\n The initial clearance rate for lesions treated by red light was 94% (30 of 32) in comparison with 72% (21 of 29) for those lesions receiving green light (P = 0.002). Over the following 12 months, there were two recurrences in the red light group and seven in the green light group reducing the clearance rates to 88% and 48%, respectively. The frequency and severity of pain experienced were similar between the two treatment groups. No hyperthermia, nor significant difference in lesional temperatures, was observed between the wavelengths studied.\n Green light is less effective than red light, at a theoretically equivalent dose, in the treatment of Bowen's disease by topical ALA-PDT.", "The efficacy and suitability of photodynamic therapy (PDT) was compared with that of cryotherapy in the treatment of 40 lesions of Bowen's disease. Lesions were randomized to receive either cryotherapy with liquid nitrogen, or PDT using a portable desktop lamp incorporating a 300 W xenon short arc discharge source. A porphyrin precursor, 5-aminolaevulinic acid (5-ALA), was applied topically 4 h before irradiation in the PDT group. Each lesion received 125 J/cm2 at a fluence rate of 70 mW/cm2. All patients were reviewed at 2-monthly intervals and treatments repeated if required. Cryotherapy produced clearance in 10 of 20 lesions after one treatment, the remaining 10 lesions requiring two or three treatment applications. PDT resulted in clearance of 15 of 20 lesions after one treatment and of the remaining five lesions after a second treatment. The probability that a lesion cleared after one treatment was greater with PDT than cryotherapy (P < 0.01). Cryotherapy was associated with ulceration (five of 20), infection (two of 20) and recurrent disease (two of 20); no such complications occurred following PDT. PDT using a non-laser light source and topical 5-ALA appears to be at least as effective as cryotherapy in the treatment of Bowen's disease with fewer adverse effects.", "We conducted a double-blind, placebo-controlled, randomized trial to evaluate the preliminary efficacy and safety of imiquimod 5% cream treatment for cutaneous squamous cell carcinoma (SCC) in situ.\n In all, 31 patients with biopsy-proven cutaneous SCC in situ were randomly assigned to placebo (vehicle) (n = 16) or imiquimod 5% cream (n = 15) daily for 16 weeks. Patients were assessed at week 28 for the primary end point, resolution of cutaneous SCC in situ.\n Of the 31 patients enrolled, 3 dropped out. Intention-to-treat analysis revealed 11 of the 15 patients (73%) in the imiquimod group achieved resolution of cutaneous SCC in situ, with no relapse during the 9-month follow-up period; none in the placebo group achieved resolution (P < .001). Imiquimod 5% cream was generally well tolerated and there were no serious adverse events.\n Topical imiquimod 5% cream has proven to be an effective treatment for cutaneous SCC in situ. However, studies to define the ideal dosing regimen and cost-effectiveness are required before it can be accepted as a recognized therapy.\n In this controlled trial, patients with cutaneous SCC in situ receiving topical imiquimod 5% cream as monotherapy experienced a high degree of clinical benefit compared with placebo.", "Efficient treatment of patients with multiple synchronous nonmelanoma skin cancers represents a therapeutic challenge.\n To study the safety and efficacy of photodynamic therapy (PDT) with verteporfin and red light in the treatment of multiple nonmelanoma skin cancers.\n Open-label, randomized, multicenter, dose-ranging phase 2 study conducted at 4 North American university-based dermatology clinics.\n Fifty-four patients with 421 multiple nonmelanoma skin cancers including superficial and nodular basal cell carcinoma and squamous cell carcinoma in situ (Bowen disease).\n A single intravenous infusion of 14 mg/m(2) of verteporfin followed 1 to 3 hours later by exposure of tumors to 60, 120, or 180 J/cm(2) of red light (688 +/- 10 nm) from a light-emitting diode panel.\n Pathologic response of treated sites was assessed at 6 months. Clinical and cosmetic responses were assessed and graded at 6 weeks, 3 months, and 6 months after verteporfin PDT, with optional follow-up visits at 12, 18, and 24 months.\n The histopathologic response, defined as absence of tumor on biopsy specimens 6 months after verteporfin PDT, ranged from 69% at 60 J/cm(2) to 93% at 180 J/cm(2). At 24 months of follow-up (276 tumors in 31 patients), the clinical complete response rate ranged from 51% at 60 J/cm(2) to 95% at 180 J/cm(2). No significant systemic adverse events were observed; most events occurred at the treated tumor sites and included events such as pain. Overall, 65% (95% confidence interval, 58%-71%) of tumors were judged to have good to excellent cosmesis at 24 months.\n A single course of verteporfin PDT showed treatment benefit for patients with multiple nonmelanoma skin cancers." ]

[ "7672157", "9202835", "3067479", "18395716", "11872201", "6411497", "19447425", "9720838", "18287793", "8957697", "16600222", "2180213", "10221237", "12623744", "19428083", "10349300", "12892384", "17550489", "15292108", "16281510", "15867002", "10757545", "17982752", "16169400", "15193480", "12568837", "9698665" ]

[ "A double-blind randomized placebo cross-over controlled trial using the antioxidant vitamin E to treat reactive oxygen species associated male infertility.", "Effects of pentoxifylline on sperm motility in normogonadotropic asthenozoospermic men.", "Pentoxifyllin treatment of oligoasthenospermic men.", "Coenzyme Q10 treatment in infertile men with idiopathic asthenozoospermia: a placebo-controlled, double-blind randomized trial.", "Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial.", "Comparison of the effectiveness of placebo, clomiphene citrate, mesterolone, pentoxifylline, and testosterone rebound therapy for the treatment of idiopathic oligospermia.", "Efficacy of coenzyme Q10 on semen parameters, sperm function and reproductive hormones in infertile men.", "Treatment of asthenozoospermia with zinc sulphate: andrological, immunological and obstetric outcome.", "Indications of the mechanisms involved in improved sperm parameters by zinc therapy.", "Lipid peroxidation and human sperm motility: protective role of vitamin E.", "Carnitine for the treatment of idiopathic asthenospermia: a randomized, double-blind, placebo-controlled trial.", "Relationship between ascorbic acid and male fertility.", "Antioxidant treatment of patients with asthenozoospermia or moderate oligoasthenozoospermia with high-dose vitamin C and vitamin E: a randomized, placebo-controlled, double-blind study.", "Sperm oxidative stress and the effect of an oral vitamin E and selenium supplement on semen quality in infertile men.", "Effects of N-acetylcysteine on semen parameters and oxidative/antioxidant status.", "[In vivo scavenging effect of ethylcysteine on reactive oxygen species in human semen].", "Magnesium-orotate supplementation for idiopathic infertile male patients: a randomized, placebo-controlled clinical pilot study.", "A randomised control trial examining the effect of an antioxidant (Menevit) on pregnancy outcome during IVF-ICSI treatment.", "Cinnoxicam and L-carnitine/acetyl-L-carnitine treatment for idiopathic and varicocele-associated oligoasthenospermia.", "[A controlled randomized trial of the use of combined L-carnitine and acetyl-L-carnitine treatment in men with oligoasthenozoospermia].", "Reduction of the incidence of sperm DNA fragmentation by oral antioxidant treatment.", "Effect of DHA supplementation on DHA status and sperm motility in asthenozoospermic males.", "May antioxidant therapy improve sperm parameters of men with persistent oligospermia after retrograde embolization for varicocele?", "Placebo-controlled double-blind randomized trial on the use of L-carnitine, L-acetylcarnitine, or combined L-carnitine and L-acetylcarnitine in men with idiopathic asthenozoospermia.", "A placebo-controlled double-blind randomized trial of the use of combined l-carnitine and l-acetyl-carnitine treatment in men with asthenozoospermia.", "Use of carnitine therapy in selected cases of male factor infertility: a double-blind crossover trial.", "The effect of oral selenium supplementation on human sperm motility." ]

[ "To determine the effectiveness of the in vivo administration of vitamin E as treatment for reactive oxygen species-associated male infertility.\n University-based center for reproductive medicine.\n Double-blind randomized placebo cross-over controlled trial.\n Thirty healthy men with high levels of reactive oxygen species generation in semen and a normal female partner.\n Patients were allocated to two groups according to the blinded randomization. Each patient received either 600 mg/d of vitamin E (Ephynal, 300 mg tablets; F. Hoffman-La Roche Ltd., Basle, Switzerland) (order A) or identical placebo tablets (order B) for 3 months. Then after a 1-month wash-out period the patients were crossed-over to the other treatment.\n Improvement in the in vitro function of the spermatozoa measured by conventional semen analysis, computerized motility assessment, determination of reactive oxygen species generation, binding to the zona pellucida of the unfertilized human oocyte in a competitive zona binding assay, development of hyperactivated motility (both spontaneous and in the presence of 20% of the natural agonist, human follicular fluid) and pregnancy.\n Rise in the blood serum vitamin E levels after treatment accompanied by improvement in one of the sperm function tests: the zona binding assay. The zona binding ratio for order A improved from 0.2 (range 0 to 0.5) before treatment to 0.5 (range 0.1 to 1.0) after treatment, the corresponding values for order B were 0.2 (range 0 to 1.0) before treatment and 0.3 (range 0.1 to 0.7) after treatment.\n Oral administration of vitamin E significantly improves the in vitro function of human spermatozoa as assessed by the zona binding test.", "Forty-seven normogonadotropic men with idiopatic asthenozoospermic were divided at random: group I (N = 22) received placebo and group II (N = 25) received 1200 mg of pentoxifylline/day during 6 months. Semen analysis was performed basal and at 3 and 6 months of the study period. No statistical changes in serum hormone concentration were found, nor in volume, sperm counts, viability, and morphology before and after treatment. Sperm motility increased following pentoxifylline treatment after 3 and 6 months from 25.5 (21.0-30.0) to 35.5 (31.5-39.0) (p < .00001) and to 42.0 (38.0-46.0) (p < .00001), respectively. Although in the placebo control cases some changes were observed in the sperm motility, they were less significant. Furthermore, progressive motility only in grade A increased with pentoxifylline from 2.5 (0.0-6.0) to 12.0 (6.0-19.5) (p < .001) at 3 months and to 22.5 (17.0-26.0) at 6 months (p < .00001). In conclusion, pentoxifylline had an additional effect rather than placebo and was useful treatment in these cases of male factor infertility.", "A randomised group of 90 men with idiopathic oligoasthenozoospermia was subjected to control study with pentoxifyllin. Pentoxifyllin was given to 51 men 1200 mg daily for 3 months. The other group of 39 infertile men was followed during the same period of time. Significant improvement was observed, in treated group, in percentage of motile sperms and normal shaped sperms after 3 months treatment. This study emphasizes that pentoxifyllin is a relatively good drug for restoring sperm motility and morphology in oligoasthenozoospermic men.", "To evaluate the effectiveness of coenzyme Q(10) treatment in improving semen quality in men with idiopathic infertility.\n Placebo-controlled, double-blind randomized trial.\n Andrology Unit, Department of Internal Medicine, Polytechnic University of Marche, Italy.\n Sixty infertile patients (27-39 years of age) with the following baseline sperm selection criteria: concentration >20 x 10(6)/mL, sperm forward motility <50%, and normal sperm morphology >30%; 55 patients completed the study.\n Patients underwent double-blind therapy with coenzyme Q(10), 200 mg/day, or placebo; the study design was 1 month of run-in, 6 months of therapy or placebo, and 3 months of follow-up.\n Variations in semen parameters used for patient selection and variations of coenzyme Q(10) and ubiquinol concentrations in seminal plasma and spermatozoa.\n Coenzyme Q(10) and ubiquinol increased significantly in both seminal plasma and sperm cells after treatment, as well as spermatozoa motility. A weak linear dependence among the relative variations, baseline and after treatment, of seminal plasma or intracellular coenzyme Q(10) and ubiquinol levels and kinetic parameters was found in the treated group. Patients with a lower baseline value of motility and levels of coenzyme Q(10) had a statistically significant higher probability to be responders to the treatment.\n The exogenous administration of coenzyme Q(10) increases the level of the same and ubiquinol in semen and is effective in improving sperm kinetic features in patients affected by idiopathic asthenozoospermia.", "To study the effects of folic acid and zinc sulfate treatment on semen variables in fertile and subfertile men.\n Double-blind, placebo-controlled interventional study.\n Two outpatient fertility clinics and nine midwifery practices in The Netherlands.\n One hundred eight fertile and 103 subfertile men.\n Both groups were randomly assigned to receive one of four treatments for 26 weeks: folic acid and placebo, zinc sulfate and placebo, zinc sulfate and folic acid, and two placebos. Folic acid was given at a daily dose of 5 mg, and zinc sulfate was given at a daily dose of 66 mg.\n Before and after treatment, standardized semen and blood samples were obtained for determinations of sperm concentration, motility, and morphology according to World Health Organization guidelines; semen morphology according to strict criteria; and blood folate and zinc concentrations. Effects of the four interventions were evaluated separately in subfertile and fertile men.\n Subfertile men demonstrated a significant 74% increase in total normal sperm count and a minor increase of 4% abnormal spermatozoa. A similar trend was observed in fertile men. Pre-intervention concentrations of folate and zinc in blood and seminal plasma did not significantly differ between fertile and subfertile men.\n Total normal sperm count increases after combined zinc sulfate and folic acid treatment in both subfertile and fertile men. Although the beneficial effect on fertility remains to be established, this finding opens avenues of future fertility research and treatment and may affect public health.", "Forty-six subfertile men with idiopathic oligospermia were randomly assigned to 6 months of treatment with a placebo, clomiphene citrate (25 or 50 mg/day), mesterolone (100 mg/day), or pentoxifylline (1200 mg/day) or 4 months of testosterone enanthate treatment (100 or 250 mg on alternate weeks). Treatment with the placebo, mesterolone, pentoxifylline, and testosterone rebound therapy did not result in a significant increase in the mean sperm concentration or pregnancy in the partners. Clomiphene citrate at both dosages significantly increased the mean sperm concentration without improving sperm motility or morphology during the 6-month treatment period. Pregnancy rates of 36.4% and 22.2% were observed in partners of men receiving clomiphene citrate 25 mg/day and 50 mg/day, respectively. This study also illustrates the difficulties in identifying suitable patients for and assessing the efficacy of different treatment regimens.", "We determined the efficacy of coenzyme Q10 supplementation on semen parameters, sperm function and reproductive hormone profiles in infertile men.\n A total of 212 infertile men with idiopathic oligoasthenoteratospermia were randomly assigned to receive 300 mg coenzyme Q10 (Kaneka, Osaka, Japan) orally daily (106 in group 1) or a similar placebo regimen (106 in group 2) during a 26-week period, followed by a 30-week treatment-free phase. Two semen analyses, acrosome reaction test, immunobead test for antisperm antibody, and determination of resting levels of luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone and inhibin B were done in all participants. Blood and seminal plasma total coenzyme Q10 was also assessed.\n Significant improvement in sperm density and motility was evident with coenzyme Q10 therapy (each p = 0.01). Using the Kruger classification sperm morphology evaluation revealed an increase in the percent of normal forms in the coenzyme Q10 group (p = 0.07). A positive correlation was found between treatment duration with coenzyme Q10 and sperm count (r = 0.46, p = 0.03) as well as with sperm motility (r = 0.45, p = 0.04) and sperm morphology (r = 0.34, p = 0.04). The coenzyme Q10 group had a significant decrease in serum follicle-stimulating hormone and luteinizing hormone at the 26-week treatment phase (each p = 0.03). By the end of the treatment phase the mean +/- SD acrosome reaction had increased from 14% +/- 8% and 15% +/- 8% to 31% +/- 11% and 16% +/- 10% in the coenzyme Q10 and placebo groups, respectively (p = 0.01).\n Coenzyme Q10 supplementation resulted in a statistically significant improvement in certain semen parameters. However, further studies are needed to draw a final conclusion and evaluate the effect of coenzyme Q10 supplementation on the pregnancy rate.", "The role of zinc therapy on infertility caused by defective sperm quality is examined.\n In this study, 100 men with asthenozoospermia were randomised into two groups--250 mg twice daily zinc therapy for 3 months and no therapy. The patients were followed up for another 6 months. Sperm parameters, circulating antisperm antibodies, sex hormones and T helper cytokines were evaluated before and after treatment for the two groups.\n There was significant improvement in the sperm quality; sperm count (P<.02), progressive motility (P<.05), fertilising capacity (P<.01) and a reduction in the incidence of antisperm antibodies (P<.01). Zinc/cadmium was higher in the zinc therapy group (P<.02). T helper cytokine, interleukin-4 level was significantly higher after zinc therapy (P<.02) while TNFalpha showed a significant decrease (P<.05).\n Zinc therapy has a role in improving sperm parameters in men with asthenozoospermia, probably through its membrane stabilising effect as an antioxidant and its effect on cellular and humoral immunity by reducing the levels of antisperm antibodies and TNFalpha and increasing that of IL-4.", "To determine possible indications of the mechanisms involved in improved sperm parameters by zinc therapy in asthenozoospermic men.\n Forty-five men with asthenozoospermia (>or=40% immotile sperm) were randomized into four therapy groups: zinc only: n = 11; zinc + vitamin E: n = 12 and zinc + vitamins E + C: n = 14 for 3 months, and non-therapy control group: n = 8. Semen analysis was done according to WHO guidelines. Malone dialdehyde, tumour necrosis factor-alpha (TNF-alpha), total antioxidant capacity, superoxide dismutase (SOD) and glutathione peroxidase were determined in the semen and serum. Antisperm antibodies IgG, IgM and IgA were evaluated by immunobeads. Sperm chromatin integrity was determined by acid denaturation by acridine orange and sperm apoptosis by light and electron microscopy. The effect of zinc on in vitro induced sperm oxidative stress by NADH was evaluated.\n Asthenozoospermia was significantly associated with oxidative stress with higher seminal malone dialdehyde (8.8 vs. 1.8 mmol/l, p < 0.001) and TNF-alpha (60 vs. 12 pg/l, p < 0.001), and low total antioxidant capacity (1.8 vs. 8.4, p < 0.01), SOD (0.8 vs. 3.1, p < 0.01) and glutathione peroxidase (1.6 vs. 4.2, p < 0.05), compared to normozoospermia. Zinc therapy alone, in combination with vitamin E or with vitamin E + C were associated with comparably improved sperm parameters with less oxidative stress, sperm apoptosis and sperm DNA fragmentation index (DFI). On the whole, there was no difference in the outcome measures between zinc only and zinc with vitamin E and combination of vitamins E + C. In the in vitro experiment zinc supplementation resulted in significantly lower DFI (14-29%, p < 0.05) compared to zinc deficiency.\n Zinc therapy reduces asthenozoospermia through several mechanisms such as prevention of oxidative stress, apoptosis and sperm DNA fragmentation.\n (c) 2008 S. Karger AG, Basel.", "Asthenospermia is the main factor of male infertility among patients consulting the Asir Infertility Center in Abha, Saudi Arabia. Lipid peroxidation occurring in both the seminal plasma and spermatozoa was estimated by malondialdehyde (MDA) concentration. Spermatozoal MDA concentration was higher in men with decreased sperm motility. The MDA concentration in the seminal plasma exhibited no relationship with sperm concentration, sperm motility, the number of immotile spermatozoa, or even the absence of spermatozoa. The MDA concentration in sperm pellet suspensions of asthenospermic and oligoasthenospermic patients was almost twice that of the normospermic males. The MDA concentration in the sperm pellet suspension from normospermic or oligospermic patients was about 10% that in the seminal plasma. However, the MDA concentration in the sperm pellet suspension of asthenospermic or oligoasthenospermic patients was about 15% that in the seminal plasma. Treatment of asthenospermic patients with oral Vitamin E significantly decreased the MDA concentration in spermatozoa and improved sperm motility. Eleven out of the 52 treated patients (21%) impregnated their spouses; nine of the spouses successfully ended with normal term deliveries, whereas the other two aborted in the first trimester. No pregnancies were reported in the spouses of the placebo-treated patients.", "To determine the effect of oral carnitine supplementation on the semen parameters of men with idiopathic asthenospermia.\n Prospective, randomized, double-blind placebo-controlled study.\n Academic tertiary referral centers.\n Male patients presenting with infertility and with sperm motility of 10%-50% were selected.\n Patients were randomized to 24-week treatment arms of oral carnitine (2,000 mg L-carnitine and 1,000 mg L-acetyl-carnitine per day) or placebo.\n Sperm motility and total motile sperm counts at baseline, 12 weeks, and 24 weeks. Seminal plasma and sperm free, acetyl, and total L-carnitine levels at baseline and at week 24.\n Twenty-one patients entered the study, with 12 patients in the carnitine arm and 9 in the placebo arm. There were no significant differences in baseline semen parameters between the carnitine and placebo arms. There was no statistically significant or clinically significant increase in motility or total motile sperm counts between baseline, 12 week, or 24 weeks in the carnitine or placebo arms.\n Carnitine supplementation demonstrated no clinically or statistically significant effect on sperm motility or total motile sperm counts in men with idiopathic asthenospermia.", "nan", "In a randomized, placebo-controlled, double-blind study we investigated whether high-dose oral treatment with vitamins C and E for 56 days was able to improve semen parameters of infertile men. Ejaculate parameters included semen volume, sperm concentration and motility, and sperm count and viability. Thirty-one patients without genital infection but with asthenozoospermia (< 50% motile spermatozoa) and normal or only moderately reduced sperm concentration (> 7 x 10(6) spermatozoa/ml) (according to WHO criteria) were examined. To investigate the influence of the epididymal storage period on semen parameters, the patients were asked to deliver two semen samples with abstinence times of 2 and 7 days both before and at the end of vitamin treatment. After randomization, the patients received either 1000 mg vitamin C and 800 mg vitamin E (n = 15) or identical placebo capsules (n = 16). No changes in semen parameters were observed during treatment, and no pregnancies were initiated during the treatment period. Combined high-dose antioxidative treatment with vitamins C and E did not improve conventional semen parameters or the 24-h sperm survival rate. Prolonged abstinence time increased ejaculate volume (P < 0.05), sperm count (P < 0.05), sperm concentration (P < 0.05) and the total number of motile spermatozoa (P < 0.05).", "Numerous studies have reported beneficial effects of antioxidant drugs on semen quality, but there is no well-defined therapeutical protocol in male infertility. This study aimed to test the effects of vitamin E and selenium supplementation on lipid peroxidation and on sperm parameters. The study included 54 voluntary and infertile men who produced semen samples for spermiogram and for spectrophotometric measurement of a lipid peroxidation marker, the malondialdehyde (MDA), and produced blood samples for high-performance liquid chromatography assessment of serum vitamin E level. The trial was randomized and open. Twenty-eight men were supplemented daily by vitamin E (400 mg) and selenium (225 microg), during 3 months. The remaining 26 patients received vitamin B (4,5 g/day) for the same duration. Only 20 patients achieved their treatment and returned for control analysis. MDA concentrations in sperm were much less than in seminal plasma and motility and viability were inversely correlated with semen MDA levels. In contrast to vitamin B supplementation, vitamin E and selenium supplementation produced a significant decrease in MDA concentrations and an improvement of sperm motility. The results confirm the protective and beneficial effects of vitamin E and selenium on semen quality and advocate their use in male infertility treatment.", "To examine whether a beneficial effect of N-acetylcysteine (NAC) on semen parameters and oxidative/antioxidant status in idiopathic male infertility exists. The production of reactive oxygen species is a normal physiologic event in various organs. However, overproduction of reactive oxygen species can be detrimental to sperm and has been associated with male infertility.\n Our study included 120 patients who had attended our clinic and were diagnosed with idiopathic infertility according to medical history and physical and seminal examination findings, as initial evaluations. The patients were divided randomly into 2 groups. Those in the study group (60 men) were given NAC (600 mg/d orally) for 3 months; the control group (60 men) received a placebo. The oxidative status was determined by measuring the total antioxidant capacity, total peroxide and oxidative stress index in plasma samples. The sperm parameters were evaluated after NAC treatment and were compared with those in the control group.\n NAC had significant improving effects on the volume, motility, and viscosity of semen. After NAC treatment, the serum total antioxidant capacity was greater and the total peroxide and oxidative stress index were lower in the NAC-treated group compared with the control group. These beneficial effects resulted from reduced reactive oxygen species in the serum and reduced viscosity of the semen. No significant differences were found in the number or morphology of the sperm between the 2 groups.\n We believe that NAC could improve some semen parameters and the oxidative/antioxidant status in patients with male infertility.", "The production of reactive oxygen species (ROS) is a normal physiological event in various organs including the testis. Overproduction of ROS, however, can be detrimental to sperm, being associated with male infertility. In vivo experiments using vitamin E (Vit. E), one of the major membrane protectants against ROS and lipid peroxidation, have shown its significant potential in treating ROS-associated male infertility. There has been no study that the scavenging drugs reduce the level of ROS in human semen. Previously we reported the in vitro scavenging effectiveness of ethylcysteine (EC) against ROS in human semen. The present study was performed in order to determine the effectiveness of the in vivo administration of EC as treatment for ROS-associated male infertility.\n Ten cases of male infertility, with the exceptions of azoospermia and pyospermia, were chosen. Patients were divided randomly into two groups. Each group received either 600 mg/day of EC (Group A) or Vit. E 600 mg/day (Group B) for 3 months. Then, after a 1-month wash-out period, the patients were switched to another treatment. Conventional semen analysis, computerized motility assessment, measurement of ROS generation and sperm function assessment by triple stain were performed before and after administration of EC and Vit. E. The levels of EC and Vit. E were also assessed in patients' blood serum and seminal plasma before and after administration of EC and Vit. E.\n Sperm density and sperm motility did not improve but sperm function had a significant tendency toward improvement after administration of EC and Vit. E. ROS levels significantly decreased only after administration of EC After administration of EC and Vit. E, their levels significantly increased in patients' blood serum but were unchanged in patients' seminal plasma.\n Since our study showed that oral administration of EC produced results similar to those of Vit. E, we conclude that EC is an effective treatment agent for ROS-associated male infertility.", "A randomized, placebo-controlled clinical pilot study was performed in order to examine the effect of magnesium-orotate in male idiopathic infertility. Ten males were treated daily for 90 consecutive days with 3000 mg magnesium-orotate (Magnerot) tablets (Group M). As a control, ten other males were treated in the same way with placebo (Group P). Conventional microscopic sperm characteristics (sperm concentration, motility ratio, total number of motile sperm cells, normal morphology ratio), plus total and ionized magnesium levels in seminal plasma and blood serum were evaluated both prior to treatment and on day 90, at the conclusion of the study. No significant changes in sperm characteristics, blood ionized or total Mg, or ejaculate total Mg levels were detected. However, ejaculate ionized Mg levels increased in Group M from 0.18 +/- 0.05 to 0.30 +/- 0.05 (mmol/l; mean +/- SD, p < 0.05). Within the observation period of 3 months, one pregnancy occurred in the partner of a male from Group M. In conclusion, magnesium-orotate treatment at a dose of 3000 mg/day leads neither to a significant improvement of sperm variables nor does it increase the pregnancy rates of female partners of treated males as compared to those of controls. Thus, magnesium-orotate treatment was not shown to be effective therapy for idiopathic male infertility.", "Evidence has accumulated supporting the role of reactive oxygen species (ROS) in the pathogenesis of sperm dysfunction among men with infertility. Damage to sperm DNA by ROS can lead to failure of conception, miscarriage or potentially even childhood cancer. The objective of this study was to examine the effect of male antioxidant treatment on embryo quality and pregnancy outcome during in vitro fertilisation-intracytoplasmic sperm injection (IVF-ICSI) treatment.\n Sixty couples with severe male factor infertility were enrolled in a prospective randomised double-blind placebo-controlled trial. Male participants were randomly assigned to take either one capsule per day of the Menevit antioxidant or an identical in appearance placebo for three months prior to their partner's IVF cycle. The primary outcome was cleavage stage embryo quality and the secondary outcomes were oocyte fertilisation rate, pregnancy rates and treatment side-effects. Approval by the local Human Research Ethics Committee was obtained prior to the commencement of this study.\n The antioxidant group recorded a statistically significant improvement in viable pregnancy rate (38.5% of transferred embryos resulting in a viable fetus at 13 weeks gestation) compared to the control group (16% viable pregnancy). No significant changes in oocyte fertilisation rate or embryo quality were detected between the antioxidant and the placebo groups. Side-effects on the Menevit antioxidant were rare (8%) and mild in nature.\n The Menevit antioxidant appears to be a useful ancillary treatment that significantly improves pregnancy rates in couples undergoing IVF-ICSI treatment for severe male factor infertility.", "The objective of this study was to detect a therapy for idiopathic and varicocele-associated oligoasthenospermia (OAT). Idiopathic and varicocele OAT patients were randomized into 3 groups. Each group was composed of varying degrees of left varicoceles (graded into 5 grades with echo-color Doppler) and of idiopathic OATs. Group 1 used a placebo, group 2 used oral L-carnitine (2 g/d) + acetyl-L-carnitine (1 g/d), group 3 used L-carnitine/acetyl-L-carnitine + 1 x 30-mg cinnoxicam suppository every 4 days. Drugs were administered for 6 months. The groups were composed as follows: group 1, 71 varicoceles and 47 idiopathic OATs; group 2, 62 varicoceles and 39 idiopathic OATs; group 3, 62 varicoceles and 44 idiopathic OATs. Sperm concentration, motility, and morphology before during and after treatments were assessed. Pregnancy rates and side effects were recorded. Group 1 did not have modified sperm patterns during treatment. Group 2 had significantly increased sperm patterns at 3 and 6 months into therapy in idiopathic patients and in patients with grades I, II, and III varicocele, but not in grades IV and V. Group 3 had significantly increased sperm parameters in all patients, with the exception of grade V varicocele. Group 3 sperm patterns proved significantly higher during therapy than group 2. All sperm patterns fell to baseline after therapy suspension. Minor side effects occurred. Pregnancy rates were 1.7% (group 1), 21.8% (group 2), and 38.0% (group 3) (P <.01). L-carnitine/acetyl-L-carnitine + cinnoxicam suppositories proved a reliable treatment for low-grade varicoceles and idiopathic OATs.", "To determine the efficacy and safety of combined L-carnitine and acetyl-L-carnitine therapy in infertile males with oligoasthenozoospermia.\n One hundred fifty patients with oligoasthenozoospermia were randomized selected into treatment and control groups. The treatment group with 90 patients were given L-carnitine (2 g/d) and acetyl-L-carnitine (1 g/d) orally, twice a day. The patients in control group were given Vitamin E 100 mg plus Vitamin C 100 mg, tid. The oral therapy lasted three months and patients accepted sperm analysis every one month. The L-carnitine level in seminal plasma was examined by high performance liquid chromatography (HPC). Side effects as well as pregnant rate were observed.\n In the treatment group, 85 patients out of 90 finished the three month treatment. Female spouses of 10 patients (11.6%) achieved pregnancy. Moreover, their forward motile sperm per ejaculation, total motile sperm, as well as the concentration of L-carnitine in seminal plasma were increased significantly (P < 0.01). In control group, 53 patients out of 60 completed three months therapy. Two pregnancy (3.7%) was observed. Though some increase was seen in number of forward motile sperm and total motile sperm per ejaculation, the changes were not statistically significant (P > 0.05). The difference of the pregnant rate between two groups was statistically significant. No side effects were found.\n Combined treatment with L-carnitine and acetyl-L-calmitine can be an effective and safe option for treating oligoasthenozoospermia by means of significantly improving forward motile sperm and total motile sperm per ejaculation, as well as increasing pregnant rates.", "Sperm DNA fragmentation is known to compromise male fertility. Previous findings have suggested the implication of oxidative stress in the etiology of this pathological condition. The present study was conducted to find out if the pathologically increased incidence of DNA fragmentation in ejaculated spermatozoa can be reduced by oral treatment with two antioxidants, vitamins C and E. Sixty-four men with unexplained infertility and an elevated (> or = 15%) percentage of DNA-fragmented spermatozoa in the ejaculate were randomized between an antioxidant treatment (1 g vitamin C and 1 g vitamin E daily for 2 months) group and a placebo group. Sperm DNA fragmentation was evaluated by terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling assay before and after treatment. No differences in basic sperm parameters were found between the antioxidant treatment and the placebo group before or after treatment. However, the percentage of DNA-fragmented spermatozoa was markedly reduced (P < .001) in the antioxidant treatment group after the treatment (9.1 +/- 7.2) as compared with the pretreatment values (22.1 +/- 7.7). No difference in the pretreatment and posttreatment incidence of sperm DNA fragmentation was observed in the placebo group. These data show that sperm DNA damage can be efficiently treated with oral antioxidants administered during a relatively short time period.", "The effects of supplementation with docosahexaenoic acid (DHA) on DHA levels in serum, seminal plasma, and sperm of asthenozoospermic men as well as on sperm motility were examined in a randomized, double-blind, placebo-controlled manner. Asthenozoospermic men (n = 28; < or =50% motility) were supplemented with 0, 400, or 800 mg DHA/d for 3 mon. Sperm motility and the fatty acid composition of serum, seminal plasma, and sperm phospholipid were determined before and after supplementation. In serum, DHA supplementation resulted in decreases in 22:4n-6 (-30% in the 800-mg DHA group only) and total n-6 (-6 and -12% in the 400- and 800-mg DHA groups, respectively) fatty acids. Increases were noted in DHA (71 and 131% in the 400- and 800-mg DHA groups, respectively), total n-3 fatty acids (42 and 67% in the 400- and 800-mg DHA groups, respectively), and the n-3/n-6 ratio (50 and 93% in the 400- and 800-mg DHA groups, respectively). In seminal plasma, DHA supplementation resulted in a decrease in 22:4n-6 (-31% in the 800-mg DHA group only) and an increase in the ratio of n-3 to n-6 (35 and 33% in the 400- and 800-mg DHA groups, respectively). There were insignificant increases in DHA and total n-3 fatty acids. In sperm, decreases were noted in 22:4n-6 (-37 and -31% in the 400- and 800-mg DHA groups, respectively). There were no other changes. There was no effect of DHA supplementation on sperm motility. The results show that dietary DHA supplementation results in increased serum--and possibly seminal plasma--phospholipid DHA levels, without affecting the incorporation of DHA into the spermatozoa phospholipid in asthenozoospermic men. This inability of DHA to be incorporated into sperm phospholipid is most likely responsible for the observed lack of effect of DHA supplementation on sperm motility.", "We performed a randomized, prospective, controlled, intention to treat study in order to determine the effectiveness of an antioxidant therapy in improve the quality of seminal fluid parameters and the natural pregnancies in men with persistent oligospermia (5-20 million/ml) 6 months after retrograde embolization. Forty-two subjects were enrolled and randomized in the study. Treated group (20 subjects) was assigned to receive antioxidant therapy (NAC 600 mg and vitamins-minerals). Untreated group (22 subjects) received no adjunctive medical therapy and was used as controls. Our data were analyzed with an intention to treat strategy. A statistically significant increase in sperm count after antioxidant therapy was recorded (P=0.009). After this therapy, no statistical differences in percentage of WHO class A motile sperm (P=0.752) and typical forms (P=0.926) were found. The univariate logistic regression analysis showed that a man treated with antioxidant therapy presented a probability to have a normal sperm count 20-fold (OR=20.1; CI 95%=1.05-43.2; P=0.014) higher than a man who was untreated. No significant impact on spontaneous pregnancies was found after antioxidant therapy. Despite this preliminary data, we show that antioxidant therapy based on a combination of NAC and micronutrient supplementation can be helpful in improve the sperm count at least in a subset of oligospermic males. However, this improving in sperm count is not associated with a significant increase in spontaneous pregnancies after 12 months.", "To evaluate the effectiveness of L-carnitine (LC) or L-acetyl-carnitine (LAC) or combined LC and LAC treatment in improving semen kinetic parameters and the total oxyradical scavenging capacity in semen.\n Placebo-controlled, double-blind, randomized trial.\n Andrology unit, Department of Internal Medicine, Polytechnic University of Marche, Italy.\n Sixty infertile men, ages 20 to 40 years, with the following baseline sperm selection criteria: concentration > 20 x 10(6)/mL, sperm forward motility < 50%, and normal sperm morphology > 30%; 59 patients completed the study.\n Patients underwent a double-blind therapy of LC 3 g/d, LAC 3 g/d, a combination of LC 2 g/d and LAC 1 g/d, or placebo. The study design was 1 month of run in, 6 months of therapy or placebo, and 3 months of follow-up evaluation.\n Variations in semen parameters used for patient selection, and variations in total oxyradical scavenging capacity of the seminal fluid.\n Sperm cell motility (total and forward, including kinetic features determined by computer-assisted sperm analysis) increased in patients to whom LAC was administered both alone or in combination with LC; combined LC + LAC therapy led to a significant improvement of straight progressive velocity after 3 months. The total oxyradical scavenging capacity of the semen toward hydroxyl and peroxyl radicals also increased and was positively correlated with the improvement of kinetic features. Patients with lower baseline values of motility and total oxyradical scavenging capacity of the seminal fluid had a significantly higher probability of responding to the treatment.\n The administration of LC and LAC is effective in increasing sperm kinetic features in patients affected by idiopathic asthenozoospemia and improves the total oxyradical scavenging capacity of the seminal fluid in the same population.", "To determine the efficacy of combined l-carnitine and l-acetyl-carnitine therapy in infertile males with oligo-astheno-teratozoospermia.\n Placebo-controlled double-blind randomized trial.\n University tertiary referral center.\n Sixty infertile patients (aged 20-40 years) with the following baseline sperm selection criteria: concentration, 10 to 40 x 10(6)/mL; forward motility, <15%; total motility, 10% to 40%; and atypical forms, <80%. Fifty-six patients completed the study.\n Patients were submitted to a combined treatment of l-carnitine (2 g/d) and l-acetyl-carnitine (1 g/d) or of placebo; the study design was 2 months' wash-out, 6 months of therapy or of placebo, and 2 months' follow-up.\n Variation in the semen parameters that were used for patient selection.\n Even though increases were seen in all sperm parameters after combined carnitine treatment, the most significant improvement in sperm motility (both forward and total) was present in patients who had lower initial absolute values of motile sperm (<4 x 10(6) forward or <5 x 10(6) total motile spermatozoa per ejaculate).\n Combined treatment with l-carnitine and l-acetyl-carnitine in a controlled study of efficacy was effective in increasing sperm motility, especially in groups with lower baseline levels.", "To determine the efficacy of L-carnitine therapy in selected cases of male factor infertility.\n Placebo-controlled, double-blind, crossover trial.\n University tertiary referral center.\n One hundred infertile patients (ages 20-40 years) with the following baseline sperm selection criteria: concentration, 10-20 x 10(6)/mL; total motility, 10%-30%; forward motility, <15%; atypical forms, <70%; velocity, 10-30 micro/s; linearity, <4. Eighty-six patients completed the study.\n Patients underwent L-carnitine therapy 2 g/day or placebo; the study design was 2 months of washout, 2 months of therapy/placebo, 2 months of washout, and 2 months placebo/therapy.\n Variation in sperm parameters used in the patients selection criteria, in particular, sperm motility. Excluding outliers, a statistically significant improvement in semen quality, greater than after the placebo cycle, was seen after the L-carnitine therapy for sperm concentration and total and forward sperm motility. The increase in forward sperm motility was more significant in those patients with lower initial values, i.e., <5 x 10(6) or <2 x 10(6) of forward motile sperm/ejaculate or sperm/mL.\n Based on a controlled study of efficacy, L-carnitine therapy was effective in increasing semen quality, especially in groups with lower baseline levels. However, these results need to be confirmed by larger clinical trials and in vitro studies.", "To determine whether the decline in selenium intake and selenium status in men in the West of Scotland might be a contributory factor to male subfertility.\n Two semen samples were collected from patients attending a subfertility clinic and those patients with samples showing reduced motility were invited to participate in an ethically approved double-blind clinically controlled trial with informed consent. Sixty-nine patients were recruited and received either placebo, selenium alone or selenium plus vitamins A, C and E daily for 3 months. A further semen sample was collected at the end of the trial. Plasma selenium status was determined at the beginning and end of the trial period, as was total sperm density and motility.\n Plasma selenium concentrations were significantly (P < 0.001) higher in both selenium-treated groups than in controls. No significant effect of treatment on sperm density was recorded. Sperm motility increased in both selenium-treated groups, in contrast to a slight decline in the placebo group, but the difference was not significant. However, as the provision of additional vitamins had no effect on any variable measured it was considered justified to combine the two selenium-treated groups and compare them with the placebo treatment. On this basis, selenium treatment significantly (P < 0.002) increased plasma selenium concentrations and sperm motility (P = 0.023) but sperm density was again unaffected. Five men (11%) achieved paternity in the treatment group, in contrast to none in the placebo group.\n This trial confirms the result of an earlier study, that selenium supplementation in subfertile men with low selenium status can improve sperm motility and the chance of successful conception. However, not all patients responded; 56% showed a positive response to treatment. The low selenium status of patients not supplemented again highlights the inadequate provision of this essential element in the Scottish diet." ]