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[ "10491060" ]

[ "Clinical benefits of lightweight compression: reduction of venous-related symptoms by ready-to-wear lightweight gradient compression hosiery." ]

[ "Medical-grade compression of class I (20-30 mmHg) and class II (30-40 mmHg) have been shown to be beneficial against venous hypertension or congestion. Relatively few studies address the effects of ready-to-wear (RTW) lightweight gradient compression pantyhose on venous symptoms.\n To perform a study comparing the effects of two different compression RTW lightweight gradient compression stockings (8-15 mmHg and 15-20 mmHg) on the venous symptoms of flight attendants.\n A prospective crossover trial of symptom evaluation in 19 flight attendants was performed in which participants rated their symptoms on a visual analog scale. During the initial phase, participants wore no compression for 2 weeks. They then wore 8-15 mmHg and 15-20 mmHg gradient compression support hose while flying over a 4-week period. Symptoms before and after wearing the gradient compression stockings were compared and statistically analyzed.\n Wearing of 8-15 mmHg gradient hose resulted in statistically significant improvement of discomfort (P < 0.01). Swelling, fatigue, aching, and tightness of the leg were all improved to a statistically significant degree (P < 0.01). For 15-20 mmHg gradient hosiery, symptoms were improved to a statistically significant or almost significant level. The difference between the 8-15 mmHg and 15-20 mmHg compression was not statistically significant.\n Use of lightweight (low compression) RTW gradient compression hosiery is very effective in improving symptoms of discomfort (P < 0.01), swelling (almost P < 0. 05), fatigue (P < 0.05), aching (P < 0.01), as well as leg tightness. Improvement of symptoms is statistically significant compared to no compression when hosiery was worn regularly during waking hours for 4 weeks." ]

[ "10406359", "8956924", "16227648", "7575227", "10328256" ]

[ "Safety and efficacy of vigabatrin and carbamazepine in newly diagnosed epilepsy: a multicentre randomised double-blind study. Vigabatrin European Monotherapy Study Group.", "Vigabatrin vs. carbamazepine monotherapy in newly diagnosed focal epilepsy: a randomized response conditional cross-over study.", "A comparative study of vigabatrin vs. carbamazepine in monotherapy of newly diagnosed partial seizures in children.", "Vigabatrin vs carbamazepine monotherapy in patients with newly diagnosed epilepsy. A randomized, controlled study.", "Open comparative long-term study of vigabatrin vs carbamazepine in newly diagnosed partial seizures in children." ]

[ "Vigabatrin is a newly licensed drug for use in patients with epilepsy. We investigated whether this drug was comparable to standard first-line monotherapy in efficacy and incidence of adverse events.\n We enrolled 459 patients with newly diagnosed, previously untreated partial epileptic seizures from 44 European centres and randomly assigned them carbamazepine 600 mg daily (n=230) or vigabatrin 2 g daily (n=229). After initial maintenance doses were reached, doses were adjusted downwards (in the case of adverse events) or upwards (in the case of seizures) by the clinician. The primary outcome was time to withdrawal because of lack of efficacy or adverse events. Secondary outcomes included efficacy (time to 6-month remission of seizures, time to first seizure after initial dose stabilisation), and adverse events (incidence and severity). Analysis was by intention to treat.\n Time to withdrawal for lack of efficacy or adverse events did not differ between groups (p=0.318). Vigabatrin was better tolerated than carbamazepine with fewer withdrawals, but was more frequently associated with psychiatric symptoms (58 [25%] vs 34 [15%]) and weight gain (25 [11%] vs 12 [5%]). Carbamazepine was associated with rash (22 [10%] vs seven [3%]). All efficacy outcomes favoured carbamazepine and failed to show equivalence between the two drugs. No significant difference was found for time to achieve 6 months of remission from seizures (p=0.058), but the most powerful outcome, time to first seizure after the first 6 weeks from randomisation, showed carbamazepine to be significantly more effective than vigabatrin (p=0.0001).\n Vigabatrin seems less effective but better tolerated than carbamazepine, which is the first-choice drug for the treatment of partial epilepsies. Vigabatrin cannot therefore be recommended as a first-line drug for monotherapy in this group of patients.", "The clinical efficacy and safety of vigabatrin (VGB) as add-on therapy for pharmaco-resistant focal epilepsies is well established. However, for an objective evaluation, the effects of the drug in the monotherapy of newly diagnosed subjects should be determined. With this aim, VGB was compared, in a randomized, response conditional cross-over study, with carbamazepine (CBZ), the most widely prescribed drug in focal epilepsies. Fifty-one patients with complex partial (CP) seizures were randomly assigned to either the VGB or the CBZ group and evaluated after an initial 4 month period. The cross-over to the alternative drug was carried out, for an analogous period, only in cases with persisting seizures or in the presence of intolerable side effects. Patients who did not respond to either drug were subsequently treated with a combination of VGB and CBZ. No significant difference was revealed in the efficacies of VGB and CBZ; a complete control of seizures was obtained in 17/37 patients (45.9%) treated with VGB and in 20/39 patients (51.3%) treated with CBZ. The side effects were somewhat more frequent (41%) and severe with CBZ than with VGB (21.6%). The power to detect a 20% difference between the two drugs was 75%. The combination of the two drugs suppressed the seizures in 5 out of 14 resistant cases. The preliminary results in this small number of patients are encouraging and suggest that VGB may be considered as a first-line drug for epilepsy with CP seizures and as a valid alternative when other monotherapies are ineffective or poorly tolerated.", "Carbamazepine (CBZ) is a drug of choice for the treatment of simple or complex partial seizures and secondary generalized seizures in adults and children. Vigabatrin (VGB) is a relatively new second line antiepileptic drug and was first registered for use in Poland more than ten years ago. Few reports have been published on the comparison of efficacy of VGB in children with epilepsy. The objective of this study is to evaluate the safety, efficacy and EEG effects of initial VGB monotherapy compared with initial CBZ monotherapy in children with newly diagnosed epilepsy. We present results of a prospective, outpatient and open study carried out in the University Hospital Center in Białystok. Twenty-six children with partial epilepsy treated with VGB and 28 patients treated with CBZ were studied. The evaluation of the efficacy of the two drugs did not reveal any significant differences. Very good (reduction > 75%) seizure control was achieved in 22 out of 26 patients (84.6%) in the VGB group. One patient had a 50-75% decrease of seizures (good effect), similarly one child had a 25-50% reduction of seizures (mild effect). In two patients, we observed increased seizures (myoclonic jerks). Very good seizure control was achieved in 17 out of 28 patients (60.7%) in the CBZ group. Good seizure control was achieved in 5 out of 28 patients (17.8%) and mild control was seen in two children. No improvement was observed in 4 (14%) of the patients. The EEG background activity was improved in VGB-treated patients. No effect on the EEG background activity was observed in CBZ-treated children. VGB seems to be a safe and effective antiepileptic drug as primary monotherapy for epilepsy in children with similar proportion of side effects as CBZ.", "To evaluate the efficacy, safety, and cognitive effects of initial vigabatrin monotherapy compared with initial carbamazepine monotherapy in patients with newly diagnosed epilepsy.\n Open, randomized, controlled design. Follow-up period of 12 months.\n University hospital with an epilepsy center.\n A total of 100 patients, aged 15 to 64 years, classified as suffering from partial seizures and/or generalized tonic-clonic seizures were randomized to either vigabatrin or carbamazepine monotherapy. Fifty-nine patients with a single epileptic seizure and no antiepileptic drug treatment served as a control population for objective safety measures.\n To evaluate the comparative efficacy and toxicity of vigabatrin and carbamazepine, the drug success rate (ie, the proportion of patients continuing successful treatment with the randomly assigned drug) after 12 months of steady-state treatment was used. To evaluate the safety of the drugs in addition to reported side effects, visual evoked potential recordings and neuropsychological evaluation were performed during follow-up.\n During the 12-month follow-up period, 60% of patients receiving vigabatrin and carbamazepine were treated successfully. Vigabatrin caused fewer side effects that required discontinuation of therapy. However, vigabatrin had to be discontinuated more often owing to lack of efficacy, and fewer of the successfully treated patients receiving vigabatrin achieved total freedom from seizures. Vigabatrin had no detrimental effects on cognitive functions. Retrieval from both episodic and semantic memory and flexibility of mental processing improved significantly in patients successfully treated with vigabatrin.\n Vigabatrin seems to be an effective and safe antiepileptic drug as primary monotherapy for epilepsy with fewer cognitive side effects than carbamazepine.", "To compare vigabatrin with carbamazepine as monotherapy in newly diagnosed children with partial epilepsy in order to evaluate the efficacy and tolerability of both drugs.\n Open and randomized with a 2-year follow-up period.\n The Infantile Neuropsychiatric Division of the Regional Pediatric Hospital, Ancona, Italy.\n Seventy children with newly diagnosed partial epilepsy were treated with vigabatrin (38 patients) or carbamazepine (32 patients).\n Vigabatrin, 50 to 60 mg/kg per day, or carbamazepine, 15 to 20 mg/kg per day, split into twice-a-day doses.\n The efficacy and tolerability of vigabatrin were compared with those of the standard treatment (carbamazepine) for this patient group.\n The efficacy of vigabatrin and carbamazepine was similar, with the suggestion of a better side effect profile with vigabatrin.\n Vigabatrin monotherapy should be considered as a monotherapeutic treatment option in patients with newly diagnosed epilepsy. However, more studies are needed to evaluate other issues of concern, such as the cognitive and behavioral adverse effects of antiepileptic drugs, to determine the most suitable therapy." ]

[ "9566830", "2707520", "353464", "9126802", "12416659", "2671116", "1343377", "6753109", "2574842", "11841050", "8225695", "1983711" ]

[ "Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial.", "[Treatment of alcoholic hepatitis with silymarin. A double-blind comparative study in 116 patients].", "[Results of a double blind study on the effect of silymarin in the treatment of acute viral hepatitis, carried out at two medical centres (author's transl)].", "Long-term (12 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients.", "Silybin-beta-cyclodextrin in the treatment of patients with diabetes mellitus and alcoholic liver disease. Efficacy study of a new preparation of an anti-oxidant agent.", "Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver.", "[Controlled study of the effect of silymarin on alcoholic liver disease].", "Effect of silymarin on chemical, functional, and morphological alterations of the liver. A double-blind controlled study.", "[Liver-protective action of silymarin therapy in chronic alcoholic liver diseases].", "Effects of silymarin MZ-80 on oxidative stress in patients with alcoholic cirrhosis. Results of a randomized, double-blind, placebo-controlled clinical study.", "A pilot study on the liver protective effect of silybin-phosphatidylcholine complex (IdB1016) in chronic active hepatitis.", "Immunomodulatory and hepatoprotective effects of in vivo treatment with free radical scavengers." ]

[ "Silymarin has protective effects in different experimental conditions, but its efficacy in human liver cirrhosis has not been completely established. Therefore, this study was carried out to determine the effect of silymarin in alcoholics with liver cirrhosis with respect to survival and clinical and laboratory changes.\n From February 1986 to June 1989, we enrolled 200 alcoholics with histologically or laparoscopically proven liver cirrhosis in a randomized, double-blind multicenter trial comparing 450 mg of silymarin (150 mg/ three times per day) with placebo. The primary outcome was time to death, and the secondary outcome was the progression of liver failure. Additional analyses were also performed in 75 patients in whom anti-hepatitis C virus antibodies were measured after completion of the trial.\n One hundred and three patients were assigned to receive silymarin and 97 to receive placebo. The two groups were well matched for demographic and baseline clinical and laboratory features. A 2-year study period was completed in 125 patients (57 receiving silymarin and 68 receiving placebo). Twenty-nine patients (15 receiving silymarin, and 14 receiving placebo) died during the trial. Survival was similar in patients receiving silymarin or placebo. The effect of silymarin on survival was not influenced by sex, the persistence of alcohol intake, the severity of liver dysfunction or by the presence of alcoholic hepatitis in the liver biopsy. Silymarin did not have any significant effect on the course of the disease. No relevant side-effects were observed in any group.\n The results of this study indicate that silymarin has no effect on survival and the clinical course in alcoholics with liver cirrhosis.", "A randomized double-blind trial of silymarin versus placebo was carried out in 116 patients with histologically proven alcoholic hepatitis, 58 of them with cirrhosis. Patients were not included in case of hepatic encephalopathy, contraindication to percutaneous liver biopsy, hepatocellular carcinoma, evident lack of discipline or refusal to enter the trial. Fifty-seven patients received silymarin orally 420 mg/day and 59 received placebo during 3 months. Biologic parameters were assessed in the serum, and a percutaneous liver biopsy was obtained at the start of the trial and 3 months later. Histologic scores of alcoholic hepatitis and fibrosis were established on each biopsy specimen by two independent pathologists. The 2 groups were comparable at inclusion; 26 p. 100 of patients were lost to follow-up at 3 months, abstinence was obtained in 46 p. 100 of patients at the end of the trial. These percentages were similar in the two groups. Four patients died of hepatic failure during the trial, 3 in the placebo group. Significant improvement in the score of alcoholic hepatitis and serum amino transferase activity, was noted in both groups during the trial, irrespective of treatment with silymarin or placebo. No side-effects were noted. Our results suggest that silymarin 420 mg/d is not clinically relevant in the treatment of moderate alcoholic hepatitis.", "In a double blind study carried out under standard conditions at two treatment centers silymarin, 2 sugar-coated tablets 70 mg three times daily, showed a definite therapeutic influence on the characteristic increased serum levels of bilirubin, GOT and GPT associated with acute viral hepatitis. The above mentioned values in 28 patients treated with silymarin were compared with those in 29 patients treated with placebo. The laboratory parameters in the silymarin group regressed more than in the placebo group after the 5th day of treatment. The number of patients having attained normal values after 3 weeks' treatment was higher in the silymarin group than in the placebo group. A statistical comparison revealed a difference between bilirubin and GOT values in the placebo and silymarin groups and a definite trend in the regression of GPT values in favour of silymarin. The course of the immune reaction in HBS Ag patients was not influenced by silymarin. As already proved by other investigators, the use of silymarin in acute viral hepatitis can lead to an accelerated regression in pathological values, thus indicating its use in the treatment of this liver disease.", "Several studies have demonstrated that diabetic patients with cirrhosis require insulin treatment because of insulin resistance. As chronic alcoholic liver damage is partly due to the lipoperoxidation of hepatic cell membranes, anti-oxidizing agents may be useful in treating or preventing damage due to free radicals. The aim of this study was to ascertain whether long-term treatment with silymarin is effective in reducing lipoperoxidation and insulin resistance in diabetic patients with cirrhosis.\n A 12-month open, controlled study was conducted in two well-matched groups of insulin-treated diabetics with alcoholic cirrhosis. One group (n=30) received 600 mg silymarin per day plus standard therapy, while the control group (n=30) received standard therapy alone. The efficacy parameters, measured regularly during the study, included fasting blood glucose levels, mean daily blood glucose levels, daily glucosuria levels, glycosylated hemoglobin (HbA1c) and malondialdehyde levels.\n There was a significant decrease (p<0.01) in fasting blood glucose levels, mean daily blood glucose levels, daily glucosuria and HbA1c levels already after 4 months of treatment in the silymarin group. In addition, there was a significant decrease (p<0.01) in fasting insulin levels and mean exogenous insulin requirements in the treated group, while the untreated group showed a significant increase (p<0.05) in fasting insulin levels and a stabilized insulin need. These findings are consistent with the significant decrease (p<0.01) in basal and glucagon-stimulated C-peptide levels in the treated group and the significant increase in both parameters in the control group. Another interesting finding was the significant decrease (p<0.01) in malondialdehyde/levels observed in the treated group.\n These results show that treatment with silymarin may reduce the lipoperoxidation of cell membranes and insulin resistance, significantly decreasing endogenous insulin overproduction and the need for exogenous insulin administration.", "In patients with non-insulin dependent diabetes mellitus (T2DM) and associated chronic liver disease, plasma levels of glucose, insulin and triglycerides are high, lipid peroxidation is increased and natural antioxidant reserves are reduced. Thus, we hypothesised that the re-balancing of cell redox levels and amelioration of liver function could result in a better glucose and lipid metabolism. To study this, we assessed the effect of a new oral formulation of an antioxidant agent - silybin-beta-cyclodextrin (named IBI/S) - in patients with chronic alcoholic liver disease and concomitant T2DM.\n Sixty outpatients were enrolled in a three-centre, double blind, randomised, IBI/S vs placebo study. Forty-two (21 in the group IBI/S - 135 mg/d silybin per os - and 21 in the placebo group) concluded the 6-month treatment period. The efficacy parameters included fasting and mean daily plasma glucose levels, glycosylated hemoglobin (HbA1c), basal, stimulated C-peptide and insulin levels, total-, HDL-cholesterol and triglycerides levels in addition to conventional liver function tests. Insulin sensitivity was estimated by HOMA-IR. Malondialdehyde (MDA) was also measured before and after treatment as an index of oxidative stress.\n Fasting blood glucose levels, which were similar at baseline in IBI/S group and in the placebo group (173.9 mg/dl and 177.1 mg/dl, respectively), decreased to 148.4 mg/dl (-14.7% vs baseline; p = 0.03) in the IBI/S group while they were virtually unchanged in the placebo group. The comparison between the groups at mo 6 (T6) also showed a significant reduction of glucose levels in the IBI/S group (p = 0.03). The same trend was observed in mean daily blood glucose levels, HbA1c and HOMA-IR, although differences were not significant. Basal and stimulated C-peptide values showed that only a few changes had occured in both groups. Such results indicate that insulin secretion was virtually unaffected, as confirmed also by the insulinemia data. Plasma triglycerides concentrations dropped from a baseline value of 186 mg/dl to 111 mg/dl (T6) in the IBI/S group, with significant differences at all instances with respect to baseline values. By contrast, triglycerides increased from 159 mg/dl at entry to 185 mg/dl (T6) in the placebo group. The difference between the groups at T6 was highly significant (p < 0.01). Total and HDL cholesterol as well as liver function tests did not change significantly during the study in both groups. MDA decreased significantly only in the group receiving IBI/S. No clinically relevant side effects were observed in either group.\n Oral administration silybin-beta-cyclodextrin in patients with T2DM and compensated chronic alcoholic liver disease causes a significant decrease in both glucose and triglyceride plasma levels. These effects may be due to the recovery of energy substrates, consistent with a reduced lipid peroxidation and an improved insulin activity.", "Silymarin, the active principle of the milk thistle Silybum marianum, protects experimental animals against various hepatotoxic substances. To determine the effect of silymarin on the outcome of patients with cirrhosis, a double blind, prospective, randomized study was performed in 170 patients with cirrhosis. 87 patients (alcoholic 46, non-alcoholic 41; 61 male, 26 female; Child A, 47; B, 37; C, 3; mean age 57) received 140 mg silymarin three times daily. 83 patients (alcoholic 45, non-alcoholic 38; 62 male, 21 female; Child A, 42; B, 32; C, 9: mean age 58) received a placebo. Non-compliant patients and patients who failed to come to a control were considered as 'drop outs' and were withdrawn from the study. All patients received the same treatment until the last patient entered had finished 2-years of treatment. The mean observation period was 41 months. There were 10 drop outs in the placebo group and 14 in the treatment group. In the placebo group, 37 (+2 drop outs) patients had died, and in 31 of these, death was related to liver disease. In the treatment group, 24 (+4 drop outs) had died, and in 18 of these, death was related to liver disease. The 4-year survival rate was 58 +/- 9% (S.E.) in silymarin-treated patients and 39 +/- 9% in the placebo group (P = 0.036). Analysis of subgroups indicated that treatment was effective in patients with alcoholic cirrhosis (P = 0.01) and in patients initially rated 'Child A' (P = 0.03). No side effects of drug treatment were observed.(ABSTRACT TRUNCATED AT 250 WORDS)", "A controlled trial on the use of Silymarin in patients with alcoholic liver disease was performed. Seventy two patients were admitted to the trial and randomly assigned to an experimental or controls group. Experimentals received 280 mg/day of Silymarin and controls an equal number of placebo tablets. Three patients on placebo and nine on Silymarin were lost from control (p = 0.035), remaining in control 34 patients receiving placebo and 25 patients receiving the drug. Both groups did not differ in their initial laboratory assessment and were followed up for an average of 15 months. Ten patients died during the follow up (5 in placebo and 5 in Silymarin); life table analysis did not show significant differences in mortality. Patients who died had lower serum albumin and prothrombin time and higher total bilirubin, alkaline phosphatases and CCLI on the initial clinical and laboratory assessment. Final laboratory values and their changes in those who survived did not differ between Silymarin and placebo. Twenty two patients on placebo (65%) and 14 on Silymarin (58%) recognized alcohol ingestion or had a positive urine sample analysis for alcohol during follow up. Those who abstained from alcohol had a significant fall in gamma glutamyl transferase during follow up. No other significant differences were observed between these two groups. It is concluded that in this trial, Silymarin did not change the evolution or mortality of alcoholic liver disease.", "One hundred and six consecutive patients with liver disease were selected on the basis of elevated serum transaminase levels. The patients were randomly allocated into a group treated with silymarin (treated) and a group receiving placebo (controls). Ninety-seven patients complete the 4-week trial-47 treated and 50 controls. In general, the series represented a relatively slight acute and subacute liver disease, mostly induced by alcohol abuse. There was a statistically highly significantly greater decrease of S-SGPT (S-ALAT) and S-SGOT (S-ASAT) in the treated group than in controls. Serum total and conjugated bilirubin decreased more in the treated than in controls, but the differences were not statistically significant. BSP retention returned to normal significantly more often in the treated group. The mean percentage decrease of BSP was also markedly higher in the treated. Normalization of histological changes occurred significantly more often in the treated than in controls.", "The effects of silymarin (Legalon) therapy on liver function tests, serum procollagen III peptide level and liver histology were studied in 36 patients with chronic alcoholic liver disease in a six month double blind clinical trial. During silymarin treatment serum bilirubin, aspartate aminotransferase and alanin-aminotransferase values have been normalized, while gamma-glutamyl transferase activity and procollagen III peptid level decreased. The changes were significant, and there was a significant difference between post-treatment values of the two groups, as well. In the placebo group only gamma-glutamyl transferase values decreased significantly but to a lesser extent than that in the silymarin group. The histological alterations showed an improvement in the silymarin group, while remained unchanged in the placebo group. These results indicate that silymarin exerts hepatoprotective activity and is able to improve liver functions in alcoholic patients.", "The role of silymarin in the treatment of liver cirrhosis is controversial.\n Clinical outcome,biochemical profile and the antiperoxidative effects of silymarin MZ-80 during 6 months treatment were investigated in patients with alcoholic liver cirrhosis.\n Sixty consecutive patients with alcoholic liver cirrhosis were randomized to receive either silymarin MZ-80 (S) (150 mg t.i.d. per day) or placebo (P) for periods of 6 months. Erythrocyte total glutathione (GSH) content, platelet malondialdehyde (MDA) and serum amino-terminal propeptide of procollagen Type III (PIIINP) were determined at baseline and at the end of treatment.\n Forty-nine patients completed the study (24 S and 25 P). The 2 groups were well-matched for demographic as well as baseline clinical and laboratory parameters. Silymarin increased total GSH at 6 months (4.5 +/- 3.4 to 5.8 +/- 4.0 micromol/g Hb) whereas, in the placebo group, GSH remained unchanged (4.1 +/- 3.9 to 4.4 +/- 4.1 micromol/gHb) (p < 0.001), and platelet-derived non-induced MDA decreased by 33% (p < 0.015). A parallel decrease in PIIINP values was seen with silymarin (1.82 1.03 to 1.36 +/- 0.5 U/ml, p < 0.033) but not with placebo (1.31 +/- 0.4 to 1.27 +/- 0.6 U/ml). There were no concurrent changes on laboratory indices of the pathology.\n Silymarin is well-tolerated and produces a small increase in glutathione and a decrease in lipid peroxidation in peripheral blood cells in patients with alcoholic liver cirrhosis. Despite these effects no changes in routine liver tests were observed during the course of therapy.", "In order to assess the liver protective activity and the antioxidant properties of a new silybin complex (IdB1016), we carried out a short-term pilot study on 20 patients with chronic active hepatitis (CAH), randomly assigned to 240 mg of silybin b.i.d. (10 patients, 4 m/6 f, mean age: 50 years) or placebo (10 patients, 2 m/8 f, mean age: 55 years). Blood samples were collected before and after 7 days of treatment for liver function tests (LFTs), malonaldehyde (MDA) as an index of lipid peroxidation, and copper (Cu) and zinc (Zn), two trace elements involved in protecting cells against free radical-mediated lipid peroxidation. In the treated group, there was a statistically significant reduction of mean (+/- SEM) serum concentrations of aspartate aminotransferase (AST) from 88.0 (+/- 13.3) to 65.9 (+/- 7.5) u/l, (p < 0.01), of alanine aminotransferase (ALT) from 115.9 (+/- 12.9) to 82.5 (+/- 10.6) u/l (p < 0.01), of gamma-glutamyltranspeptidase (gamma-GT) from 51.4 (+/- 9.3) to 41.3 (+/- 4.2) u/l (p < 0.02) and of total bilirubin (TB) from 0.76 (+/- 0.08) to 0.53 (+/- 0.04) mg/dl (p < 0.05). Alkaline phosphatase (AP) fell slightly from 143.4 (+/- 6.4) to 137.5 (+/- 7.8) u/l. There were no significant changes in MDA, Cu or Zn serum concentrations. These results show that IdB1016 may improve LFTs related to hepatocellular necrosis and/or increases membrane permeability in patients affected by CAH.", "The hepatoprotective and immunomodulatory effects of silymarin and amino-imidazol-carboxamid-phosphate were studied in 60 patients with compensated alcoholic cirrhosis of the liver in a one month double blind clinical trial. Treatment with both drugs normalized the elevated levels of aspartate aminotransferase, alanine aminotransferase and serum bilirubin, markedly reduced the high level of gamma-glutamyl transferase, increased lectin-induced lymphoblasttransformation, decreased the percentage of CD8+ cells and suppressed lymphocytotoxicity. None of these changes occurred in the placebo-treated group. Thus the hepato-protective effects of silymarin and amino-imidazol-carboxamid-phosphate are accompanied by changes in parameters of cellular immunoreactivity of the treated patients." ]

[ "9820259", "15280133", "20168104", "15924530", "17265548" ]

[ "Moxibustion for correction of breech presentation: a randomized controlled trial.", "Acupuncture plus moxibustion to resolve breech presentation: a randomized controlled study.", "Moxibustion for breech version: a randomized controlled trial.", "A randomised controlled trial of moxibustion for breech presentation.", "Effects of three different stimulations (acupuncture, moxibustion, acupuncture plus moxibustion) of BL.67 acupoint at small toe on fetal behavior of breech presentation." ]

[ "Traditional Chinese medicine uses moxibustion (burning herbs to stimulate acupuncture points) of acupoint BL 67 (Zhiyin, located beside the outer corner of the fifth toenail), to promote version of fetuses in breech presentation. Its effect may be through increasing fetal activity. However, no randomized controlled trial has evaluated the efficacy of this therapy.\n To evaluate the efficacy and safety of moxibustion on acupoint BL 67 to increase fetal activity and correct breech presentation.\n Randomized, controlled, open clinical trial.\n Outpatient departments of the Women's Hospital of Jiangxi Province, Nanchang, and Jiujiang Women's and Children's Hospital in the People's Republic of China.\n Primigravidas in the 33rd week of gestation with normal pregnancy and an ultrasound diagnosis of breech presentation.\n The 130 subjects randomized to the intervention group received stimulation of acupoint BL 67 by moxa (Japanese term for Artemisia vulgaris) rolls for 7 days, with treatment for an additional 7 days if the fetus persisted in the breech presentation. The 130 subjects randomized to the control group received routine care but no interventions for breech presentation. Subjects with persistent breech presentation after 2 weeks of treatment could undergo external cephalic version anytime between 35 weeks' gestation and delivery.\n Fetal movements counted by the mother during 1 hour each day for 1 week; number of cephalic presentations during the 35th week and at delivery.\n The intervention group experienced a mean of 48.45 fetal movements vs 35.35 in the control group (P<.001; 95% confidence interval [CI] for difference, 10.56-15.60). During the 35th week of gestation, 98 (75.4%) of 130 fetuses in the intervention group were cephalic vs 62 (47.7%) of 130 fetuses in the control group (P<.001; relative risk [RR], 1.58; 95% CI, 1.29-1.94). Despite the fact that 24 subjects in the control group and 1 subject in the intervention group underwent external cephalic version, 98 (75.4%) of the 130 fetuses in the intervention group were cephalic at birth vs 81 (62.3%) of the 130 fetuses in the control group (P = .02; RR, 1.21; 95% CI, 1.02-1.43).\n Among primigravidas with breech presentation during the 33rd week of gestation, moxibustion for 1 to 2 weeks increased fetal activity during the treatment period and cephalic presentation after the treatment period and at delivery.", "In many Western countries breech presentation is an indication for elective Cesarean section. In order to correct fetal presentation, the stimulation of the acupoint BL67 by moxibustion, acupuncture or both has been proposed. Since no studies had previously been carried out on Western populations, pregnant Italian women at 33-35 weeks gestational age carrying a fetus in breech presentation were enrolled in a randomized, controlled trial involving an active BL67 point stimulation and an observation group.\n A total of 240 women at 33-35 weeks of gestation carrying a fetus in breech presentation were randomized to receive active treatment (acupuncture plus moxibustion) or to be assigned to the observation group. Bilateral acupuncture plus moxibustion was applied at the BL67 acupoint (Zhiyin). The primary outcome of the study was fetal presentation at delivery.\n Fourteen cases dropped out. The final analysis was thus made on 226 cases, 114 randomized to observation and 112 to acupuncture plus moxibustion. At delivery, the proportion of cephalic version was lower in the observation group (36.7%) than in the active-treatment group (53.6 %) (p = 0.01). Hence, the proportion of Cesarean sections indicated for breech presentation was significantly lower in the treatment group than in the observation group (52.3% vs. 66.7%, p = 0.03).\n Acupuncture plus moxibustion is more effective than observation in revolving fetuses in breech presentation. Such a method appears to be a valid option for women willing to experience a natural birth.", "To estimate the efficacy of moxibustion between 34 and 38 weeks of gestation to facilitate the cephalic version of fetuses in breech presentation and the acceptability of this method by women.\n We conducted a randomized controlled trial in a Swiss university hospital maternity unit. We proposed to stimulate the acupoint BL 67 by moxibustion daily for 2 weeks for 212 consenting women between 34 and 36 weeks of gestation with a single fetus in breech presentation. We did the intervention three times weekly in the hospital and a teaching session and information leaflet on the technique for additional daily therapy at home. The control group received expectant management care. The availability of external cephalic version was maintained for both groups. The main outcome measure was the comparison of the proportion of women with cephalic presentation at delivery.\n Baseline characteristics were similar between groups, except more nulliparous women were randomized to moxibustion. The percentage of versions was similar between groups: 18% in the moxibustion group compared with 16% in the control group (relative risk 1.12, 95% confidence interval 0.62 to 2.03). Adjustment for the imbalance in parity did not change these results. The frequency of cesarean delivery was similar (64% compared with 58% in the moxibustion group and the control group, respectively). Acceptability of the intervention and women's perceptions of moxibustion were favorable.\n We observed no beneficial effect of moxibustion to facilitate the cephalic version of fetuses in breech presentation. Despite this lack of proven effectiveness, women had positive opinions on the intervention.\n ClinicalTrials.gov, www.clinicaltrials.gov,NCT00890474.\n I.", "To evaluate the efficacy of moxibustion for the correction of fetal breech presentation in a non-Chinese population.\n Single-blind randomised controlled trial (RCT).\n Six obstetric departments in Italy.\n Healthy non-Chinese nulliparous pregnant women at 32-33 weeks + 3 days of gestational age with the fetus in breech presentation.\n Random assignment to treatment or observation. Treatment consisted of moxibustion (stimulation with heat from a stick of Artemisia vulgaris) at the BL 67 acupuncture point (Zhiyin) for one or two weeks. Two weeks after recruitment, each participant was subjected to an ultrasonic examination of the fetal presentation.\n Number of participants with cephalic presentation in the 35th week.\n The study was interrupted when 123 participants had been recruited (46% of the planned sample). Intermediate data monitoring revealed a high number of treatment interruptions. At this point no difference was found in cephalic presentation in the 35th week (treatment group: 22/65, 34%; control group: 21/58, 36%; RR 0.95; 99% CI 0.59-1.5).\n The results underline the methodological problems evaluating of a traditional treatment transferred from a different cultural context. They do not support either the effectiveness or the ineffectiveness of moxibustion in correcting fetal breech presentation.", "The aim of the study was to evaluate cardiovascular effects and fetal behavior during moxibustion, acupuncture or acupuncture plus moxibustion applied on the BL.67 acupoint of women (beside the outer corner of the 5th toenail) in fetal breech presentation. During the acupoint stimulation (20 min, two times a week), the women were submitted to computerized non-stress test. Fourteen cases were treated by both acupuncture and moxibustion, 15 cases by moxibustion and 10 cases by acupuncture. In 56% of cases, fetal position was converted from breech position to cephalic one; the success share was 80% for moxibustion, 28% for acupuncture, 57% for acupuncture plus moxibustion; the conversion, on average, was achieved after 3 sessions. Statistical analysis indicated that acupuncture plus moxibustion was able to reduce fetal heart rate during the application of stimuli while acupuncture and moxibustion separately did not affect such parameter. Moreover, moxibustion and acupuncture with moxibustion reduced fetal movements while acupuncture only appears ineffective. The present study suggests that fetal movements were reduced by both acupuncture plus moxibustion and moxibustion and that fetal heart rate was reduced just by acupuncture plus moxibustion. The mechanisms leading the effect on fetal heart rate and fetal movements remain to be clarified. Even though further studies are needed, such preliminar report mainly investigated the impact of different stimula on the BL.67 acupoint. Unfortunately these small series of data do not allow us to draw any conclusion about the effectiveness of the different treatments." ]

[ "1599892", "22527786", "8398955", "22145255", "20613476", "15721731", "3826597", "18547293" ]

[ "Effect of subarachnoid morphine on the incidence of spinal headache.", "Effect of dexamethasone on the frequency of postdural puncture headache after spinal anesthesia for cesarean section: a double-blind randomized clinical trial.", "PDPH in obstetric anesthesia: comparison of 24-gauge Sprotte and 25-gauge Quincke needles and effect of subarachnoid administration of fentanyl.", "Dexamethasone in preventing post-dural puncture headache: a randomized, double-blind, placebo-controlled trial.", "Cosyntropin for prophylaxis against postdural puncture headache after accidental dural puncture.", "Oral multidose caffeine-paracetamol combination is not effective for the prophylaxis of postdural puncture headache.", "Postoperative headache in young patients after spinal anaesthesia.", "Epidural morphine injections for prevention of post dural puncture headache." ]

[ "The addition of fentanyl to hyperbaric local anesthetics has been shown to reduce the incidence of post dural puncture headache in the obstetric patient. This study was undertaken to evaluate the effects of subarachnoid morphine on the incidence of headache.\n Eighty-two healthy patients undergoing cesarean delivery with spinal anesthesia were studied. All patients were hydrated with 1500 ml lactated Ringer's solution. Patients were randomly assigned to receive, in a double-blind fashion, 0.2 mg of either morphine (Group 1, n = 40) or saline (Group 2, n = 42) in 0.2 ml volume mixed with 0.75% bupivacaine in 8.25% dextrose plus 0.2 ml 1:1000 epinephrine. Spinal anesthesia was induced using a 25-gauge spinal needle at L3-4 interspace with the bevel, in most cases, parallel to the dural fibers. Patients were followed for three days to evaluate the incidence and severity of headache using a four-category rank scale (none, mild, moderate, severe). Data were analyzed for statistical significance using Student's t-test or chi-square test as appropriate. A p value less than 0.05 was considered significant. Results. The incidence of post dural puncture headache did not differ significantly between groups. Eight patients in Group 1 versus nine patients in Group 2 developed headache (p greater than 0.05). Similarly, the use of blood patch or intravenous caffeine sodium benzoate to treat the headache did not differ significantly between groups.\n It is concluded from our study that subarachnoid morphine did not decrease the incidence of post dural puncture headache in the obstetric patient.", "In this study, we evaluated the effect of dexamethasone used as a prophylaxis for nausea and vomiting on the incidence of postdural puncture headache (PDPH) in pregnant women receiving spinal anesthesia for cesarean section. In a prospective, randomized, double-blind, placebo-controlled study, 372 women under spinal anesthesia received 8 mg of dexamethasone or placebo intravenously just after the umbilical cord was clamped. The rate of PDPH and correlated risk factors were evaluated. The prevalence of nausea and vomiting in the dexamethasone and placebo groups was 54.4 and 51.7%, respectively. There was no statistically meaningful difference between the results (P value = 0.673). The overall incidence rate of PDPH was 10.8%, with 28 cases from the dexamethasone group compared with 11 subjects from the placebo group (P value = 0.006). This effect was most prominent on the first day (P value = 0.046) and disappeared on the second day after spinal anesthesia (P value = 0.678). Prophylactic treatment with 8 mg of dexamethasone not only increases the severity and incidence of PDPH, but is also ineffective in decreasing the prevalence of intra-operative nausea and vomiting during cesarean section. The treatment is a significant risk factor for the development of PDPH.", "Postdural puncture headache (PDPH) is a frequent complication of spinal anesthesia. Some investigators have recommended the use of the Sprotte needle to reduce the incidence of this serious complication. This study prospectively compared the incidence of PDPH with two spinal needles of different size and design: the 24-gauge Sprotte (noncutting point) versus the 25-gauge Quincke (diamond, cutting point). The hypothesis that subarachnoid fentanyl will reduce the incidence of PDPH, as suggested in the literature, was also studied.\n Only patients for emergency or elective cesarean delivery were studied. One hundred ninety four patients were randomly assigned to receive spinal anesthesia with one of the two needles (Sprotte, n = 96; Quincke, n = 98). Simultaneously, each patient was assigned to receive hyperbaric 0.75% bupivacaine local anesthetic or a combination of the same concentration of local anesthetic with 20 micrograms of fentanyl (Sprotte with fentanyl, n = 47; Sprotte without fentanyl, n = 49; Quincke with fentanyl, n = 49; Quincke without fentanyl, n = 49). All patients were evaluated during the first 4 postoperative days, and follow-up telephone interviews were conducted 3 weeks after discharge.\n Four patients (4.2%) in the Sprotte group and seven (7.1%) in the Quincke group developed PDPH. Three out of four patients with headache in the Sprotte and four out of seven in the Quincke group received fentanyl as an adjunct for spinal anesthesia. Two patients in the Sprotte group required an epidural blood patch as a therapy for PDPH. Two patients in the Quincke group had severe headache and required an epidural blood patch.\n In the current study, the use of the 24-gauge Sprotte spinal needle resulted in a low incidence of severe PDPH, but was not significantly different when compared with the use of a 25-gauge Quincke needle (oriented parallel to the longitudinal dural fibers). The addition of fentanyl to hyperbaric bupivacaine spinal anesthesia did not reduce the risk of PDPH.", "Spinal anesthesia is major complication is Post-Dural Puncture Headache (PDPH) which is an intense and debilitating event. We decided to assess if intravenous administration of dexamethasone can decrease the incidence and/or intensity of this kind of headache. For this purpose 178 patients, who were supposed to undergo lower extremity orthopedic surgery, were enrolled in the study . Before spinal anesthesia was initiated, the first group (DXM-group) received 2 mL intravenous (i.v) dexamethasone whereas the second group (PCB-group) received 2 mL i.v. normal saline. After termination of surgery, a 7 days follow-up started to observe the possible occurrence and intensity of PDPH. There was no statistically significant difference between DMX and PCB groups regarding the incidence of PDPH. However, the intensity of headache differed between the two groups being less severe if IV dexamethasone had been given prophylactically. Dexamethasone can be used to decrease the severity of PDPH in patients who receive spinal anesthesia.", "The aim of the current study was to investigate the effect of administration of cosyntropin after accidental dural puncture (ADP) on the incidence of postdural puncture headache (PDPH) and the need for therapeutic epidural blood patch (EBP).\n Ninety parturients who suffered an ADP were studied. After delivery, patients were randomly assigned to one of two equal-sized groups. In group I (cosyntropin group), patients received cosyntropin in a dose of 1 mg intravenously. In group II (control group), patients received an equal volume of normal saline.\n Fifteen patients (33%) in the cosyntropin group suffered from PDPH, compared with 31 patients (68.9%) in the control group (P = 0.001). Significantly fewer patients in the cosyntropin group required an EBP, compared with the control group (5 patients [11.1%] vs. 13 patients [28.9%], respectively; P = 0.035). The Kaplan-Meier curves for the occurrence of PDPH showed a hazard ratio of 0.32 (95% CI = 0.16-0.55, P < 0.0001). The time from ADP to occurrence of PDPH was significantly longer in the cosyntropin group (27.2 [7.7] h) in comparison with the control group (17.5 [4.9] h; P < 0.001). However, there were no statistically significant differences among patients who developed PDPH in both groups with regard to the severity or duration of PDPH or with regard to the need for EBP or for repeat EBP (P > 0.05).\n Administration of cosyntropin after ADP in parturients was associated with significant reduction in the incidence of PDPH and need for EBP and significant prolongation of the time from ADP to occurrence of PDPH.", "To investigate the effects of different doses of oral caffeine-paracetamol combinations in postdural puncture headache (PDPH) prophylaxis.\n Prospective, randomized, placebo-controlled, blinded study.\n University hospital.\n A total of 210 ASA physical status I and II patients undergoing lower extremity surgery.\n Patients were randomly divided into 3 groups. One hour before the spinal anesthesia, the first group (n = 70) received placebo, the second group (n = 70) received 500-mg paracetamol + 75-mg caffeine, and the third group (n = 70) received 500-mg paracetamol + 125-mg caffeine orally. The same doses were repeated every 6 hours for 3 days. Patients were then interviewed on days 1, 2, 3, 4, and 7 to inquire about any PDPH. The interviewer was unaware of the PDPH prophylaxis group members. Patients who were discharged early were interviewed by telephone.\n Postdural puncture headache occurred in 11 patients (15.7%) in group 1, 10 patients (% 14.28) in group 2, and 10 patients (% 14.28) in group 3. The differences between the groups were insignificant (P > .05). The complications due to spinal anesthesia were similar in the 3 groups. Side effects of caffeine such as lack of sleep, tachycardia, and hypertension were not observed in groups 2 or 3.\n Prophylactic administration of paracetamol-caffeine combinations at the stated doses does not prevent PDPH.", "Spinal anaesthesia was performed on 247 young adult patients with a 25-G needle. Rectal administration of indomethacin had no significant effect on the incidence of postdural puncture headache, which occurred in 16.8% of patients who received the drug compared to 24.5% who received a placebo. A history of headache pre-operatively did not influence the incidence of postlumbar puncture headache.", "A prospective, randomised, double-blind trial was conducted to study the effect of epidural morphine in prevention of post dural puncture headache in 25 parturients after inadvertent dural puncture. Women were randomly allocated to receive two epidural injections, 24 h apart, of either 3 mg morphine in 10 ml saline (morphine group) or 10 ml saline (saline group). The incidence of headache and need for therapeutic epidural blood patch were reported. There was a significant difference in the incidence of headache between the two groups: 3/25 (12%) in the morphine group and 12/25 (48%) in the saline group (p = 0.014). Therapeutic epidural blood patches were required in six patients in the saline group and none of the patient in the morphine group (p = 0.022). It was concluded that epidural morphine appears to be a simple and effective technique for prevention of post dural puncture headache after accidental dural puncture in high risk obstetric patients." ]

[ "16367987", "12410780", "7734458", "9313020", "7851278", "15607843", "20575820", "8257551", "7851281", "3275523", "16118380", "16042639", "16524668", "12237786", "17315409", "15223097", "12633912", "16203961" ]

[ "A comparison of buprenorphine and lofexidine for community opiate detoxification: results from a randomized controlled trial.", "A randomized controlled trial of buprenorphine in the management of short-term ambulatory heroin withdrawal.", "A preliminary investigation of outcome following gradual or rapid buprenorphine detoxification.", "Three methods of opioid detoxification in a primary care setting. A randomized trial.", "A controlled comparison of buprenorphine and clonidine for acute detoxification from opioids.", "A double-blind, double-dummy, randomized, prospective pilot study of the partial mu opiate agonist, buprenorphine, for acute detoxification from heroin.", "Buprenorphine and carbamazepine as a treatment for detoxification of opiate addicts with multiple drug misuse: a pilot study.", "Buprenorphine in opiate withdrawal: a comparison with clonidine.", "Opiate detoxification of methadone maintenance patients using lefetamine, clonidine and buprenorphine.", "A clinical trial of buprenorphine: comparison with methadone in the detoxification of heroin addicts.", "Anesthesia-assisted vs buprenorphine- or clonidine-assisted heroin detoxification and naltrexone induction: a randomized trial.", "A multi-center randomized trial of buprenorphine-naloxone versus clonidine for opioid detoxification: findings from the National Institute on Drug Abuse Clinical Trials Network.", "Well-being, psychosocial factors, and side-effects among heroin-dependent inpatients after detoxification using buprenorphine versus clonidine.", "Detoxification of opiate addicts with multiple drug abuse: a comparison of buprenorphine vs. methadone.", "A randomized trial of one-day vs. three-day buprenorphine inpatient detoxification protocols for heroin dependence.", "Opioid detoxification using high doses of buprenorphine in 24 hours: a randomized, double blind, controlled clinical trial.", "Opioid detoxification with buprenorphine, clonidine, or methadone in hospitalized heroin-dependent patients with HIV infection.", "Comparison of pharmacological treatments for opioid-dependent adolescents: a randomized controlled trial." ]

[ "To investigate whether a buprenorphine opiate detoxification regimen can be considered to be at least as clinically effective as a lofexidine regimen.\n An open-label randomized controlled trial (RCT) using a non-inferiority approach. Non-inferiority is demonstrated if, within a 95% confidence interval, buprenorphine performs within a preset tolerance limit of clinically acceptable difference in outcomes and completion rates between the two treatments.\n Individuals ready for heroin detoxification were given information about the trial and invited to participate. Consenting participants (n = 210) were then randomized to one of the two treatments. Detoxification was undertaken in a specialist out-patient clinic according to predefined protocols. The primary outcome was whether or not an individual completed the detoxification. Abstinence at 1-month follow-up was used as a secondary outcome measure. Additional secondary outcome measures were substance use, dependence, psychological health, social satisfaction, and treatment satisfaction. Data were also collected for individuals who declined randomization and instead chose their treatment (n = 271).\n A total of 46% of those on lofexidine and 65% of those on buprenorphine completed detoxification. Of these, 35.7% of the lofexidine and 45.9% of the buprenorphine groups reported abstinence at 1 month. Of those not completing detoxification abstinence was reported at 27.5% and 29.0%, respectively; 271 individuals who opted not to be allocated randomly and instead chose one of the two treatments produced similar results\n Buprenorphine is at least as effective as lofexidine detoxification treatment. Whether or not individuals were randomized to, or chose, a treatment appeared not to affect the study's outcome.", "To determine whether buprenorphine is more effective than clonidine and other symptomatic medications in managing ambulatory heroin withdrawal.\n Open label, prospective randomized controlled trial examining withdrawal and 4-week postwithdrawal outcomes on intention-to-treat.\n Two specialist, out-patient drug treatment centres in inner city Melbourne and Sydney, Australia.\n One hundred and fourteen dependent heroin users were recruited. Participants were 18 years or over, and with no significant other drug dependence, medical or psychiatric conditions or recent methadone treatment. One hundred and one (89%) participants completed a day 8 research interview examining withdrawal outcomes, and 92 (81%) completed day 35 research interview examining postwithdrawal outcomes.\n Participants randomized to control (n = 56) (up to 8 days of clonidine and other symptomatic medications) or experimental (n = 58) (up to 5 days of buprenorphine) withdrawal groups. Following the 8-day withdrawal episode, participants could self-select from range of postwithdrawal options (naltrexone, substitution maintenance, or counselling).\n Retention in withdrawal; heroin use during withdrawal; and retention in drug treatment 4 weeks after withdrawal.\n Withdrawal severity; adverse events, and heroin use in the postwithdrawal period.\n The experimental group had better treatment retention at day 8 (86% versus 57%, P = 0.001, 95% CI for numbers needed to treat (NNT) = 3-8) and day 35 (62% versus 39%, P = 0.02, 95% CI for NNT = 4-18); used heroin on fewer days during the withdrawal programme (2.6 +/- 2.5 versus 4.5 +/- 2.3, P < 0.001, 95% CI = 1-2.5 days) and in the postwithdrawal period (9.0 +/- 8.2 versus 14.6 +/- 10, P < 0.01, 95% CI = 1.8-9.4); and reported less withdrawal severity. No severe adverse events reported.\n Buprenorphine is effective for short-term ambulatory heroin withdrawal, with greater retention, less heroin use and less withdrawal discomfort during withdrawal; and increased postwithdrawal treatment retention than symptomatic medications.", "Eight opioid-dependent individuals were maintained on daily sublingual buprenorphine (8 mg) for 28 days and assigned randomly to one of two outpatient detoxification schedules under double-blind, double-dummy conditions. The two detoxification schedules were buprenorphine gradual (36 days; N = 3) or buprenorphine rapid (12 days; N = 5). Outcome variables were subject- and observer-ratings of opioid withdrawal, treatment retention and illicit-opioid use. Outcome measures were similar for the two groups during buprenorphine maintenance. Increases in subject-rated opioid withdrawal and illicit-opioid use, and a drop in treatment retention occurred during rapid detoxification. Stable subject-rated opioid withdrawal and treatment retention, and less illicit-opioid use occurred during gradual detoxification. These data suggest that gradual reduction in buprenorphine dose is likely to produce superior treatment outcomes than more rapid buprenorphine detoxification.", "Opioid detoxification in a primary care setting followed by ongoing substance abuse treatment may be appropriate for selected opioid-dependent patients.\n To compare three pharmacologic protocols for opioid detoxification in a primary care setting.\n Randomized, double-blind clinical trial with random assignment to treatment protocols.\n A free-standing primary care clinic affiliated with drug treatment programs.\n 162 heroin-dependent patients.\n Three detoxification protocols: donidine, combined donidine and naltrexone, and buprenorphine.\n Successful detoxification (that is, when study participants received a full opioid-blocking dose [50 mg] of naltrexone), treatment retention (8 days), and withdrawal symptoms.\n Overall, 65% of participants (36 of 55) who received clonidine, 81% (44 of 54) who received combined clonidine and naltrexone, and 81% (43 of 53) who received buprenorphine were successfully detoxified. Retention did not differ significantly across the groups: 65% of participants (36 of 55) who received clonidine, 54% (29 of 54) who received combined clonidine and naltrexone, and 60% (32 of 53) who received buprenorphine. Participants who received buprenorphine had a significantly lower mean withdrawal symptom score than those who received clonidine or combined clonidine and naltrexone.\n Participants in the combined clonidine and naltrexone group and those in the buprenorphine group were more likely to complete detoxification, although retention at 8 days did not differ among the groups. Participants who were assigned to the buprenorphine group experienced less severe withdrawal symptoms than those assigned to the other two groups.", "We compared the short-term efficacy of a high-dose, 3 day regimen of buprenorphine to a standard 5-day course of clonidine in attenuating the signs and symptoms of the acute opioid abstinence syndrome during rapid detoxification from heroin in 25 men and women admitted to a closed inpatient research ward for this randomized, double-blind, parallel-group trial. Among the 18 completers, there were no significant differences between the buprenorphine and clonidine groups on five subjective and six physiological measures. However, clonidine lowered blood pressure and buprenorphine provided more effective early relief of withdrawal symptoms.", "The optimum dose of buprenorphine for acute inpatient heroin detoxification has not been determined. This randomized, double-blind, double-dummy, pilot study compares two buprenorphine sublingual tablet dosing schedules to oral clonidine. Heroin users (N = 30) who met DSM-IV criteria for opioid dependence and achieved a Clinical Opiate Withdrawal Scale (COWS) score of 13 (moderate withdrawal), were randomized to receive higher dose buprenorphine (HD, 8-8-8-4-2 mg/day on days 1-5), lower dose buprenorphine (LD, 2-4-8-4-2 mg/day on days 1-5), or clonidine (C, 0.2-0.3-0.3-0.2-0.1 mg QID on days 1-5). COWS scores were obtained QID. Twenty-four hours after randomization, the percentages of subjects who achieved suppression of withdrawal, as defined by four consecutive COWS scores <12, were: C = 11%, LD = 40%, and HD = 60%. Generalized estimating equation regression models, controlling for baseline COWS and time, indicated that COWS scores over the course of 5 days were lower in both LD and HD compared to C (chi(2)(2) = 13.28, P = 0.001). Similar analyses examining scores over time on the Adjective Rating Scale for Withdrawal (ARSW) and on a Visual Analog Scale of Opiate Craving (VAS) indicated an overall treatment effect on the VAS accounted for by a significant difference between HD and C, but no overall treatment effect on the ARSW. There were no discontinuations due to treatment-related adverse events. Both HD and LD regimens are safe and efficacious treatment for opioid detoxification, but HD demonstrated superiority to C on a greater number of measures.", "The growing tendency of opioid addicts to misuse multiple other drugs leads to the investigation of new pharmacostrategies to prevent patients from suffering life-threatening complications and minimize the withdrawal symptoms. The short-term efficacy of a 10-day low-dose buprenorphine/19-day carbamazepine regime (n = 15) to a 14-day oxazepam/19-day carbamazepine regime (n = 12) in an open-labelled 21-day inpatient detoxification treatment was compared. Twenty-seven men and women dependent on opioids and misusing other drugs admitted to a detoxification unit were included in this protocol. Eighteen of 27 patients (67%) completed the study. Four non-completers (27%) received buprenorphine/carbamazepine (four of 15) and five non-completers (42%) were treated with oxazepam/carbamzepine (five of 12), but the difference in the dropout rate between the two treatment strategies was not significant.The buprenorphine/carbamazepine regime provided significantly more effective relief of withdrawal symptoms during the first week of treatment. No severe side effects occurred during treatment in both groups. The present study supports the hypothesis that buprenorphine/carbamazepine is more effective than oxazepam/carbamazepine in rapid opioid detoxification in patients with additional multiple drug misuse and both regimens were safe with no unexpected side effects.", "Clinical efficacy of buprenorphine in controlling withdrawal symptoms was compared against clonidine among 44 opiate dependent males. Subjective and objective withdrawal symptoms were assessed by withdrawal rating scales daily for 10 days. The subjects were randomly assigned to fixed dose schedule of either buprenorphine (0.6-1.2 mg per day, sublingually) or clonidine (0.3-0.9 mg per day, oral) for 10 days. Buprenorphine was found superior to clonidine in alleviating most of the subjective and objective opiate withdrawal symptoms. Subjective symptoms declined earlier among the subjects receiving buprenorphine. No untoward side-effects of buprenorphine were noticed.", "Thirty-nine methadone maintenance patients were included in a 9-day, double blind, randomized, inpatient detoxification trial. Methadone was tapered to 10 mg/day and then patients were assigned to one of these 3 protocols: clonidine (0.3-0.9 mg/day), lefetamine (60-240 mg/day), buprenorphine (0.15-0.9 mg/day). Buprenorphine treatment was significantly superior to clonidine and to lefetamine (F = 3.96 df = 2, 29 P < 0.05) in controlling objective, subjective and psychological withdrawal symptomatology. Clonidine was more effective than lefetamine in suppressing withdrawal in the first 3 days of treatment (day 3: F = 4.10 df = 2, 30 P < 0.05), and this trend was apparent on the objective and psychological items. In addition to evaluations of the efficacy of the single drugs used, the study showed that tapering methadone to low doses before entering the pharmacologically assisted discontinuation phase was clinically acceptable in detoxification from long-term methadone treatment.", "The efficacy of buprenorphine and methadone was compared in the outpatient detoxification of heroin addicts. Forty-five patients were randomized to receive either sublingual buprenorphine or oral methadone under double-dummy and double-blind conditions to study the pharmacology of buprenorphine in a 90-day detoxification protocol. The patients were administered either 2 mg buprenorphine or 30 mg methadone for 3 weeks followed by 4 weeks of dose reductions and 6 weeks of placebo medication. No significant between-group differences were seen on measures of treatment retention, drug use, or symptom report. During the hydromorphone challenge, methadone attenuated opioid effects to a greater extent than did buprenorphine on both physiologic (pupil constriction) and self-report measures. However, this did not result in greater abuse of illicit opioid drugs by subjects taking buprenorphine. The results of this clinical trial indicated that buprenorphine was acceptable to patients and as effective as methadone in the detoxification treatment of heroin addicts.", "Rapid opioid detoxification with opioid antagonist induction using general anesthesia has emerged as an expensive, potentially dangerous, unproven approach to treat opioid dependence.\n To determine how anesthesia-assisted detoxification with rapid antagonist induction for heroin dependence compared with 2 alternative detoxification and antagonist induction methods.\n A total of 106 treatment-seeking heroin-dependent patients, aged 21 through 50 years, were randomly assigned to 1 of 3 inpatient withdrawal treatments over 72 hours followed by 12 weeks of outpatient naltrexone maintenance with relapse prevention psychotherapy. This randomized trial was conducted between 2000 and 2003 at Columbia University Medical Center's Clinical Research Center. Outpatient treatment occurred at the Columbia University research service for substance use disorders. Patients were included if they had an American Society of Anesthesiologists physical status of I or II, were without major comorbid psychiatric illness, and were not dependent on other drugs or alcohol.\n Anesthesia-assisted rapid opioid detoxification with naltrexone induction, buprenorphine-assisted rapid opioid detoxification with naltrexone induction, and clonidine-assisted opioid detoxification with delayed naltrexone induction.\n Withdrawal severity scores on objective and subjective scales; proportions of patients receiving naltrexone, completing inpatient detoxification, and retained in treatment; proportion of opioid-positive urine specimens.\n Mean withdrawal severities were comparable across the 3 treatments. Compared with clonidine-assisted detoxification, the anesthesia- and buprenorphine-assisted detoxification interventions had significantly greater rates of naltrexone induction (94% anesthesia, 97% buprenorphine, and 21% clonidine), but the groups did not differ in rates of completion of inpatient detoxification. Treatment retention over 12 weeks was not significantly different among groups with 7 of 35 (20%) retained in the anesthesia-assisted group, 9 of 37 (24%) in the buprenorphine-assisted group, and 3 of 34 (9%) in the clonidine-assisted group. Induction with 50 mg of naltrexone significantly reduced the risk of dropping out (odds ratio, 0.28; 95% confidence interval, 0.15-0.51). There were no significant group differences in proportions of opioid-positive urine specimens. The anesthesia procedure was associated with 3 potentially life-threatening adverse events.\n These data do not support the use of general anesthesia for heroin detoxification and rapid opioid antagonist induction.", "The clinical effectiveness of buprenorphine-naloxone (bup-nx) and clonidine for opioid detoxification in in-patient and out-patient community treatment programs was investigated in the first studies of the National Institute of Drug Abuse Clinical Trials Network.\n Diagnostic and Statistical Manual version IV (DSM IV)-diagnosed opioid-dependent individuals seeking short-term treatment were randomly assigned, in a 2 : 1 ratio favoring bup-nx, to a 13-day detoxification using bup-nx or clonidine.\n A total of 113 in-patients (77 bup-nx, 36 clonidine) and 231 out-patients (157 bup-nx, 74 clonidine) participated. Supportive interventions included appropriate ancillary medications and standard counseling procedures guided by a self-help handbook. The criterion for treatment success was defined as the proportion of participants in each condition who were both retained in the study for the entire duration and provided an opioid-free urine sample on the last day of clinic attendance. Secondary outcome measures included use of ancillary medications, number of side effects reported and withdrawal and craving ratings.\n A total of 59 of the 77 (77%) in-patients assigned to the bup-nx condition achieved the treatment success criterion compared to eight of the 36 (22%) assigned to clonidine, whereas 46 of the 157 (29%) out-patients assigned to the bup-nx condition achieved the treatment success criterion, compared to four of the 74 (5%) assigned to clonidine.\n The benefits of bup-nx for opioid detoxification are supported and illustrate important ways in which clinical research can be conducted in community treatment programs.", "Previous studies comparing buprenorphine and clonidine provided little information about subjective factors associated with the effective management of opioid withdrawal. This study sought to compare detoxification programs using these medications with regard to side-effects and related distress, general well-being, perceived self-efficacy and social support. A total of 200 treatment-seeking heroin-dependent patients, aged 18-50, were randomly assigned to buprenorphine or clonidine inpatient withdrawal treatments over 10days followed by 11days of relapse prevention measures. A semi-structured interview and a battery of self-rating scales assessing parameters of the interest were administered to the patients who completed the 10-day detoxification protocol with buprenorphine (n=90) and clonidine (n=50). Chi-square statistics and analysis of covariance were performed to examine between-group differences. Compared with patients treated with clonidine, patients who received buprenorphine developed significantly less side-effects and related distress, and had higher senses of well-being, self-efficacy and social support. The findings suggest that buprenorphine is preferable for inpatient detoxification due to its side-effects profile and positive effects on well-being and psychosocial variables. These early benefits of buprenorphine could enable consequent maintenance treatment.", "Over the last few years, there has been a growing tendency for opioid addicts to abuse multiple drugs, although many patients are in substitution therapy with methadone. Abuse of multiple drugs leads to a more complicated withdrawal syndrome; it is therefore necessary to investigate new drug strategies as a treatment for detoxification. Buprenorphine appears to be an effective and safe drug in opioid-addicted patient detoxification. In this study, we have compared the short-term efficacy of an 11-day low-dose buprenorphine/14-day carbamazepine regime [BPN/CBZ] (n = 14) to an 11-day methadone/14-day carbamazepine regime [MET/CBZ] (n = 12) in a double-dummy, randomized 14-day inpatient detoxification treatment study. Twenty-six inpatients met the DSM-IV criteria for opioid dependence and were included in this study. All patients abused various additional drugs. Fourteen of 26 patients (53.8 %) completed the study. Seven non-completers (seven of 12 = 58.3 %) were treated with methadone/carbamazepine and five non-completers (five of 14 = 35.7 %) received buprenorphine/carbamazepine, but the difference in the dropout rate was not significant. However, patients with buprenorphine/carbamazepine showed significantly fewer withdrawal symptoms after the first two weeks of treatment. The present study supports the hypothesis that buprenorphine/carbamazepine is more effective than methadone/carbamazepine in detoxification strategies for opioid addict with additional multiple drug abuse. No severe side effects occurred during treatment in either group.", "Detoxification from opioids remains an important first step in the treatment of many patients with opioid dependence. Several pharmacologic regimens have been used for opioid detoxification. In the United States, the partial mu-opioid agonist, buprenorphine (BUP) is the most recently approved pharmacotherapy for opioid detoxification and replacement. The literature in recent years has described detoxification protocols using a single high dose of BUP and a three-day BUP regimen. In many settings, such as drug-free programs, a single-dose detoxification protocol would be of significant benefit. There have been no prior studies comparing one-day and three-day BUP-assisted opioid withdrawal. In this pilot study, we conducted an open-label, randomized trial of one-day vs. three-day BUP/naloxone sublingual tablet-assisted opioid withdrawal. Twenty patients from a therapeutic community treatment program were randomly assigned to receive either 32 mg sublingual BUP over one hour (one-day group), or 32 mg sublingual BUP over three days (three-day group). Nine of 10 subjects (90 percent) in each group completed seven days in the detoxification protocol. There was no statistically significant difference between the two groups in all other outcome variables, including retention in the treatment program, intensity of withdrawal signs and symptoms, amounts of adjunct medications used, and ability to produce opiate-free urine. This study further validates the feasibility of the single high dose of BUP as a rapid detoxification method.", "In recent years, interest in shortening of opioid detoxification has increased with the rising demands to find more cost-effective approaches for treatment of opioid dependence. This study was designed to evaluate the efficacy of administration of high doses of buprenorphine during 24 h in the management of acute opioid withdrawal. A total of 40 treatment-seeking opioid dependents were admitted and randomly assigned to two groups in a double blind, parallel trial. Buprenorphine was administered intramuscularly. Twenty patients received 12 mg buprenorphine in 24 h and the remaining 20 patients treated with conventional doses of buprenorphine tapered down over 5 days. Variables that were assessed included retention in treatment, rates of successful detoxification, the Subjective Opiate Withdrawal Scale (OOWS) scores, the Objective Opiate Withdrawal Scale (SOWS) scores, intensity of craving, drug side effects, and levels of hepatic enzymes (ALT and AST). There was no significant difference between the two groups on most variables. The main difference was in the time that maximal withdrawal symptoms occurred, which in the experimental protocol group appeared early while in the conventional protocol group appeared later during the detoxification period. Moreover, the experimental protocol was not only tolerated well but also accompanied with significantly less elevation in the ALT levels compared to the conventional treatment. However, patients in this group used more indomethacin and trazodone for symptom palliation. This study suggests that administration of high doses of buprenorphine in 24 h may be a reasonable approach for shortening of opioid detoxification. However, a larger study to confirm our results is warranted.", "With the growing role of intravenous drug use in the transmission of HIV infection, HIV-infected patients frequently present with comorbid opioid dependence. Yet, few empirical evaluations of the efficacy and consequences of opioid detoxification medications in medically ill HIV-infected patients have been reported. In a randomized, double-blind clinical trial, we evaluated the impact of three medications on the signs and symptoms of withdrawal and on the pain severity in heroin-dependent HIV-infected patients (N=55) hospitalized for medical reasons on an inpatient AIDS service. Patients received a 3-day pharmacologic taper with intramuscular buprenorphine (n=21), oral clonidine (n=16), or oral methadone (n=18), followed by a clonidine transdermal patch on the fourth day. Observed and self-reported measures of opioid withdrawal and pain were taken 1-3 times daily for up to 4 days. Opiate administration used as medically indicated for pain was also recorded. Observer- and subject-rated opiate withdrawal scores decreased significantly following the first dose of medication and overall during treatment. Among all 55 subjects, self-reported and observer-reported pain decreased after treatment (on average observer-rated opioid withdrawal scale (OOWS) scores declined 5.6 units and short opioid withdrawal scale (SOWS) declined 4.8 units, P<0.001, for both) with no indication of increased pain during medication taper. There were no significant differences of pain decline and other measures of withdrawal between the three treatment groups. During the intervention period, supplemental opiates were administered as medically indicated for pain to 45% of the patients; only 34% of men versus 62% of women received morphine (P<0.05). These findings suggest buprenorphine, clonidine, and methadone regimens each decrease opioid withdrawal in medically ill HIV-infected patients.", "The prevalence of heroin and other opioid use has markedly increased among adolescents in the last decade; however, virtually no research has been conducted to identify effective treatments for this population.\n To evaluate the relative efficacy of 2 pharmacotherapies, the partial opioid agonist buprenorphine hydrochloride and the centrally active alpha(2)-adrenergic blocker clonidine hydrochloride, in the detoxification of opioid-dependent adolescents.\n A double-blind, double-dummy, parallel-groups randomized controlled trial conducted in a university-based research clinic from October 2001 to December 2003. Patients were a volunteer sample of 36 adolescents who met DSM-IV criteria for opioid dependence (ages 13-18 years eligible).\n Participants were randomly assigned to a 28-day, outpatient, medication-assisted withdrawal treatment with either buprenorphine or clonidine. Both medications were provided along with thrice weekly behavioral counseling and incentives contingent on opiate abstinence. Postdetoxification, all participants were offered the opportunity for continued treatment with the opiate antagonist, naltrexone hydrochloride.\n Treatment retention, opiate abstinence, and human immunodeficiency virus risk behavior, along with measures of withdrawal and medication effects.\n A significantly greater percentage of adolescents who received buprenorphine were retained in treatment (72%) relative to those who received clonidine (39%) (P<.05). For those in the buprenorphine group, a significantly higher percentage of scheduled urine test results were opiate negative (64% vs 32%; P = .01). Participants in both groups reported relief of withdrawal symptoms and drug-related human immunodeficiency virus risk behavior. Those in the buprenorphine condition generally reported more positive effects of the medication. No evidence of opioid intoxication or psychomotor impairment was observed. Sixty-one percent of participants in the buprenorphine condition and 5% of those in the clonidine group initiated treatment with naltrexone.\n Combining buprenorphine with behavioral interventions is significantly more efficacious in the treatment of opioid-dependent adolescents relative to combining clonidine and behavioral interventions." ]

[ "10811675" ]

[ "Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy." ]

[ "To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non-small-cell lung cancer who had previously been treated with platinum-based chemotherapy. Secondary end points included assessment of response (docetaxel arm only), toxicity, and quality of life.\n Patients with performance statuses of 0 to 2 and stage IIIB/IV non-small-cell lung cancer with either measurable or evaluable lesions were eligible for entry onto the study if they had undergone one or more platinum-based chemotherapy regimens and if they had adequate hematology and biochemistry parameters. They were excluded if they had symptomatic brain metastases or if they had previously been treated with paclitaxel. Patients were stratified by performance status and best response to cisplatin chemotherapy and were then randomized to treatment with docetaxel 100 mg/m(2) (49 patients) or 75 mg/m(2) (55 patients) or best supportive care. Patients in both arms were assessed every 3 weeks.\n One hundred four patients (103 of whom were eligible for entry onto the study) were well balanced for prognostic factors. Of 84 patients with measurable lesions, six (7. 1%) achieved partial responses (three patients at each dose level). Time to progression was longer for docetaxel patients than for best supportive care patients (10.6 v 6.7 weeks, respectively; P <.001), as was median survival (7.0 v 4.6 months; log-rank test, P =.047). The difference was more significant for docetaxel 75 mg/m(2) patients, compared with corresponding best supportive care patients (7.5 v 4.6 months; log-rank test, P =.010; 1-year survival, 37% v 11%; chi(2) test, P =.003). Febrile neutropenia occurred in 11 patients treated with docetaxel 100 mg/m(2), three of whom died, and in one patient treated with docetaxel 75 mg/m(2). Grade 3 or 4 nonhematologic toxicity, with the exception of diarrhea, occurred at a similar rate in both the docetaxel and best supportive care groups.\n Treatment with docetaxel is associated with significant prolongation of survival, and at a dose of 75 mg/m(2), the benefits of docetaxel therapy outweigh the risks." ]

[ "3148039", "10978851", "21699587", "6119492", "9661120", "15286958", "12464864", "16839996", "11822956", "19629583", "12055582" ]

[ "Improvement of nutritional measures during preoperative parenteral nutrition in patients selected by the prognostic nutritional index: a randomized controlled trial.", "Oral dietary supplements in pre- and postoperative surgical patients: a prospective and randomized clinical trial.", "An unblinded randomised controlled trial of preoperative oral supplements in colorectal cancer patients.", "Preoperative parenteral feeding in patients with gastrointestinal carcinoma.", "Preoperative oral supplement with immunonutrients in cancer patients.", "Randomized clinical trial of the effects of preoperative and postoperative oral nutritional supplements on clinical course and cost of care.", "Preoperative oral arginine and n-3 fatty acid supplementation improves the immunometabolic host response and outcome after colorectal resection for cancer.", "Perioperative nutritional support: a randomised clinical trial.", "Nutritional approach in malnourished surgical patients: a prospective randomized study.", "Attenuation of the systemic inflammatory response and infectious complications after gastrectomy with preoperative oral arginine and omega-3 fatty acids supplemented immunonutrition.", "A randomized controlled trial of preoperative oral supplementation with a specialized diet in patients with gastrointestinal cancer." ]

[ "Patients undergoing major gastrointestinal surgery who had a prognostic nutritional index (PNI) score of greater than 30% were randomized to receive a preoperative course of 10 days of intravenous nutrition or to undergo surgery at the next convenient operation list. Two groups of 17 patients were well matched for age, sex, and nutritional status. Although they underwent diverse operations, the extent of these was similar: 12 +/- 3 days of parenteral nutrition resulted in weight gain, 3.2 +/- 2.3 kg p less than 0.01; increased triceps skinfold, 0.6 +/- 1.2 mm p less than 0.05; improved immunological state, p less than 0.02; and improved PNI, 5.5 +/- 10.1% p less than 0.05. The changes in serum albumin and transferrin were not significant. There were only three major complications with one death in the treatment group but this was not significantly different from the control group which had six major complications and three deaths. This study suggests that patients with demonstrable nutritional depletion who require major gastrointestinal surgery will benefit from a preoperative course of parenteral nutrition, but to conclusively prove this a large and probably multicentre study will be required.", "It has been suggested that the routine provision of oral dietary supplements (ODS) in postoperative surgical patients is of benefit in terms of morbidity and length of hospital stay. The aim of this study was to evaluate the effects of both pre- and postoperative ODS in patients undergoing an elective laparotomy. Patients requiring elective major gastrointestinal surgery were prospectively randomized into one of four groups: Group I received ODS in addition to normal diet both pre- and postoperatively, Group II were given ODS in the preoperative period only, Group III received ODS only in the postoperative period, and Group IV did not receive any supplements. Assessments of nutritional status, voluntary food intake, weight loss, serum albumin, morbidity and mortality, anxiety and depression, and postoperative activity levels were performed, and comparisons made between the groups. One hundred patients were included in the study. The mean daily energy intake from preoperative ODS was 507 +/- 140 kcal, significantly more than the 252 +/- 195 kcal in the postoperative period (P < 0.001). The postoperative voluntary food intake in patients receiving ODS was not significantly different from that in patients receiving normal diet alone (1090 versus 1268 kcal, 46.2 versus 49.1 g protein, P > 0. 05). All groups demonstrated an overall weight loss, with no significant differences between the groups, and there was no demonstrable effect on clinical outcome. At 6 mo postoperatively there were no differences between the study groups in terms of levels of activity. These results suggest that the routine use of perioperative ODS in well-nourished patients undergoing major gastrointestinal surgery confers no clinical or functional benefit.", "Perioperative oral supplementation has been shown to reduce post-operative complications. However, the use of preoperative standard oral supplements in a cohort of colorectal cancer patients has not been evaluated. The present study examined whether preoperative supplements are beneficial in this group.\n In a randomised controlled trial, patients were assigned to receive 400 mL of oral supplement and dietary advice or dietary advice alone. Primary outcome was the number of post-operative complications. One hundred and twenty-five patients were recruited (59 randomised to the intervention group and 66 to the control group) and nine were excluded.\n In the intervention group, 24 (44%) patients had a complication compared to 26 (42%) in the control group (P = 0.780). In the intervention and control groups, there were eight (15%) and 16 (25%) surgical site infections, respectively (P = 0.140) and seven (13%) and 11 (17%) chest infections, respectively (P = 0.470). Subgroup analysis for hypothesis generation included 83 (71%) weight-losing patients, where there was a significant reduction in surgical site infections using the Buzby definition (P = 0.034), although this was not the case for the Centre for Disease Control definition (P = 0.052).\n There was no evidence that preoperative supplements were beneficial in reducing the number of complications, although there may be some benefit for surgical site infections in selected weight-losing preoperative patients.\n © 2011 The Authors. Journal of Human Nutrition and Dietetics © 2011 The British Dietetic Association Ltd.", "In a comparative clinical trial to examine the influence of 10 days of preoperative parenteral nutrition (PPN) on the postoperative complication rate for gastrointestinal carcinoma 59 patients (controls) received the regular hospital diet and 66 received PPN. The two groups were similar in nutritional status and in distribution of site and stage of tumour and type of operation. The rates of postoperative wound infection, pneumonia, major complications, and mortality were generally lower in the PPN group, but the differences were significant only for major complications and mortality. The clinical results can be explained by the improvement in various indices of humoral and cellular immunocompetence and the protein status in the PPN group and their deterioration in the control group during the preoperative course.", "Early postoperative enteral nutrition with immune-enhancing supplements has helped to restore immune function and reduce infectious complications in patients with cancer undergoing major gastrointestinal operations. The aim of this study was to evaluate the effectiveness of similar supplements (containing arginine and arginine plus omega-3 fatty acids) given preoperatively for 1 week before cancer surgery.\n In this randomized, double-blinded study, patients scheduled to undergo elective resection of upper gastrointestinal tumors were given one of three different oral liquid supplemental diets (control, arginine, arginine plus omega-3 fatty acids) to be taken each day for 7 days before surgery. Blood samples were obtained upon enrollment, on the morning of surgery, and on postoperative day 1 for analysis of immunologic function.\n Mean serum ornithine (a metabolite of arginine) levels were significantly higher compared with controls, but no significant increase in mean serum arginine levels was noted on the morning of surgery for those patients who received arginine as part of the supplement. In conjunction with these findings, there were no differences among groups in mean lymphocyte mitogenesis, mean peripheral blood mononuclear cell production of cytokines, or clinical outcomes.\n Use of oral liquid supplements in this fashion did not improve lymphocyte proliferation or monocyte functions in patients with cancer undergoing major surgery.", "Postoperative oral nutritional supplementation has been shown to be of clinical benefit. This study examined the clinical effects and cost of administration of oral supplements both before and after surgery.\n This was a randomized clinical trial conducted in three centres. Patients undergoing lower gastrointestinal tract surgery were randomized to one of four groups: group CC received no nutritional supplements, group SS took supplements both before and after surgery, group CS received postoperative supplements only, and group SC were given supplements only before surgery. Preoperative supplements were given from the time it was decided to operate to 1 day before surgery. Postoperative supplements were started when the patient was able to take free fluids and continued for 4 weeks after discharge from hospital. Data collected included weight change, complications, length of stay, nutritional intake, anthropometrics, quality of life and detailed costings covering all aspects of care.\n Some 179 patients were randomized, of whom 27 were withdrawn and 152 analysed (CC 44, SS 32, CS 35, SC 41). Dietary intake was similar in all four groups throughout the study. Mean energy intake from preoperative supplements was 536 and 542 kcal/day in the SS and SC groups respectively; that 2 weeks after discharge from hospital was 274 and 361 kcal/day in the SS and CS groups respectively. There was significantly less postoperative weight loss in the SS group than in the CC and CS groups (P < 0.050), and significantly fewer minor complications in the SS and CS groups than the CC group (P < 0.050). There were no differences in the rate of major complications, anthropometrics and quality of life. Mean overall costs were greatest in the CC group, although differences between groups were not significant.\n Perioperative oral nutritional supplementation started before hospital admission for lower gastrointestinal tract surgery significantly diminished the degree of weight loss and incidence of minor complications, and was cost-effective.\n Copyright 2004 British Journal of Surgery Society Ltd.", "Previous trials showed that perioperative immunonutrition improved outcome in patients with gastrointestinal cancer. This study was designed to appraise the impact of the simple preoperative oral arginine and n-3 fatty acids supplementation on immune response, gut oxygenation, and postoperative infections.\n Two hundred patients with colorectal neoplasm were randomized to: (a) oral intake for 5 days before surgery of a formula enriched with arginine and n-3 fatty acids (pre-op group; n = 50); (b) same preoperative treatment prolonged after surgery by jejunal infusion (peri-op group; n = 50); (c) oral intake for 5 days before surgery of a standard isoenergetic, isonitrogenous formula (control group; n = 50); and (d) no supplementation before and after operation (conventional group; n = 50). The immune response was measured by phagocytosis ability of polymorphonuclear cells and delayed hypersensitivity response to skin tests. Gut oxygenation and microperfusion were assessed by polarographic probes and laser Doppler flowmetry, respectively.\n The 4 groups were comparable for demographics, comorbidity, and surgical variables. The 2 groups receiving immunoutrients (pre-op and peri-op) had a significantly better immune response, gut oxygenation, and microperfusion than the other 2 groups. Intent-to-treat analysis showed an overall infection rate of 12% in pre-op, 10% in peri-op, 32% in control, and 30% in conventional groups (P <.04 pre-op and peri-op vs control and conventional).\n Preoperative oral arginine and n-fatty acids improves the immunometabolic response and decreases the infection rate. Postoperative prolongation with such supplemented formula has no additional benefit.", "Ever since methods of artificial nutritional support became available, attempts have been made using this form of treatment to reduce mortality and morbidity in surgical patients. Many trials have addressed this question, but very few have given a meaningful answer because of conceptual and methodological flaws. We therefore undertook a prospective randomised trial investigating the effects of at least 10 days pre-operative total parenteral nutrition (TPN) (n = 51) or total enteral nutrition (TEN) (n = 50) providing 150% basal energy expenditure (BEE) non-protein energy, to reduce major postoperative complications and mortality in a homogeneous patient group with signs of depletion. 50 patients served as a depleted control group (D) and 49 patients served as a non-depleted reference group (ND) and were operated upon without delay. Depleted control patients suffered significantly more septic complications than did patients in the non-depleted reference group (p < 0.05). There was no significant difference, however, in septic complications between either of the nutritional support groups and the non-depleted control group. In high risk patients, with weight loss >10% of body weight and over 500 ml blood loss during operation, a significant decrease in major complications was observed (p < 0.05) as a result of nutritional support. We conclude that pre-operative nutritional support, in patients with severe depletion, results in a reduction in major complications to a degree that justifies its routine use in this selected group of patients.", "Perioperative administration of a supplemented enteral formula may decrease postoperative morbidity.\n Randomized clinical trial.\n Department of surgery at a university hospital.\n One hundred ninety-six registered malnourished patients (weight loss > or = 10%) who were candidates for major elective surgery for malignancy of the gastrointestinal tract.\n After randomization (n = 150), one group received postoperative enteral feeding with a standard diet within 12 hours of surgery (control group; n = 50). Another group orally received 1 L/d for 7 consecutive days of a liquid diet enriched with arginine, omega-3 fatty acids, and RNA (preoperative group; n = 50). After surgery, patients were given the same standard enteral formula as the control group. A third group orally received 1 L/d for 7 consecutive days of the enriched liquid diet. After surgery, patients were given enteral feeding with the same enriched formula (perioperative group; n = 50).\n Postoperative complications and length of hospital stay.\n The 3 groups were comparable for baseline demographics, biochemical markers, comorbidity factors, and surgical variables. The intent-to-treat analysis showed that the total number of patients with complications was 24 in the control group, 14 in the preoperative group, and 9 in the perioperative group (P =.02, control group vs perioperative group). Postoperative length of stay was significantly shorter in the preoperative (13.2 days) and perioperative (12.0 days) groups than in the control group (15.3 days) (P =.01 and P =.001, respectively, vs the control group).\n Perioperative immunonutrition seems to be the best approach to support malnourished patients with cancer.", "Past trials have shown perioperative immunonutrition to improve the outcome for patients with gastric cancer. The present study was designed to evaluate the effect of preoperative oral immunonutrition on cellular immunity, the duration of the systemic inflammatory response syndrome (SIRS), and detailed postoperative complications in patients with gastric cancer.\n Sixty patients with gastric cancer were randomly assigned to two groups: one group received immune-enhanced formulas supplemented with arginine and omega-3 fatty acids (immune-enhancing diet (ID) group, n = 30); the other received standard formulas (conventional diet (CD) group, n = 30) for 7 days before the operation. These groups were well matched in terms of age, sex, operations, cancer stages, and intraoperative variables. The postoperative outcome was evaluated based on clinical variables, including postoperative infectious complications, noninfectious complications, and SIRS duration. In addition, the perioperative state of cellular immunity was evaluated and compared between the two groups.\n The incidence of postoperative infectious complications in the ID group (6%) was significantly (p < 0.05) lower than that of the CD group (28%). The duration of SIRS in the ID group (0.77 +/- 0.9 days) was significantly (p < 0.05) shorter than that in the CD group (1.34 +/- 1.45 days). The postoperative lymphocyte and CD4(+)T-cell counts significantly decreased (p < 0.05) in both groups. However, the number of CD4(+)T-cells on preoperative day 1 and postoperative day 7 was significantly (p < 0.05) higher in the ID group than in the CD group.\n Preoperative oral immune-enhanced formulas supplemented with arginine and omega-3 fatty acids enhanced the immune status of the patients, reduced the duration of SIRS, and decreased the incidence of postoperative infectious complications. CD4(+)T-cell immunity likely played an important role in the modulation of the postoperative immune and inflammatory response after gastrectomy.", "Perioperative nutrition with specialized enteral diets improves outcome when compared with standard formulas. A post-hoc analysis suggested preoperative administration as the most important period. Thus, we designed a study to understand prospectively whether preoperative supplementation could be as efficacious as the perioperative approach and superior to a conventional treatment (no artificial nutrition) in reducing postoperative infections and length of hospital stay.\n A total of 305 patients with preoperative weight loss <10% and cancer of the gastrointestinal tract were randomized to receive the following: (1) oral supplementation for 5 days before surgery with 1 L/day of a formula enriched with arginine, omega-3 fatty acids, and RNA, with no nutritional support given after surgery (preoperative group, n = 102); (2) the same preoperative treatment plus postoperative jejunal infusion with the same enriched formula (perioperative group, n = 101); and (3) no artificial nutrition before and after surgery (conventional group; n = 102).\n The 3 groups were comparable for all baseline and surgical characteristics. Intention-to-treat analysis showed a 13.7% incidence of postoperative infections in the preoperative group, 15.8% in the perioperative group, and 30.4% in the conventional group (P = 0.006 vs. preoperative; P = 0.02 vs. perioperative). Length of hospital stay was 11.6 +/- 4.7 days in the preoperative group, 12.2 +/- 4.1 days in the perioperative group, and 14.0 +/- 7.7 days in the conventional group (P = 0.008 vs. preoperative and P = 0.03 vs. perioperative).\n Preoperative supplementation is as effective as perioperative administration in improving outcome. Both strategies seem superior to the conventional approach." ]

[ "10693095", "1575555", "9310515" ]

[ "Does supine positioning increase apnea, bradycardia, and desaturation in preterm infants?", "Effect of positioning on the breathing pattern of preterm infants.", "Effect of nursing in the head elevated tilt position (15 degrees) on the incidence of bradycardic and hypoxemic episodes in preterm infants." ]

[ "The purpose of this study was to determine the effects of prone and supine positioning on the cardiorespiratory stability of preterm infants with apnea and bradycardia.\n A total of 22 preterm infants with symptomatic apnea and bradycardia (gestational age of 26.9 +/- 1.8 weeks and birth weight of 865 +/- 235 gm) were monitored for 24 hours (in four sequential 6-hour blocks) for apnea, bradycardia, and oxygen desaturation in alternating positions (prone or supine) following randomization. Postconceptional age at the time of study was 31.9 +/- 3.0 weeks. Respiratory rate, heart rate, and transcutaneous oxygen saturation were continuously monitored. All episodes of apnea (> or = 10 seconds), bradycardia (< 100 beats per minute), and oxygen desaturation (< 90%) were recorded on an event monitor. Episodes of apnea, bradycardia, and oxygen desaturation were defined as clinically significant if the following criteria were met: apnea, > or = 15 seconds; bradycardia, < 90 beats per minute; and oxygen desaturation, < 80%. All other recorded episodes were considered mild. The episodes were analyzed for statistical significance using the paired t-test.\n No significant differences (p > 0.05) in the incidence of clinically significant apnea, bradycardia, or desaturation between supine and prone positions were seen in these preterm infants.\n Our results suggest that the cardiorespiratory stability of preterm infants is not significantly compromised by supine positioning.", "Respiration, as judged by gas exchange and pulmonary function, is improved in preterm infants kept in the prone rather than the supine position. The influence of position on the breathing pattern as documented by the pneumogram was studied in 14 stable preterm infants with recent clinical apnoea. Ten of the infants had oximetry and nasal flow studies simultaneously with the impedance pneumogram. Each infant had consecutive nocturnal pneumograms, one in the prone, one in the supine position. The infants were kept for more than six hours in the assigned position. A significant increase in apnoea density and in periodic breathing was found in the supine v the prone position (mean (SE) 4.5 (0.7)% v 2.5 (0.5)%, and 13.6 (3.2)% v 7.7 (2.2)%, respectively). There was no positional difference in the incidence of bradycardia and prolonged apnoea. The examination of obstructive apnoea, mixed apnoea, and cyanotic spells did not reveal a consistent disparity between the two positions. These findings indicate an increase in central apnoea in preterm infants kept predominantly in the supine position. Possible relations of positional changes to lung mechanics are discussed. When evaluating pneumograms, attention must be given to the position in which they were performed.", "We investigated whether nursing in the head elevated tilt position (HETP), compared with the horizontal position, has any effect on the incidence of bradycardic and hypoxemic episodes in preterm infants.\n Twelve spontaneously breathing preterm infants with idiopathic recurrent apnea were studied in a randomized controlled crossover trial. Nine infants were treated with aminophylline. Each spent a total of 24 hours in the horizontal prone position and a total of 24 hours in HETP (prone, 15 degrees). The position was changed in random order every 6 hours. Thoracic impedance, heart rate, and arterial oxygen saturation were recorded continuously. The frequency of isolated hypoxemia (arterial saturation <80%), of isolated bradycardia (heart rate <90 beats per minute), and of mixed events was analyzed and compared without knowledge of the allocated position.\n In total, there were significantly fewer bradycardic and/or hypoxemic episodes (28.2%) in HETP compared with the horizontal position (mean difference, 13.35 episodes/24 hours; 95% confidence interval [CI]: 5.9- 20.8). The decrease was largest for isolated hypoxemic episodes (48.5%; mean difference, 11.74 episodes/24 hours; 95% CI: 6.1-17.4). Isolated bradycardic episodes (mean difference, 2.27 episodes/24 hours; 95% CI: -0.78-5.31) and mixed events were not decreased significantly in HETP.\n Nursing in a moderately tilted position (15 degrees) reduces hypoxemic events in preterm infants. This intervention is easy to apply, quickly reversible, and can be combined with drugs such as aminophylline." ]

[ "6337667", "458990", "9638316", "9453690", "2665385" ]

[ "Placebo--the drug of choice in female motor urge incontinence?", "An objective comparison of the effects of parenterally administered drugs in patients suffering from detrusor instability.", "[Intravesical instillation of trospium chloride, oxybutynin and verapamil for relaxation of the bladder detrusor muscle. A placebo controlled, randomized clinical test].", "Prospective study comparing hyoscyamine, doxazosin, and combination therapy for the treatment of urgency and frequency in women.", "[Comparative studies of the effect of mictonorm (propiverin hydrochloride) and Spasuret (flavoxate hydrochloride) on the bladder detrusor muscle]." ]

[ "In a randomised double-blind cross-over trial of 19 females with motor urge incontinence but without bladder suspension defect, the effects of 14 days' treatment with emepronium bromide 200 mg qid, flavoxate chloride 200 mg qid or placebo qid were compared by means of micturition charts, the patients' drug preferences and evaluation of side effects. Placebo was the only drug giving rise to a statistically significant decrease in the frequency of voidings, incontinence and nocturia. Forty-seven per cent of the patients preferred placebo and side effects were less frequent during treatment with this medication. No differences could be demonstrated between the effects of emepronium bromide and flavoxate chloride. Perhaps detrusor instability is not always the main reason for the voiding dysfunction in these patients, in whom the effect of placebo was equal or superior to the effect of \"active drugs\" and superior to no treatment at all.", "Cystometric changes produced by 3 parenterally administered drugs, flavoxate hydrochloride, emepronium bromide and imipramine hydrochloride, have been evaluated in 15 female patients with detrusor instability. Each patient was given 2 of the 3 drugs and cystometric recordings were done 10 and 30 minutes after the administration of each drug. Emepronium bromide was found to be the only drug to cause a significant improvement in bladder capacity and reduction in detrusor pressure.", "Therapy of detrusor hyperactivity with anticholinergic agents often is followed by adverse drug reactions. Intravesical application may be an interesting alternative. A randomised, single-blind, placebo-controlled, mono-centre clinical trial was carried out in 84 patients with urgency or urge incontinence. Due to intravesical administration of oxybutynin (CAS 5633-20-5) (n = 21) and trospium chloride (CAS 10405-02-4) (n = 21), respectively, a significant increase in maximum bladder capacity and decrease of detrusor pressure accompanied by an increase of residual urine were found in comparison to placebo in urodynamical investigations. Improvement of uninhibited bladder contractions occurred leading to higher filling volume. Under verapamil (CAS 152-11-4) (n = 21) no marked changes in the efficacy variables were found compared with placebo. All patients completed the study and were assessed with regard to efficacy and safety. No adverse events or marked changes in the vital signs were reported. The immediate onset of effect and the lack of adverse drug reactions suggest that treatment with topical oxybutynin or trospium chloride is an effective alternative in patients with intolerable side effects when orally treated. In addition, intravesical administration may be indicated in patients with bladder spasms due to indwelling catheter or in order to increase bladder capacity before percutaneous cystostomy.", "Anticholinergics are commonly used for the treatment of frequency, urgency, and urge incontinence in women. Alpha-blockers have been shown to have a modulating effect on bladder smooth muscle but are not commonly used clinically for this indication. To evaluate the clinical effectiveness of each treatment as well as the combination therapy, we performed an open prospective study comparing these agents. Between September 1994 and October 1995, 34 women aged 28-91 (mean age, 62) received either 0.375 mg of sustained-release hyoscyamine twice a day or 2 mg doxazosin QHS prior to being crossed over to the other drug and/or the combination. Symptoms were assessed using an expanded American Urological Association (AUA) symptoms score, which included questions regarding incontinence at completion of each therapeutic phase. Evaluation included 6-channel urodynamics. All three therapies were noted to be effective in reducing AUA symptom scores. By urodynamic evaluation, a greater percentage of patients with increased voiding pressures or decreased compliance responded to doxazosin than hyoscyamine. Side effects were noted to be less prevalent with doxazosin than with the other therapies. There appears to be a significant role for alpha-blockers in the treatment of voiding symptoms in women.", "46 patients suffering from urgency/urge incontinency were treated with Mictonorm and Spasuret in a crossing-over study. In consideration of the placebo effect in this disease both agents were tested versus a non-verum. The application period was 4 weeks and the dosage was 45 mg/d Mictonorm and 300 mg/d Spasuret, respectively. Both with Mictonorm and with Spasuret a significant reduction of micturition frequency and an increase of the compliance could be observed, whereas the placebo was ineffective. A markedly growth of the maximal bladder capacity (16.9%) was obtained only by Mictonorm. Both agents keep likewise to an improvement of the symptoms or urgency/urge incontinency. Side effects could observed in a small size without a breaking-off of the treatment." ]

[ "18395869" ]

[ "Anxiety levels in women undergoing prenatal maternal serum screening for Down syndrome: the effect of a fast reporting system by mobile phone short-message service." ]

[ "To study the effect of fast reporting by mobile phone short-message service (SMS) on anxiety levels in women undergoing prenatal biochemical screening for Down syndrome.\n From January 2005 to December 2006, 2782 women undergoing prenatal biochemical serum screening were randomized into fast reporting by SMS (group A) or without mobile phone reporting (group B). Anxiety levels were measured with the Spielberger State-Trait Anxiety Inventory (STAI) before prenatal screen testing, before the appointed clinic (when the SMS report had already been given to group A), and 3 days after the appointed clinic (when the full screening report had been given to groups A and B).\n For screen-negative women, anxiety scores did not differ between groups before prenatal screen testing and 3 days after the appointed clinic. The state-anxiety scores measured on the second occasion had declined significantly in group A. The state-anxiety scores in both groups increased over the 3-week period after being informed of positive screen results. The trait- and state-anxiety scores at all points did not differ between the two groups of screen-positive women.\n The provision of a routine reporting system plus additional SMS report revealed some overall benefits in reducing anxiety among women with screen-negative result.\n 2008 John Wiley & Sons, Ltd" ]

[ "7531132", "10699690", "9231677", "11230886", "17998689" ]

[ "Palliative endobronchial brachytherapy for central lung tumors. A prospective, randomized comparison of two fractionation schedules.", "Combined Nd-YAG laser/HDR brachytherapy versus Nd-YAG laser only in malignant central airway involvement: a prospective randomized study.", "Does additional brachytherapy improve the effect of external irradiation? A prospective, randomized study in central lung tumors.", "External irradiation versus external irradiation plus endobronchial brachytherapy in inoperable non-small cell lung cancer: a prospective randomized study.", "Optimization of dose and fractionation of endobronchial brachytherapy with or without external radiation in the palliative management of non-small cell lung cancer: a prospective randomized study." ]

[ "Remote high dose rate brachytherapy is an effective local treatment modality for central lung tumors and has the potential to improve survival time. Optimal dose and fractionation schemes have not been identified yet. We conducted a prospective randomized study to compare two treatment schedules in terms of survival time, local tumor control, and possible complications.\n Group 1 received 4 brachytherapies with a dose of 3.8 Gy (at a 10-mm depth) on a weekly basis, and group 2 received 2 treatments with 7.2 Gy (at a 10-mm depth) at a 3-week interval. At a depth of 5 mm, the calculated doses would be 8 and 15 Gy. This study is still ongoing. Here we report interim results.\n Ninety-three patients with advanced cancer were included in the study; 44 were in group 1 and 49, in group 2. Both groups were comparable regarding age, sex, tumor stage, Karnofsky performance status, and histologic findings.\n A mean total irradiation dose of 13.4 +/- 5.2 Gy for group 1 and 13.7 +/- 4.4 for group 2 were applied (calculated at 10 mm from the source axis, equivalent to 27.9 Gy in group 1 and 28.5 Gy in group 2 at a 5-mm depth).\n The 1-year survival rate was 11.4% in group 1 and 20.4% in group 2. No significant difference in survival time was found, but mean survival was longer in group 2 (49 weeks) than in group 1 (26 weeks). Local control after 3 months was comparable in both groups. Fatal hemoptysis occurred at a similar rate in group 1 (22.2%) and in group 2 (21.1%).\n High-dose rate brachytherapy with 2 x 7.2 Gy with a 3-week interval is equivalent to a 4 x 3.8-Gy regimen on a weekly basis. The shorter treatment schedule is more convenient for patients, does not cause more side effects, and provides an equal local tumor control.", "Laser debulking and prosthetic stents are useful modalities in the palliative treatment of initial inoperable or recurrent lung cancer. Recently, endobrochial brachytherapy was introduced to extend the duration of palliation and reduce the number of endoscopic treatments. This trial compares Nd-YAG laser alone and associated to high dose rated (HDR)-brachytherapy.\n From 1995 to 1998, 29 consecutive patients, with non-small cell lung cancer (NSCLC) and central airway involvement, were randomized in two groups: group 1 (15 patients) received Nd-YAG laser only; group 2 (14 patients) underwent a combined Nd-YAG laser/ HDR brachytherapy treatment.\n There was no mortality or morbidity related to the treatment. The period free from symptoms was 2.8 months for group 1 and increased to 8.5 months in group 2 (P<0.05). The disease's progression free period grew from 2.2 months of group 1 to 7.5 months of group 2 (P<0.05) and the number of further endoscopic treatment reduced from 15 to 3 (P<0.05).\n The results confirm the potential of brachytherapy to prolong relief from symptoms, lessen disease progression and reduce costs of treatment. A detailed analysis is presented of both groups.", "Endobronchial brachytherapy has become more widely used to increase the total local dose of irradiation (\"boost\") applied for the treatment of lung cancer. Apart from treatment for local stenosis, endobronchial brachytherapy in combination with external irradiation (EI) has the potential to improve local tumor control and perhaps prolong survival, but the real benefit has not been proven yet. To evaluate the possible effects of external irradiation with an additional boost of high dose rate (HDR) brachytherapy, we conducted a prospective randomized study.\n Design-two groups were compared: Group 1 was treated with external radiotherapy alone (planned dose 60 Gy); Group 2 received an additional boost of HDR brachytherapy of scheduled 4.8 Gy each (at 10 mm from the source axis) before and after external irradiation. Patients-98 patients with advanced inoperable lung cancer were included in the study, 42 in Group 1 and 56 in Group 2. Both groups were comparable with respect to age, sex, tumor stage, Karnofsky performance status (KPS), and histology.\n A mean total external irradiation dose of 50.5 +/- 14.1 Gy in Group 1 and 50 +/- 12.5 Gy in Group 2 was applied. Group 2 received an additional dose of 7.44 +/- 2.6 Gy (at 10 mm depth) through brachytherapy. The median survival time in both groups was comparable (28 weeks and 27 weeks, respectively). In patients with squamous cell carcinoma (68 patients) Group 2 showed an advantage in median survival with borderline significance (40 vs. 33 weeks, p = 0.09). Group 2 showed also a better local tumor control in all patients; patients with squamous cell carcinoma had a significantly longer period of local tumor control. Fatal hemoptysis was the cause of death in 6 (14.2%) patients in Group 1 and 11 (18.9%) in Group 2 (p = 0.53).\n High dose rate brachytherapy in patients with inoperable lung cancer increased local control in our randomized study when used in combination with external irradiation. Survival time was also longer, but with no clear statistical significance. This applied especially to patients with squamous cell carcinomas. There was no statistically significant difference in the incidence of fatal hemoptysis between the two groups.", "No randomized studies are available on the additional value of endobronchial brachytherapy (EBB) to external irradiation (XRT) regarding palliation of respiratory symptoms (RS). A prospective randomized study was initiated to test the hypothesis that the addition of EBB to XRT provides higher levels of palliation of dyspnea and other RS and improvement of quality of life (QoL) in patients with non-small cell lung cancer (NSCLC) with endobronchial tumour.\n Patients with previously untreated NSCLC, stages I-IIIb, WHO-performance status of 0-3 and with biopsy proven endobronchial tumour in the proximal airways were eligible. EBB consisted of two fractions of 7.5 Gy at 1 cm on day 1 and 8. XRT started at day 2. The XRT dose was 30 Gy (2 weeks) or 60 Gy (6 weeks). The EORTC QLQ-C30 and QLQ-LC13 were assessed before treatment and 2 weeks, 6 weeks, 3, 6 and 12 months after treatment. Re-expansion of collapsed lung was tested by the inspiratory vital capacity (IVC) and CT scan of the chest.\n Ninety-five patients were randomized between arm 1 (XRT alone) (n=48) or arm 2 (XRT+EBB) (n=47). The arms were well balanced regarding pre-treatment characteristics and QoL scores. The compliance for QoL-assessment was >90% at all times. No significant difference between the trial arms was observed with respect to response of dyspnea. However, a beneficial effect of EBB was noted concerning the mean scores of dyspnea over time (P=0.02), which lasted for 3 months. This benefit was only observed among patients with an obstructing tumour of the main bronchus. A higher rate of re-expansion of collapsed lung was observed in arm 2 (57%) compared to arm 1 (35%) (P=0.01). The inspiratory vital capacity (IVC) assessed 2 weeks after radiotherapy improved with 493 cm(3) in arm 2 and decreased 50 cm(3) in arm 1 (P=0.03). No difference was noted regarding the incidence of massive haemoptysis (13 vs. 15%).\n The addition of EBB to XRT in NSCLC is safe and provides higher rates of re-expansion of collapsed lung resulting in a transient lower levels of dyspnea. This beneficial effect was only observed among patients with obstructing tumours in the main bronchus.", "Endobronchial brachytherapy (EBBT) is an established modality for the palliation in advanced non-small cell lung cancer. We compared three different schedules using EBBT with or without external radiation (XRT) in this setting.\n Forty-five patients were randomized to three treatment arms. Arm A received XRT to a dose of 30 Gy/10 fr/2 weeks and two sessions of EBBT 8 Gy each. Arm B received the same XRT and a single session of EBBT 10 Gy at 1 cm. Arm C received only a single fraction of brachytherapy to a dose of 15 Gy at 1 cm without XRT. Symptomatic response rates, duration of symptom palliation, obstruction scores, quality of life outcomes and complications were assessed and compared.\n The overall symptomatic response rates were 91% for dyspnea, 84% for cough, 94% for hemoptysis and 83% for obstructive pneumonia. There was no significant difference between the arms. The median time to symptom relapse was 4-8 months for all symptoms and the median time to symptom progression was 6-11 months. The results were comparable between groups except for hemoptysis, where a shorter palliation was seen in Arm C that achieved statistical significance (P < 0.01). Quality of life showed significant improvement, with maximum benefit in Arm A. Complication rates were low. Only one patient died of fatal hemoptysis.\n EBBT is thus a safe and effective palliative tool in advanced non-small cell lung cancer, either alone or in conjunction with XRT. The difference between the treatment arms were not statistically significant in most categories, but patients treated with XRT and two endobronchial sessions of 8 Gy had the most consistent benefit in terms of all the parameters studied." ]

[ "12941673", "15190043", "19776136", "19064532", "18504447", "16027246", "18400709", "18716168", "19583878", "20036019", "20090776", "18045712", "20823377", "15712594", "12791625", "20620742", "17609490" ]

[ "Chocolate and blood pressure in elderly individuals with isolated systolic hypertension.", "Flavonoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults.", "Effect of cocoa powder on the modulation of inflammatory biomarkers in patients at high risk of cardiovascular disease.", "Cocoa consumption for 2 wk enhances insulin-mediated vasodilatation without improving blood pressure or insulin resistance in essential hypertension.", "Effect of cocoa flavanols and exercise on cardiometabolic risk factors in overweight and obese subjects.", "Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives.", "A double-blind, placebo-controlled, randomized trial of the effects of dark chocolate and cocoa on variables associated with neuropsychological functioning and cardiovascular health: clinical findings from a sample of healthy, cognitively intact older adults.", "Blood pressure is reduced and insulin sensitivity increased in glucose-intolerant, hypertensive subjects after 15 days of consuming high-polyphenol dark chocolate.", "Dark chocolate or tomato extract for prehypertension: a randomised controlled trial.", "Effects of sugar-sweetened and sugar-free cocoa on endothelial function in overweight adults.", "Dose-related effects of flavanol-rich cocoa on blood pressure.", "Acute effect of oral flavonoid-rich dark chocolate intake on coronary circulation, as compared with non-flavonoid white chocolate, by transthoracic Doppler echocardiography in healthy adults.", "Effects on peripheral and central blood pressure of cocoa with natural or high-dose theobromine: a randomized, double-blind crossover trial.", "Regular consumption of a flavanol-rich chocolate can improve oxidant stress in young soccer players.", "Dietary flavanols and procyanidin oligomers from cocoa (Theobroma cacao) inhibit platelet function.", "Improvement of endothelial function with dietary flavanols is associated with mobilization of circulating angiogenic cells in patients with coronary artery disease.", "Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial." ]

[ "nan", "Dark chocolate derived from the plant (Theobroma cacao) is a rich source of flavonoids. Cardioprotective effects including antioxidant properties, inhibition of platelet activity, and activation of endothelial nitric oxide synthase have been ascribed to the cocoa flavonoids.\n To investigate the effects of flavonoid-rich dark chocolate on endothelial function, measures of oxidative stress, blood lipids, and blood pressure in healthy adult subjects.\n The study was a randomized, double-blind, placebo-controlled design conducted over a 2 week period in 21 healthy adult subjects. Subjects were randomly assigned to daily intake of high-flavonoid (213 mg procyanidins, 46 mg epicatechin) or low-flavonoid dark chocolate bars (46 g, 1.6 oz).\n High-flavonoid chocolate consumption improved endothelium-dependent flow-mediated dilation (FMD) of the brachial artery (mean change = 1.3 +/- 0.7%) as compared to low-flavonoid chocolate consumption (mean change = -0.96 +/- 0.5%) (p = 0.024). No significant differences were noted in the resistance to LDL oxidation, total antioxidant capacity, 8-isoprostanes, blood pressure, lipid parameters, body weight or body mass index (BMI) between the two groups. Plasma epicatechin concentrations were markedly increased at 2 weeks in the high-flavonoid group (204.4 +/- 18.5 nmol/L, p < or = 0.001) but not in the low-flavonoid group (17.5 +/- 9 nmol/L, p = 0.99).\n Flavonoid-rich dark chocolate improves endothelial function and is associated with an increase in plasma epicatechin concentrations in healthy adults. No changes in oxidative stress measures, lipid profiles, blood pressure, body weight or BMI were seen.", "Epidemiologic studies have suggested that flavonoid intake plays a critical role in the prevention of coronary heart disease. Because atherosclerosis is considered a low-grade inflammatory disease, some feeding trials have analyzed the effects of cocoa (an important source of flavonoids) on inflammatory biomarkers, but the results have been controversial.\n The objective was to evaluate the effects of chronic cocoa consumption on cellular and serum biomarkers related to atherosclerosis in high-risk patients.\n Forty-two high-risk volunteers (19 men and 23 women; mean +/- SD age: 69.7 +/- 11.5 y) were included in a randomized crossover feeding trial. All subjects received 40 g cocoa powder with 500 mL skim milk/d (C+M) or only 500 mL skim milk/d (M) for 4 wk. Before and after each intervention period, cellular and serum inflammatory biomarkers related to atherosclerosis were evaluated.\n Adherence to the dietary protocol was excellent. No significant changes in the expression of adhesion molecules on T lymphocyte surfaces were found between the C+M and M groups. However, in monocytes, the expression of VLA-4, CD40, and CD36 was significantly lower (P = 0.005, 0.028, and 0.001, respectively) after C+M intake than after M intake. In addition, serum concentrations of the soluble endothelium-derived adhesion molecules P-selectin and intercellular adhesion molecule-1 were significantly lower (both P = 0.007) after C+M intake than after M intake.\n These results suggest that the intake of cocoa polyphenols may modulate inflammatory mediators in patients at high risk of cardiovascular disease. These antiinflammatory effects may contribute to the overall benefits of cocoa consumption against atherosclerosis. This trial was registered in the Current Controlled Trials at London, International Standard Randomized Controlled Trial Number, at controlled-trials.com as ISRCTN75176807.", "Essential hypertension is characterized by reciprocal relations between endothelial dysfunction and insulin resistance. Cocoa flavanols stimulate production of the vasodilator nitric oxide from vascular endothelium.\n The objective was to test the hypothesis that consumption of cocoa may simultaneously lower blood pressure, improve endothelial dysfunction, and ameliorate insulin resistance in subjects with essential hypertension.\n We conducted a randomized, placebo-controlled, double-blind, crossover trial of a flavanol-rich cocoa drink (150 mL twice a day, approximately 900 mg flavanols/d) in individuals with essential hypertension (n = 20). Antihypertensive medications were discontinued before study enrollment. After a 7-d cocoa-free run-in period, cocoa or flavanol-poor placebo (approximately 28 mg flavanols/d) treatment for 2 wk was followed by a 1-wk washout and then crossover to the other treatment arm. Blood pressure was measured thrice weekly. At baseline and after each treatment period, we assessed insulin sensitivity (hyperinsulinemic-isoglycemic glucose clamp) and insulin-stimulated changes in brachial artery diameter and forearm skeletal muscle capillary recruitment (Doppler ultrasound with or without microbubble contrast).\n Cocoa treatment for 2 wk increased insulin-stimulated changes in brachial artery diameter when compared with placebo [median percentage increase from baseline (25th-75th percentile): 8.3 (4.2-11.3) compared with 5.9 (-0.3 to 9.6); P < 0.04]. Nevertheless, cocoa treatment did not significantly reduce blood pressure or improve insulin resistance and had no significant effects on skeletal muscle capillary recruitment, circulating plasma concentrations of adipocytokines, or endothelial adhesion molecules.\n Daily consumption of flavanol-rich cocoa for 2 wk is not sufficient to reduce blood pressure or improve insulin resistance in human subjects with essential hypertension. This trial was registered at clinicaltrials.gov as NCT00099476.", "Impaired endothelial function in obesity may reduce blood flow to sites of metabolism, contributing to impaired fat oxidation and insulin resistance. This study investigated the effects of cocoa flavanols and regular exercise, interventions known to improve endothelial function, on cardiometabolic function and body composition in obese individuals.\n Overweight and obese adults were randomly assigned to high-flavanol cocoa (HF, 902 mg flavanols), HF and exercise, low-flavanol cocoa (LF, 36 mg flavanols), or LF and exercise for 12 weeks (exercise duration was 3 x 45 min per week at 75% of age-predicted maximum heart rate). Body composition was assessed by dual-energy X-ray absorptiometry at 0 and 12 weeks. Brachial artery flow-mediated dilatation (FMD), supine blood pressure (BP) and fasting plasma insulin, and glucose levels were assessed at 0, 6 and 12 weeks, respectively. Insulin sensitivity/resistance was determined using the modified homeostasis model assessment of insulin resistance (HOMA2).\n A total of 49 subjects (M=18; F=31) completed the intervention. Baseline averages were as follows: body mass index=33.5 kg/m(2); BP=123/76 mm Hg; HOMA2=2.4; FMD=4.3%; rate of fat oxidation during exercise=0.34 g min(-1); abdominal fat=45.7% of total abdominal mass. Compared to LF, HF increased FMD acutely (2 h post-dose) by 2.4% (P<0.01) and chronically (over 12 weeks; P<0.01) by 1.6% and reduced insulin resistance by 0.31% (P<0.05), diastolic BP by 1.6 mm Hg and mean arterial BP by 1.2 mm Hg (P<0.05), independent of exercise. Regular exercise increased fat oxidation during exercise by 0.10 g min(-1) (P<0.01) and reduced abdominal fat by 0.92% (P<0.05).\n Although HF consumption was shown to improve endothelial function, it did not enhance the effects of exercise on body fat and fat metabolism in obese subjects. However, it may be useful for reducing cardiometabolic risk factors in this population.", "Consumption of flavanol-rich dark chocolate (DC) has been shown to decrease blood pressure (BP) and insulin resistance in healthy subjects, suggesting similar benefits in patients with essential hypertension (EH). Therefore, we tested the effect of DC on 24-hour ambulatory BP, flow-mediated dilation (FMD), and oral glucose tolerance tests (OGTTs) in patients with EH. After a 7-day chocolate-free run-in phase, 20 never-treated, grade I patients with EH (10 males; 43.7+/-7.8 years) were randomized to receive either 100 g per day DC (containing 88 mg flavanols) or 90 g per day flavanol-free white chocolate (WC) in an isocaloric manner for 15 days. After a second 7-day chocolate-free period, patients were crossed over to the other treatment. Noninvasive 24-hour ambulatory BP, FMD, OGTT, serum cholesterol, and markers of vascular inflammation were evaluated at the end of each treatment. The homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and insulin sensitivity index (ISI) were calculated from OGTT values. Ambulatory BP decreased after DC (24-hour systolic BP -11.9+/-7.7 mm Hg, P<0.0001; 24-hour diastolic BP -8.5+/-5.0 mm Hg, P<0.0001) but not WC. DC but not WC decreased HOMA-IR (P<0.0001), but it improved QUICKI, ISI, and FMD. DC also decreased serum LDL cholesterol (from 3.4+/-0.5 to 3.0+/-0.6 mmol/L; P<0.05). In summary, DC decreased BP and serum LDL cholesterol, improved FMD, and ameliorated insulin sensitivity in hypertensives. These results suggest that, while balancing total calorie intake, flavanols from cocoa products may provide some cardiovascular benefit if included as part of a healthy diet for patients with EH.", "In recent years, there has been increased interest in the potential health-related benefits of antioxidant- and phytochemical-rich dark chocolate and cocoa.\n The objective of the study was to examine the short-term (6 wk) effects of dark chocolate and cocoa on variables associated with neuropsychological functioning and cardiovascular health in healthy older adults.\n A double-blind, placebo-controlled, fixed-dose, parallel-group clinical trial was used. Participants (n = 101) were randomly assigned to receive a 37-g dark chocolate bar and 8 ounces (237 mL) of an artificially sweetened cocoa beverage or similar placebo products each day for 6 wk.\n No significant group (dark chocolate and cocoa or placebo)-by-trial (baseline, midpoint, and end-of-treatment assessments) interactions were found for the neuropsychological, hematological, or blood pressure variables examined. In contrast, the midpoint and end-of-treatment mean pulse rate assessments in the dark chocolate and cocoa group were significantly higher than those at baseline and significantly higher than the midpoint and end-of-treatment rates in the control group. Results of a follow-up questionnaire item on the treatment products that participants believed they had consumed during the trial showed that more than half of the participants in both groups correctly identified the products that they had ingested during the experiment.\n This investigation failed to support the predicted beneficial effects of short-term dark chocolate and cocoa consumption on any of the neuropsychological or cardiovascular health-related variables included in this research. Consumption of dark chocolate and cocoa was, however, associated with significantly higher pulse rates at 3- and 6-wk treatment assessments.", "Flavanols from chocolate appear to increase nitric oxide bioavailability, protect vascular endothelium, and decrease cardiovascular disease (CVD) risk factors. We sought to test the effect of flavanol-rich dark chocolate (FRDC) on endothelial function, insulin sensitivity, beta-cell function, and blood pressure (BP) in hypertensive patients with impaired glucose tolerance (IGT). After a run-in phase, 19 hypertensives with IGT (11 males, 8 females; 44.8 +/- 8.0 y) were randomized to receive isocalorically either FRDC or flavanol-free white chocolate (FFWC) at 100 g/d for 15 d. After a wash-out period, patients were switched to the other treatment. Clinical and 24-h ambulatory BP was determined by sphygmometry and oscillometry, respectively, flow-mediated dilation (FMD), oral glucose tolerance test, serum cholesterol and C-reactive protein, and plasma homocysteine were evaluated after each treatment phase. FRDC but not FFWC ingestion decreased insulin resistance (homeostasis model assessment of insulin resistance; P < 0.0001) and increased insulin sensitivity (quantitative insulin sensitivity check index, insulin sensitivity index (ISI), ISI(0); P < 0.05) and beta-cell function (corrected insulin response CIR(120); P = 0.035). Systolic (S) and diastolic (D) BP decreased (P < 0.0001) after FRDC (SBP, -3.82 +/- 2.40 mm Hg; DBP, -3.92 +/- 1.98 mm Hg; 24-h SBP, -4.52 +/- 3.94 mm Hg; 24-h DBP, -4.17 +/- 3.29 mm Hg) but not after FFWC. Further, FRDC increased FMD (P < 0.0001) and decreased total cholesterol (-6.5%; P < 0.0001), and LDL cholesterol (-7.5%; P < 0.0001). Changes in insulin sensitivity (Delta ISI - Delta FMD: r = 0.510, P = 0.001; Delta QUICKI - Delta FMD: r = 0.502, P = 0.001) and beta-cell function (Delta CIR(120) - Delta FMD: r = 0.400, P = 0.012) were directly correlated with increases in FMD and inversely correlated with decreases in BP (Delta ISI - Delta 24-h SBP: r = -0.368, P = 0.022; Delta ISI - Delta 24-h DBP r = -0.384, P = 0.017). Thus, FRDC ameliorated insulin sensitivity and beta-cell function, decreased BP, and increased FMD in IGT hypertensive patients. These findings suggest flavanol-rich, low-energy cocoa food products may have a positive impact on CVD risk factors.", "Flavanol-rich chocolate and lycopene-rich tomato extract have attracted interest as potential alternative treatment options for hypertension, a known risk factor for cardiovascular morbidity and mortality. Treatment of prehypertension (SBP 120-139/DBP 80-89 mmHg) may forestall progression to hypertension. However, there has been only limited research into non-pharmacological treatment options for prehypertension. We investigated the effect of dark chocolate or tomato extract on blood pressure, and their acceptability as an ongoing treatment option in a prehypertensive population.\n Our trial consisted of two phases: a randomised controlled three-group-parallel trial over 12 weeks (phase 1) followed by a crossover of the two active treatment arms over an additional 12-week period (phase 2). Group 1 received a 50 g daily dose of dark chocolate with 70% cocoa containing 750 mg polyphenols, group 2 were allocated one tomato extract capsule containing 15 mg lycopene per day, and group 3 received one placebo capsule daily over 8 weeks followed by a 4-week washout period. In phase 2 the active treatment groups were crossed over to receive the alternative treatment. Median blood pressure, weight, and abdominal circumference were measured 4-weekly, and other characteristics including physical activity, general health, energy, mood, and acceptability of treatment were assessed by questionnaire at 0, 8 and 20 weeks. We analysed changes over time using a linear mixed model, and one time point differences using Kruskal-Wallis, Fisher's-Exact, or t-tests.\n Thirty-six prehypertensive healthy adult volunteers completed the 6-month trial. Blood pressure changes over time within groups and between groups were not significant and independent of treatment. Weight and other characteristics did not change significantly during the trial. However, a marked difference in acceptability between the two treatment forms (chocolate or capsule) was revealed (p < 0.0001). Half of the participants allocated to the chocolate treatment found it hard to eat 50 g of dark chocolate every day and 20% considered it an unacceptable long-term treatment option, whereas all participants found it easy and acceptable to take a capsule each day for blood pressure.\n Our study did not find a blood pressure lowering effect of dark chocolate or tomato extract in a prehypertensive population. Practicability of chocolate as a long-term treatment option may be limited.\n http://www.anzctr.org.au Identifier: ACTRN12609000047291.", "Studies of cocoa suggest an array of cardiovascular benefits; however, the effects of daily intake of sugar-free and sugar-sweetened cocoa beverages on endothelial function (EF) have yet to be established.\n 44 adults (BMI 25-35 kg/m2) participated in a randomized, controlled, crossover trial. Participants were randomly assigned to a treatment sequence: sugar-free cocoa beverage, sugar-sweetened cocoa beverage, and sugar-sweetened cocoa-free placebo. Treatments were administered daily for 6 weeks, with a 4-week washout period.\n Cocoa ingestion improved EF measured as flow-mediated dilation (FMD) compared to placebo (sugar-free cocoa: change, 2.4% [95% CI, 1.5 to 3.2] vs. -0.8% [95% CI, -1.9 to 0.3]; difference, 3.2% [95% CI, 1.8 to 4.6]; p<0.001 and sugar-sweetened cocoa: change, 1.5% [95% CI, 0.6 to 2.4] vs. -0.8% [95% CI, -1.9 to 0.3]; difference, 2.3% [95% CI, 0.9 to 3.7]; p=0.002). The magnitude of improvement in FMD after consumption of sugar-free versus sugar-sweetened cocoa was greater, but not significantly. Other biomarkers of cardiac risk did not change appreciably from baseline. BMI remained stable throughout the study.\n Daily cocoa ingestion improves EF independently of other biomarkers of cardiac risk, and does not cause weight gain. Sugar-free preparations may further augment endothelial function.\n Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.", "Consumption of flavanol-containing cocoa products has been shown to lower blood pressure (BP), but the minimum dose required to reduce BP is not known. This study aimed to examine the effect of three different doses of cocoa flavanols (CF) on 24-h mean arterial BP. Twenty four hour ambulatory BP (24-ABP) monitoring was performed in 32 men and 20 postmenopausal women with untreated mild hypertension (seated clinic BP >130/85 and <160/100 mm Hg). Participants were randomized and instructed to consume daily a reconstituted cocoa beverage containing 33, 372, 712 or 1052 mg day(-1) of CF for 6 weeks in a double-blind, parallel comparison. Seated clinic BP and 24-h ABP were measured at 0, 3 and 6 weeks. Seated clinic BP did not change during the study period. There were significant reductions in 24-h systolic (5.3+/-5.1 mm Hg; P=0.001), diastolic (3+/-3.2 mm Hg; P=0.002) and mean arterial BP (3.8+/-3.2 mm Hg; P=0.0004) at the 1052 mg day(-1) CF only. No reduction in BP was seen at any other dose. No evidence of dose-response was seen in this experiment. The highest dose of 1052 mg CF per day was found to significantly lower BP. These results support previous evidence for CF to lower BP, however more research is needed to establish the most effective dose and food matrix.", "To assess the effects of the oral intake of flavonoid-rich dark chocolate on coronary circulation, we measured coronary flow velocity reserve (CFVR) by noninvasive transthoracic Doppler echocardiography (TTDE) in healthy adult subjects.\n The study was a randomized, single-blind design conducted for 2 weeks in 39 healthy men (mean age 29.7+/-3.9 years, range 23-40 years). Subjects were randomly assigned a daily intake of either flavonoid-rich dark chocolate (Meiji Black Chocolate 45 g, Meiji Seika kaisya Ltd, including cacao polyphenol 550 mg/day, 200 kcal) or non-flavonoid white chocolate (Meiji White Chocolate 35 g, Meiji Seika kaisya Ltd, including cacao polyphenol 0 mg/day, 140 kcal) as a control. CFVR was recorded by TTDE, and assessed before and after 2 weeks of intake. At the same time, we also assessed serum asymmetric dimethylarginine, 8-isoprostanes, and malondialdehyde-modified low-density lipoprotein (MDA-LDL) as markers of oxidative stress.\n Flavonoid-rich dark chocolate consumption significantly improved CFVR (3.38+/-0.49 before intake, 4.28+/-0.85 after intake; p<0.01), whereas non-flavonoid white chocolate consumption did not (3.28+/-0.49 before intake, 3.16+/-0.49 after intake; p=0.44). All predictor variables were used as dependent variables in a multiple regression model of the incremental change in CFVR after 2 weeks of chocolate intake. Intake of dark (but not white) chocolate, MDA-LDL, triglyceride (TG) and heart rate (HR) significantly influenced the change of CFVR after 2 weeks of intake (p<0.01) according to the multiple regression formula: Y=1.01X(1)-0.005X(2)-0.003X(3)-0.017X4 (Y=change in CFVR after 2 weeks of chocolate intake, X1=intake of dark (but not white) chocolate, X2=MDA-LDL, X3=TG, X4=HR).\n Flavonoid-rich dark chocolate intake significantly improved coronary circulation in healthy adults, independent of changes in oxidative stress parameters, blood pressure and lipid profile, whereas non-flavonoid white chocolate had no such effects.", "Flavanol-rich cocoa products have been reported to lower blood pressure. It has been suggested that theobromine is partially responsible for this effect. We tested whether consumption of flavanol-rich cocoa drinks with natural or added theobromine could lower peripheral and central blood pressure. In a double-blind, placebo-controlled 3-period crossover trial we assigned 42 healthy individuals (age 62±4.5 years; 32 men) with office blood pressure of 130 to 159 mm Hg/85 to 99 mm Hg and low added cardiovascular risk to a random treatment sequence of dairy drinks containing placebo, flavanol-rich cocoa with natural dose consisting of 106 mg of theobromine, or theobromine-enriched flavanol-rich cocoa with 979 mg of theobromine. Treatment duration was 3 weeks with a 2-week washout. The primary outcome was the difference in 24-hour ambulatory systolic blood pressure between placebo and active treatment after 3 weeks. The difference in central systolic blood pressure between placebo and active treatment was a secondary outcome. Treatment with theobromine-enriched cocoa resulted in a mean±SE of 3.2±1.1 mm Hg higher 24-hour ambulatory systolic blood pressure compared with placebo (P<0.01). In contrast, 2 hours after theobromine-enriched cocoa, laboratory peripheral systolic blood pressure was not different from placebo, whereas central systolic blood pressure was 4.3±1.4 mm Hg lower (P=0.001). Natural dose theobromine cocoa did not significantly change either 24-hour ambulatory or central systolic blood pressure compared with placebo. In conclusion, theobromine-enriched cocoa significantly increased 24-hour ambulatory systolic blood pressure while lowering central systolic blood pressure.", "The consumption of a diet rich in certain flavonoids, including the flavanol sub-class, has been associated with a reduced risk for vascular disease. We evaluated the effects of the regular consumption (14 d) of a flavanol-containing milk chocolate (FCMC) or cocoa butter chocolate (CBC) on variables related to vascular disease risk, oxidative stress and physical activity. Twenty-eight free-living, young (18-20 years old) male soccer players consumed daily 105 g of FCMC (168 mg of flavanols) or CBC (< 5 mg of flavanols), as part of their normal diet. The consumption of FCMC was significantly associated with a decrease in diastolic blood pressure (- 5 mm Hg), mean blood pressure (- 5 mm Hg), plasma cholesterol (-11%), LDL-cholesterol (-15%), malondialdehyde (- 12%), urate (- 11%) and lactate dehydrogenase (LDH) activity (- 11%), and an increase in vitamin E/cholesterol (+ 12%). No relevant changes in these variables were associated with CBC consumption. No changes in the plasma levels of (-)-epicatechin were observed following analysis of fasting blood samples. In conclusion, FCMC consumption was associated with changes in several variables often associated with cardiovascular health and oxidant stress. The presence of significant quantities of flavanols in FCMC is likely to have been one of the contributing factors to these results.", "Flavonoids may be partly responsible for some health benefits, including antiinflammatory action and a decreased tendency for the blood to clot. An acute dose of flavanols and oligomeric procyanidins from cocoa powder inhibits platelet activation and function over 6 h in humans.\n This study sought to evaluate whether 28 d of supplementation with cocoa flavanols and related procyanidin oligomers would modulate human platelet reactivity and primary hemostasis and reduce oxidative markers in vivo.\n Thirty-two healthy subjects were assigned to consume active (234 mg cocoa flavanols and procyanidins/d) or placebo (< or = 6 mg cocoa flavanols and procyanidins/d) tablets in a blinded parallel-designed study. Platelet function was determined by measuring platelet aggregation, ATP release, and expression of activation-dependent platelet antigens by using flow cytometry. Plasma was analyzed for oxidation markers and antioxidant status.\n Plasma concentrations of epicatechin and catechin in the active group increased by 81% and 28%, respectively, during the intervention period. The active group had significantly lower P selectin expression and significantly lower ADP-induced aggregation and collagen-induced aggregation than did the placebo group. Plasma ascorbic acid concentrations were significantly higher in the active than in the placebo group (P < 0.05), whereas plasma oxidation markers and antioxidant status did not change in either group.\n Cocoa flavanol and procyanidin supplementation for 28 d significantly increased plasma epicatechin and catechin concentrations and significantly decreased platelet function. These data support the results of acute studies that used higher doses of cocoa flavanols and procyanidins.", "In patients with coronary artery disease (CAD) medically managed according to currently accepted guidelines, we tested whether a 1-month dietary intervention with flavanol-containing cocoa leads to an improvement of endothelial dysfunction and whether this is associated with an enhanced number and function of circulating angiogenic cells (CACs).\n Dietary flavanols can improve endothelial dysfunction. The CACs, also termed endothelial progenitor cells, are critical for vascular repair and maintenance of endothelial function.\n In a randomized, controlled, double-masked, cross-over trial, 16 CAD patients (64+/-3 years of age) received a dietary high-flavanol intervention (HiFI [375 mg]) and a macronutrient- and micronutrient-matched low-flavanol intervention (LoFI [9 mg]) twice daily in random order over 30 days.\n Endothelium-dependent vasomotor function, as measured by flow-mediated vasodilation of the brachial artery, improved by 47% in the HiFI period compared with the LoFI period. After HiFI, the number of CD34+/KDR+-CACs, as measured by flow cytometry, increased 2.2-fold as compared with after LoFI. The CAC functions, as measured by the capacity to survive, differentiate, proliferate, and to migrate were not different between the groups. The HiFI led to a decrease in systolic blood pressure (mean change over LoFI: -4.2+/-2.7 mm Hg), and increase in plasma nitrite level (mean change over LoFI: 74+/-32 nM). Applying a mixed-effects linear regression model, the results demonstrated a significant increase in flow-mediated vasodilation and a decrease in systolic blood pressure with increasing levels of CD34+/KDR+-CACs.\n Sustained improvements in endothelial dysfunction by regular dietary intake of flavanols are associated with mobilization of functional CACs. (Effect of Cocoa Flavanols on Vascular Function in Optimally Treated Coronary Artery Disease Patients: Interaction Between Endothelial Progenitor Cells, Reactivity of Micro- and Macrocirculation; NCT00553774).\n Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.", "Regular intake of cocoa-containing foods is linked to lower cardiovascular mortality in observational studies. Short-term interventions of at most 2 weeks indicate that high doses of cocoa can improve endothelial function and reduce blood pressure (BP) due to the action of the cocoa polyphenols, but the clinical effect of low habitual cocoa intake on BP and the underlying BP-lowering mechanisms are unclear.\n To determine effects of low doses of polyphenol-rich dark chocolate on BP.\n Randomized, controlled, investigator-blinded, parallel-group trial involving 44 adults aged 56 through 73 years (24 women, 20 men) with untreated upper-range prehypertension or stage 1 hypertension without concomitant risk factors. The trial was conducted at a primary care clinic in Germany between January 2005 and December 2006.\n Participants were randomly assigned to receive for 18 weeks either 6.3 g (30 kcal) per day of dark chocolate containing 30 mg of polyphenols or matching polyphenol-free white chocolate.\n Primary outcome measure was the change in BP after 18 weeks. Secondary outcome measures were changes in plasma markers of vasodilative nitric oxide (S-nitrosoglutathione) and oxidative stress (8-isoprostane), and bioavailability of cocoa polyphenols.\n From baseline to 18 weeks, dark chocolate intake reduced mean (SD) systolic BP by -2.9 (1.6) mm Hg (P < .001) and diastolic BP by -1.9 (1.0) mm Hg (P < .001) without changes in body weight, plasma levels of lipids, glucose, and 8-isoprostane. Hypertension prevalence declined from 86% to 68%. The BP decrease was accompanied by a sustained increase of S-nitrosoglutathione by 0.23 (0.12) nmol/L (P < .001), and a dark chocolate dose resulted in the appearance of cocoa phenols in plasma. White chocolate intake caused no changes in BP or plasma biomarkers.\n Data in this relatively small sample of otherwise healthy individuals with above-optimal BP indicate that inclusion of small amounts of polyphenol-rich dark chocolate as part of a usual diet efficiently reduced BP and improved formation of vasodilative nitric oxide.\n clinicaltrials.gov Identifier: NCT00421499." ]

[ "15215806", "19289640", "16737850" ]

[ "The Warfarin/Aspirin Study in Heart failure (WASH): a randomized trial comparing antithrombotic strategies for patients with heart failure.", "Randomized trial of warfarin, aspirin, and clopidogrel in patients with chronic heart failure: the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial.", "Efficacy of antithrombotic therapy in chronic heart failure: the HELAS study." ]

[ "Heart failure is commonly associated with vascular disease and a high rate of athero-thrombotic events, but the risks and benefits of antithrombotic therapy are unknown.\n The current study was an open-label, randomized, controlled trial comparing no antithrombotic therapy, aspirin (300 mg/day), and warfarin (target international normalized ratio 2.5) in patients with heart failure and left ventricular systolic dysfunction requiring diuretic therapy. The primary objective was to demonstrate the feasibility and inform the design of a larger outcome study. The primary clinical outcome was death, nonfatal myocardial infarction, or nonfatal stroke.\n Two hundred seventy-nine patients were randomized and 627 patient-years exposure were accumulated over a mean follow-up time of 27 +/- 1 months. Twenty-six (26%), 29 (32%), and 23 (26%) patients randomized to no antithrombotic treatment, aspirin, and warfarin, respectively, reached the primary outcome (ns). There were trends to a worse outcome among those randomized to aspirin for a number of secondary outcomes. Significantly (P =.044) more patients randomized to aspirin were hospitalized for cardiovascular reasons, especially worsening heart failure.\n The Warfarin/Aspirin Study in Heart failure (WASH) provides no evidence that aspirin is effective or safe in patients with heart failure. The benefits of warfarin for patients with heart failure in sinus rhythm have not been established. Antithrombotic therapy in patients with heart failure is not evidence based but commonly contributes to polypharmacy.", "Chronic heart failure remains a major cause of mortality and morbidity. The role of antithrombotic therapy in patients with chronic heart failure has long been debated. The objective of this study was to determine the optimal antithrombotic agent for heart failure patients with reduced ejection fractions who are in sinus rhythm.\n This prospective, randomized clinical trial of open-label warfarin (target international normalized ratio of 2.5 to 3.0) and double-blind treatment with either aspirin (162 mg once daily) or clopidogrel (75 mg once daily) had a 30-month enrollment period and a minimum of 12 months of treatment. We enrolled 1587 men and women >/=18 years of age with symptomatic heart failure for at least 3 months who were in sinus rhythm and had left ventricular ejection fraction of </=35%. The primary outcome was the time to first occurrence of death, nonfatal myocardial infarction, or nonfatal stroke. For the primary composite end point, the hazard ratios were as follows: for warfarin versus aspirin, 0.98 (95% CI, 0.86 to 1.12; P=0.77); for clopidogrel versus aspirin, 1.08 (95% CI, 0.83 to 1.40; P=0.57); and for warfarin versus clopidogrel, 0.89 (95% CI, 0.68 to 1.16; P=0.39). Warfarin was associated with fewer nonfatal strokes than aspirin or clopidogrel. Hospitalization for worsening heart failure occurred in 116 (22.2%), 97 (18.5%), and 89 (16.5%) patients treated with aspirin, clopidogrel, and warfarin, respectively (P=0.02 for warfarin versus aspirin).\n The primary outcome measure and the mortality data do not support the primary hypotheses that warfarin is superior to aspirin and that clopidogrel is superior to aspirin.", "It is not clear if long-term antithrombotic treatment has a beneficial effect on the incidence of thromboembolism in chronic heart failure (CHF). The HELAS study (Heart failure Long-term Antithrombotic Study) is a multicentre, randomised, double-blind, placebo-controlled trial to evaluate antithrombotic treatment in patients with CHF.\n 197HF patients (EF <35%) were enrolled. Patients with Ischaemic Heart Disease were randomised to receive either aspirin 325mg or warfarin. Patients with Dilated Cardiomyopathy (DCM) were randomised to receive either warfarin or placebo.\n Analysis of the data from 312 patient years showed an incidence of 2.2 embolic events per 100 patient years, with no significant difference between groups. The incidence of myocardial infarction, hospitalisation, exacerbation of heart failure, death and haemorrhage were not different between the groups. No peripheral or pulmonary emboli were reported. Echocardiographic follow-up for 2years showed an overall increase in left ventricular ejection fraction from 28.2+/-6 to 30.3+/-7 p<0.05, which was most obvious in patients with DCM taking warfarin (EF 26.8+/-5.3 at baseline, 30.7+/-10 at 2 years, p<0.05).\n (1) Overall embolic events are rare in heart failure regardless of treatment. (2) Treatment does not seem to affect outcome." ]

[ "21620064", "10625238", "20620518", "9039930", "16918535", "16724337" ]

[ "Sequential versus contemporaneous portal and arterial reperfusion during liver transplantation.", "Hemodynamic profiles during piggyback liver grafts using arterial or portal revascularization.", "Rocuronium profile during orthotopic liver transplantation: effect of changing the order of vascular clamp release at reperfusion of the hepatic graft.", "Randomized controlled trial to evaluate flush and reperfusion techniques in liver transplantation.", "Retrograde reperfusion via vena cava lowers the risk of initial nonfunction but increases the risk of ischemic-type biliary lesions in liver transplantation--a randomized clinical trial.", "Hemodynamic profile and tissular oxygenation in orthotopic liver transplantation: Influence of hepatic artery or portal vein revascularization of the graft." ]

[ "Although sequential portal and arterial revascularization (SPAr) is the most common method of graft reperfusion at liver transplantation (OLT), contemporaneous portal and hepatic artery revascularization (CPAr) has been used to reduce arterial ischemia to the bile ducts. The aim of this study was to prospectively compare SPAr (group 1; n=19) versus CPAr (group 2; n=21) among 40 consecutive OLT from heart-beating donors. There were no differences in the demographics characteristics, Model for End-stage Liver Disease scores, indication for OLT and donor parameters between the groups. OLT was performed using the piggyback technique. The biliary anastomosis was performed in all cases by a duct-to-duct technique with a T-tube in 32% versus 29% of cases without a T tube (P=.83). In the CPAr group, the liver was reperfused simultaneously via the portal vein and hepatic artery. CPAr showed a longer warm ischemia (66 ± 8 vs 37 ± 7 minutes; P<.001), while SPAr had a longer arterial ischemia 103 ± 42 vs 66 ± 8 minutes (P=.0004). Recovery of graft function was similar. There was no primary nonfunction and delayed graft function occurred among 10% versus 9%. Liver function tests were similar between the two groups up to 90 days case of follow-up- One-year graft and patient survivals were, respectively, 89% and 95% versus 94% and 100% (P=.29). At a median follow-up of 13 ± 6 versus 14 ± 7 months, biliary complications included anastomotic stenoses in 15% versus 19% (P=.78) and intrahepatic non-anastomotic biliary strictures in 26% versus none (P=.01) for SPAr and CPAr, respectively. CPAr was safe and feasible, reducing the incidence of intrahepatic biliary strictures by decreasing the duration of arterial ischemia to the intrahepatic bile ducts.\n Copyright © 2011 Elsevier Inc. All rights reserved.", "The order of revascularization in human liver grafts is still discussed. This study tries to answer this question in terms of hemodynamic data.\n Fifty-nine patients were randomized in this study to compare hemodynamic data just before and 15 minutes after revascularization of liver grafts in relation to first hepatic artery (n = 29) or first portal vein (n = 30) revascularization procedure.\n Hemodynamic variations were significantly greater in the portal vein group than in the hepatic artery group in terms of mean arterial pressure, cardiac index, central venous pressure, pulmonary capillary pressure, and systemic vascular resistance. The latter decreased from 741.8 +/- 390.3 to 659.9 +/- 411.1 dynes/ cm5 (NS) in the hepatic artery group versus 807.7 +/-336.7 to 439.7 +/- 215 dynes/cm5 (p < 0.05) in the portal vein group. Clinical results and postoperative complications, graft characteristics, patient survival, and graft survival were not significantly different between the groups.\n Initial arterial revascularization of the liver graft leads to a more stable hemodynamic profile during revascularization of the liver graft after vascular unclamping. This technique is always feasible and has become our reference procedure.", "Clearance of rocuronium in the neohepatic period may be a criterion for graft function during orthotopic liver transplantation (OLT). Our goal was to demonstrate that changes in rocuronium elimination are caused mainly by variations in blood volume at reperfusion. We have explored the influence on rocuronium plasma concentrations of changing the order of vascular unclamping at graft reperfusion.\n Thirty patients were randomized at graft reperfusion: initial arterial revascularization (IAR; n = 14) wherein the hepatic artery was released first, and initial portal revascularization (IPR; n = 16) wherein the portal vein was released first. Tracheal intubation was facilitated by rocuronium (1 mg/kg) with an infusion initiated at 0.25 mg kg(-1) h(-1) to maintain a response to the first stimulus of the train of four <25% of controls. Rocuronium plasma concentrations (RPC) were measured throughout the transplantation.\n No differences were observed in rocuronium consumption at different stages. RPCs decreased after reperfusion, with primarily portal unclamping responsible. In 6 patients of the IAR group and 5 patients of the IPR group, RPC at 60 minutes after reperfusion was higher than previous values. Indicators of graft dysfunction among those 11 did not differ from the other patients. Two patients in the IPR group required retransplantation without any relation to changes in RPCs.\n The increase of blood flow produced by portal vein unclamping influenced RPCs; no relation was observed between RPCs and graft outcomes.", "To determine the impact of different flush and reperfusion techniques on postreperfusion syndrome (PRS) and postoperative graft function, 100 transplants were randomly assigned into four groups as follows: group 1 (n=31), portal vein flush, no vena caval venting; group 2 (n=21), hepatic arterial flush, no vena caval venting; group 3 (n=29), portal vein flush with vena caval venting; and group 4 (n=19), hepatic artery flush with vena caval venting. Donor and recipient characteristics were similar. Extensive intraoperative and postoperative monitoring was performed and measurements were documented immediately before reperfusion and at 1, 5, 15, and 30 min after reperfusion. PRS was defined by three criteria: mean arterial pressure (MAP) <60 mmHg at 1 min after reperfusion, MAP <60 mmHg at 5 min after reperfusion, and a decrease of 30% or more for the MAP percent area under the curve during the initial 5 min after reperfusion (%AUC). Using these definitions, the overall incidence of PRS was 21%, 8%, and 43%, respectively. Group 1 was the most hemodynamically stable; the incidence of PRS in group 1 was 2/31 (7%) at 1 min and 8/31 (25%) using %AUC criteria compared with 7/21 (33%) at 1 min and 12/21 (57%) using %AUC criteria for group 2 (P<0.05). The patients in groups 3 and 4 (vena caval venting) demonstrated smaller percentage increases in serum potassium levels (as determined by %AUC; 4.3+/-6.8 and 0.3+/-5.4, vs. 15.1+/-8.1 for group 1 and 22.9+/-8.2 for group 2). The difference between group 4 and group 2 was statistically significant (P<0.05). The increases in serum potassium did not translate into increased cardiac or hemodynamic instability. Combining all data obtained over the first 30 min after reperfusion, there was no statistically significant difference in hemodynamic or biochemical changes noted among the four groups. Postoperative liver function was similar among the four groups. We conclude that portal vein flush without vena caval venting provided a lower incidence of PRS than any other technique. Vena caval venting decreased the release of potassium into the circulation. Postoperative graft function was not significantly affected by flush and reperfusion techniques.", "Initial nonfunction (INF) and biliary complications such as ischemic-type biliary lesion (ITBL) remain two major complications in clinical orthotopic liver transplantation (OLT). The influence of ischemia and reperfusion injury (I/R) as a significant risk factor for both complications is widely unquestioned. A new reperfusion technique that reduces I/R injury should lead to a reduction in both INF and ITBL. One hundred and thirty two OLT patients were included in this study and randomized into two groups. Group A underwent standard reperfusion with anterograde simultaneous arterial and portal reperfusion and group B received retrograde reperfusion via the vena cava before sequential anterograde reperfusion of portal vein and hepatic artery. Serum transaminase level as a surrogate parameter for I/R injury and serum bilirubin level as a parameter for graft function were significantly reduced during the first week after OLT in group B. INF rate was 7.7% in group A and 0% in group B (P = 0.058). ITBL incidence was 4.55% in group A versus 12.3% in group B (P = 0.053). Retrograde reperfusion seemed to be beneficial for hepatocytes, but was detrimental for the biliary epithelium. The unexplained increased incidence of ITBL after retrograde reperfusion will be focus of further investigation.", "We performed a prospective, randomized study of adult patients undergoing orthotopic liver transplantation, comparing hemodynamic and tissular oxygenation during reperfusion of the graft. In 30 patients, revascularization was started through the hepatic artery (i.e., initial arterial revascularization) and 10 minutes later the portal vein was unclamped; in 30 others, revascularization was started through the portal vein (i.e., initial portal revascularization) and 10 minutes later the hepatic artery was unclamped. The primary endpoints of the study were mean systemic arterial pressure and the gastric-end-tidal carbon dioxide partial pressure (PCO(2)) difference. The secondary endpoints were other hemodynamic and metabolic data. The pattern of the hemodynamic parameters and tissue oxygenation values during the dissection and anhepatic stages were similar in both groups At the first unclamping, initial portal revascularization produced higher values of mean pulmonary pressure (25 +/- 7 mm of Hg vs. 17 +/- 4 mm of Hg; P < 0.05) and wedge and central venous pressures. At the second unclamping, initial portal revascularization produced higher values of cardiac output and mean arterial pressure (87 +/- 15 mm of Hg vs. 79 +/- 15 mm of Hg; P < 0.05) and pulmonary blood pressure. Postreperfusion syndrome was present in 13 patients (42.5%) in the arterial group and in 11 patients (36%) in the portal group. During revascularization, the values of gastric and arterial pH decreased in both groups and recovered at the end of the procedure, but were more accentuated in the initial arterial revascularization group. In conclusion, we found that initial arterial revascularization of the graft increases pulmonary pressure less markedly, so it may be indicated for those patients with poor pulmonary and cardiac reserve. Nevertheless, for the remaining patients, initial portal revascularization offers more favorable hemodynamic and metabolic behavior, less inotropic drug use, and earlier normalization of lactate and pH values.\n (c) 2006 AASLD" ]

[ "12887037", "15040556", "12504399", "15941413" ]

[ "Efficacy of amodiaquine alone and combined with sulfadoxine-pyrimethamine and of sulfadoxine pyrimethamine combined with artesunate.", "Efficacy of chloroquine, amodiaquine, sulphadoxine-pyrimethamine and combination therapy with artesunate in Mozambican children with non-complicated malaria.", "Sulfadoxine/pyrimethamine alone or with amodiaquine or artesunate for treatment of uncomplicated malaria: a longitudinal randomised trial.", "A randomized, placebo-controlled, double-blind trial on sulfadoxine-pyrimethamine alone or combined with artesunate or amodiaquine in uncomplicated malaria." ]

[ "The safety and the efficacy of amodiaquine (AQ) alone, AQ plus sulfadoxine-pyrimethamine (SP) (AQ plus SP), and artesunate (ART) plus SP (ART plus SP), three possible alternatives to chloroquine (CQ), were investigated in 379 Rwandan children 6-59 months old with uncomplicated Plasmodium falciparum malaria who visited one urban/peri-urban health center and two rural health centers. The three treatment regimens were well tolerated and no serious adverse effects were observed. Children treated with AQ plus SP had less clinical failures than those treated with ART plus SP (odds ratio [OR] = 0.25, 95% confidence interval [CI] = 0.06-0.81, P = 0.01) or AQ alone (OR = 0.33, 95% CI = 0.07-1.10, P = 0.08). Even after new infections were excluded, AQ plus SP was still significantly more efficacious than ART plus SP (P = 0.05). At day 14, the mean packed cell volume was significantly higher in the AQ plus SP group compared with the ART plus SP group (P = 0.02) and with the AQ alone group (P = 0.01). In Rwanda, AQ plus SP has been chosen to replace CQ as a first-line treatment. However, this is considered an interim measure and new combinations, possibly co-formulated, should be identified and tested.", "This paper reports a two-phase study in Manhiça district, Mozambique: first we assessed the clinical efficacy and parasitological response of Plasmodium falciparum to chloroquine (CQ), sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ), then we tested the safety and efficacy in the treatment of uncomplicated malaria, of three combinations: AQ + SP, artesunate (AR) + SP and AQ + AR. Based on the WHO (1996, WHO/MAL/96.1077) in vivo protocol, we conducted two open, randomized, clinical trials. Children aged 6-59 months with axillary body temperature > or = 37.5 degrees C and non-complicated malaria were randomly allocated to treatment groups and followed up for 21 days (first and second trial) and 28 days (first trial). The therapeutic efficacy of AQ (91.6%) was better than that of SP (82.7%) and CQ (47.1%). After 14 days, 69% of the strains were parasitologically resistant to CQ, 21.4% to SP and 26% to AQ. Co-administration of AQ + SP, AR + SP and AQ + AR was safe and had 100% clinical efficacy at 14-day follow-up. The combination therapies affected rapid fever clearance time and reduced the incidence of gametocytaemia during follow-up.", "New antimalarial treatments are urgently needed in sub-Saharan Africa. Improved therapies should decrease failure rates in the short term, but their effect on incidence of subsequent episodes of malaria is little studied. We aimed to compare the short-term and long-term effectiveness of three antimalarial regimens in children from Kampala, Uganda.\n We randomly allocated healthy children aged 6 months to 5 years to receive 25 mg/kg sulfadoxine and 1.25 mg/kg pyrimethamine plus either placebo, 25 mg/kg amodiaquine, or 12 mg/kg artesunate. Participants were followed up for 1 year and received the same preassigned treatment for every new episode of uncomplicated malaria diagnosed during follow-up. Recrudescent and new infections were distinguished by comparison of polymorphisms in merozoite surface protein 2 (MSP2). Our primary endpoint was the total number of treatments for malaria per time at risk. Analyses were done per protocol.\n 183 (61%) of 316 participants were diagnosed with at least one episode of uncomplicated malaria. A total of 577 episodes of uncomplicated Plasmodium falciparum malaria were treated with study drugs; all regimens were safe and well tolerated. Clinical treatment failure after 14 days was significantly more frequent in the sulfadoxine/pyrimethamine group (38 of 215, 18%) compared with either the sulfadoxine/pyrimethamine plus amodiaquine group (two of 164, 1%; p<0.0001) or sulfadoxine/pyrimethamine plus artesunate group (one of 198, 1%; p<0.0001). After 28 and 42 days, patients in the sulfadoxine/pyrimethamine plus amodiaquine group were significantly less likely to develop malaria than were those in the other groups. Overall, sulfadoxine/pyrimethamine plus amodiaquine reduced the rate of subsequent treatments for malaria by 54% (95% CI 36-66, p<0.0001) compared with sulfadoxine/ pyrimethamine alone and by 37% (12-54, p=0.007) compared with sulfadoxine/pyrimethamine plus artesunate.\n Sulfadoxine/pyrimethamine plus amodiaquine could be used as an inexpensive regimen to decrease the rate of subsequent episodes of malaria.", "The therapeutic efficacy of sulfadoxine-pyrimethamine (SP) alone, SP plus amodiaquine (AQ), and SP plus artesunate (AS) was assessed in a randomized, placebo-controlled, and double-blind trial among 438 children with uncomplicated Plasmodium falciparum malaria in northern Ghana. Clinical and parasitological responses were monitored for 28 days following treatment; 86%, 98% and 97% of SP-, SP + AQ-, and SP + AS-treated patients achieved adequate clinical and parasitological response (ACPR) within 2 weeks, respectively. Parasite clearance was better with SP + AS than with SP or SP + AQ treatment but re-infections were more common. Polymerase chain reaction (PCR)-corrected rates of ACPR at day 28 were 72.2% for SP, 94.1% for SP + AQ (P < 0.0001), and 94.5% for SP + AS (P < 0.0001). Gametocyte prevalence and density 1 week after treatment were highest in children treated with SP, and lowest in patients receiving SP + AS. No severe adverse events attributable to study medication were observed. In northern Ghana, more than one of four children suffered SP treatment failure within 4 weeks. Both SP + AQ and SP + AS are efficacious alternative therapeutic options in this region. Although SP + AS and SP + AQ treatments have virtually identical cure rates, rapid parasite clearance and pronounced gametocidal effects are the advantages of the former, whereas cost and a lower rate of late re-infections are those of the latter." ]

[ "19858981", "16272914", "15947831", "14763702", "19398787" ]

[ "Pin site care during circular external fixation using two different protocols.", "Multicenter pin care study.", "Evaluation of effectiveness of 10% polyvinylpyrrolidone-iodine solution against infections in wire and pin holes for Ilizarov external fixators.", "No difference between daily and weekly pin site care: a randomized study of 50 patients with external fixation.", "Diluted povidone-iodine versus saline for dressing metal-skin interfaces in external fixation." ]

[ "Treatment of tibial fractures with Ilizarov external fixation is a valuable treatment alternative; however, development of problems at the pin site is one of the major drawbacks of this technique. Moreover, there is no general agreement regarding pin site care. The purpose of this study was to compare the efficacy of two different pin site care techniques after treatment of tibial fractures with an Ilizarov external fixator.\n Prospective randomized study.\n Department of Orthopaedic Surgery of education and research hospital.\n In this prospective randomized study, we followed up 610 pin sites in 39 cases using two different pin site care protocols.\n For the first 15 days, patients in both groups cleaned each pin site using sterile gauze impregnated with 10% polyvinylpyrrolidone iodine (Polyod) every 3 days. After 15 days, patients in group 1 (20 cases, 310 pin sites) were advised to perform pin care by daily showering and brushing the pin sites with soap and an ordinary soft toothbrush, whereas patients in group 2 (19 cases, 300 pin sites) were advised to perform pin care by daily showering and cleaning the crusts using sterile gauze impregnated with 10% polyvinylpyrrolidone iodine (Polyod). Each pin site was denominated according to location.\n Pin sites were inspected and graded on a scale of 0 to 5 according to slight modification of the system of Dahl described by Gordon et al during outpatient visits on the 5th, 10th, 15th, 30th, 45th, 60th, 75th, 90th, 120th, and 150th days of follow up after the operation until fixator removal. Grade 1 and grade 2 infections were categorized as minor infection not requiring any extra pin site care and grade 3 and above infections as major infection.\n Minor infection rate of all pin sites was determined as 50.7% in group 1 and 43.6% in group 2. Major infection rate was determined as 3.5% in group 1 and 3.7% in group 2. No statistically significant difference was noted between the two groups (all P > 0.05).\n Pin site care can be performed without impairing patient comfort and without prohibition of showering. Pin site care can be self-managed by the patients without complex sterilization techniques.", "Pin-site infection is a common complication of external fixation. Because few studies have compared methods of pin care that reduce infection rate, there is a need for evidence-based practice guidelines for pin-site care.\n Two of 10 original clinical centers completed a prospective, randomized pin-care study between May 2000 and May 2002 to determine which of seven methods for caring for skeletal pins (external fixator, traction, or halo) resulted in the fewest pin-site infections.\n The 92 subjects had an average infection rate of 34%, and the 527 pins had a rate of 20%. Thirty patients (98 pins) had stage II infections, two patients (12 pins) had stage III infections, and none had deep infection or osteomyelitis. The protocols were (1) half-strength peroxide cleansing and gauze wraps (45%), (2) half-strength peroxide cleansing and Xeroform wraps (9%), (3) saline cleansing and gauze wraps (33%), (4) saline cleansing and Xeroform wraps (26%), (5) antibacterial soap-and-water cleansing and gauze (38%), (6) antibacterial soap-and-water cleansing and Xeroform gauze (50%), and (7) stable dressings with no pin cleansing (36%). Logistic regression analysis demonstrated significant inverse relationships (p = .05) between infection rate and age, as well as fixator type; the latter may be related to exposed threads.\n Results suggest that other factors outside the realm of this study may affect children's pin-site infection rate and that half-strength peroxide and Xeroform dressings were superior to soap-and-water cleansing. This pilot study indicates a need for further research with a larger sample size and for exploring factors in a younger population.", "Superficial infection at wire and pin insertions in the skin is a frequent disorder among patients utilizing the Ilizarov method. The objective of this study was to evaluate the effectiveness of daily topical application of 10% polyvinylpyrrolidone-iodine solution against infections of the holes for Kirschner wires and Schanz pins among patients using Ilizarov external fixators, in comparison with cleaning these holes only with 0.9% sterile physiological saline solution.\n Controlled randomized clinical trial, in the Orthopedics and Traumatology Outpatient Clinic, Hospital São Paulo, and Orthopedics and Traumatology Center of Jundiaí.\n 30 patients were treated using the Ilizarov technique: 15 were instructed to apply 0.9% physiological saline dressing on the wire and pin insertions and 15 to apply 0.9% physiological saline plus 10% polyvinylpyrrolidone-iodine. Patients were evaluated at outpatient return visits for identification of signs and symptoms of superficial infection at wire and pin insertion sites. Samples were collected from cases of purulent exudate secretion, for culturing and clinical tests.\n The chi-squared and Fischer exact tests were applied, but no statistically significant association between the intervention of topical polyvinylpyrrolidone-iodine solution and the prevention of infections at wire and pin insertions could be found.\n Topical 10% polyvinylpyrrolidone-iodine solution applied daily to Kirschner wire and Schanz pin insertions did not reduce the incidence of superficial infection at these holes, in comparison with mechanical removal of dirt using 0.9% physiological saline solution.", "We investigated whether there were any differences in the frequency and severity of pin site infections by performing pin site care daily or once a week. We studied patients operated on for gonarthrosis by the hemicallotasis technique, using hydroxyapatite-coated pins in the metaphyseal bone and standard pins in the diaphyseal bone.\n 50 patients were prospectively randomized to daily (n = 27) or weekly (n = 23) pin site care. We evaluated pin sites, the occurrence of pain (VAS), the use of antibiotics and analgesics and complications every week. Bacterial cultures were taken from each pin site at 1, 6 and 10 weeks and from the pins on removal.\n We found no differences between daily or weekly pin site care as regards the frequency and severity of pin site infections, pain, or the use of antibiotics and analgesics. Grade I infections (Checketts-Otterburns classification) occurred around 11% of the pins and grade II infections around 4%. 70% of the bacterial cultures were negative. The most frequent bacteria were coagulase negative staphylococcus and corynebacterium. Antibiotics were given an average of 47 days. More problems occurred around the proximal pins. 5/200 (all proximal) pins were clinically loose on removal.\n Pin site care once a week seems appropriate.", "To compare infection rates associated with 2 dressing solutions for metal-skin interfaces.\n 60 patients who underwent distraction osteogenesis with external fixators were equally randomised into 2 dressing solution groups (diluted povidone-iodine vs. saline). Fixations were attained using either rigid stainless steel 5-mm diameter half pins or smooth stainless steel 1.8-mm diameter wires. Half-pin fixation had one metal-skin interface, whereas wire fixation had 2 interfaces. Patients were followed up every 2 weeks for 6 months.\n Of all 788 metal-skin interfaces, 143 (18%) were infected: 72 (19%) of 371 in the diluted povidone-iodine group and 71 (17%) of 417 in the saline group. Dressing solution and patient age did not significantly affect infection rates. Half-pin fixation was more likely to become infected than wire fixation (25% vs 15%).\n Saline is as effective as diluted povidone-iodine as a dressing solution for metal-skin interfaces of external fixators. Saline is recommended in view of its easy availability and lower costs." ]

[ "3514543", "14147023", "4948768", "4604665", "3895365", "4866169" ]

[ "Bornaprine vs placebo in Parkinson disease: double-blind controlled cross-over trial in 30 patients.", "A CRITICAL ANALYSIS OF THE EFFECTS OF TRIHEXYPHENIDYL (ARTANE) ON THE COMPONENTS OF THE PARKINSONIAN SYNDROME.", "Levodopa and orphenadrine hydrochloride in Parkinsonism.", "KR 339 in the treatment of Parkinsonian tremor.", "[Bornaprine in the treatment of parkinsonian tremor].", "Mehixene hydrochloride and parkinsonian tremor." ]

[ "The study covers 30 patients with idiopathic Parkinson disease, 13 men and 17 women, aged between 50 and 70, on stabilized L-Dopa and/or bromocriptine, which failed to ensure adequate control of the symptoms, especially tremor. To this regimen was added Bornaprine/placebo in randomized sequence. The patients were tested according to the Webster Rating Scale before, during and after each stage of the treatment. Statistical analysis of the results showed the superiority of Bornaprine over the placebo in reducing tremor (p less than 0.01) and, to a lesser degree, some other parkinsonian symptoms. No noteworthy side effects were found apart from dryness of the mouth, which was more frequent with Bornaprine.", "nan", "nan", "nan", "We report the results of a double-blind placebo controlled study of bornaprine, an anticholinergic drug, in the treatment of Parkinson's disease. We studied 17 patients presenting persistent tremor in spite of a stable long-term L-Dopa therapy. The bornaprine, in doses of 8 mg/die, compared with placebo significantly improves tremor. Only mild side effects occurred. We think the bornaprine may be of value in the treatment of parkinsonian tremor.", "nan" ]

[ "8229487", "9447532", "10791521", "9200358", "8774514", "10852192", "10344707", "8151722" ]

[ "A multicenter randomized trial comparing two surfactants for the treatment of neonatal respiratory distress syndrome. National Institute of Child Health and Human Development Neonatal Research Network.", "Comparative efficacy of exosurf and survanta surfactants on early clinical course of respiratory distress syndrome and complications of prematurity.", "Pumactant and poractant alfa for treatment of respiratory distress syndrome in neonates born at 25-29 weeks' gestation: a randomised trial.", "A multicenter randomized masked comparison trial of synthetic surfactant versus calf lung surfactant extract in the prevention of neonatal respiratory distress syndrome.", "A multicenter randomized, masked comparison trial of natural versus synthetic surfactant for the treatment of respiratory distress syndrome.", "Randomized trial comparing natural and synthetic surfactant: increased infection rate after natural surfactant?", "Neonatal respiratory care and infant mortality in emerging countries.", "Modified bovine surfactant (Survanta) versus a protein-free surfactant (Exosurf) in the treatment of respiratory distress syndrome in preterm infants: a pilot study." ]

[ "To compare the efficacy of two surfactants, Exosurf Neonatal (Burroughs Wellcome Co.) and Survanta (Ross Laboratories), for the treatment of neonatal respiratory distress syndrome.\n Multicenter randomized trial.\n Eleven tertiary care university neonatal intensive care units participating in the National Institute of Child Health and Human Development Neonatal Research Network.\n Newborn infants (n = 617) weighing 501 to 1500 gm with respiratory distress syndrome who were receiving assisted ventilation with 30% oxygen or more within 6 hours of birth were enrolled between January 1991 and January 1992.\n Infants were randomly assigned to receive up to four intratracheal doses of either Exosurf Neonatal (n = 309) or Survanta (n = 308).\n The occurrence of death or bronchopulmonary dysplasia 28 days after birth and the average fraction of inspired oxygen (FIO2) and mean airway pressure (MAP) during the first 72 hours after treatment.\n Death or bronchopulmonary dysplasia occurred in 67% of the infants in the Exosurf group and 62% of those in the Survanta group (adjusted relative risk, 1.07; 95% confidence interval, 0.96 to 1.20). During the 72 hours after the first surfactant dose, the average FIO2 (+/- SEM) was 0.50 +/- 0.01 for Exosurf and 0.42 +/- 0.01 for Survanta (difference, 0.08; 95% confidence interval, 0.05 to 0.11); the average MAP (+/- SEM) was 7.64 +/- 0.21 cm H2O for Exosurf and 6.93 +/- 0.21 cm H2O for Survanta (difference, 0.71 cm H2O; 95% confidence interval, 0.13 to 1.29 cm H2O). There was no difference between the groups in the incidence of other neonatal morbidities or in the duration of hospitalization, assisted ventilation, or supplemental oxygen administration.\n We found no difference between treatment groups in the incidence of death or bronchopulmonary dysplasia, although we did observe a difference in the initial response to treatment as measured by FIO2 and MAP.", "To determine the comparative efficacy of Exosurf Neonatal and Survanta surfactants on the early course of respiratory distress syndrome (RDS), arterial blood gases, ventilatory support, outcome morbidity rate, and complications of prematurity and RDS.\n Medical records from 203 premature newborn infants undergoing mechanical ventilation for respiratory distress syndrome, and who received up to four rescue doses of either Exosurf or Survanta, were retrospectively reviewed.\n All groups were comparable for birth weight and gestational age. Although the two randomized groups were similar in severity of RDS based on fraction of inspired oxygen (FIO2) and ventilatory support, a significantly greater improvement in respiratory function as evidenced by FIO2, mean airway pressure, alveolar-arterial partial pressure of oxygen difference, and oxygen index, was observed in the Survanta group from 12 hours (p < 0.05) through 48 hours (p < 0.01). Comparison of outcome morbidity rate by gestational age showed a higher occurrence of retinopathy of prematurity (p < 0.02) among the older infants (28 to 32 weeks) who were treated with Exosurf.\n Survanta exerted a significantly faster response in the early clinical course of RDS compared with Exosurf. However, no difference in the impact on eventual respiratory outcome was observed. We therefore conclude that both surfactants are effective for the treatment of RDS.", "Exogenous surfactant preparations vary in their constitution and biophysical properties. Synthetic and animal-derived preparations lower the rate of death compared with controls. No significant differences in mortality or important long-term clinical outcomes have been shown between them in randomised trials. We did a randomised controlled trial to compare pumactant, a synthetic surfactant, with poractant alfa, an animal-derived surfactant, both of which are widely used in the UK.\n We enrolled 212 neonates born between 25 weeks' and 29 weeks and 6 days' gestation who were intubated for presumed surfactant deficiency and were free from life-threatening malformations. We randomly assigned 105 neonates poractant alfa, and 107 pumactant. The primary outcome was duration of high-dependency care and mortality was a secondary outcome. Analysis was by intention to treat.\n Outcome data were analysed for 199 babies. The trial was stopped on the recommendation of the data and safety monitoring committee because mortality assumed a greater importance than the primary outcome. Predischarge mortality differed significantly between groups, in favour of poractant alfa (14.1 vs 31.0%, p=0.006; odds ratio 0.37 [95% CI 0.18-0.76). This difference was sustained after adjustment for centre, gestation, birthweight, sex, plurality, and use of antenatal steroids.\n Mortality was unexpectedly lower among neonates who received poractant alfa than among those who received pumactant, and was independent of all the variables we investigated. Stopping the trial early may have widened the difference between the treatment groups.", "To compare the efficacy and safety of a synthetic surfactant (Exosurf Neonatal, Burroughs Wellcome Co) and a surfactant extract of calf lung lavage (Infasurf, IND #27,169, ONY, Inc) in the prevention of neonatal respiratory distress syndrome (RDS).\n Ten-center randomized masked comparison trial.\n Premature infants (n = 871) <29 weeks gestational age by best obstetric estimate.\n Infants were randomly assigned to a course of treatment with Exosurf Neonatal (n = 438) or Infasurf (n = 433) at birth, and if still intubated, at 12 and 24 hours of age. Crossover treatment was allowed within 72 hours of age if severe respiratory failure (defined as two consecutive a/A PO2 ratios </=.10) persisted after three doses of the randomized surfactant. Primary\n Three primary outcome measures of efficacy [the incidence of RDS; the incidence of RDS death; and the incidence of survival without bronchopulmonary dysplasia at 28 days after birth] were compared using linear regression techniques.\n Of 871 randomized infants, 18 infants did not receive treatment with a study surfactant, and 25 infants did not meet all eligibility criteria. The primary analysis of efficacy was performed in the 846 eligible infants and analysis of safety outcomes in the 853 infants who received study surfactant. Demographic characteristics did not differ between the two treatment groups. Compared with Exosurf, Infasurf treatment resulted in a 62% decrease in the incidence of RDS (Infasurf, 16% vs Exosurf, 42%) and a 70% decrease in RDS death (Infasurf, 1.7% vs Exosurf, 5.4%) but did not increase the incidence of survival without bronchopulmonary dysplasia at 28 days. Treatment with Infasurf resulted in significant improvement in several secondary outcome measures. Infasurf-treated infants had lower average FIO2 (Infasurf, .33 [SEM] vs Exosurf, .42; difference .08; 95% confidence interval [CI], .06 to .11) and average mean airway pressure (Infasurf, 6.0 cm H2O vs Exosurf, 7.1 cm H2O; difference 1.1 cm H2O; 95% CI, .7 to 1.6 cm H2O) for the first 72 hours of life. Crossover surfactant treatment was significantly less frequent in the Infasurf compared with the Exosurf group (Infasurf, 1% vs Exosurf, 6%). Complications (bradycardia, clinical airway obstruction, and transcutaneous arterial desaturation) associated with second and third, but not initial, surfactant treatments were observed more frequently in the Infasurf treatment group. Infasurf-treated infants had significantly less air leak (</=7 days) (Infasurf, 8% vs Exosurf, 14%; adjusted relative risk [ARR] .55; 95% CI, .37 to .81). Severe intraventricular hemorrhage (IVH) (grade 3 and 4) did not differ between the two groups (Infasurf, 11.8% vs Exosurf, 8.3%; ARR 1.41; 95% CI, .94 to 2.09) but total IVH occurred more frequently in Infasurf-treated infants (Infasurf, 39.0% vs Exosurf, 29.9%; ARR, 1.30; 95% CI, 1.08 to 1.57).\n Significant reductions in the incidence of RDS, the severity of early respiratory disease, the incidence of pulmonary air leaks associated with RDS, and the mortality attributable to RDS suggest that Infasurf is a more effective surfactant preparation than Exosurf Neonatal in the prophylaxis of RDS. However, Infasurf prophylaxis as used in this study was also associated with a greater risk of total but not severe IVH.", "To compare the efficacy and safety of two surfactant preparations in the treatment of respiratory distress syndrome (RDS).\n We conducted a randomized, masked comparison trial at 21 centers. Infants with RDS who were undergoing mechanical ventilation were eligible for treatment with two doses of either a synthetic (Exosurf) or natural (Infasurf) surfactant if the ratio of arterial to alveolar partial pressure of oxygen was less than or equal to 0.22. Crossover treatment was allowed within 96 hours of age if severe respiratory failure (defined as two consecutive arterial/alveolar oxygen tension ratios < or = 0.10) persisted after two doses of the randomly assigned surfactant. Four primary outcome measures of efficacy (the incidence of pulmonary air leak (< or = 7 days); the severity of RDS; the incidence of death from RDS; and the incidence of survival without bronchopulmonary dysplasia (BPD) at 28 days after birth) were compared by means of linear regression techniques.\n The primary analysis of efficacy was performed in 1033 eligible infants and an analysis of safety outcomes in the 1126 infants who received study surfactant. Preentry demographic characteristics and respiratory status were similar for the two treatment groups, except for a small but significant difference in mean gestational age (0.5 week) that favored the infasurf treatment group. Pulmonary air leak (< or = 7 days) occurred in 21% of Exosurf- and 11% of infasurf-treated infants (adjusted relative risk, 0.53; 95% confidence interval, 0.40 to 0.71; p < or = 0.0001). During the 72 hours after the initial surfactant treatment, the average fraction of inspired oxygen (+/-SEM) was 0.47 +/- 0.01 for Exosurf- and 0.39 +/- 0.01 for infasurf-treated infants (difference, 0.08; 95% confidence interval, 0.06 to 0.10; p < 0.0001); the average mean airway pressure (+/-SEM) was 8.6 +/- 0.1 cm H2O; for Exosurf- and 7.2 +/- 0.1 cm H2O for Infasurf-treated infants (difference, 1.4 cm H2O; 95% confidence interval, 1.0 to 1.8 cm H2O; p < 0.0001). The incidences of RDS-related death, total respiratory death, death to discharge, and survival without bronchopulmonary dysplasia at 28 days after birth did not differ. The number of days of more than 30% inspired oxygen and of assisted ventilation, but not the duration of hospitalization, were significantly lower in Infasurf-treated infants.\n Compared with Exosurf, Infasurf provided more effective therapy for RDS as assessed by significant reductions in the severity of respiratory disease and in the incidence of air leak complications.", "The efficacy of a natural porcine surfactant and a synthetic surfactant were compared in a randomized trial. In three neonatal intensive care units, 228 neonates with respiratory distress and a ratio of arterial to alveolar partial pressure of oxygen <0.22 were randomly assigned to receive either Curosurf 100 mgkg-1 or Exosurf Neonatal 5 ml.kg-1. After Curosurf, the fraction of inspired oxygen was lower from 15 min (0.45 +/- 0.22 vs 0.70 +/- 0.22, p = 0.0001) to 6 h (0.48 +/- 0.26 vs 0.64 +/- 0.23, p = 0.0001) and the mean airway pressure was lower at 1 h (8.3 +/- 3.2 mm H20 vs 9.4 +/- 3.1 mm H20, p = 0.01). Thereafter the respiratory parameters were similar. The duration of mechanical ventilation (median 6 vs 5 d) and the duration of oxygen supplementation (median 5 vs 4 d) were similar for Curosurf and Exosurf. After Curosurf, C-reactive protein value over 40 mg l-1 occurred in 45% (vs 12%; RR 3.62, 95%CI 2.12-6.17, p = 0.001), leukopenia in 52% (vs 28%; RR 1.85, 95% CI 1.31-2.61, p = 0.001) and bacteraemia in 11% (vs 4%; RR 3.17, 95% CI 1.05-9.52, p < 0.05). We conclude that when given as rescue therapy Curosurf had no advantage compared with Exosurf in addition to the more effective initial response. Curosurf may increase the risk of infection.", "nan", "We undertook a prospective, randomized, non-blinded pilot study to determine whether infants with respiratory distress syndrome (RDS) who were treated with protein-containing bovine surfactant (Survanta, Ross/Abbott Laboratories, Columbus, Ohio) had earlier and larger responses in gas exchange when compared with similar infants treated with a synthetic surfactant (Exosurf, Burroughs Wellcome, Research Triangle Park, North Carolina). Forty-one infants weighing between 600 g and 1750 g at birth with RDS of sufficient severity to require assisted ventilation with an FiO2 > 0.39 were enrolled in the study and treated with surfactant from 1 to 8 hours after birth. Infants were randomly selected to receive treatment with either Exosurf or Survanta. Despite randomization, the Survanta group was overrepresented with factors associated with greater severity of RDS (lower birthweight, more males, and fewer African Americans). No statistically significant difference was found in the primary outcome measure (arterial/alveolar PaO2 > 0.3 at 24 hours) by univariate or multivariate analysis. The percentage of responders in the Survanta-treated group was significantly increased 24 hours after treatment in two of four secondary measures of oxygenation when analyzed by univariate tests using one-tailed P values. Based on these results, we anticipate that acute outcomes after Survanta or Exosurf will approximate those found in this trial and that differences in measures of oxygenation between treatment groups will approximate 30% to 50% 24 hours after initial treatment." ]

[ "15380964", "10083497", "12387959", "10551650", "12176463", "9422416", "9884248", "15376310", "1721333", "12149762", "9583863", "12783400", "7520105" ]

[ "Tacrolimus and steroids versus ciclosporin microemulsion, steroids, and azathioprine in children undergoing liver transplantation: randomised European multicentre trial.", "Mycophenolate mofetil in combination with tacrolimus versus Neoral after liver transplantation.", "Tacrolimus versus microemulsified ciclosporin in liver transplantation: the TMC randomised controlled trial.", "A pilot study of immunosuppressive monotherapy in liver transplantation: tacrolimus versus microemulsified cyclosporin.", "A randomised trial comparing the efficacy and safety of tacrolimus with microemulsified cyclosporine after liver transplantation.", "Prednisone withdrawal 14 days after liver transplantation with mycophenolate: a prospective trial of cyclosporine and tacrolimus.", "A prospective randomized trial of mycophenolate mofetil with neoral or tacrolimus after orthotopic liver transplantation.", "Impact of tacrolimus versus cyclosporine in hepatitis C virus-infected liver transplant recipients on recurrent hepatitis: a prospective, randomized trial.", "A randomized trial of primary liver transplantation under immunosuppression with FK 506 vs cyclosporine.", "Cardiac function after orthotopic liver transplantation and the effects of immunosuppression: a prospective randomized trial comparing cyclosporin (Neoral) and tacrolimus.", "Comparison of tacrolimus with microemulsion cyclosporine as primary immunosuppression in hepatitis C patients after liver transplantation.", "Early steroid withdrawal after liver transplantation: the Canadian tacrolimus versus microemulsion cyclosporin A trial: 1-year follow-up.", "Randomised trial comparing tacrolimus (FK506) and cyclosporin in prevention of liver allograft rejection. European FK506 Multicentre Liver Study Group." ]

[ "Results of studies in adult recipients of liver allograft suggest that tacrolimus is more efficacious than ciclosporin microemulsion in the prevention of acute rejection. We aimed to compare these drugs in children undergoing liver transplantation.\n This 12-month multicentre, open-label, parallel-group, randomised study compared a dual tacrolimus regimen (tacrolimus/corticosteroids, n=93) with a triple ciclosporin microemulsion regimen (ciclosporin microemulsion/corticosteroids/azathioprine, n=92) in children who had had liver transplants (age < or =16 years, bodyweight < or =40 kg). Initial oral daily doses were 0.30 mg/kg for tacrolimus and 10 mg/kg for ciclosporin microemulsion. Primary endpoint was the incidence of and time to first histologically proven acute rejection. We excluded patients from analysis if they did not receive the study drug, or were given incorrect medication. Otherwise patients were analysed in accordance with their random treatment allocation, irrespective of whether they switched medication during the trial.\n Median age was 22 months (IQR 9-56) in the tacrolimus group and 17 months (9-54) in the ciclosporin microemulsion group. We noted no difference between treatment groups with respect to patient survival (93.4% vs 92.2%; p=0.77) or graft survival (92.3% vs 85.4%; p=0.16) at month 12 after transplant. The acute rejection free rate at study end (Kaplan-Meier method) was 55.5% for patients on tacrolimus and 40.2% for patients on ciclosporin microemulsion (p=0.0288). The Kaplan-Meier estimate of patients free from corticosteroid-resistant acute rejection at study end was 94.0% for tacrolimus-treated patients and 70.4% for ciclosporin-microemulsion-treated patients (p<0.0001). Overall, incidence of adverse events did not differ between groups.\n Tacrolimus is a safe and effective treatment for the prevention of rejection after liver transplantation in children.", "nan", "Calcineurin inhibitors are the most commonly used immunosuppressive drugs in liver transplantation, but the optimum initial immunosuppression regimen is not known. The aim of our study was to compare tacrolimus with microemulsified ciclosporin, in a regimen with standardised concomitant immunosuppressive therapy.\n In all liver transplant centres in the UK and Republic of Ireland, 606 patients undergoing a first orthotopic liver transplantation were randomly assigned open-label tacrolimus or microemulsified ciclosporin. Primary outcome was the combined frequency (whichever occurred first) of death, retransplantation, or treatment failure for immunological reasons, analysed by intention to treat.\n 96% of patients received the treatment allocated to them. The primary outcome was reached in 62 (21%) of 301 patients in the tacrolimus group versus 99 (32%) of 305 allocated microemulsified ciclosporin (relative risk 0.63 [95% CI 0.48-0.84], p=0.001; time-to-event analysis log-rank test p=0.002): deaths (50 [17%] vs 72 [24%]); retransplantations (11 [4%] vs 31 [10%]) treatment failure for immunological reasons (6 [2%] vs 12 [4%]). The relative risk for the composite outcome was in favour of tacrolimus. The main causes of death in both trial groups were sepsis and multiple organ failure (31 [10%] vs 30 [10%]), and the main cause for retransplantation was hepatic artery thrombosis (6 [2%] vs 17 [6%]). Renal dysfunction and the need for antihypertensive therapy were much the same in both groups. Tacrolimus was more diabetogenic.\n Clinical outcome at 1 year was better with tacrolimus-based immunosuppression than with microemulsified ciclosporin during the first year after liver transplantation. Tacrolimus should be the first choice of calcineurin inhibitor for patients receiving their first liver graft.", "Many reports of successful early withdrawal of regular maintenance steroids in transplant recipients have appeared in recent years. The question now arises whether, in the current age of powerful nonsteroidal immunosuppressants such as Neoral and Tacrolimus, routine administration of steroids posttransplant is necessary at all. This single center pilot study reports on the feasibility, safety, and efficacy of single agent immunosuppression \"ab initio\" with either Neoral or Tacrolimus, and no routine or maintenance steroids.\n A total of 64 adult patients receiving first liver grafts for a variety of indications were randomized to receive either Neoral 5 mg/kg BDS or Tacrolimus 0.05 mg/kg BDS orally. Liver biopsies were performed on postoperative days 5 and 10, and whenever else clinically indicated. Rejection episodes were treated with 1.0 g of Methylprednisolone daily for 3 consecutive days. A further episode of rejection after two courses of Methylprednisolone was considered to be monotherapy failure, and consequently other immunosuppressive agents, usually Prednisolone 1 mg/kg/day, was started on a regular basis, tapering slowly.\n Actuarial 1 year survival was 85% for Tacrolimus patients, and 78% for Neoral patients (P = NS), with 80% for Tacrolimus and 73.5% for Neoral at 30 months. Graft survival at 1 and 2.5 years was 73 and 62% for Tacrolimus and Neoral, respectively (P = NS). Two-thirds of patients in both groups showed biopsy evidence of acute cellular rejection. Rejection severity measured by a histological scoring system was similar for both patient groups. Additional longterm immunosuppressive therapy was necessary in 36% of patients receiving Neoral, compared with 13% of Tacrolimus patients (P = NS). No graft was lost on account of acute or chronic rejection. Short-term pulse steroid therapy to treat acute rejection was necessary for 60% of Tacrolimus patients and 40% of Neoral patients.\n Tacrolimus or Neoral monotherapy after liver transplantation provides adequate immunosuppression for 87% of Tacrolimus patients and 64% of Neoral patients. In this study, 33% of patients in both groups showed no evidence of acute rejection, either clinically, biochemically or histologically, and were not exposed to steroids at any time. Evaluation of the long-term morbidity related to the side effects of the immunosuppressants given as monotherapy, for example, renal impairment and posttransplant lymphoproliferative disorder, and the effect on recurrent viral hepatitis in the graft, would be suitable areas for further study.", "nan", "The long-term complications of immunosuppressive therapy such as diabetes, hypercholesterolemia, and hypertension are a major source of morbidity in liver transplant recipients. In this prospective, randomized, open-label study we completely withdrew prednisone (PRED) 14 days after liver transplantation in an effort to decrease these metabolic complications. Patients were maintained on mycophenolate mofetil (MMF) in combination with either cyclosporine (CsA; Neoral formulation) or tacrolimus (TAC). Thus, we also were able to compare CsA to TAC in patients not receiving PRED with respect to efficacy, toxicity, and effect on posttransplant metabolic complications.\n A total of 71 patients were randomized to receive either TAC-MMF (n=35) or CsA-MMF (n=36) after liver transplantation and were analyzed for patient and graft survival. Fifty-eight patients continued the immunosuppressive protocol for at least 6 months after transplantation and were analyzed for the incidence of acute rejection and the prevalence of diabetes, hypertension, and hypercholesterolemia.\n The 6-month patient survival rates were 94.4% for CsA-MMF and 88.6% for TAC-MMF. Corresponding 6-month graft survival rates were 88.7% and 85.71% with no immunologic graft losses in either group. The incidence of biopsy-proven acute rejection was 46% for CsA-MMF and 42.3% for TAC-MMF. Six patients were converted from CsA to TAC (four for recurrent rejection) and seven patients were converted from TAC to CsA (four for neurotoxicity). Only one patient (in the TAC-MMF group) developed new-onset posttransplant diabetes. In contrast, four of eight patients in the CsA-MMF group who were diabetic before transplant became nondiabetic in the first 3 months after transplant. The mean serum cholesterol level was significantly lower in the TAC-MMF group than in the CsA-MMF group (145.2+/-41.8 mg/dl and 190.3+/-62.2, respectively; P<0.001) and the incidence of hypertension was lower in the TAC-MMF group (12% vs. 30.3% in the CsA-MMF group, P<0.01). Both groups had a lower incidence of metabolic complications compared with a historical group (n=100) maintained on CsA and PRED (10 mg/day at 6 months).\n MMF in combination with either TAC or CsA allows withdrawal of PRED 14 days after liver transplantation with a moderate rejection rate and no immunologic graft losses. Early PRED withdrawal decreases posttransplant diabetes, hypercholesterolemia, and hypertension, but patients maintained on TAC have lower serum cholesterol levels and a lower incidence of hypertension than CsA-treated patients.", "The success of liver transplantation in this decade has become the stimulus to extend the donor and recipient pool. Reducing early posttransplant morbidity to maintain our success, as we expand our frontiers, has led us to focus on balanced testing of multidrug immunosuppression regimens.\n A prospective trial in orthotopic liver transplantation using Mycophenolate Mofetil and an identical steroid taper with randomization of patients to Neoral (N) or Tacrolimus (FK) is the basis of this report. This was an intent-to-treat study designed to compare the 6-month primary endpoints of rejection and infection and to compare the 6-month secondary endpoints of liver function, renal function, bone marrow function, hypertension, and serum cholesterol levels.\n Ninety-seven patients completed the 6-month follow-up period (N=49, FK=48). The actual 6-month patient and graft survival rates were 98% and 94%, respectively. There was no difference in the number of patients with rejection episodes (N=11, FK=8) (P=0.61). There were 24 infections (3 cytomegalovirus) in the FK group and 30 infections (9 cytomegalovirus) in the N group. The cholesterol levels at 6 months were not significantly different (P=0.07) between the groups. The other secondary 6-month endpoints were not significantly different, except total bilirubin, which was lower in the FK arm (P=0.02).\n The use of Mycophenolate Mofetil with N or FK and an identical steroid taper after orthotopic liver transplantation is associated with excellent graft and patient survival, and at 6 months, only 191% of the patients experienced rejection, with a 48% overall infection rate.", "Hepatitis C virus (HCV)-induced cirrhosis is the commonest indication for orthotopic liver transplantation, but HCV recurrence is nearly universal and may worsen patient / graft outcomes. The frequency and severity of HCV recurrence has apparently increased in recent years, raising concern about a possible role for newer immunosuppression regimens in this increase, including potentially tacrolimus. We randomized 79 patients to receive tacrolimus or cyclosporine as primary immunosuppressant posttransplantation. A pathologist blinded to treatment reviewed serial liver biopsies. Month 12 cumulative probabilities of histological hepatitis C recurrence for tacrolimus- and cyclosporine-treated patients were .38 and .54 (P = .19) and failure / death were .25 and .28, respectively (P = .789). Although cyclosporine-treated patients had significantly larger increases in median serum HCV RNA levels (months 1, 6, and 12), no significant differences were observed between the two treatment arms in histologically-diagnosed HCV recurrence / survival rates. In conclusion, choice of calcineurin inhibitors does not impact severity of recurrent HCV.", "nan", "There are several case reports in the literature that describe cardiac complications in the first few weeks after orthotopic liver transplantation (OLT) in patients receiving tacrolimus as their primary immunosuppressive therapy. In this study, we investigated the cardiac function of patients on tacrolimus (T) compared with those on cyclosporin (C) (Neoral; Novartis, Basel, Switzerland) immunosuppression, after OLT, in a prospective randomized trial. We randomized 40 adult patients with cirrhosis to either T or C with azathioprine and prednisolone immunosuppression and followed up on them for 3 months after OLT. All had detailed clinical, biochemical, electrocardiographic and echocardiographic assessments at regular intervals. Abnormalities in cardiac function were common after OLT and significant deterioration in left ventricular diastolic function was demonstrable up to 3 months in both patient groups. Cardiac function was similar in the T and C arms and no significant electrocardiographic differences were observed, although reduced heart rate variability (HRV) and higher mean serum brain natriuretic peptide (BNP) levels were identified in the T group. The percentage increase in posterior wall thickness was higher in the T group. Cardiac dysfunction as shown by worsening echocardiographic measures of left ventricular diastolic function and by clinical cardiac events is common in the first 3 months after OLT in patients with cirrhosis. HRV and BNP values in the T group were worse than in the C group, but this was not translated to an increase in cardiac clinical events in this study.", "Immunosuppression in patients with hepatitis C virus (HCV) following orthotopic liver transplantation can lead to significant increases in serum viral loads. Our aim was to analyze the effect of a randomized study of two immunosuppressive agents (tacrolimus vs. microemulsion cyclosporine) on the outcome of HCV patients following orthotopic liver transplantation.\n From December 1995 to September 1996, 50 adult patients transplanted for HCV cirrhosis were randomly assigned to receive tacrolimus (Prograf) (group 1, 25 patients) or microemulsion cyclosporine (Neoral) (group 2, 24 patients). All patients received alpha-interferon after transplantation, and the overall steroid doses were no different between the groups. Serum RNA levels were measured by signal amplification of Chiron. Biopsies were taken when transaminases were greater than 2x base line or when there was an inappropriate response to alterations in immunosuppression regimens.\n There were more episodes of rejection in the Neoral group, but there were no differences in bacterial and viral infections, nor in the rate of HCV recurrence between the two groups. There were seven deaths in group 1 and eight in group 2. Overall patient and graft survival rates in the Prograf and Neoral groups at 18 months were 72 and 68% and 67 and 64%, respectively.\n (a) Both immunosuppression regimens had similar HCV recurrence rates; (b) there were no differences in bacterial or opportunistic infections; and (c) patient and graft survival was similar between the two groups.", "Corticosteroid therapy contributes significant toxicity to liver transplantation. The safety and efficacy of early steroid withdrawal were determined in patients treated with either tacrolimus or microemulsion cyclosporin A (micro-CsA). The primary outcome was the proportion of patients who were steroid-free 1 year posttransplantation. From the seven Canadian adult liver transplant centers, 143 patients were randomly allocated oral treatment with either tacrolimus (n = 71) or micro-CsA (n = 72), together with corticosteroids and azathioprine. Eligibility criteria for steroid withdrawal included freedom from acute rejection for a minimum of 3 months, and prednisone </=0.15 mg/kg/d. In eligible patients, the daily steroid dose was reduced by 2.5 mg each month until complete discontinuation was achieved. At 1 year after transplantation, 75% of the tacrolimus patients and 63% of the micro-CsA patients were steroid-free (P =.20). Of all of the patients who became eligible for steroid withdrawal, steroid discontinuation was achieved in over 80%. One-year patient survival was 97% with tacrolimus and 89% with micro-CsA (P =.052). Graft survival was 97% and 86%, respectively (P =.017). The overall incidence of acute rejection during the first year was 35% with tacrolimus and 43% with micro-CsA (P =.26). There was no difference in survival, acute rejection, or rate of steroid withdrawal when adjusting for hepatitis C. All acute rejection episodes experienced during steroid withdrawal were steroid-responsive. Steroid-resistant rejection occurred in 5.6% of the tacrolimus and 9.7% of the micro-CsA patients. One patient, in the micro-CsA group, experienced refractory rejection. Chronic rejection was not observed in either group. The toxicity profiles were similar. Postoperative serum creatinine levels were similar, and dialysis was required in less than 10% of patients in each group. Infectious complications were similar in both groups. Neurotoxicity was a serious adverse event in 13% and 10% of patients receiving tacrolimus and micro-CsA, respectively. Early steroid withdrawal is safe and effective after liver transplantation using either tacrolimus plus azathioprine or micro-CsA plus azathioprine immunoprophylaxis.", "Studies in the USA and Japan have shown that tacrolimus (FK506) is a potent immunosuppressant. To compare the efficacy and safety of tacrolimus-based and conventional cyclosporin-based immunosuppressive regimens we recruited 545 liver transplant recipients from eight European centres into a randomised open trial. Analysis of the data at 12 months post-transplant showed that tacrolimus was associated with a significant reduction in acute, refractory acute, and chronic rejection episodes. The rates were, for acute rejection, tacrolimus 40.5% vs 49.8% cyclosporin (p = 0.040; absolute difference 9.3% [95% CI 0.9-17.8%]). For refractory acute and chronic rejections the comparisons were 0.8% vs 5.3% (p = 0.005) and 1.5% vs 5.3% (p = 0.032). There results were seen despite significantly lower corticosteroid usage. The incidence of infection was also lower in patients receiving tacrolimus. Patient and graft survival rates were not significantly different (tacrolimus 82.9% and 77.5%; cyclosporin 77.5% and 72.6%). Safety data were comparable--the most serious events being renal impairment, disturbances of glucose metabolism, and neurological complications--but these events were more common in the tacrolimus group. In this trial tacrolimus had advantages over cyclosporin in respect of lower rejection rates, even though less concurrent immunosuppression was administered." ]

[ "8481745", "8288183" ]

[ "A trial of two cognitive-behavioural methods of treating drug-resistant residual psychotic symptoms in schizophrenic patients: I. Outcome.", "Coping-skills training versus a problem-solving approach with schizophrenic patients." ]

[ "Despite neuroleptic medication, many schizophrenic patients continue to experience residual positive psychotic symptoms. These residual symptoms cause distress and disability. We report a controlled trial of two cognitive-behavioural treatments to alleviate residual hallucinations and delusions. Forty-nine patients were recruited into the trial, of whom 27 entered the trial and completed post-treatment assessment, and 23 were reassessed at six-month follow-up. Patients were randomly allocated to either coping strategy enhancement (CSE) or problem solving (PS). Half the patients were allocated to a high-expectancy positive demand condition and half to a counter-demand condition to evaluate expectation of improvement. Patients receiving either cognitive-behavioural treatment showed significant reductions in psychotic symptoms compared with those in the waiting period, who showed no improvement. There was some evidence, although equivocal, that patients receiving CSE improved more than those receiving PS. There was no evidence that improvements generalised to negative symptoms or social functioning, nor was there evidence that expectancy of treatment benefit contributed to the treatment effect.", "nan" ]

[ "16913215", "17962710", "20487575", "21411836", "16054520", "17353072", "20485304", "20403940", "19896252", "20803023", "12214543", "18986600", "21477383" ]

[ "[Effect of Lactobacillus casei on the incidence of infectious conditions in children].", "The effect of probiotics on respiratory infections and gastrointestinal symptoms during training in marathon runners.", "Reducing the risk of infection in the elderly by dietary intake of yoghurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1.", "Daily probiotic's (Lactobacillus casei Shirota) reduction of infection incidence in athletes.", "Effect of Lactobacillus gasseri PA 16/8, Bifidobacterium longum SP 07/3, B. bifidum MF 20/5 on common cold episodes: a double blind, randomized, controlled trial.", "Treatment of acute otitis media with probiotics in otitis-prone children-a double-blind, placebo-controlled randomised study.", "Use of a fermented dairy probiotic drink containing Lactobacillus casei (DN-114 001) to decrease the rate of illness in kids: the DRINK study. A patient-oriented, double-blind, cluster-randomized, placebo-controlled, clinical trial.", "Lactobacillus GG in the prevention of nosocomial gastrointestinal and respiratory tract infections.", "Lactobacillus GG in the prevention of gastrointestinal and respiratory tract infections in children who attend day care centers: a randomized, double-blind, placebo-controlled trial.", "Randomised, double-blind and placebo-controlled study using new probiotic lactobacilli for strengthening the body immune defence against viral infections.", "[The nutritional status change the effectiveness of a dietary supplement of lactic bacteria on the emerging of respiratory tract diseases in children].", "Specific probiotics in reducing the risk of acute infections in infancy--a randomised, double-blind, placebo-controlled study.", "Lactobacillus fermentum (PCC®) supplementation and gastrointestinal and respiratory-tract illness symptoms: a randomised control trial in athletes." ]

[ "To analyse the effect of continuous consumption of Lactobacillus casei (DN-114001) fermented milk on the incidence of the infectious disorders frequent in children. FIELD: Infant and child population\n children from 3 to 12 years from two schools in Barcelona. A total of 251 children from both sexes participated in the study.\n A nutritional intervention study was carried out during 20 weeks with a parallel, prospective, double-blind and randomised by pragmatic clusters design. Participants were children from 3 to 12 years from two schools in Barcelona. One of the centres was assigned to receive two daily units of Actimel\" and the other to two units of Placebo. From the 251 participants, 109 receiving placebo and 142 receiving Actimel\". Basal demographic characteristics and clinical history data were recorded, and the symptoms related to infectious disorders or other illnesses were monitored at weeks 12, 16 and 20. The analysis of the data was carried out on the intention-to-treat (ITT) population, being the principal endpoint the duration of respiratory and gastrointestinal symptoms.\n A one day difference, but non-significant, was seen in the median of total duration of days with illness through the study (Actimel group: 1 day vs Placebo group: 2 days). The same nonsignificant difference was also seen in the duration of days with respiratory (high and low respiratory tract infections) and with gastrointestinal (diarrhoea, vomiting, stomach pain and constipation) disorders. There was a statistical significantly difference found in favour of Actimel in the duration of the low respiratory tract infections, bronchitis or pneumonia, and in the duration of fatigue. There was also detected a lower incidence of children with low respiratory tract infections (32% vs. 49%) and with fatigue (3% vs. 13%) in the Actimel group compared to placebo. The satisfaction levels with the nutritional intervention were very high, over 80%.\n The study shows a tendency to the reduction of duration and incidence of some infectious disorders in those children receiving two daily Actimel during 20 weeks.", "Heavy exercise is associated with an increased risk of upper respiratory tract infections. Strenuous exercise also causes gastrointestinal (GI) symptoms. In previous studies probiotics have reduced respiratory tract infections and GI symptoms in general populations including children, adults, and the elderly. These questions have not been studied in athletes before. The purpose of this study was to investigate the effect of probiotics on the number of healthy days, respiratory infections, and GI-symptom episodes in marathon runners in the summer. Marathon runners (N = 141) were recruited for a randomized, double-blind intervention study during which they received Lactobacillus rhamnosus GG (LGG) or placebo for a 3-mo training period. At the end of the training period the subjects took part in a marathon race, after which they were followed up for 2 wk. The mean number of healthy days was 79.0 in the LGG group and 73.4 in the placebo group (P = 0.82). There were no differences in the number of respiratory infections or GI-symptom episodes. The duration of GI-symptom episodes in the LGG group was 2.9 vs. 4.3 d in the placebo group during the training period (P = 0.35) and 1.0 vs. 2.3 d, respectively, during the 2 wk after the marathon (P = 0.046). LGG had no effect on the incidence of respiratory infections or GI-symptom episodes in marathon runners, but it seemed to shorten the duration of GI-symptom episodes.", "Immune senescence potentially leads to an increased risk of infections. It is desirable to augment the immune system and protect against infections by daily consumption of immunostimulatory food. The present study evaluated whether the intake of yoghurt fermented with Lactobacillus delbrueckii ssp. bulgaricus (L. bulgaricus) OLL1073R-1 has an effect on resistance to the common cold. We conducted two independent studies, in which fifty-seven (median age 74.5 years) and eighty-five healthy elderly individuals (median age 67.7 years) were participants. In each study, the subjects were divided into two groups based on age and sex and instructed to eat 90 g yoghurt or drink 100 ml milk once per d over an 8- or 12-week period. A meta-analysis of the results of these two independent studies showed the risk of catching the common cold was about 2.6 times lower (OR 0.39; P = 0.019) in the yoghurt group than in the milk group and the increase of natural killer cell activity was significantly higher in the yoghurt group than in the milk group (P = 0.028). In addition, the quality of life score for the 'eye/nose/throat' system after intake was significantly higher in the yoghurt group than in the milk group and the improvement of the score was correlated with the promotion of natural killer cell activity. In conclusion, consumption of yoghurt fermented with L. bulgaricus OLL1073R-1 augmented natural killer cell activity and reduced the risk of catching the common cold in elderly individuals.", "The purpose of this study was to examine the effects of a probiotic supplement during 4 mo of winter training in men and women engaged in endurance-based physical activities on incidence of upper respiratory-tract infections (URTIs) and immune markers. Eighty-four highly active individuals were randomized to probiotic (n = 42) or placebo (n = 42) groups and, under double-blind procedures, received probiotic (PRO: Lactobacillus casei Shirota [LcS]) or placebo (PLA) daily for 16 wk. Resting blood and saliva samples were collected at baseline and after 8 and 16 wk. Weekly training and illness logs were kept. Fifty-eight subjects completed the study (n = 32 PRO, n = 26 PLA). The proportion of subjects on PLA who experienced 1 or more weeks with URTI symptoms was 36% higher than those on PRO (PLA 0.90, PRO 0.66; p = .021). The number of URTI episodes was significantly higher (p < .01) in the PLA group (2.1 ± 1.2) than in the PRO group (1.2 ± 1.0). Severity and duration of symptoms were not significantly different between treatments. Saliva IgA concentration was higher on PRO than PLA, significant treatment effect F(1, 54) = 5.1, p = .03; this difference was not evident at baseline but was significant after 8 and 16 wk of supplementation. Regular ingestion of LcS appears to be beneficial in reducing the frequency of URTI in an athletic cohort, which may be related to better maintenance of saliva IgA levels during a winter period of training and competition.", "The aim of this study was to investigate whether the consumption of Lactobacillus gasseri PA 16/8, Bifidobacterium longum SP 07/3, B. bifidum MF 20/5 (5 x 10(7) cfu/tablet) during at least 3 months influences the severity of symptoms and the incidence and duration of the common cold.\n A randomized, double-blind, placebo-controlled intervention study was performed over at least 3 months during two winter/spring periods. Four hundred and seventy nine healthy adults (aged 18-67) were supplemented daily with vitamins and minerals with or without the probiotic bacteria. Cellular immune parameters were evaluated in a randomly drawn subgroup of 122 volunteers before and after 14 days of supplementation. During common cold episodes, the participants recorded symptoms daily. Stool samples were collected before and after 14 days of probiotic supplementation to quantify fecal Lactobacilli and Bifidobacteria using qRT-PCR.\n The total symptom score, the duration of common cold episodes, and days with fever during an episode were lower in the probiotic-treated group than in the control group: 79.3+/-7.4 vs. 102.5+/-12.2 points (P = 0.056), 7.0+/-0.5 vs. 8.9+/-1.0 days (P = 0.045), 0.24+/-0.1 vs. 1.0+/-0.3 days (P = 0.017). A significantly higher enhancement of cytotoxic plus T suppressor cells (CD8+) and a higher enhancement of T helper cells (CD4+) was observed in the probiotic-treated group. Fecal lactobacilli and bifidobacteria increased significantly after probiotic supplementation.\n The intake of probiotic bacteria during at least 3 months significantly shortened common cold episodes by almost 2 days and reduced the severity of symptoms.", "To examine whether probiotics would reduce the occurrence or duration of acute otitis media (AOM), or the nasopharyngeal carriage of otitis pathogens in otitis-prone children.\n During this double-blind, placebo-controlled, randomised, 24-week intervention, 309 otitis-prone children (10 months-6 years) consumed either one probiotic capsule (Lactobacillus rhamnosus GG and LC705, Bifidobacterium breve 99 and Propionibacterium freudenreichii JS) (n=155) or placebo (n=154) daily. Clinical examinations were carried out and nasopharyngeal samples taken three times. Parents recorded the symptoms of upper respiratory infection (URI) in a diary.\n Probiotic treatment did not reduce the occurrence (probiotic vs. placebo: 72% vs. 65%, OR=1.48, 95% CI 0.87-2.52, p=n.s.) or the recurrence ( three) of AOM episodes (18% vs. 17%, OR=1.04, 95% CI 0.55-1.96, p=n.s.). The median duration of AOM episodes was 5.6 (IQR 3.5-9.4) vs. 6.0 (IQR 4.0-10.5) days, respectively (p= n.s.). There was a tendency showing a reduction in the occurrence of recurrent (4 to 6) respiratory infections in the probiotic group (OR for 4 URIs: 0.56, 95%CI 0.31-0.99, p=0.046; OR for 6 URIs: 0.59, 95% CI 0.34 to 1.03, p=n.s.). Probiotics did not affect the carriage of Streptococcus pneumoniae or Haemophilus influenzae, but increased the prevalence of Moraxella catarrhalis (OR=1.79, 95% CI 1.06-3.00, p=0.028).\n Probiotics did not prevent the occurrence of AOM or the nasopharyngeal carriage of otitis pathogens in otitis-prone children. A tendency showing a reduction in recurrent respiratory infections must be confirmed in further studies.", "To evaluate whether a fermented dairy drink containing the probiotic strain Lactobacillus casei DN-114 001 could reduce the incidence of common infectious diseases (CIDs) and the change of behavior because of illness in children.\n We conducted a double-blinded, randomized, placebo-controlled allocation concealment clinical trial in the Washington, DC metropolitan area. Participants were 638 children 3-6 years old in daycare/schools. The intervention was a fermented dairy drink containing a specific probiotic strain or matching placebo with no live cultures for 90 consecutive days. Two primary outcomes were assessed: incidence of CIDs and change of behavior because of illness (both assessed by parental report).\n The rate of change of behavior because of illness was similar among active and control groups. However, the incidence rate for CIDs in the active group (0.0782) is 19% lower than that of the control group (0.0986) (incidence rate ratio=0.81, 95% CI: 0.65, 099) P=0.046.\n Daily intake of a fermented dairy drink containing the probiotic strain L. casei DN-114 001 showed some promise in reducing overall incidence of illness, but was primarily driven by gastrointestinal infections and there were no differences in change of behavior.", "The incidence of nosocomial infections, predominantly gastrointestinal and respiratory, in children in developed countries is high, ranging from 5% to 44%. There is no effective strategy for preventing these infections. The objective of our study was to investigate the role of Lactobacillus GG (LGG) in preventing nosocomial gastrointestinal and respiratory tract infections at a pediatric hospital.\n We conducted a randomized, double-blind, placebo-controlled trial of 742 hospitalized children. They were randomly allocated to receive for their hospitalization LGG at a dose of 10(9) colony-forming units in 100 mL of a fermented milk product (LGG group, n = 376) or placebo that was the same postpasteurized fermented milk product without LGG (placebo group, n = 366).\n In the LGG group, compared with the placebo group, we found a significantly reduced risk for gastrointestinal infections (relative risk [RR]: 0.40 [95% confidence interval (CI): 0.25-0.70]; number needed to treat: 15 [95% CI: 9-34)], respiratory tract infections (RR: 0.38 [95% CI: 0.18-0.85]; number needed to treat: 30 [95% CI: 16-159]), vomiting episodes (RR: 0.5 [95% CI: 0.3-0.9]), diarrheal episodes (RR: 0.24 [95% CI: 0.10-0.50]), episodes of gastrointestinal infections that lasted >2 days (RR: 0.40 [95% CI: 0.25-0.70]), and episodes of respiratory tract infections that lasted >3 days (RR: 0.4 [95% CI: 0.2-0.9]). Groups did not differ in hospitalization duration (P = .1).\n LGG administration can be recommended as a valid measure for decreasing the risk for nosocomial gastrointestinal and respiratory tract infections in pediatric facilities.", "The aim of our study was to investigate the role of Lactobacillus GG (LGG) in the prevention of gastrointestinal and respiratory tract infections in children who attend day care centers.\n We conducted a randomized, double-blind, placebo-controlled trial in 281 children who attend day care centers. They were randomly allocated to receive LGG at a dose of 10(9) colony-forming units in 100ml of a fermented milk product (LGG group, n=139) or placebo that was the same post-pasteurized fermented milk product without LGG (placebo group, n=142) during the 3-month intervention period.\n Compared to the placebo group, children in the LGG group had a significantly reduced risk of upper respiratory tract infections (RR 0.66, 95% CI 0.52 to 0.82, NNT 5, 95% CI 4 to 10), a reduced risk of respiratory tract infections lasting longer than 3 days (RR 0.57, 95% CI 0.41 to 0.78, NNT 5, 95% CI 4 to 11), and a significantly lower number of days with respiratory symptoms (p<0.001). There was no risk reduction in regard to lower respiratory tract infections (RR 0.82, 95% CI 0.24 to 2.76). Compared with the placebo group, children in the LGG group had no significant reduction in the risk of gastrointestinal infections (RR 0.63, 95% CI 0.38 to 1.06), vomiting episodes (RR 0.60, 95% CI 0.29 to 1.24), and diarrheal episodes (RR 0.63, 95% CI 0.35 to 1.11) as well as no reduction in the number of days with gastrointestinal symptoms (p=0.063).\n LGG administration can be recommended as a valid measure for decreasing the risk of upper respiratory tract infections in children attending day care centers.\n Copyright 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.", "The aim of this study was to investigate whether consumption of Lactobacillus plantarum HEAL 9 (DSM 15312) and Lactobacillus paracasei 8700:2 (DSM 13434) could affect naturally acquired common cold infections in healthy subjects.\n A randomised, parallel, double-blind placebo-controlled study was performed to investigate whether intake of this probiotic mixture could reduce the risk of common cold episodes, number of days with common cold symptoms, frequency and severity of symptoms, and cellular immune response in common cold infections. A total of 272 subjects were supplemented daily with either 10(9) cfu (colony forming units) of probiotics (N = 135) or control (N = 137) for a 12-week period.\n The incidence of acquiring one or more common cold episode was reduced from 67% in the control group to 55% in the probiotic group (p < 0.05). Also, the number of days with common cold symptoms were significantly (p < 0.05) reduced from 8.6 days in the control group to 6.2 days, in the probiotic group, during the 12-week period. The total symptom score was reduced during the study period from a mean of 44.4 for the control group to 33.6 for the probiotic group. The reduction in pharyngeal symptoms was significant (p < 0.05). In addition, the proliferation of B lymphocytes was significantly counteracted in the probiotic group (p < 0.05) in comparison with the control group.\n In conclusion, intake of the probiotic strains Lactobacillus plantarum HEAL 9 (DSM 15312) and Lactobacillus paracasei 8700:2 (DSM 13434) reduces the risk of acquiring common cold infections.", "One hundred children 6 to 24 month old, normal or undernourished according to weight for height index, received during three months--autumn to winter--a dietary supplement of live Lactobacillus acidophilus and Lactobacillus Casei, 10(7)-10(8)/ml in fermented milk (LB) or an equivalent amount of fluid milk (L) as control. Children's follow-up was performed as outpatients in the Hospital Posadas (Great Buenos Aires). Episodes of respiratory tract infections were recorded and classified according to severity as: Pneumonia (N); Bronchitis (B), Recurrent Obstructive Bronchitis (BOR) and upper respiratory tract infections (CVAS). 58% of children fitted the study protocol, 22 in the LB and 36 in the L group; 21 were undernourished and 37 presented normal weight/height. No deaths were recorded. Total episodes were 103: 34 in LB and 69 in L, that means a frequency of 1.55 and 1.92 episodes/children respectively. In LB a maximum of 3 episodes/children was recorded, meanwhile the number reached 7 in L (p = 0.0373). Severity was higher in L than LB: 0.06 vs. 0 for N; 0.69 vs. 0.45 for B + BOR and 1.17 vs. 1.09 for CVAS. In the control group frequency of severe pathologies was about twice in undernourished than in normal: 0.08 vs. 0.04 for N; 1.08 vs. 0.50 for B + BOR; no difference was found for CVAS. Live lactobacillus supplement suppressed pneumonia and decreased bronchitis in undernourished as well as in normal. In this study undernutrition not only increased the chance of suffering severe acute respiratory tract infections but also impaired the effectiveness of the supplement to decrease severity. The effect is explained on the basis of the immunocompetence depression linked to an inadequate nutritional status.", "A randomised, double-blind, placebo-controlled study was conducted to determine whether probiotics might be effective in reducing the risk of infections in infancy. Infants requiring formula before the age of 2 months were recruited from community well-baby clinics. Infant formula supplemented with the probiotics Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb-12 or placebo was administered daily until the age of 12 months. Incidence of early infections (before the age of 7 months) and incidence of recurrent (three or more) infections during the first year of life were recorded as the main outcome measures of the study. During the first 7 months of life, seven out of thirty-two (22 %) infants receiving probiotics and twenty out of forty (50 %) infants receiving placebo experienced acute otitis media (risk ratio (RR) 0.44 (95 % CI 0.21, 0.90); P = 0.014) and antibiotics were prescribed for ten out of thirty-two (31 %) infants receiving probiotics and twenty-four out of forty (60 %) infants receiving placebo (RR 0.52 (95 % CI 0.29, 0.92); P = 0.015). During the first year of life, nine out of thirty-two (28 %) infants receiving probiotics and twenty-two out of forty (55 %) infants receiving placebo encountered recurrent respiratory infections (RR 0.51 (95 % CI 0.27, 0.95); P = 0.022). These data suggest that probiotics may offer a safe means of reducing the risk of early acute otitis media and antibiotic use and the risk of recurrent respiratory infections during the first year of life. Further clinical trials are warranted.", "Probiotics purportedly reduce symptoms of gastrointestinal and upper respiratory-tract illness by modulating commensal microflora. Preventing and reducing symptoms of respiratory and gastrointestinal illness are the primary reason that dietary supplementation with probiotics are becoming increasingly popular with healthy active individuals. There is a paucity of data regarding the effectiveness of probiotics in this cohort. The aim of this study was to evaluate the effectiveness of a probiotic on faecal microbiology, self-reported illness symptoms and immunity in healthy well trained individuals.\n Competitive cyclists (64 males and 35 females; age 35 ± 9 and 36 ± 9 y, VO2max 56 ± 6 and 52 ± 6 ml.kg-1.min-1, mean ± SD) were randomised to either probiotic (minimum 1 × 109 Lactobacillus fermentum (PCC®) per day) or placebo treatment for 11 weeks in a double-blind, randomised, controlled trial. The outcome measures were faecal L. fermentum counts, self-reported symptoms of illness and serum cytokines.\n Lactobacillus numbers increased 7.7-fold (90% confidence limits 2.1- to 28-fold) more in males on the probiotic, while there was an unclear 2.2-fold (0.2- to 18-fold) increase in females taking the probiotic. The number and duration of mild gastrointestinal symptoms were ~2-fold greater in the probiotic group. However, there was a substantial 0.7 (0.2 to 1.2) of a scale step reduction in the severity of gastrointestinal illness at the mean training load in males, which became more pronounced as training load increased. The load (duration×severity) of lower respiratory illness symptoms was less by a factor of 0.31 (99%CI; 0.07 to 0.96) in males taking the probiotic compared with placebo but increased by a factor of 2.2 (0.41 to 27) in females. Differences in use of cold and flu medication mirrored these symptoms. The observed effects on URTI had too much uncertainty for a decisive outcome. There were clear reductions in the magnitude of acute exercise-induced changes in some cytokines.\n L. fermentum may be a useful nutritional adjunct for healthy exercising males. However, uncertainty in the effects of supplementation on URTI and on symptoms in females needs to be resolved.\n The trial was registered in the Australia and New Zealand Clinical Trials Registry (ACTRN12611000006943)." ]

[ "2528477", "1534881", "6381101", "923836", "4370851" ]

[ "Second-look operative laparoscopy 1 year following reproductive surgery.", "The effect of short-interval laparoscopic lysis of adhesions on pregnancy rates following Nd-YAG laser photocoagulation of polycystic ovaries.", "The efficacy of postoperative hydrotubation: a randomized prospective multicenter clinical trial.", "Salipingostomy: results of two different methods of treatment.", "Three comparative techniques on tubo-plasty." ]

[ "To evaluate the efficacy of a second-look operative laparoscopy following a reproductive surgery, a randomized study was conducted on women who failed to conceive 1 year following terminal salpingostomy or following salpingo-ovariolysis by laparotomy. There is no significant difference in the cumulative probability of pregnancy at 12, 24, and 36 months follow-up between women who underwent second-look operative laparoscopy 1 year after salpingo-ovariolysis (27%, 67%, and 67%) and women who were continued to be observed expectantly (27%, 45%, and 52%, respectively). The cumulative probability of conception at 12, 24, and 36 months follow-up in women who underwent second-look laparoscopy 1 year after salpingostomy was 6%, 18%, and 18% and in women who were observed expectantly was 5%, 21%, and 27%, respectively (P = no significant). The incidence of ectopic pregnancy which was high (about one-half of patients who conceived) was also not affected by this procedure. This study suggests that second-look operative laparoscopy 1 year after terminal salpingostomy or salpingo-ovariolysis does not increase the pregnancy rate or decrease the incidence of ectopic pregnancy. Women who fail to conceive 1 year after a reproductive surgery still maintain some of their reproductive potential, but the risk of having an ectopic pregnancy is high.", "Laparoscopic Nd-YAG laser photocoagulation of the ovaries was performed in 40 anovulatory women with clomiphene citrate-resistant polycystic ovary disease. Following this procedure, the subjects were randomly assigned to have either a second-look laparoscopy with lysis of adhesions within 3-4 weeks of the initial laparoscopy (N = 19) or expectant management (N = 20). One patient assigned to the laparoscopy group refused the procedure. Minimal and mild adhesions that did not distort the normal tubo-ovarian relationship were encountered in 13 patients (68%) in the second-look laparoscopy group; these adhesions were easily lysed using sharp or blunt dissection. The pregnancy rates over 6 months were similar in the two groups (47% in the second-look group and 55% in the expectant-management group; P greater than .05). These data suggest that early laparoscopic lysis of adhesions does not improve short-term conception rates following laparoscopic Nd-YAG laser photocoagulation of polycystic ovaries.", "Term pregnancies following surgery on patients with distal tubal obstruction have been disappointingly few. There has been continuing interest in whether postoperative hydrotubation increases the rate of pregnancy following salpingoneostomy and fimbrioplasty. This hypothesis was tested in a prospective, randomized, multicenter clinical trial. Patients with no infertility factors other than distal fimbrial disease were randomly assigned to either a control group (no hydrotubation, n = 86) or one of two treatment groups (hydrotubation with lactated Ringer's solution, n = 60, or lactated Ringer's solution containing hydrocortisone, n = 60). The statistical evaluation of differences among treatment groups was based on the Cox Proportional Hazards Model, which allows for covariable adjustment and for the inclusion of all patients regardless of the length of follow-up. A significant difference in the live birth rate could not be demonstrated among the groups studied (P = 0.36). The probability of a successful live birth among women treated by hydrotubation with hydrocortisone was about one-half that of the other groups (P = 0.12). Patients with moderate and severe disease had a substantially lower probability of pregnancy than those with mild disease (P = 0.013 and P = 0.0016, respectively). The probability of pregnancy increased somewhat as the number of previous pregnancies increased (P = 0.12). In this clinical trial, a beneficial effect following postoperative hydrotubation could not be demonstrated.", "nan", "nan" ]

[ "1547671", "2768576", "8545141", "10150323", "8364943", "1491864", "9256142" ]

[ "Effect of treatment with capsaicin on daily activities of patients with painful diabetic neuropathy. Capsaicin Study Group.", "Topical capsaicin treatment of chronic postherpetic neuralgia.", "Double-blind, placebo-controlled study of the application of capsaicin cream in chronic distal painful polyneuropathy.", "A double-blind comparison of topical capsaicin and oral amitriptyline in painful diabetic neuropathy.", "A randomized vehicle-controlled trial of topical capsaicin in the treatment of postherpetic neuralgia.", "The postmastectomy pain syndrome and topical capsaicin: a randomized trial.", "Phase III placebo-controlled trial of capsaicin cream in the management of surgical neuropathic pain in cancer patients." ]

[ "To establish the effects of topically applied capsaicin on daily activities in patients with painful diabetic neuropathy.\n Investigators at 12 sites enrolled 277 men and women with painful peripheral polyneuropathy and/or radiculopathy in an 8-wk double-blind vehicle-controlled study with parallel randomized treatment assignments. Participants were unresponsive or intolerant to conventional therapy and were experiencing pain that interfered with functional activities and/or sleep. Either 0.075% capsaicin cream or vehicle cream was applied to the painful areas 4 times/day. A visual analogue scale of pain intensity and baseline measurements of the pain's interference with the ability to walk, work, participate in recreational activities, use shoes and socks, sleep, and eat were recorded at onset and at 2-wk intervals. A physician's global evaluation scale assessed changes in pain status from baseline.\n Statistically significant differences are percentage of patients with improvement in favor of capsaicin versus vehicle: 69.5 vs 53.4% with clinical improvement in pain status (P = 0.012), 26.1 vs. 14.6% with improvement in walking (P = 0.029), 18.3 vs. 9.2% with improvement in working (P = 0.019), 29.5 vs. 20.3% with improvement in sleeping (P = 0.036), and 22.8 vs. 12.1% with improvement in participating in recreational activities (P = 0.037).\n The results from this study suggest that topical 0.075% capsaicin is effective for reducing pain in patients with painful diabetic neuropathy with subsequent improvement in daily activities, enhancing the quality of the patient's life.", "Uncontrolled studies have indicated that topically applied capsaicin may be a safe and effective treatment for postherpetic neuralgia. In a double-blind study 32 elderly patients with chronic postherpetic neuralgia were treated with either capsaicin cream or its vehicle for a 6-week period. Response to treatment was evaluated by visual analogue scales of pain and of pain relief, together with changes in a categoric pain scale and in a physician's global evaluation. Significantly greater relief in the capsaicin-treated group compared with vehicle was observed for all efficacy variables. After 6 weeks almost 80% of capsaicin-treated patients experienced some relief from their pain. Because capsaicin avoids problems with drug interactions and systemic toxicity, we suggest that topical capsaicin be considered for initial management of postherpetic neuralgia.", "We have completed a 12-week double-blind, placebo-controlled randomized study on the efficacy of the application of capsaicin (CAPS) cream (0.075%) in the treatment of chronic distal painful polyneuropathy. Forty patients were enrolled and 39 completed the study. The 2 limbs were randomly assigned to CAPS or placebo (PLAC). The cream was applied 4 times a day. The first tube contained the active PLAC, methyl nicotinate. In the final 4 weeks (single-blind wash-out phase), PLAC was administered bilaterally. Efficacy was evaluated using the following scales: (1) investigator global, (2) patient global, (3) visual analog (VAS) of pain severity, (4) VAS of pain relief, (5) activities of daily living, and (6) allodynia. Patients were examined at onset and at monthly intervals using a neurologic disability scale, nerve conduction studies, computer-assisted sensory examination for vibration and thermal cooling and warming, QSART (quantitative sudomotor axon reflex test) and quantitative flare response. There was no statistical evidence of efficacy of CAPS cream over PLAC for any of the pain indices. At early time points (1-4 weeks), there were a small number of indices that favored the PLAC. The percent of limbs that improved on the investigator's global scale were 51.3 vs. 53.8 at 4 weeks, 56.4 vs. 64.1 at 8 weeks and 59 vs. 66.7 at 12 weeks for CAPS vs. PLAC; no statistically significant difference was found. All the safety indices showed no difference between sides. We interpret the early hyperalgesia on the CAPS side as being responsible for the better performance of PLAC at early time points. The large percentage of limbs that improved may be a pronounced PLAC response.", "An 8-week double-blind, multicenter, parallel study compared the safety and efficacy of topical capsaicin and oral amitriptyline in patients with painful diabetic neuropathy involving the feet. Two hundred thirty-five patients were randomized to treatment with either capsaicin cream or amitriptyline capsules. Capsaicin-treated patients received inactive capsules, and amitriptyline-treated patients applied vehicle cream. A visual analogue scale of pain intensity and measurements of interference by pain with functional activities were recorded at onset and at 2-week intervals. A visual analogue scale of pain relief and physicians' global evaluation assessed changes in pain status from baseline. Topical capsaicin and oral amitriptyline produced equal and statistically significant improvements in pain over the course of the study. By the end of week 8, 76% of patients in each group experienced less pain, with a mean reduction in intensity of more than 40%. By the end of the study, the interference with daily activities by pain had diminished significantly (P = .001) in both groups, including improvements in sleeping and walking. No systemic side effects were observed in patients treated with topical capsaicin. Most patients receiving amitriptyline experienced at least one systemic side effect, ranging from somnolence (46%) to neuromuscular (23%) and cardiovascular (9%) adverse effects. Topically applied capsaicin is an equally effective but considerably safer alternative to amitriptyline for relief of the pain of diabetic neuropathy.", "A large double-blind, vehicle-controlled study of 143 patients with chronic postherpetic neuralgia (PHN) was performed to evaluate the degree of efficacy of topically applied capsaicin 0.075% cream. In addition, the safety and efficacy of long-term application of topical capsaicin in PHN was assessed by following patients in an open-label study for up to 2 years. In the double-blind phase, 143 patients with PHN of 6 months' duration or longer were enrolled. Since epidemiologic studies of patients who receive no treatment have shown that only 10% to 25% of those with PHN after 1 month will still have pain at 1 year, two separate efficacy analyses were performed: one with all evaluable patients (n = 131) and the other with 93 patients whose PHN lasted for longer than 12 months prior to study startup. All efficacy variables, including the physician's global evaluation of reduction in PHN pain, changes in pain severity on the categoric scale, visual analogue scale for pain severity, visual analogue scale for pain relief, and functional capacity scale, showed significant improvement at nearly all time points throughout the study for both patient groups, based on duration of PHN pain. In contrast, the group receiving vehicle cream remained essentially unchanged. Data from the long-term, open-label phase (up to 2 years, n = 77), which immediately followed the 6-week blinded phase, showed that the clinical benefit in patients treated for a short (6-week) period with topical capsaicin could be maintained or amplified in most patients (86%) during prolonged therapy. There were no serious adverse effects observed or reported throughout the trial; in fact, the only side effect associated with capsaicin treatment was the burning or stinging at local sites of application (in 9% of patients) during exposures of up to 2 years (long-term phase). On the basis of these data, we conclude that capsaicin 0.075% cream is a safe and effective treatment for the pain of postherpetic neuralgia and should be considered for initial management of patients with this condition.", "This paper describes a randomized parallel trial of topical 0.075% capsaicin versus vehicle (placebo) in the postmastectomy pain syndrome (PMPS). The study was double-blind in design; however, this was compromised by the burning sensation induced by capsaicin. We could not demonstrate a significant difference in the visual analogue scale (VAS) for steady pain although a trend was present. A significant difference was found, however, in the VAS for jabbing pain, in category pain severity scales, and in overall pain relief scales in favour of capsaicin. Five of 13 patients on capsaicin were categorized as good-to-excellent responses with 8 (62%) having 50% or greater improvement. Only 1 of 10 cases had a good response to vehicle with 3 rated as 50% or better.", "A minority of cancer survivors develops long-term postsurgical neuropathic pain. Based on evidence that capsaicin, the pungent ingredient in hot chili peppers, might be useful for treating neuropathic pain, we developed the present clinical trial.\n Ninety-nine assessable patients with postsurgical neuropathic pain were entered onto this study. After stratification, patients were to receive 8 weeks of a 0.075% capsaicin cream followed by 8 weeks of an identical-appearing placebo cream, or vice versa. A capsaicin/placebo cream was to be applied to the painful site four times daily. Treatment evaluation was performed by patient-completed weekly questionnaires.\n During the first 8-week study period, the capsaicin-cream arm was associated with substantially more skin burning, skin redness, and coughing (P < .0001 for each). Nonetheless, treatment was stopped for patient refusal or toxicity just as often while patients were receiving the placebo as compared with the capsaicin. The capsaicin cream arm had substantially more pain relief (P = .01) after the first 8 weeks, with an average pain reduction of 53% versus 17%. On completion of the 16-week study period, patients were asked which treatment period was most beneficial. Of the responding patients, 60% chose the capsaicin arm, 18% chose the placebo arm, and 22% chose neither (P = .001).\n A topical capsaicin cream decreases postsurgical neuropathic pain and, despite some toxicities, is preferred by patients over a placebo by a three-to-one margin among those expressing a preference." ]

[ "12735675", "18606533", "18328683", "15521371", "21189151", "18462564", "10653049", "11217910", "16449264", "16095144", "10856143", "15256389", "15641629", "17654129", "16490581", "14533658", "18206361" ]

[ "Addition of salmeterol to fluticasone propionate treatment in moderate-to-severe asthma.", "Maintaining asthma control in persistent asthma: comparison of three strategies in a 6-month double-blind randomised study.", "Does measuring BHR add to guideline derived clinical measures in determining treatment for patients with persistent asthma?", "Fluticasone propionate and salmeterol administered via Diskus compared with salmeterol or fluticasone propionate alone in patients suboptimally controlled with short-acting beta2-agonists.", "Long-term treatment with fluticasone propionate/salmeterol via Diskus improves asthma control versus fluticasone propionate alone.", "Asthma exacerbations in African Americans treated for 1 year with combination fluticasone propionate and salmeterol or fluticasone propionate alone.", "Salmeterol/fluticasone propionate (50/500 microg) in combination in a Diskus inhaler (Seretide) is effective and safe in the treatment of steroid-dependent asthma.", "Clinical equivalence of salmeterol/fluticasone propionate in combination (50/100 microg twice daily) when administered via a chlorofluorocarbon-free metered dose inhaler or dry powder inhaler to patients with mild-to-moderate asthma.", "Adding salmeterol to an inhaled corticosteroid: long term effects on bronchial inflammation in asthma.", "The safety of twice-daily treatment with fluticasone propionate and salmeterol in pediatric patients with persistent asthma.", "Salmeterol and fluticasone propionate combined in a new powder inhalation device for the treatment of asthma: a randomized, double-blind, placebo-controlled trial.", "Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study.", "Efficacy and safety of fluticasone propionate/salmeterol HFA 134A MDI in patients with mild-to-moderate persistent asthma.", "Initiation of maintenance therapy with salmeterol/fluticasone propionate combination therapy in moderate asthma: a comparison with fluticasone propionate.", "Efficacy and tolerability of fluticasone propionate/salmeterol administered twice daily via hydrofluoroalkane 134a metered-dose inhaler in adolescent and adult patients with persistent asthma: a randomized, double-blind, placebo-controlled, 12-week study.", "Efficacy and safety of fluticasone propionate 44 microg/salmeterol 21 microg administered in a hydrofluoroalkane metered-dose inhaler as an initial asthma maintenance treatment.", "Efficacy and safety of fluticasone propionate/salmeterol 250/50 mcg Diskus administered once daily." ]

[ "This study was designed to determine whether the benefit of adding salmeterol was superior to doubling the dose of fluticasone propionate (FP) over 6 months, compared to a control group who remained on a lower dose of FP. The multi-centre, double-blind, parallel group study involved 496 symptomatic asthmatic patients with a history of exacerbations on 500-800 micrograms (microg) inhaled corticosteroids (ICS) twice daily (b.d.) in a broadly representative group of 100 hospitals and general practices in six countries. Two doses of FP--250 microg b.d. (FP250) or 500 microg b.d. (FP500)--were compared with the lower dose of FP plus a long-acting beta2-agonist, salmeterol 50 microg b.d. (SM/FP250). Patients symptomatic on the run-in dose of FP250 alone formed the control group in the treatment period. Over 6 months, SM/FP250 significantly improved mean morning peak expiratory flow rates (amPEF) by 42.1 l/min, more than twice the improvement achieved with either dose of FP alone. SM/FP250 also resulted in more symptom-free days and nights (P < 0.002) and days and nights with no relief medication (P < 0.001). The number of severe exacerbations was low: 3, 6 and 8% in the SM/FP250, low- and high-dose FP groups, respectively. This study confirms that adding salmeterol to low-dose inhaled FP offers greater improvements than either maintaining or doubling the dose of FP. Significant benefit was gained from adding salmeterol in a group of patients who appeared to have been at the top of their steroid dose-response curve receiving FP250. There was no evidence of tolerance and a low incidence of exacerbations in all treatment groups.", "In patients controlled with SFC250 Diskus bd, this double-blind, randomised 6-month study compared continuing SFC250 to stepping down to either SFC100 bd or FP250 bd. Six hundred and three patients previously using 1,000 microg BDP (or equivalent) daily +LABA and controlled according to investigator's judgement were recruited. Patients received SFC250 bd during an 8-week open run-in period. Four hundred and seventy six patients (mean age=43 years, mean FEV(1)=2.9+/-1.0) who fulfilled the randomisation criterion ('Well-controlled' asthma according to the GOAL weekly definition for the last 2 weeks of the run-in period) entered a 24-week treatment period. The statistical hypothesis was based on a non-inferiority of SFC100 or FP250 compared to SFC250. The main criterion was the change from baseline in morning PEF over weeks 1-12 in the per-protocol population. The non-inferiority limit was -15 L/min. At inclusion, the three treatment groups were well balanced. Mean morning PEF was 476, 470 and 465 L/min in the SFC250, SFC100 and FP250 groups, respectively. The adjusted mean change in morning PEF over weeks 1-12 was +1.76+/-2.43 L/min for SFC250, -3.07+/-2.32 L/min for SFC100 and -16.51+/-2.46 L/min for FP250. SFC100 was at least as effective as SFC250 (treatment difference -4.83 [-12.39; 2.72], p=0.151) whereas FP250 was not (treatment difference -18.27 [-26.05; -10.49], p<0.001). Similar results were observed over weeks 13-24 in morning PEF (SFC100-SFC250=-4.54+/-3.84, p=0.238; FP250-SFC250=-20.11+/-3.92, p<0.0001). Secondary endpoints showed a similar pattern. Over weeks 1-12, SFC250 was significantly more effective than FP250 on evening PEF, daily symptoms and bronchodilator use. There was no difference between SFC100 and SFC250. The mean annual rate of moderate exacerbations was 0.16 in both SFC 250 and SFC 100 groups, and 0.21 in FP 250 group (ns, Poisson analysis). All treatments were well tolerated.\n In patients achieving asthma control with SFC250, stepping treatment down with SFC100 was at least as effective on lung function and symptoms as continuing SFC250, whereas FP250 was not.", "Little is known about the use of biomarkers in guiding treatment decisions in routine asthma management. The objective of this study was to determine whether adding a LABA to an ICS would control bronchial hyperresponsiveness (BHR) at an overall lower dose of ICS when titration of medication was based upon the assessment of routine clinical measures with or without the measurement of BHR.\n After a 2-week run-in period, subjects (> or = 12 years) were randomized to one of three treatment groups. Two groups followed a BHR treatment strategy (based on clinical parameters [lung function, asthma symptoms, and bronchodilator use] and BHR) and were treated with either fluticasone propionate/salmeterol (FSC(BHR) group) or fluticasone propionate (FP(BHR) group) (n=156 each). The third group followed a clinical treatment algorithm (based on clinical parameters alone) and were treated with fluticasone propionate (FP(REF) group; n=154). All treatments were administered via Diskus. Treatment doses were adjusted as needed every 8 weeks for 40 weeks according to the subject's derived severity class, which was based on clinical measures of asthma control with or without BHR.\n The mean total daily inhaled corticosteroids (ICS) dose during the double-blind treatment period was lower, although not statistically significant, in the FSC(BHR) group compared with the FP(BHR) group (a difference of -42.9 mcg; p=0.07). Compared with the FP(REF) group, the mean total daily ICS dose was higher in the FSC(BHR) group (a difference of 85.2 mcg) and was significantly higher in the FP(BHR) group (a difference of 131.2 mcg, p=0.037).\n This study demonstrated that for most subjects, control of BHR was maintained when treatment was directed toward control of clinical parameters. In addition, there was a trend towards control of BHR and clinical measures at a lower dose of ICS when used concurrently with salmeterol.", "Optimal therapy for many patients with persistent asthma requires control of both main components of this disease: inflammation and bronchoconstriction.\n To compare the efficacy and safety of initiating maintenance therapy with an inhaled, long-acting beta2-agonist and an inhaled corticosteroid administered from a single device with that of the individual agents alone.\n A 12-week, randomized, double-blind study was conducted in patients 12 years and older with persistent asthma who were symptomatic while taking as-needed, short-acting beta2-agonists alone. Treatments were administered twice daily via the Diskus device: salmeterol, 50 microg; fluticasone propionate, 100 microg; or fluticasone propionate, 100 microg, with salmeterol, 50 microg.\n Of 555 patients screened, 267 were randomly assigned to treatment. At end point, fluticasone propionate and salmeterol significantly increased predose forced expiratory volume in 1 second (FEV1) compared with salmeterol alone (0.51 +/- 0.05 L vs 0.38 +/- 0.04 L, P = .04). Fluticasone propionate and salmeterol significantly increased area under the serial FEV1 curve at treatment week 12 relative to predose FEV1 (baseline) on treatment day 1 (AUCb1, 8.4 +/- 0.6 L/h; P < or = .02) compared with salmeterol (6.2 +/- 0.5 L/h) and fluticasone propionate (7.0 +/- 0.6 L/h). Fluticasone propionate and salmeterol were significantly (P < or = .02) more effective than the individual agents used alone in improving morning and evening peak expiratory flow rate and asthma symptoms. In addition, fluticasone propionate and salmeterol effectively reduced rescue albuterol use (P < or = .04). All treatments were well tolerated.\n In patients symptomatic while taking short-acting beta2-agonists alone, initial maintenance treatment of the 2 main components of asthma, inflammation and smooth muscle dysfunction, with fluticasone propionate and salmeterol, 100 and 50 microg, administered via the Diskus results in greater improvements in overall asthma control compared with treatment of either component alone.", "This 52-week study was designed to assess the safety and efficacy of fluticasone propionate/salmeterol combination (FSC) 250/50 micrograms versus fluticasone propionate (FP) 250 micrograms in subjects with persistent asthma symptomatic on open-label FP 100 micrograms. The primary objective of this study was to show that FSC 250/50 micrograms was superior to FP 250 micrograms at increasing pulmonary function as measured by forced expiratory volume in 1 second over a 52-week treatment period. A secondary objective was to compare the rate of asthma attacks defined as (1) a sustained 2-day decrease in morning peak expiratory flow or increase in albuterol use for 2 consecutive days, (2) an asthma exacerbation requiring systemic corticosteroids, or (3) an unscheduled clinic or hospital visit for acute asthma symptoms. Three hundred six subjects received FSC 250/50 micrograms and 315 subjects received FP 250 micrograms. Both treatments were administered twice daily. Treatment with FSC 250/50 micrograms resulted in a significant improvement in lung function compared with FP 250 micrograms (p < 0.001). Additionally, treatment with FSC 250/50 micrograms resulted in a reduction in the rate of exacerbations of asthma (i.e., requiring systemic corticosteroids or unscheduled urgent care intervention) compared with FP 250 micrograms (0.170 versus 0.273, respectively; p = 0.017). There was no differentiation between treatments for less severe attacks of asthma. FSC 250/50 micrograms showed consistently greater improvement in lung function, symptom control, and decreased albuterol use. In addition, FSC 250/50 micrograms-treated subjects experienced fewer severe asthma exacerbations than subjects treated with FP 250 micrograms.", "This long-term prospective study was conducted in African Americans with persistent asthma to examine the safety and effectiveness of the combination of the inhaled corticosteroid, fluticasone propionate (FP), and the long-acting beta-agonist, salmeterol, compared with FP alone.\n This was a randomized, double-blind, parallel group, multi-center trial in adolescent and adult subjects >/=12 years of age symptomatic on a low dose of an inhaled corticosteroid (ICS). The study consisted of a 2-week screening period on low dose ICS; a 4-week open-label FP 250 mcg twice daily (BID) run-in; a 52-week double-blind period (FP/salmeterol [FSC] 100/50 mcg [n=239] or FP 100 mcg [n=236] BID), and a 4-week FP 250 mcg BID run-out period. Annualized exacerbation rate was the primary outcome for comparing the two treatments. Other measures of asthma control included peak expiratory flow, asthma symptoms, and albuterol use. Safety was assessed through adverse events.\n Exacerbation rates were not significantly different in those treated with FSC 100/50 mcg (0.449 per year) compared with FP 100 mcg (0.529 per year, p=0.169). When the per-protocol analysis was applied, the rates were 0.465 and 0.769 per year for FSC 100/50 mcg and FP 100 mcg, respectively. Treatment with FSC 100/50 mcg provided statistically greater improvements in lung function measures and nighttime awakenings (p</=0.050) and demonstrated numerically lower daily symptoms (p=0.216) and albuterol use (p=0.122). Two subjects treated with FSC 100/50 mcg were hospitalized for an asthma exacerbation compared to three treated with FP 100 mcg. The overall incidence of adverse effects during double-blind treatment was similar between the FSC 100/50 mcg and FP 100 mcg treatment groups (61% and 68%, respectively). Frequent study visits were required of subjects during this long-term study, and it remains unknown whether this intervention may affect generalizability.\n In this large, prospective study among African Americans with asthma, the addition of salmeterol to FP resulted in a similar low rate of exacerbations and improved other markers of asthma control. Both FSC 100/50 mcg and FP 100 mcg were well-tolerated, and the overall safety-profiles were similar over 1 year of treatment.", "This multicentre double-blind, double-dummy study compared the safety and efficacy of a new combination Diskus inhaler containing both salmeterol 50 microg and fluticasone propionate 500 microg (Seretide, GlaxoWellcome, France) with the same doses of the two drugs delivered via separate Diskus inhalers and with the same dose of fluticasone propionate alone. Patients were eligible for study entry if they had received an inhaled corticosteroid continuously for 12 weeks prior to run-in, and had received treatment with beclomethasone dipropionate or budesonide 1500-2000 microg day(-1) or fluticasone propionate 750-1000 microg day(-1) for at least 4 weeks prior to run-in. In total, 503 patients receiving inhaled corticosteroids were randomized to 28 weeks' treatment with either salmeterol/fluticasone propionate (50/500 microg) via a single Diskus inhaler (combination) and placebo, or salmeterol 50 microg and fluticasone propionate 500 microg administered via separate Diskus inhalers (concurrent), or fluticasone propionate 500 microg and placebo. All treatments were administered twice daily, mean morning peak expiratory flow rate (PEFR) and asthma symptoms were measured for the first 12 weeks and safety data were collected throughout the 28-week study. Over weeks 1 to 12, improvement in adjusted mean morning PEFR was 35 and 33 l min(-1), respectively, in the combination and concurrent therapy treatment groups (12 and 10% increase from baseline, respectively). The mean difference between treatments was -3 l min(-1) (90% confidence interval -10.4 l min(-1)) which was within the criteria for clinical equivalence. However, the combination therapy was statistically significantly superior to fluticasone propionate alone for mean morning PEFR (P<0.001) and other measures of lung function, whilst clinical equivalence of the combination and concurrent therapies was observed. All three treatments were well tolerated. In addition, there were no differences between the three treatments in either the c.hange in serum cortisol or urinary cortisol concentrations, which, for each treatment group, were no significantly different from baseline at the end of the treatment period. Thus, the combination of salmeterol and fluticasone propionate in a single inhaler is as well tolerated and effective in achieving asthma control in steroid-dependent patients as the separate administration of the two drugs, and both combination and concurrent therapy are superior to administration of the same dose of corticosteroid alone.", "This multi-centre, randomized, double-blind, double-dummy, parallel-group study was designed to investigate the hypothesis of equivalent efficacy and comparable safety of two inhaled presentations of salmeterol/fluticasone propionate combination product (SALM/FP) 50/100 microg administered twice daily to patients with mild-to-moderate asthma for 12 weeks. The delivery systems were a 25/50 microg strength hydrofluoroalkane (HFA) metered-dose inhaler (MDI) and a Diskus inhaler (50/100 microg strength). A third group received FP 100 microg twice daily via a chlorofluorocarbon MDI (50 microg strength). A total of 497 patients aged 11-79 years with reversible airways obstruction who were symptomatic on inhaled corticosteroid (ICS) therapy and had room for improvement in lung function were randomized to treatment in a double-blind, parallel-group design (SALM/FP MDI: n=165; SALM/FP Diskus: n=167; FP MDI: n=165) for 12 weeks. A total of 383 patients completed the study according to the protocol. According to the primary efficacy variable, increase in mean morning PEF over weeks 1-12, the two inhaled presentations of SALM/FP were clinically equivalent (adjusted mean increases 43 and 46 l min(-1); treatment difference 3 l min(-1); 95% confidence interval: -6 to 11 l min(-1)). Equivalence was also demonstrated by all secondary efficacy measures. The SALM/FP MDI was significantly superior to the FP MDI for increase in mean morning PEF (treatment difference 19 l min(-1); P<0.001) and for all secondary measures except FEV1 and symptom-free nights. There was no significant difference between the groups with respect to adverse events and serum cortisol levels. These results demonstrate that the SALM/FP 25/50 microg HFA MDI (two inhalations twice daily) is clinically equivalent to the SALM/FP 50/100 microg Diskus (one inhalation twice daily). Patients switching to SALM/FP from other MDI-based asthma treatments may now do so without a change of delivery device.", "Addition of the long acting beta2 agonist salmeterol to inhaled corticosteroids leads to better symptomatic asthma control than increasing the dose of inhaled corticosteroids. However, little is known about the long term effects of adding salmeterol on the asthmatic inflammatory process, control of which is considered important for the long term outcome of asthma.\n After a 4 week fluticasone run-in period, 54 patients with allergic asthma were randomised to receive twice daily treatment with fluticasone 250 microg with or without salmeterol 50 microg for 1 year in a double blind, parallel group design (total daily dose of fluticasone 500 microg in both treatment groups). Primary outcomes were sputum eosinophil numbers and eosinophil cationic protein concentrations. Secondary outcomes were neutrophil associated sputum parameters and a respiratory membrane permeability marker. The effects on allergen induced changes were determined before and at the end of the treatment period.\n Adding salmeterol to fluticasone resulted in improved peak expiratory flow, symptom scores, rescue medication usage, and bronchial hyperresponsiveness (p < 0.05 for all). There was no sustained effect on sputum cell differential counts and cytokine concentrations during the treatment period or on changes induced by allergen challenge at the end of treatment (p > 0.05). However, adding salmeterol significantly reduced sputum ratios of alpha2-macroglobulin and albumin during the treatment period (p = 0.001).\n The addition of salmeterol to fluticasone produces no sustained effect on allergen induced cellular bronchial inflammation but leads to a significant improvement in size selectivity of plasma protein permeation across the respiratory membrane. This may contribute to the improved clinical outcome seen in patients with allergic asthma when a long acting beta2 agonist is combined with inhaled corticosteroids.", "For children older than 5 years with asthma who remain symptomatic despite inhaled corticosteroid (ICS) therapy, the preferred treatment is to add an inhaled long-acting beta2-agonist vs increasing the ICS dose.\n To compare the safety of twice-daily treatment with inhaled fluticasone propionate plus the inhaled long-acting beta2-agonist salmeterol with that of fluticasone propionate used alone in children aged 4 to 11 years with persistent asthma.\n A randomized, multicenter, double-blind, active-controlled, parallel-group study in 203 children with persistent asthma who were symptomatic during ICS therapy. Patients received fluticasone propionate-salmeterol (100/50 microg) or fluticasone propionate (100 microg) alone twice daily for 12 weeks.\n The safety profile of fluticasone propionate-salmeterol was similar to that of fluticasone propionate alone. The overall incidence of adverse events was 59% for fluticasone propionate-salmeterol and 57% for fluticasone propionate. Both treatments were well tolerated. Two patients receiving fluticasone propionate-salmeterol and 5 receiving fluticasone propionate withdrew from the study because of worsening asthma. Changes in heart rate, blood pressure, and laboratory variables were infrequent and were similar between treatments. No patients had clinically significant abnormal electrocardiographic findings during treatment. Geometric mean 24-hour urinary cortisol excretion at baseline and after 12 weeks of treatment was comparable within and between groups; no patient in either group had abnormally low 24-hour urinary cortisol excretion after 12 weeks of treatment. The incidence of withdrawals due to asthma exacerbations was 2% in the fluticasone propionate-salmeterol group and 5% in the fluticasone propionate group.\n In pediatric patients with persistent asthma, fluticasone propionate-salmeterol twice daily was well tolerated, with a safety profile similar to that of fluticasone propionate used alone.", "Many patients with persistent asthma need both long-acting bronchodilators and inhaled corticosteroids for optimal asthma control.\n Our purpose was to compare the efficacy and safety of salmeterol 50 microg combined with fluticasone 100 microg (in a combination dry powder product) with that of placebo, fluticasone, or salmeterol alone.\n A 12-week randomized, double-blind, multicenter study was conducted in 356 patients aged 12 years or older with asthma. After a 14-day screening period, patients were randomized to treatment with salmeterol 50 microg combined with fluticasone 100 microg (combination product), salmeterol 50 microg, fluticasone 100 microg, or placebo administered in the Diskus dry powder inhaler (GlaxoWellcome, UK) twice daily.\n Mean change in FEV(1) at end point was significantly (P < or =.003) greater with the combination product (0.51 L) compared with placebo (0.01 L), salmeterol (0.11 L), and fluticasone (0.28 L). The combination product significantly increased (P < or =.013) area under the curve compared with placebo and fluticasone on day 1 and compared with placebo, salmeterol, and fluticasone at week 1 and week 12. Patients in the combination product group were less likely to withdraw from the study because of worsening asthma compared with those in the other groups (P < or =.020). The combination product significantly increased (P < or =.012) morning PEF (combination, 52.5 L/min; placebo, -23.7 L/min; salmeterol, -1.7 L/min; fluticasone, 17.3 L/min) and evening PEF at end point compared with the other groups. The combination product significantly (P < or =.025) reduced symptom scores and albuterol use compared with the other treatments and increased the percentage of nights with no awakenings and the percentage of days with no symptoms compared with placebo and salmeterol. All treatments were equally well tolerated.\n Salmeterol 50 microg and fluticasone 100 microg combined in the Diskus powder delivery device offers significant clinical advantages over salmeterol or fluticasone alone at the same doses.", "For most patients, asthma is not controlled as defined by guidelines; whether this is achievable has not been prospectively studied. A 1-year, randomized, stratified, double-blind, parallel-group study of 3,421 patients with uncontrolled asthma compared fluticasone propionate and salmeterol/fluticasone in achieving two rigorous, composite, guideline-based measures of control: totally and well-controlled asthma. Treatment was stepped-up until total control was achieved (or maximum 500 microg corticosteroid twice a day). Significantly more patients in each stratum (previously corticosteroid-free, low- and moderate-dose corticosteroid users) achieved control with salmeterol/fluticasone than fluticasone. Total control was achieved across all strata: 520 (31%) versus 326 (19%) patients after dose escalation (p < 0.001) and 690 (41%) versus 468 (28%) at 1 year for salmeterol/fluticasone and fluticasone, respectively. Asthma became well controlled in 1,071 (63%) versus 846 (50%) after dose escalation (p < 0.001) and 1,204 (71%) versus 988 (59%) at 1 year. Control was achieved more rapidly and at a lower corticosteroid dose with salmeterol/fluticasone versus fluticasone. Across all strata, 68% and 76% of the patients receiving salmeterol/fluticasone and fluticasone, respectively, were on the highest dose at the end of treatment. Exacerbation rates (0.07-0.27 per patient per year) and improvement in health status were significantly better with salmeterol/fluticasone. This study confirms that the goal of guideline-derived asthma control was achieved in a majority of the patients.", "The objective of this study was to compare the efficacy and safety of fluticasone propionate (FP) (44 microg)/salmeterol (21 microg) delivered as two inhalations twice daily via a single hydrofluoroalkane (HFA 134a) metered dose inhaler (MDI) (FSC) with that of placebo HFA 134a (PLA), fluticasone propionate 44 microg chlorofluorocarbon (CFC) alone and salmeterol 21 microg CFC alone (S) in patients (n=360) with persistent asthma previously treated with beta2-agonists (short- or long-acting) or inhaled corticosteroids (ICS). After 12 weeks of treatment, patients treated with FSC had a significantly greater increase (p < or = 0.006) in mean FEV1 AUC(bl) compared with PLA, FP, or S. At end point, mean change from baseline in morning predose FEV1 for FSC (0.58 L) was significantly (p < or = 0.004) greater than PLA (0.14 L), FP (0.36 L), and S (0.25 L). Patients treated with FSC also had a significantly higher probability of remaining in the study without being withdrawn due to worsening asthma (2%) compared with those in the PLA (29%) and S (25%) groups (p < 0.001). Finally, treatment with FSC resulted in significantly (p < or = 0.007) greater improvements in morning and evening peak expiratory flow, need for rescue albuterol, and asthma symptom scores compared with FP, S, and PLA. The safety profile of FSC was also similar to FP or S alone. Initial maintenance treatment of the two main components of asthma, inflammation, and smooth muscle dysfunction (e.g., bronchoconstriction), with FSC results in greater overall improvements in asthma control compared with treatment of either individual component alone.", "The objective of this study was to investigate initial maintenance treatment with salmeterol/fluticasone propionate (Seretide) 50/250 microg twice daily (SFC) compared with fluticasone propionate (Flixotide) 250 microg twice daily (FP) (both via Diskus inhaler, GlaxoSmithKline, Greenford, UK) in patients with moderate persistent asthma currently only treated with inhaled short-acting beta2-agonists. A total of 362 adults and adolescents (12 to 80 years of age) were randomized to this 12-week double-blind parallel-group study. The primary endpoint was mean morning peak expiratory flow (PEF). Secondary efficacy endpoints included median percentages of symptom-free and rescue-free days and nights; the percentage of patients who achieved the pre-defined criteria for well-controlled asthma over weeks 5 to 12; and the incidence of asthma exacerbations. Safety was assessed by the incidence of adverse events. Superiority of SFC over FP alone was demonstrated for the primary and each secondary endpoint. The difference in adjusted mean change from baseline in morning PEF between SFC and FP was 21 L/min (95% CI: 11, 31; p<0.001). Significantly more patients achieved well-controlled asthma during treatment with SFC (46%) compared with FP (32%) (odds ratio 1.84; 95% CI: 1.17, 2.89; p=0.008). Both treatments were safe and well-tolerated. This study demonstrates that initial maintenance treatment with SFC 50/250 mug twice daily provides superior efficacy to FP 250 microg twice daily alone in patients with moderate persistent asthma.", "This study compared the efficacy and tolerability of the combination of fluticasone propionate (FP) and salmeterol (SAL) delivered via a single hydrofluoroalkane (HFA) 134a metered-dose inhaler (MDI) with those of its 2 components alone delivered via a chlorofluorocarbon (CFC) MDI and placebo (PLA) delivered via HFA MDI in adolescent and adult patients with persistent asthma that was not controlled by medium doses (equivalent to FP 440-660 microg/d) of inhaled corticosteroids (ICSs).\n This was a randomized, double-blind,placebo-controlled, parallel-group study consisting of a 2-week, single-blind, placebo run-in period followed by a 12-week, double-blind treatment period. Participants had to be > or =12 years of age and have a diagnosis of asthma requiring pharmacotherapy for at least 6 months before the study. Patients had to have used ICS therapy for > or =3 months before the study and at a consistent dose for the previous month. Lack of asthma control was defined as a forced expiratory volume in 1 second (FEV(1)) that was 40% to 85% of the predicted value. Patients could not enter the double-blind treatment period if they had 3 days when they required >12 puffs of rescue albuterol per day or >3 nighttime awakenings due to asthma that required treatment with albuterol during the 7 days before the randomization visit. Patients were randomized to receive one of the following treatments delivered via MDI twice daily for 12 weeks: FSC 220/42 microg HFA (2 inhalations of FSC 110/21 microg; 125 microg/21 microg ex-valve); FP 220 microg CFC (2 inhalations of FP 110 microg); SAL 42 microg CFC (2 inhalations of 21 microg); or 2 inhalations of PLA HFA. The primary efficacy end point for FSC versus FP was the mean area under the 12-hour serial FEV(1) curve relative to the prerandomization baseline (FEV(1) AUC(bl)). The primary efficacy end points for FSC versus SAL were the mean change from baseline in morning predose FEV(1) at end point and the probability of not being withdrawn from the study due to worsening asthma. Tolerability assessments included electrocardiograms, routine clinical laboratory tests, vital signs, oropharyngeal examinations, and physical examinations. Adverse events were assessed at each clinic visit.\n Thirty-two adolescent and 333 adult patients were randomly assigned to receive double-blind treatment. The treatment groups were comparable at baseline with respect to demographic characteristics (mean age, 38-41 years; white race, 78%-88%) and pulmonary function (mean percent predicted FEV(1), 68%-69%; mean asthma symptom score, 1.6 [scale 0-5]; and mean daily albuterol use, 3.1 puffs). After 12 weeks of treatment, the mean FEV(1) AUC(bl) was significantly greater in patients who received FSC compared with those who received FP, SAL, or PLA (7.0, 3.6, 5.3, and 1.4 L-h, respectively; all comparisons, P < or = 0.020). At end point, the mean change from baseline in morning predose FEV(1) for FSC was significantly greater than that for FP, SAL, and PLA (0.41, 0.19, 0.15, and -0.12 L; all comparisons, P < or = 0.001). During 12 weeks of treatment, 7% of patients receiving FSC were withdrawn due to worsening asthma, compared with 24% of patients receiving SAL and 54% of patients receiving PLA (P < 0.001); 11% of patients receiving FP were withdrawn due to worsening asthma. Treatment with FSC resulted in significant improvements in morning and evening peak expiratory flow compared with FP, SAL, and PLA (both, P < 0.001); need for rescue albuterol compared with FP and PLA (P < or =0.005); and asthma symptom scores compared with PLA (P < 0.001). The tolerability of FSC was similar to that of FP or SAL alone. The incidence of possibly drug-related adverse events was generally similar across treatment groups, and the most common (occurring in > or= 2% of patients) were headache (1%-4%), throat irritation (1%-2%), candidiasis of the mouth/throat (0%-2%), unspecified oropharyngeal plaques (0%-2%), and palpitations (0%-2%).\n In these adolescent and adult patients whose asthma was not controlled by medium doses of an ICS, FSC delivered via HFA 134a MDI (2 inhalations of 110/21-microg strength administered BID) was more effective in improving lung function than FP or SAL monotherapy or PLA. All treatments were well tolerated.", "We wanted to evaluate whether treatment with an inhaled corticosteroid and an inhaled long-acting beta2-agonist is more effective than an inhaled corticosteroid alone for patients using as-needed albuterol who are initiating maintenance treatment.\n To compare the efficacy and safety of twice-daily fluticasone propionate (FP) 88 microg and salmeterol 42 microg combined in a chlorofluorocarbon (CFC)-free (hydrofluoroalkane 134a) metered-dose inhaler (MDI) with the individual agents alone, each delivered through an MDI containing CFC propellants, in patient with persistent asthma previously uncontrolled with as-needed short-acting beta2-agonists alone.\n Patients with asthma (n = 283) were randomized to twice-daily treatment for 12 weeks with FP 88 microg combined with salmeterol 42 microg (FSC) in a CFC-free MDI or the individual components alone from CFC-containing MDIs.\n At endpoint, mean change from baseline in morning predose forced expiratory volume in 1 second was significantly (P < or = 0.016) greater with FSC (0.69 L) compared with FP (0.51 L) or salmeterol (0.47 L). Fewer patients treated with FSC withdrew due to worsening asthma (1%) compared with FP (3%) or salmeterol (8%; P = 0.024). FSC significantly increased (P < or = 0.002) morning and evening peak expiratory flow rate at endpoint (66.5 and 51.5 L/min, respectively) compared with FP (43.0 and 29.9 L/min, respectively) and salmeterol (29.2 and 21.6 L/min, respectively). In addition, asthma symptom scores were reduced, and percentages of days with no asthma symptoms increased in all treatment groups.\n Treatment with FSC in a CFC-free MDI is more effective than FP or salmeterol alone in asthma patients who are symptomatic taking short-acting beta2-agonists alone.", "The twice daily administration of an inhaled corticosteroid (ICS) and long-acting beta(2)-agonist (LABA) has been shown to be effective in achieving asthma control. The once daily administration of an ICS/LABA may be a treatment option for some patients.\n To assess the effectiveness of fluticasone propionate (FP)/salmeterol via a single inhaler (FSC) administered once daily compared with FP once daily, FSC twice daily, or placebo.\n A 12-week, randomized, double-blind multicenter study conducted in 844 patients > or = 12 years of age who were symptomatic while using a short-acting beta(2)-agonist alone. Blinded treatments included: FSC 250/50 mcg once daily in the evening (FSC 250/50 QD), FP 250 mcg once daily in the evening (FP 250 QD), FSC 100/50 mcg twice daily (FSC 100/50 mcg BID), or placebo. All treatments were delivered via the Diskus device.\n All treatments demonstrated greater improvements in efficacy measures compared with placebo. Overall, the greatest improvements were observed in the patients receiving FSC, either once or twice daily, compared with the FP 250 QD group. The two FSC treatments were similar except that QD dosing did not maintain improvements in lung function for 24h compared with twice daily dosing. All treatments were well tolerated. No suppression of HPA axis, as assessed by 24-h urinary cortisol excretion, was observed in any of the active treatment groups.\n In patients symptomatic on a short-acting beta(2)-agonist alone, FSC 100/50 mcg BID was shown to provide better efficacy than a higher strength (FSC 250/50 mcg) administered once daily. However, a once daily regimen was effective and may be a valuable treatment option for some patients. Registered at (http://ctr.gsk.co.uk/welcome.asp) (SAS30022)." ]

[ "9451758", "18060943", "11966480", "17023012", "14745915", "14577813" ]

[ "Population-based case-control study of teratogenic potential of corticosteroids.", "Maternal corticosteroid use and orofacial clefts.", "Risk of intrauterine growth retardation, malformations and other birth outcomes in children after topical use of corticosteroid in pregnancy.", "The cosmetic use of skin-lightening products during pregnancy in Dakar, Senegal: a common and potentially hazardous practice.", "First trimester exposure to corticosteroids and oral clefts.", "Maternal drug use and infant cleft lip/palate with special reference to corticoids." ]

[ "The teratogenic potential of oral and topical corticosteroid treatment during pregnancy was evaluated in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1994. Corticosteroid tablet pregnancy exposure was 1.55% among 20,830 malformed cases and 1.41% among 35,727 healthy control births (P = 0.2). Corticosteroid ointment pregnancy exposure was 0.35% among malformed and 0.33% among control births (P = 0.7). The absolute risk of oral and ointment corticosteroid treatment was low in pregnancy and particularly in the second and third months of gestation, i.e., in the critical period for major congenital abnormalities. The adjusted odds ratio and the analysis of case-control pairs did not show any association between the rate of different congenital abnormalities and the corticosteroid treatment in the second and third months of gestation. Thus, treatments with corticosteroids in pregnancy do not appear to noticeably increase the risk of congenital abnormalities in humans.", "The purpose of this study was to examine whether maternal corticosteroid use during pregnancy is associated with delivering an infant with an orofacial cleft.\n This study included data on deliveries from the National Birth Defects Prevention Study, which is a population-based case-control study. Exposures were assessed by telephone interviews for mothers of 1141 cases with cleft lip +/- cleft palate (CLP), 628 with cleft palate (CP), and 4143 controls.\n Mothers of 33 infants with CLP (2.9%), mothers of 6 infants with CP (1.0%), and 72 control subjects (1.7%) reported corticosteroid use from 4 weeks before through 12 weeks after conception. The crude odds ratio for \"any\" vs \"no\" use was 1.7 (95% CI, 1.1-2.6) for CLP and 0.5 (0.2-1.3) for CP. When analyzed by route of administration and medication components, odds ratios for CLP tended to be elevated, and odds ratios for CP tended to be close to 1.\n Our results suggest a moderately increased risk of CLP among women who use corticosteroids during early pregnancy.", "Topical corticosteroids are frequently used drugs, but little is known of the exposure during pregnancy and birth outcome.\n In a population-based follow-up study restricted to primigravida women, we examined the risk of low birth weight, malformations and other birth outcomes following pregnancy upon exposure to topical corticosteroids. We compared the offspring of 363 women exposed to topical corticosteroids during pregnancy with 9263 controls, who received no prescriptions at all.\n The prevalence of malformations was 2.9% among 170 infants exposed during the first trimester and 3.6% among the controls. Adjusted odds ratios for low birth weight, malformations and preterm delivery among women receiving weak/medium strong corticosteroids were 0.7 (95% CI 0.17-2.85), 0.93 (95% CI 0.23-3.80) and 1.04 (95% CI 0.56-1.92), respectively, and adjusted odds ratios for strong/very strong corticosteroids were 1.23 (95% CI 0.45-3.37), 0.56 (95% CI 0.14-2.28) and 0.99 (95% CI 0.54-1.84), respectively.\n The study showed no increased risk of low birth weight, malformations or preterm delivery in the offspring of women exposed to topical corticosteroid during pregnancy.", "Many women of childbearing age from sub-Saharan Africa use topical skin lighteners, some of which present a risk of toxic systemic effects. The goals of this study were to evaluate, in this environment, the frequency of this practice during pregnancy, as well as eventual consequences on pregnancy. Ninety-nine women from 6 to 9 months pregnant were randomly selected among those attending a standard maternal centre in Dakar for a prenatal visit. Investigations consisted of questions about the use of skin lighteners, a standard clinical examination, follow-up until delivery and a morning blood sample for plasma cortisol levels. Sixty-eight of the 99 selected women used skin lighteners during their current pregnancy, the main active ingredients being hydroquinone and highly potent steroids (used by 64 and 28 women, respectively). No difference in the main outcomes of pregnancy were found between skin-lightener users and the others; however, women using highly potent steroids, when compared with those who did not, had a statistically significant lower plasma cortisol level and a smaller placenta, and presented a higher rate of low-birth-weight infants. Skin lightening is a common practice during pregnancy in Dakar, and the use of steroids may result in consequences in the mother and her child.", "The possible association between oral cleft in the newborn and maternal exposure to corticoids during pregnancy is still controversial. The aim of this study was to test this association by a case-control analysis using the large multicentric MADRE database.\n The MADRE database is a collection of information on malformed infants with a history of maternal first-trimester drug exposure. Nine malformation registries participate in the data collection. Cases were defined as infants presenting with a cleft palate or cleft lip, and exposure was defined by the use of corticosteroids during the first trimester of pregnancy.\n After 12 years of data collection, the database includes data on 11,150 malformed infants. A slight association is observed between exposure to corticoids for systemic use and the occurrence of cleft lip with or without cleft palate (OR, 2.59; 95% CI, 1.18-5.67).\n If the observed association is real, an interpretation is suggested, based on a likely interaction between corticosteroids and environmental dioxins. It is indeed possible that human fetuses may become sensitive to the teratogenic effect of corticosteroids when they are exposed in utero to environmental pesticides as well.\n Copyright 2003 Wiley-Liss, Inc.", "To study the association between maternal drug use in early pregnancy and orofacial cleft in the infant.\n Register analysis based on prospectively collected information.Patients: All delivered women in Sweden July 1, 1995, through December 31, 2001.\n Presence of orofacial cleft in infant.\n Prospective information on maternal drug use during the first trimester, as reported in early pregnancy, was studied in 1142 infants with orofacial clefts, isolated or with other malformations, excluding chromosome anomalies. Any drug use was not associated with clefts (odds ratio [OR] = 0.98, 95% confidence interval [95% CI] = 0.85 to 1.13), with isolated clefts (OR = 0.92) with isolated median cleft palate (OR = 1.03, 95% CI = 0.79 to 1.36) or with isolated cleft lip with or without cleft palate (OR = 0.86, 95% CI = 0.71 to 1.05). Reported use of multivitamins, folic acid, or B(12) was not associated with a decrease in orofacial cleft risk (OR = 1.00, 95% CI = 0.63 to 1.52). ORs above 2 were seen for some drugs: sulfasalazine, naproxen, and anticonvulsants, but only a few exposed cases occurred. An association between glucocorticoid use and infant cleft was indicated and seemed to be strongest for median cleft palate.\n Maternal drug use seems to play only a small role for the origin of orofacial clefts, at least in Sweden." ]

[ "11788172" ]

[ "The effect of garlic tablet on plasma lipids and platelet aggregation in nulliparous pregnants at high risk of preeclampsia." ]

[ "This study was designed to determine the effect of garlic tablet (Garlet) on plasma lipids, and platelet aggregation and the efficacy of this treatment in the prevention of preeclampsia.\n In a randomized, single-blind, placebo-controlled study, 100 primigravidas with positive roll-over test were treated with daily doses of 800mg Garlet/day (n=50) or 800mg/day placebo (n=50) during the third trimester of pregnancy. Serum total cholesterol, LDL-and HDL-cholesterol, triglyceride, and platelet aggregation were measured before and after the treatment. Blood pressure, weight, and edema were also examined during the entire study period.\n In the case group, there was no significant difference in the means of total cholesterol, HDL, LDL, and triglyceride before and after the experiment. Furthermore, the inhibition of platelet aggregation did not show any significant difference before and after the treatment. There were not any significant difference in the means of HDL, LDL, triglyceride, inhibition of platelet aggregation, the means of systolic and diastolic blood pressure and the mean arterial blood pressure (MAP), between the two groups, but there was a significant difference in the means of total cholesterol (P=0.038) and hypertension alone (P=0.043).\n The administration of 800mg/day of Garlet during the third trimester of pregnancy was effective in reducing the occurrence of hypertension alone, but it was no effective in preventing of preeclampsia." ]

[ "8281698", "2244556", "10704160", "7608429", "8006281", "3050522" ]

[ "Combination antithrombotic therapy in unstable rest angina and non-Q-wave infarction in nonprior aspirin users. Primary end points analysis from the ATACS trial. Antithrombotic Therapy in Acute Coronary Syndromes Research Group.", "Usefulness of antithrombotic therapy in resting angina pectoris or non-Q-wave myocardial infarction in preventing death and myocardial infarction (a pilot study from the Antithrombotic Therapy in Acute Coronary Syndromes Study Group).", "Randomized trial comparing intravenous nitroglycerin and heparin for treatment of unstable angina secondary to restenosis after coronary artery angioplasty.", "Low molecular weight heparin versus regular heparin or aspirin in the treatment of unstable angina and silent ischemia.", "Comparison of the effect of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina.", "Aspirin, heparin, or both to treat acute unstable angina." ]

[ "The purpose of this study was to compare combination antithrombotic therapy with aspirin plus anticoagulation versus aspirin alone, when added to conventional antianginal therapy in patients with unstable rest angina or non-Q-wave myocardial infarction who were nonprior aspirin users.\n Two hundred fourteen patients were randomized; 109 were randomized to receive aspirin alone (162.5 mg daily) and 105 to receive a combination of aspirin plus anticoagulation, ie, aspirin 162.5 mg daily plus heparin (activated partial thromboplastin time, two times control) followed by aspirin 162.5 mg daily plus warfarin (international normalized ratio, 2 to 3). Trial therapy was begun by 9.5 +/- 8.8 hours of qualifying pain and was continued for 12 weeks. Primary end points were recurrent angina with ECG changes, myocardial infarction, and/or death. Analysis by intention to treat of primary events at 12 weeks was performed. At 14 days, there was a significant reduction in total ischemic events in the combination group versus aspirin alone (10.5% versus 27%, P = .004). An efficacy analysis of primary events at 12 weeks also revealed a large reduction in total ischemic events in the combination group versus aspirin alone (13% versus 25%, P = .06). Bleeding complications were slightly more common with combination therapy.\n In nonprior aspirin users, combination antithrombotic therapy with aspirin plus anticoagulation significantly reduces recurrent ischemic events in the early phase of unstable angina.", "In a prospective pilot trial of antithrombotic therapy in the acute coronary syndromes (ATACS) of resting and unstable angina pectoris or non-Q-wave myocardial infarction, 3 different antithrombotic regimens in the prevention of recurrent ischemic events were compared for efficacy. Ninety-three patients were randomized to receive aspirin (325 mg/day), or full-dose heparin followed by warfarin, or the combination of aspirin (80 mg/day) plus heparin and then warfarin. Trial antithrombotic therapy was added to standardized antianginal medication and continued for 3 months or until an end point was reached. Analysis, by intention-to-treat, of the 3-month end points, revealed the following: recurrent ischemia occurred in 7 patients (22%) after aspirin, in 6 patients (25%) after heparin and warfarin, and in 16 patients (43%) after aspirin combined with heparin and then warfarin; coronary revascularization occurred in 12 patients (38%) after aspirin, in 12 patients (50%) after heparin and warfarin, and in 22 patients (60%) after aspirin combined with heparin and then warfarin; myocardial infarction occurred in 1 patient (3%) after aspirin, in 3 patients (13%) after heparin and warfarin, and in no patient after aspirin combined with heparin and then warfarin; no deaths occurred after aspirin or after aspirin combined with heparin and then warfarin, but 1 patient (4%) died after warfarin alone; major bleeding occurred in 3 patients (9%) after aspirin, in 2 patients (8%) after heparin and warfarin, and in 3 patients (8%) after aspirin combined with heparin and then warfarin. Recurrent myocardial ischemia occurred at 3 +/- 3 days after randomization.(ABSTRACT TRUNCATED AT 250 WORDS)", "The treatment of unstable angina targets the specific pathophysiological thrombotic process at the site of the active culprit lesion. In unstable angina due to a restenotic lesion, smooth muscle cell proliferation and increased vasoreactivity may play a more important role than thrombus formation. Therefore, the relative benefits of nitroglycerin and heparin might differ in unstable angina associated with restenosis compared with classic unstable angina.\n We randomized 200 patients hospitalized for unstable angina within 6 months after angioplasty (excluding those with intracoronary stents) to double-blind administration of intravenous nitroglycerin, heparin, their combination, or placebo for 63+/-30 hours. Recurrent angina occurred in 75% of patients in the placebo and heparin-alone groups, compared with 42.6% of patients in the nitroglycerin-alone group and 41.7% of patients in the nitroglycerin-plus-heparin group (P<0.003). Refractory angina requiring angiography occurred in 22.9%, 29.2%, 4. 3%, and 4.2% of patients, respectively (P<0.002). The odds ratios for being event free were 0.24 (95% CI, -0.13 to 0.45, P=0.0001) for nitroglycerin versus no nitroglycerin and 0.98 (95% CI, -0.55 to 1. 73, P=NS) for heparin versus no heparin. No patient died or suffered myocardial infarction.\n Intravenous nitroglycerin is highly effective in preventing adverse ischemic events (recurrent or refractory angina) in patients with unstable angina secondary to restenosis, whereas heparin has no effect.", "This study was designed to test the hypothesis that low molecular weight heparin may lessen the severity of ischemic events in patients with unstable angina.\n Unstable angina is a thrombotic process that requires intensive medical treatment. Although current treatments can reduce the number of complications, serious bleeding continues to occur. Nadroparin calcium, a low molecular weight heparin, seems to be a safe therapeutic agent that does not require laboratory monitoring.\n A total of 219 patients with unstable angina entered the study at a mean time of 6.17 h after the last episode of rest pain. Patients were randomized to receive aspirin (200 mg/day [group A]), aspirin plus regular heparin (400 IU/kg body weight per day intravenously and titered by activated partial thromboplastin time [group B]) and aspirin plus low molecular weight heparin (214 UIC/kg anti-Xa twice daily subcutaneously [group C]). The major end points determined for the in-hospital period were 1) recurrent angina, 2) myocardial infarction, 3) urgent revascularization, 4) major bleeding, and 5) death. Minor end points were 1) silent myocardial ischemia, and 2) minor bleeding. Event rates were tested by chi-square analysis.\n Recurrent angina occurred in 37%, 44% and 21% of patients in groups A, B and C, respectively, and was significantly less frequent in group C than in either group A (odds ratio 2.26, 95% confidence interval [CI] 1 to 5.18, p = 0.03) or group B (odds ratio, 3.07, 95% CI 1.36 to 7.00, p = 0.002). Nonfatal myocardial infarction was present in seven patients in group A, four in group B and none in group C (group B vs. A, p = 0.5; group C vs. A, p = 0.01). Urgent revascularization was performed in nine patients in group A, seven in group B and one in group C (C vs. A, p = 0.01). Two episodes of major bleeding occurred in group B. Silent myocardial ischemia was present in 38%, 41% and 25% of patients in groups A, B and C, respectively, and was significantly less frequent in group C than group B (odds ratio 2.12, 95% CI 0.97 to 4.69, p = 0.04). Minor bleeding was detected in 10 patients in group B, 1 patient in group C (B vs. C, p = 0.01) and no patient in group A (A vs. B, p = 0.003).\n In this study, treatment with aspirin plus a high dose of low molecular weight heparin during the acute phase of unstable angina was significantly better than treatment with aspirin alone or aspirin plus regular heparin.", "This study compared the effects of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina.\n Transient myocardial ischemia occurring in patients with unstable angina is associated with an adverse prognosis. Heparin and aspirin are two drugs used frequently in the treatment of this condition, but the effect of combination therapy versus aspirin alone on transient myocardial ischemia is unknown.\n Two hundred eighty-five consecutive patients with unstable angina were randomized to receive either intravenous heparin plus oral aspirin (150 mg once daily) (Group H + A) or aspirin alone (Group A). Patients also received a beta-adrenergic blocking agent, diltiazem and intravenous nitrates. ST segment monitoring was performed for the 1st 48 h of treatment. Patients were followed up for the duration of their in-hospital stay.\n One hundred fifty-four patients (30 women, mean [+/- SEM] age 58.3 +/- 0.8 years) received heparin and aspirin (Group H + A), and 131 patients (26 women, mean age 60.6 +/- 0.8 years) received aspirin only (Group A). ST segment monitoring (11,622 h) yielded 244 episodes of transient myocardial ischemia of a total duration of 7,819 min. There were no significant differences between the two treatment arms in the number of patients with transient myocardial ischemia (27 [18%] in Group H + A vs. 31 [24%] in Group A), number of episodes (96 in Group H + A vs. 148 in Group A) or total duration of transient myocardial ischemia (2,911 min in Group H + A vs. 4,908 min in Group A). The incidence of in-hospital myocardial infarction or death was significantly higher in patients with transient myocardial ischemia (53% vs. 22%, p < 0.0001). Five of the six deaths occurred in patients with transient myocardial ischemia. Event-free survival from myocardial infarction or death was similar in both treatment groups. Preadmission therapy with aspirin was associated with a lower in-hospital infarction rate (19% vs. 34%, p = 0.01).\n The presence of transient myocardial ischemia in patients with unstable angina is associated with a significantly higher incidence of myocardial infarction or death in hospital. Combined therapy with heparin and aspirin compared with aspirin alone makes no difference in the development of these events, nor does it reduce the development of transient myocardial ischemia.", "We tested the usefulness of aspirin (325 mg twice daily), heparin (1000 units per hour by intravenous infusion), and a combination of the two in the early management of acute unstable angina pectoris in a double-blind, randomized, placebo-controlled trial involving 479 patients. The patients entered the study as soon as possible after hospital admission (at a mean [+/- SD] of 7.9 +/- 8.0 hours after the last episode of pain), and the study was ended after 6 +/- 3 days, when definitive therapy had been selected. Major end points--refractory angina, myocardial infarction, and death--occurred in 23, 12, and 1.7 percent of the 118 patients receiving placebo, respectively. Heparin was associated with a decrease in the occurrence of refractory angina (P = 0.002). The incidence of myocardial infarction was significantly reduced in the groups receiving aspirin (3 percent; P = 0.01), heparin (0.8 percent; P less than 0.001), and aspirin plus heparin (1.6 percent, P = 0.003), and no deaths occurred in these groups. There were too few deaths overall to permit evaluation of the effect of treatment on this end point. The combination of aspirin and heparin had no greater protective effect than heparin alone but was associated with slightly more serious bleeding (3.3 vs. 1.7 percent). We conclude that in the acute phase of unstable angina, either aspirin or heparin treatment is associated with a reduced incidence of myocardial infarction, and there is a trend favoring heparin over aspirin. Heparin treatment is also associated with a reduced incidence of refractory angina." ]

[ "12202066", "21071561", "12933772", "19748883", "16289314" ]

[ "Effectiveness of the \"Smoke-Free Class Competition\" in delaying the onset of smoking in adolescence.", "Effects of Smokefree Class Competition 1 year after the end of intervention: a cluster randomised controlled trial.", "Prevention of smoking in adolescents with lower education: a school based intervention study.", "Adverse effects of a social contract smoking prevention program among children in Québec, Canada.", "Lack of sustainable prevention effect of the \"Smoke-Free Class Competition\" on German pupils." ]

[ "This paper examines the effectiveness of the \"Smoke-Free Class Competition\" in delaying the onset of smoking in adolescence. Each participating class must decide if they want to be a \"smoke-free class\" for the 6-month period from fall to spring. Classes monitor their (non-)smoking behavior and report it to the teacher regularly. Classes in which pupils refrain from smoking for this period of time participate in a prize draw, in which they can win a number of attractive prizes.\n To evaluate the effectiveness of the competition, a sample of 131 participating and nonparticipating classes (number of pupils 2,142; mean age 12.9 years, SD = 0.98) was compared with regard to their smoking behavior. Smoking status was determined by self-assessment on three occasions: (a) prior to the beginning of the competition, (b) 1 month after the competition, and (c) 1 year after the start of the competition.\n From pretest to posttest smoking increased by 7.5% in the comparison group, while it decreased by 0.2% in the intervention group (OR = 2.19; P < 0.001). In the follow-up measurement, a clear increase in smoking prevalence occurs in all groups; however, the pupils in the intervention condition still have a significant lower increase of smoking (OR = 1.45; P < 0.01). Moreover, with regard to the nonsmokers at baseline, pupils in the comparison group showed significantly higher prevalences in smoking than the intervention group in the postmeasurement, 7.8 versus 13.9% (OR = 1.98; P < 0.001), as well as in the in the follow-up-measurement, 17 versus 21.3% (OR = 1.36; P < 0.05).\n The results suggest that the participation in the competition could delay the onset of smoking in adolescence.", "The Smokefree Class Competition, a school-based smoking prevention intervention, is widely disseminated in Europe. Participating classes commit themselves to be smoke-free and self-monitor their smoking status. Classes that remain smoke-free for 6 months can win prizes. Effects of the intervention on current smoking, initiation and progression of smoking were investigated.\n Cluster randomised controlled trial. 84 schools (208 classes with 3490 students; mean age 12.6 years, 50.4% female) in Saxony-Anhalt, Germany, were randomly assigned to intervention or control condition. A baseline survey was conducted before the implementation of the programme, while post-test and follow-up surveys were carried out 7 (immediately after the end of the competition), 12 and 19 months after baseline. Effects of participation in the programme on current and lifetime smoking were analysed by multilevel models controlling for confounding variables.\n Intervention students smoking occasionally at baseline smoked less frequently than students taking not part in the intervention at 7 and 12 months after baseline. Persistent beneficial programme effects were also found for lifetime smoking: intervention students were less likely to progress from experimental to established use.\n Data suggest that Smokefree Class Competition reduces the probability of progressing from occasional and experimental stages of smoking to more established forms of use.\n Trial registration ISRCTN27091233 in Current Control Trial Register.", "To assess the effect of an antismoking intervention focusing on adolescents in lower education. Students with lower education smoke more often and perceive more positive norms, and social pressure to smoke, than higher educated students. An intervention based on peer group pressure and social influence may therefore be useful to prevent smoking among these students.\n Group randomised controlled trial.\n 26 Dutch schools that provided junior secondary education.\n 1444 students in the intervention and 1118 students in the control group, all in the first grade, average age 13 years.\n Three lessons on knowledge, attitudes, and social influence, followed by a class agreement not to start or to stop smoking for five months and a class based competition.\n Comparison of smoking status before and immediately after and one year after the intervention, using multilevel analysis.\n In the intervention group, 9.6% of non-smokers started to smoke, in the control group 14.2%. This leads to an odds ratio of 0.61 (95% CI= 0.41 to 0.90) to uptake smoking in the intervention group compared with the control group. One year after the intervention, the effect was no longer significant.\n In the short-term, an intervention based on peer pressure decreases the proportion of adolescents with lower education who start smoking. Influencing social norms and peer pressure would therefore be a promising strategy in terms of preventing smoking among adolescents. The results also suggest that additional interventions in later years are needed to maintain the effect.", "To evaluate the impact of a smoke-free class competition in elementary schools in Québec, Canada before widespread dissemination of the program across the province.\n In a quasiexperimental study design, 843 students in 27 schools exposed to \"Mission TNT.06\" were compared to 1213 students in 57 matched comparison schools. Baseline data were collected in grade 6 prior to implementation of the program. Follow-up data were collected in grade 7 after students had transitioned to secondary school.\n The program improved knowledge about the harmful effects of second-hand smoke, but had no impact on knowledge about the harmful effects of smoking, attitudes about the acceptability of cigarettes, beliefs about the tobacco industry, or self-efficacy to resist peer pressure to smoke. After exposure to the program, intervention students were more likely to misreport their smoking status and to report unfavourable attitudes about classmates who smoke.\n Mission TNT.06 may encourage young smokers to misreport their smoking status and to marginalise classmates who smoke. These findings prompted recommendations to conduct more in-depth evaluation of the smoke-free class competition before widespread dissemination of the program across the province.", "This study examines the effectiveness of the school-based campaign \"Smoke-Free Class Competition\" as a means of preventing young non-smokers from taking up smoking.\n Based on two measurements of the Heidelberg Children's Panel Study (1998 and 2000), a longitudinal sample of 1704 pupils was examined: 948 in the intervention group and 756 in the control group. In order to evaluate the effects of the intervention, we compared the smoking behavior in the intervention and the control group at two points in time, shortly before, and 18 months after the intervention, on an individual case basis.\n (1) Stabilization of never-smoking rates: the proportion of pupils remaining a never-smoker at the follow-up is 62.1% in the intervention group and 61.5% in the control group (OR 1.02, 95% CI: 0.83-1.24); (2) Lowering of relapse rates among ex-smokers: the proportion of former smokers who had not started smoking again in the follow-up is 45.1% in the intervention group and 41.4% in the control group (OR 1.07, 95% CI: 0.77-1.49).\n The \"Smoke-Free Class Competition\" did not prevent smoking among adolescents and does not appear to be an effective substitute to the complete ban of tobacco advertising, the abolition of vending machines and the creation of smoke-free environments in German schools." ]

[ "10656954", "8798871", "10773786", "8542159", "11961630", "10805546", "7851857", "7833515", "9112894", "14738324", "11353965", "1416164", "9706511", "11071403", "7776273", "10353554", "8211620", "8102542", "7910083", "7824868", "10791184", "8784319", "12376782", "9649045", "9479724", "8362533", "7612367", "9015941", "10881952", "7953415", "12679946", "9696444", "11052308", "7618966", "9408302" ]

[ "Videolaparoscopic cholecystectomy induces a hemostasis activation of lower grade than does open surgery.", "Pulmonary mechanics during laparoscopic surgery.", "Laparoscopic and laparotomic cholecystectomy: a randomized trial comparing postoperative respiratory function.", "Effects of laparoscopic cholecystectomy on global respiratory muscle strength.", "Pulmonary function after laparoscopic and open cholecystectomy.", "Systemic and cell-mediated immune response after laparoscopic and open cholecystectomy in patients with chronic liver disease. A randomized, prospective study.", "Effects of surgical trauma of laparoscopic vs. open cholecystectomy.", "Metabolic responses to cholecystectomy: open vs. laparoscopic approach.", "Systemic stress response after laparoscopic or open cholecystectomy: a randomized trial.", "Effects of open vs. laparoscopic cholecystectomy on oxidative stress.", "Hemodynamic and pulmonary changes during open, carbon dioxide pneumoperitoneum and abdominal wall-lifting cholecystectomy. A prospective, randomized study.", "Comparison of postoperative respiratory function after laparoscopy or open laparotomy for cholecystectomy.", "Endocrine and immune response to injury after open and laparoscopic cholecystectomy.", "Comparison of postoperative acute-phase reactants in patients who underwent laparoscopic v open cholecystectomy: a randomized study.", "Open versus laparoscopic cholecystectomy: a comparison of postoperative temperature.", "Comparative evaluation of the inflammatory mediators in patients undergoing laparoscopic versus conventional cholecystectomy.", "The evolution of postoperative ileus after laparoscopic cholecystectomy. A comparative study with conventional cholecystectomy and sympathetic blockade treatment.", "Laparoscopic and open cholecystectomy. A prospective, randomized study.", "[Laparoscopic versus open cholecystectomy: a prospective randomized study].", "Comparison of sequential and fixed-sample designs in a controlled clinical trial with laparoscopic versus conventional cholecystectomy.", "Laparoscopic versus open cholecystectomy: effect on pulmonary function tests.", "A prospective randomized comparison of the metabolic and stress hormonal responses of laparoscopic and open cholecystectomy.", "Evaluation of oxidative stress in laparoscopic cholecystectomy.", "Laparoscopic vs. open cholecystectomy in patients aged 65 and older.", "Hemodynamic and pulmonary changes during and after laparoscopic cholecystectomy. A comparison with traditional surgery.", "Pulmonary function after cholecystectomy performed through Kocher's incision, a mini-incision, and laparoscopy.", "[A cost analysis of laparoscopic cholecystectomy compared with the open technic].", "A prospective randomised study of laparoscopic v. open cholecystectomy in aged patients with cholecystolithiasis.", "Laparoscopic or open cholecystectomy: a prospective randomised trial to compare postoperative pain, pulmonary function, and stress response.", "Laparoscopic versus open cholecystectomy: hospitalization, sick leave, analgesia and trauma responses.", "Operative stress response and energy metabolism after laparoscopic cholecystectomy compared to open surgery.", "Pulmonary function and complications after laparoscopic cholecystectomy.", "Operative stress response is reduced after laparoscopic compared to open cholecystectomy: the relationship with postoperative pain and ileus.", "Laparoscopic cholecystectomy does not prevent the postoperative protein catabolic response in muscle.", "Inflammatory mediators and surgical trauma regarding laparoscopic access: free radical mediated reactions." ]

[ "Tissue injury after trauma and surgery may induce alterations in blood coagulation and fibrinolysis, and the hypercoagulable state observed after surgery can be associated with the risk of postoperative thromboembolic complications. Recently, videolaparoscopic (VLPS) cholecystectomy has been introduced, and its advantages over the open procedure seem related to the reduced surgical trauma. The aim of this study was to investigate hemostatic system alterations in patients who undergo open and VLPS cholecystectomy.\n Fibrinogen, prothrombin fragment F1+2, D-dimer, and plasminogen activator inhibitor type-1 (PAI-1) activity was determined in 10 patients who underwent open (group A) and 10 patients who underwent VLPS cholecystectomy (group B), respectively. Blood samples were obtained the day of surgery in the morning (B1), after anesthesia (A1), 1 hour after the start of surgery (S1), then 30 min (E.05) and 24 h (E.24) after the surgery.\n No significant differences were observed in baseline values between groups A and B for the parameters investigated. At 24 h after surgery, fibrinogen increased significantly (p < 0.05) in group A and also was significantly higher than in group B (p < 0.05). In group A, a marked increase in F1+2 levels (p < 0.01) was observed in all the samples, with the maximum values on the first day after surgery (3.7 nmol/l; 1.2-6.0 nmol/l), whereas in group B, a slight but significant increase in F1+2 levels (2.1 nmol/l; 1.1-3.9 nmol/l; p < 0.01) was observed only 30 min after the end of surgery. In both groups A and B, D-dimer markedly increased after surgery, without statistical significant differences between the two groups at any time. The PAI-1 activity plasma levels remained in the normal range during and after surgery in both groups.\n These results indicate that VLPS surgery induces an activation of the clotting system that, although of low degree and short duration, can lead to a transient prothrombotic state.", "nan", "The fact that pulmonary complications occur in 20-60% of the patients subjected to abdominal operations clearly indicates that the lungs are the most endangered organ during the postoperative period.\n The aim of this study was to demonstrate the impact of cholecystectomy on postoperative respiratory disturbances by comparing the laparotomic cholecystectomy with laparoscopic gallbladder removal.\n A hundred cholecystectomized patients were included in the prospective randomized clinical trial. Half of the patients were operated on by the laparotomic procedure, whereas the other half underwent laparoscopic cholecystectomy. Spirometric parameters, arterial blood gases, and acid-base balance were determined before the operation, and at 6, 24, 72 and 144 h postoperatively. Abdominal distension was assessed by auscultating intestinal peristaltics, abdominal circumference measurement, and time interval to restitution of defecation.\n Six hours postoperatively, the values of ventilation parameters decreased on average by 40-50% from the baseline preoperative values in both groups of patients. The group of patients submitted to laparotomic cholecystectomy had significantly lower spirometric values and slower recovery of the ventilation parameters than the laparoscopic cholecystectomy group. Abdominal circumference was significantly greater and the time needed for restitution of peristaltics and defecation was significantly longer in the laparotomic cholecystectomy group compared to the group of laparoscopic cholecystectomy.\n Statistically significant impairments including hypoxia, hypocapnia and hyperventilation were observed in the patients submitted to laparotomic cholecystectomy, indicating the presence of objective respiratory risk, especially in elderly patients and patients with obstructive pulmonary diseases or cardiac insufficiency.\n Copyright 2000 S. Karger AG, Basel", "Laparoscopic cholecystectomy has a better postoperative outcome than the traditional open technique, which has been shown to significantly affect respiratory muscle function. The aim of this study was to investigate the effects of laparoscopic surgery on respiratory function, and particularly that of the respiratory muscles. Respiratory muscle strength was assessed in 26 patients who underwent laparoscopic cholecystectomy and in 25 who underwent open cholecystectomy by measuring mouth pressure during maximum static inspiratory (PImax) and expiratory (PEmax) efforts. PImax, PEmax, and blood gases were measured 24 h preoperatively (-24 h) as well as 24 h (+24 h) and 48 h (+48 h) postoperatively. FEV1 and FVC were measured at -24 h and +48 hr, and the ratio of FEV1 to FVC (FEV1/FVC) was calculated. PImax decreased at +24 h and +48 h in both groups, but this decrease was significantly greater in the patients who had open surgery, (p < 0.01, and p < 0.005, respectively). Similarly, PEmax was significantly smaller in the open- than in the laparoscopic-surgery group (p < 0.0001) at +48 h. Spirometric indices showed a more severe restrictive defect at +48 h after open surgery than after laparoscopy (p = 0.01). The arterial oxygen tension (PaO2) was significantly greater in the laparoscopic- than in the open-surgery group at +24 h (p < 0.007). Laparoscopic cholecystectomy caused smaller decreases in respiratory muscle strength than did open surgery. This accords with the hypothesis of phrenic nerve inhibition during open surgery. The results are of clinical importance, since they may explain the different outcomes with the two techniques.", "Laparotomy causes a significant reduction of pulmonary function, and atelectasis and pneumonia occur after open cholecystectomy. In this prospective, randomized study, we evaluated the hypothesis that pulmonary function is less restricted after laparoscopic cholecystectomy (LC) than after open cholecystectomy (OC).\n Sixty patients underwent laparoscopic (n = 30) or open (n = 30) cholecystectomy. The two groups did not differ significantly in age, sex, intraoperative findings, and preoperative pulmonary function. Pulmonary function tests, arterial blood-gas analysis, and chest radiographs were obtained in both groups before operation and on postoperative day 1.\n The forced expiratory volume in 1 s (mean +/- SD values; OC, 1.49 +/- 0.77 L/s; LC, 2.33 +/- 0.80 L/s; p > 0.0001) and the forced vital capacity (OC, 2.40 +/- 0.66 L; LC, 2.93 +/- 1.05 L; p > 0.01) were more suppressed in patients having OC than in those having LC. Similar results were found for the peak expiratory flow (OC, 3.51 +/- 1.35 L/s; LC, 4.27 +/- 1.66 L/s; p > 0.05), expiratory reserve volume (OC, 0.73 +/- 0.34 L; LC, 0.92 +/- 0.43 L; p > 0.05), and the midexpiratory phase of forced expiratory flow (FEF25-75) (OC, 1.45 +/- 0.54 L/s; LC, 1.60 +/- 0.73 L/s; NS). Laparoscopic cholecystectomy was associated with a significantly lower incidence of (30 vs 70%) and less severe atelectasis and better oxygenation.\n Pulmonary function is better preserved after LC than after OC.", "As impaired immune function observed in cirrhotic patients is known to increase the risk of postoperative complications, the immunological response to surgery was investigated.\n Twenty-eight patients with postnecrotic liver cirrhosis or chronic hepatitis C and symptomatic gallstone disease were randomly allocated to laparoscopic (LC) or open cholecystectomy (OC). Changes in concentrations of cytokines (TNF-alpha, IL-1beta, IL-6, IL-8 and IL-10) were followed and the effect of surgical trauma on the distribution of lymphocyte subpopulations (CD3, CD4, CD8, CD16 and CD19) and NK cell cytotoxicity were measured.\n After OC a decrease in circulating CD3 (p < 0.05) and CD4 (p < 0.05) and an increase in CD19 (p < 0.05) cells were detected in contrast to LC after which only CD16 cells decreased (p = 0.05). The number of CD3 cells was higher after LC than after OC (p < 0.01), whereas the number of CD19 cells was higher after OC than after LC (p < 0.01). NK cell cytotoxicity was reduced after LC (p < 0.05). In cirrhotic patients circulating cytokines were unaffected by OC, whereas TNF-alpha (p < 0.05) and IL-1beta (p < 0.05) were reduced after LC. In chronic hepatitis IL-1beta decreased after OC (p = 0.05) and IL-10 was significantly higher after LC than following OC (p < 0.05).\n The immune response is less pronounced after a laparoscopic procedure compared to a conventional approach in patients with chronic liver disease.", "The effects of surgical trauma resulting from laparoscopic cholecystectomy and open cholecystectomy, were compared by assessing the postoperative acute phase alterations of selected plasma proteins, hormones and lymphocyte subpopulations in fifty-seven patients prior to elective cholecystectomy. Patients were prospectively randomized to undergo either laparoscopic cholecystectomy (n = 30) or open cholecystectomy (n = 27). Duration of operation and general anesthesia was similar in the two patient groups. The laparoscopic cholecystectomy patients had a shorter postoperative stay in hospital (3.1 (0.5) days vs. 7.1 (1.6) days; p < 0.001). In open cholecystectomy patients a significantly greater postoperative acute phase increase in plasma C-reactive protein (p < 0.001), cortisol (p < 0.05), and prolactin blood level (p < 0.001) was recorded. The postoperative acute phase decrease in the blood total-T-lymphocyte count (CD3 cells) and in the activated-lymphocyte count (OKDR cells) was significantly greater after open cholecystectomy (p < 0.05). These results, showing that acute phase responses are less marked after laparoscopic cholecystectomy than after open cholecystectomy, support the concept that the laparoscopic procedure is less traumatic.", "Laparoscopic cholecystectomy is considered a minor surgical procedure. In a prospective, randomized study, we compared the metabolic responses to surgery in two groups of patients submitted to open or laparoscopic cholecystectomy. The aim of the study was to verify if the latter caused less metabolic changes. Blood samples were drawn before the operation (basal), 1 h and 2 h after skin incision, and on the first and second postoperative days. The following parameters were studied: cortisol, renin, and leukocytes, including subpopulations. The mean values for age, weight, height, basal neutrophil and lymphocyte counts, basal values of cortisol and renin of patients, and sex distribution of group 1 patients (open, n = 20) matched with those for group 2 (laparoscopic, n = 20), with the exception of age (p < 0.05). No differences were detected between the two groups in terms of cortisol and renin values. However, the neutrophil count 1 h after skin incision was statistically significantly higher with the laparoscopic approach (p < 0.05). The lymphocyte count on the second postoperative day was also statistically significantly higher in group 2 (p < 0.05). We conclude that when a cholecystectomy is performed, the laparoscopic approach has no advantage over the open approach from the standpoint of the metabolic responses we studied. It appears that leukocytes have a more rapid return to normal values after laparoscopic cholecystectomy. Although pneumoperitoneum is known to be responsible for important cardiorespiratory changes, no worse response was found in the laparoscopic group than in the open group.", "Surgical injury induces a systemic endocrine-metabolic response which is proportional to the severity of surgical stress. Laparoscopic cholecystectomy is associated with a favourable clinical outcome compared with open cholecystectomy suggesting that surgical injury is reduced.\n In a randomized clinical trial of 41 patients undergoing laparoscopic cholecystectomy and 42 patients undergoing open cholecystectomy, the neuroendocrine and metabolic stress responses were compared. Plasma levels of cortisol, adrenaline, noradrenaline, glucose, interleukin (IL) 6 and C-reactive protein (CRP) were measured before, during and at 4, 8 and 24 h after operation.\n Plasma levels of cortisol and catecholamines increased during and after both laparoscopic and open cholecystectomy; however, their postoperative responses during and after both laparoscopic and open cholecystectomy; however, their postoperative responses were significantly higher (P < 0.05) after open cholecystectomy. Glucose, IL-6 and CRP levels also increased after operation and were significantly higher (P < 0.05) in the open cholecystectomy group.\n The neuroendocrine stress response and inflammatory response following laparoscopic cholecystectomy were significantly reduced compared with those after open cholecystectomy.", "Elective laparoscopic cholecystectomy is established as the treatment of choice for symptomatic cholecystolithiasis and is now proposed for the treatment of acute cholecystitis. The aim of this study is to evaluate biochemical aspects of open (OC) and laparoscopic cholecystectomy (LC). We measured the levels of malondialdehyde (MDA) and the levels of nitrite+nitrate as stable end products of nitric oxide (NO). MDA and nitrite+nitrate levels were increased at both surgical procedures compared to preoperative period, but the rise was more significant in OC than LC. These results showed that both OC and LC caused an increase in oxidative stress. However LC caused significantly less oxidative stress and the changes during surgery returned to preoperative values after LC in a shorter period. The beneficial effects of laparoscopic surgery may be related, partially, to less oxidative stress in the immediate postoperative period.", "Carbon dioxide (CO2) pneumoperitoneum effects are still controversial. The aim of this study was to investigate cardiopulmonary changes in patients subjected to different surgical procedures for cholecystectomy.\n In this study, 15 patients were assigned randomly to three groups according to the surgical procedure to be used: open cholecystectomy (OC), CO2 pneumoperitoneum cholecystectomy (PP), and laparoscopic gasless cholecystectomy (abdominal wall lifting [AWL]), respectively. A pulmonary artery catheter was used for hemodynamic monitoring in all patients. A subcutaneous multiplanar device (Laparo Tenser) was used for abdominal wall lifting. To avoid misinterpretation of results, conventional anesthesia was performed with all parameters, and the position of the patients held fixed throughout surgery. The following parameters were analyzed: mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), cardiac index (CI), stroke volume index (SVI), central venous pressure (CVP), systemic vascular resistances index (SVRI), mean pulmonary arterial pressure (MPAP), pulmonary capillary wedge pressure (PCWP), pulmonary vascular resistances index (PVRI), peak inspiratory pressure (PIP), end-tidal CO2 pressure (ETCO)2, CO2 arterial pressure (PaCO2), and arterial pH.\n All the operations were completed successfully. The Laparo Tenser allowed good exposition of the surgical field. A slight impairment of the cardiopulmonary functions, with reduction of SVRI, MAP, and CI and elevation of pulmonary pressures and vascular resistance, followed induction of anesthesia. However, these effects tended to normalize in the OC and AWL groups over time. In contrast, CO2 insufflation produced a complex hemodynamic and pulmonary syndrome resulting in increased right- and left side filling pressures, significant cardiac index reduction, derangement of the respiratory mechanics, and respiratory acidosis. All of these effects normalized after desufflation.\n Cardiopulmonary adverse effects of general anesthesia were significant but transitory and normalized during surgery. Carbon dioxide pneumoperitoneum caused a significant impairment in cardiopulmonary functions. In high-risk patients, gasless laparoscopy may be preferred for reliability and absence of cardiopulmonary alterations.", "Cholecystectomy performed via laparotomy is associated with reduction of lung volumes including functional residual capacity that may lead to postoperative hypoxia and atelectasis. Laparoscopic cholecystectomy is associated with faster recovery compared to open laparotomy and cholecystectomy. To determine whether laparoscopic cholecystectomy was associated with less pulmonary dysfunction, 20 patients (ASA Physical Status I) undergoing elective cholecystectomy were randomly assigned to surgical teams performing either laparoscopy or open laparotomy for cholecystectomy. Patients in whom one or the other surgical technique had to be performed for medical or psychologic indications were excluded from the study. A standardized anesthetic technique and postoperative analgesic regimen were used. Forced vital capacity and forced expiratory volume in 1 s; functional residual capacity determined by a closed-circuit, constant volume helium dilution technique; and arterial O2 and CO2 tensions were measured preoperatively and at 6, 24, and 72 h postcholecystectomy. Forced vital capacity and forced expiratory volume in 1 s were significantly greater (P less than 0.05) in the laparoscopy compared to the laparotomy group at 6, 24, and 72 h postoperatively. Forced vital capacity relative to preoperative values was significantly (P less than 0.05) greater in patients with laparoscopy (24 h, 70 +/- 14%; 72 h, 91 +/- 6%) compared to open laparotomy (24 h, 57 +/- 23%; 72 h, 77 +/- 14%). Similarly, forced expiratory volumes in 1 s relative to preoperative values were significantly (P less than 0.05) greater in patients with laparoscopy (24 h, 85 +/- 13%; 72 h, 92 +/- 9%) compared to open laparotomy (24 h, 54 +/- 22%; 72 h, 77 +/- 11%).(ABSTRACT TRUNCATED AT 250 WORDS)", "There is clinical evidence that the surgical insult experienced by patients who undergo laparoscopic cholecystectomy (LC) differs significantly from that experienced by those undergoing open cholecystectomy (OC). LC is accompanied by less pain, better ventilatory function and almost total absence of secondary paralytic ileus. The aim of the present study was to investigate the endocrine and immune response to the injury induced by both types of surgery. To this end, the relationship between levels of hormones of the hypothalamus-hypophysis-adrenal axis (indicators of stress) and cytokine levels was analyzed.\n Blood samples from subjects undergoing either OC (n = 14) or LC (n = 14) were obtained 24 h before surgery and 24 h and 7 days after surgery. Serum concentrations of interleukin-6 (IL-6), interleukin-1 (IL-1), interleukin-10 (IL-10) and prolactin were determined using enzyme-linked immunosorbent assay. Cortisol and GH concentrations were determined by radioimmunoassay.\n Twenty-four hours after surgery, prolactin, GH and cortisol levels were higher than preoperative values in both OC and LC groups. Seven days after surgery, cortisol and GH levels had normalized but prolactin levels were maintained. No significant differences in hormone levels were detected between OC and LC groups. IL-6 levels were significantly higher in the OC group 7 days after intervention. Correlation analysis between levels of cytokines and hormones indicated that prolactin, at concentrations exceeding physiological values, regulates levels of IL-1 (p 0.3271, p < 0.05) and IL-6 (p = 0.3765, p < 0.01). Although levels were similar in both groups, cortisol was shown to exert weak but significant, linear control on IL-6 levels (r = 0.4569, p < 0.001).\n A similar hormonal response to surgical insult was produced in patients subjected to OC and LC. IL-6 levels seem to be the most indicative of injury. Prolactin is the main hormone involved in the regulation of cytokines produced in response to this type of stress and is thought to exert control over the production of IL-6.", "We investigated the effect of laparoscopic v open cholecystectomy on acute-phase reactants.\n Fifty patients were randomized to laparoscopic (Group 1) and 50 to open (Group 2) cholecystectomy. Preoperative and postoperative values for acute-phase reactants (ceruloplasmin, fibrinogen, Westergren sedimentation rate, alpha-1-antitrypsin, haptoglobin, and C-reactive protein) in blood samples were compared.\n Acute-phase reactants and length of hospitalization were significantly lower in patients who underwent a laparoscopic cholecystectomy than in those who underwent an open cholecystectomy.\n Laparoscopic cholecystectomy appears associated with a less intense stress response and less tissue damage than open cholecystectomy.", "Laparoscopic cholecystectomy has been shown to allow better postoperative pulmonary function than open cholecystectomy, with less incidence of lung atelectasis. As atelectasis following abdominal surgery is responsible for most febrile episodes in the first 48 h, it was postulated that with minimally invasive surgery there may be a parallel improvement in the incidence of postoperative fever. This study was designed to evaluate this hypothesis. Seventy-eight patients were randomly divided into two groups. Thirty-eight had an open cholecystectomy and 40 underwent the laparoscopic approach. Twenty-one of the 38 patients (55%) following open cholecystectomy had early febrile episodes compared with only 6 of the 40 (15%) in the laparoscopic cholecystectomy group. We concluded that there was a lower incidence of febrile episodes following laparoscopic cholecystectomy and suggest that this was related to improved pulmonary function and minimal surgical trauma.", "Injury induces systemic inflammatory response. The degree of response is proportionate to the trauma.\n Patients with ultrasound-proven gall stones posted for operation were randomized into two groups. Laparoscopic cholecystectomy was performed in one group while the other group underwent conventional cholecystectomy. Peripheral venous blood samples for inflammatory mediators, namely tumour necrosis factor, C-reactive protein, oxygen release from monocytes and polymorphonuclear leucocytes were drawn 1 day before surgery and repeated on the first and third days after surgery. Partial pressure of arterial oxygen was also measured in both groups. Only patients who met selection criteria and had uncomplicated postoperative courses were included in the study. There was a total of 40 patients for the final analysis, 20 in each group.\n There was no significant difference (P > 0.1) in age, sex or body mass index in both groups of patients. The level of all of the inflammatory mediators was elevated on the first postoperative day; however, the elevation was significantly less following laparoscopic cholecystectomy compared to conventional cholecystectomy (P < 0.01). Although the values came down on the third postoperative day, they remained above the respective controls. Postoperative hypoxaemia was significantly more in patients of conventional than laparoscopic cholecystectomy (P < 0.001).\n Trauma-induced inflammatory response is significantly less following laparoscopic cholecystectomy compared to conventional cholecystectomy. It appears to be related to degree of trauma.", "Our study is prompted by the arrival of laparoscopic cholecystectomy in connection with the evolution of postoperative ileus (PI) and by its avoidance of the intraabdominal handling implied in conventional cholecystectomy. With this aim a prospective, controlled, randomized, and blind clinical trial was designed using 100 patients divided into five groups (n = 20): I, conventional cholecystectomy (CC): II, CC+injection of 20 ml bupivacaine 0.5% into the mesentery root; III, CC + 7.5 mg propranolol i.v. and 0.5 mg neostigmine s.c., postoperatively until the first defecation; IV, II+III; and V, laparoscopic cholecystectomy. The shortest period of PI was observed in group V. This period increases notably in group IV (53 h), group II (72 h), and group III (84 h) relative to the control group with (89 h). This reduction in PI time runs parallel with an improvement in the patient's general state of well-being. We concluded that after laparoscopic cholecystectomy PI is nonexistent. Furthermore, this study confirms the correlation between the avoidance of intraabdominal manipulation and the evolution of postoperative ileus.", "To compare laparoscopic with open cholecystectomy.\n Prospective random control trial.\n Central Hospital of Akershus, Nordbyhagen, Norway.\n 74 consecutive patients due to undergo elective cholecystecomy between October 1990 and June 1991.\n Two patients were excluded from randomisation, and two were withdrawn after randomisation. The remaining 70 were randomly allocated to open or laparoscopic cholecystectomy (n = 35 in each group).\n Duration of operation and postoperative stay in hospital, amount of postoperative pain, incidence of complications, and duration of convalescence and sick leave.\n Laparoscopic cholecystectomy took twice as long as open (median [range] 100 [52-180] minutes compared with 50 [15-115], p < 0.01), but patients stayed in hospital half the time (2 [1-9] days compared with 4 [2-22], p < 0.01); required less opiate analgesia (4 [0-20] doses compared with 6 [0-13], p = 0.02; took less sick leave (11 [4-267] days (n = 18) compared with 34 [20-48] (n = 22), p < 0.01); and spent less time in convalescence (8 [3-40] days (n = 17) compared with 49 [10-247] (n = 12), p < 0.01). There were six complications in the laparoscopy group and seven in the open cholecystectomy group.\n Because of the significant differences between laparoscopic and open cholecystectomy we have now adopted the laparoscopic method as our standard, but we think that we can improve our results further by refining our operative techniques and giving our patients more information.", "A prospective randomized study of laparoscopic versus open cholecystectomy was carried out fro December 1991 to June 1992 at the Chang Gung Memorial Hospital. Laparoscopic cholecystectomy was performed in 50 cases in group A and open cholecystectomy in 51 cases in group B. All patients had a preoperative history of biliary tract disease and most had gall stones proved by sonography. There was no operative mortality in either group and the postoperative complication rates were 4.4% and 2% in group A and B respectively (p > 0.05). Prolonged operative time in group A was 85.7 +/- 25.2 min vs group B 48.0 +/- 13.9 min (p < 0.001). Postoperative bowel function recovery with toleration of a regular diet in group A was faster than group B (45.6 +/- 19.2 hrs vs 55.2 +/- 11.0 hrs, p < 0.001). The need for postoperative narcotic drugs with demerol injection was less in group A (40%) than group B (86%) (p < 0.001). The total cost for group A was NT $42139 +/- 7135 and for group B was NT $38085 +/- 7578 (p > 0.05). The interval of return to full activity for group A was shorter than group B (12.8 +/- 8.8 days vs 35.9 +/- 20.6 days respectively p < 0.001). Recurrent symptoms within the 6 to 13 month postoperative follow up period was 8% in group A and 11.7% in group B (p > 0.05). Only one patient in group B was proved to have a recurrent common bile duct stone by endoscopic retrograde cholangiography and received choledocholithotomy again.", "The aim of this study was to compare a fixed-sample and a sequential design with regard to study duration, sample size, and medical results in a real-life situation.\n A randomized study comparing laparoscopic and conventional cholecystectomy was carried out with a fixed-sample design, parallel with a sequential design. The main variable was duration of postoperative convalescence.\n In the fixed-sample trial the necessary number of patients was calculated to be 72. The sequential trial was conclusive after inclusion of 24 patients and reduced the duration of the study from 43 to 18 weeks. Additionally, the sequential trial reached the same conclusions as the fixed-sample trial in all the observed variables except for one.\n The present study indicates that sequential design should be used more frequently in clinical trials, to involve the smallest possible number of patients necessary to reach a conclusion.", "Operations often cause impairment in respiration due to pain. This study was designed to compare the changes in pulmonary function tests after open and laparoscopic cholecystectomy.\n Two groups of 35 patients were randomly set up. Each patient had 3 pulmonary function tests performed and 2 postero-anterior grid chest roentgenograms taken. All of these data were evaluated by the same group of investigators.\n After taking into consideration the difference between pulmonary function tests, values were not significant (P < or = 0.05). All pulmonary function test values decreased significantly on the 1st postoperative day (P < or = 0.05). When postero-anterior chest roentgenograms were compared no clinically evident atelectasis except 3 lineary was seen in the laparoscopic cholecystectomy group, whereas 5 lineary, 7 focal, and 3 segmentary atelectasia were encountered in the open cholecystectomy group (P < or = 0.05).\n We believe that laparoscopic cholecystectomy has more advantages when speaking of postoperative pulmonary function tests and atelectasia.", "In a relatively short period of time, therapeutic laparoscopy has become an everyday part of the general surgeon's life. Although laparoscopy provides distinct clinical advantages, it is not yet clear that it lessens the stress response typical of elective surgical procedures, and as such, the morbidity of surgery. The hypothesis that laparoscopic cholecystectomy produces less of a metabolic and stress hormonal response than open cholecystectomy was tested in a prospective randomized trial.\n Twenty otherwise healthy women between 18 and 45 years of age with a history of uncomplicated symptomatic cholelithiasis undergoing either laparoscopic (n = 10) or open cholecystectomy (n = 10) were studied. The hormonal response of the adrenocortical (serum adrenocorticotropic hormone, cortisol, and urinary free cortisol), adrenomedullary (plasma and urinary epinephrine and norepinephrine), thyroid (thyroid-stimulating hormone, thyroxine, and triiodothyronine), pituitary (antidiuretic hormone and growth hormone), and glucose (serum glucose, glucagon, and insulin) homeostatic axes were measured serially over a 24-hour period.\n No difference was seen between the laparoscopic and open groups in operative time (mean plus or minus standard error of the mean, 70 +/- 6 minutes compared with 77 +/- 6.3 minutes) or hospital stay 1.3 +/- 0.2 compared with 1.1 +/- 0.1 days). Assessment of postoperative pain using an analog pain score was less in the laparoscopic group (4.9 +/- 1.3 compared with 12.3 +/- 2.5, p = 0.01). The response of the adrenocortical, adrenomedullary, thyroid, and glucose axes were similar or identical in both groups. Antidiuretic hormone levels were greater in the laparoscopic group at one hour intraoperatively (281 +/- 79 pg/mL compared with 54 +/- 18 pg/mL, p < 0.01), and at extubation (122 +/- 18 pg/mL compared with 36 +/- 7 pg/mL, p < 0.01). Serum glucose levels were greater immediately following laparoscopic cholecystectomy. Glucose and insulin levels were greater at four, 12, and 24 hours after open cholecystectomy.\n Elective laparoscopic and open cholecystectomy for uncomplicated cholelithiasis result in similar degrees of perioperative hormonal stimulation. The different hormonal responses in the immediate and later postoperative periods after laparoscopic and open cholecystectomy suggest differential stressful stimuli between the two procedures.", "We conducted a prospective study to evaluate the effect of CO2 pneumoperitoneum and increased intra-abdominal pressure on arterial blood gases, end-tidal CO2 (ETCO2), nitric oxide (NO), blood and tissue malondialdehyde (MDA), and total antioxidant (TAOx) levels during laparoscopic cholecystectomy.\n Fifty selected patients with cholelithiasis were randomized to undergo either laparoscopic or open surgery. Blood samples were taken pre-, mid-, and postinsufflation, and 24 h postoperatively. To determine the tissue MDA level, tissue samples were taken from the gallbladder just after removal.\n The increased levels of ETCO2 and PCO2, caused by CO2 pneumoperitoneum resulted in a minimal decrease in blood pH during the laparoscopic surgery. Although low levels of blood MDA were seen 30 min after the start of laparoscopy, due to less oxidative stress response and tissue trauma, increased levels of tissue MDA levels indicated that the gallbladder was more traumatized during laparoscopic dissection and handling. NO levels were slightly lower in the laparoscopic cholecystectomy (LC) group, but there were no significant differences compared with the open cholecystectomy group (OC). TAOx levels were similar in both groups 30 min after the start the procedure, but were much lower in the LC group 24 h postoperatively.\n These findings suggest that the antioxidant defense system is stimulated less with less oxidative stress, providing further evidence to support the opinion that LC is a safe technique.", "Laparoscopic cholecystectomy (LC) has displaced open cholecystectomy (OC) in the management of cholelithiasis. However, there are few studies on the role of this technique in patients who run a high risk of surgical complications. We performed a prospective study in 264 patients aged >65 years undergoing surgery for symptomatic cholelithiasis. They were divided into two groups according to the surgical technique performed: OC (131 patients) and LC (133 patients). Conversion from LC to OC was necessary in 11 patients (8.3%). Mean surgery time was 70.9 min for the OC group and 75 min for the LC group. The LC group had a lower rate of postoperative complications (13.53%) than the OC group (23.6%). The incidence of mild complications was similar in both groups; however, the rate of moderate complications was significantly higher in the OC group. Hospital stay was significantly longer in the OC group (9.9 days) than in the LC group (3.71 days). These results suggest that LC should be indicated in elderly patients, as they are better than those obtained with with OC and involve a lower morbidity rate and shorter hospital stay.", "The cardiopulmonary changes experienced by patients who undergo laparoscopic cholecystectomy (LC) and the prognostic value of patient characteristics are not well understood.\n Cardiorespiratory changes were investigated in 120 patients undergoing LC or open cholecystectomy (OC). The results and their relation to patient variables were statistically evaluated.\n The most significant cardiorespiratory changes were (A-a)PO2 increase during OC; decrease of pH and compliance and increase of peak airway pressure during LC; impairment of arterial blood gas mean values and respiratory muscle strength; atelectasis and pneumonia (five cases) after OC; and lamellar atelectasis (two cases) after LC. Significant adverse prognostic factors related to intra- and postoperative LC cardiorespiratory changes were ASA class greater than I, FEF75-85% < 900 ml, and PaO2 < 10.4 kPa (PPV, 71.4% and 46.6%, respectively).\n LC carries no significant cardiorespiratory changes provided that intraoperative monitoring of hemodynamics and respiratory parameters is done for the study of blood gas values in all patients at risk.", "Comparative pulmonary function after cholecystectomy performed through Kocher's incision, a mini-incision, and laparoscopy was evaluated. Forty-five patients were randomly and prospectively divided into three groups of 15 each, depending on the surgical access employed. Forced vital capacity (FVC), forced expiratory volume at 1 second (FEV1), and forced expiratory flow at 25% to 75% (FEF25-75%) were determined 1 to 3 days before and 16 to 24 hours after cholecystectomy. The percent reduction of FVC (p = 0.0170), FEV1 (p = 0.0191), and FEF25-75% (p = 0.0045) was smaller after laparoscopic cholecystectomy than after Kocher's incision cholecystectomy. The percent reduction of FVC (p = 0.0170) was smaller after mini-incision cholecystectomy than after Kocher's incision cholecystectomy. There was no difference in the FEV1 (p = 0.0971) or FEF25-75% (p = 0.2058) between these two groups. FEF25-75% was significantly less impaired in the laparoscopic group than in the mini-incision group (p = 0.0327). No difference between these two groups was found in FVC (p = 0.5755) or FEV1 (p = 0.3952). It is concluded that postoperative pulmonary function is less impaired after laparoscopic cholecystectomy than after either mini-incision or Kocher's incision cholecystectomy.", "The aim of this study was to compare the cost of laparoscopic cholecystectomy with that of open cholecystectomy.\n We analyzed the cost of both procedures regarding hospital stay, days of work lost and the cost derived from the morbidity of the complications of each technique in two groups of patients. With these data we were able to calculate direct and indirect costs of both procedures and compare them.\n Morbidity was similar in both groups and had no influence in the cost; cost of the material used for laparoscopic cholecystectomy was higher; hospital stay and days of lost work were significantly lower for the laparoscopic procedure than for the open one. The total cost of laparoscopic cholecystectomy was 23% cheaper than that of open cholecystectomy.\n Laparoscopic cholecystectomy appears to be cheaper than open cholecystectomy. As the laparoscopic technique becomes more widespread its cost might decrease even further.", "Between August 1992 and July 1993, 27 patients aged 70 years of older with cholelithiasis were prospectively randomised into 2 groups. Fifteen patients underwent laparoscopic cholecystectomy and 12 patients underwent open cholecystectomy. Shorter operation time (93.3 +/- 25.3 minutes v. 176.3 +/- 26.1 minutes, P < 0.00001), fewer postoperative analgesic requirements (0.53 +/- 0.52 days v. 2.00 +/- 0.74 days, P < 0.00001), shorter postoperative hospital stay (3.93 +/- 1.71 days v. 7.92 +/- 0.79 days, P < 0.00001) and better cosmesis were found in the laparoscopic cholecystectomy group. The above data suggest that laparoscopic cholecystectomy is the treatment of choice for cholecystolithiasis in elderly patients.", "Open cholecystectomy (OC) has been superseded by laparoscopic cholecystectomy (LC) for the treatment of cholelithiasis, although this fashion has not been validated by prospective studies. Our aim was to compare the two techniques.\n Prospective, randomised, open study.\n University hospital, Finland.\n 49 patients who required cholecystectomy for cholelithiasis confirmed by ultrasound.\n 49 patients were randomly allocated to LC (n = 27) or OC (n = 22): 25 and 22, respectively, eventually had the operation. LC was done using a four-trocar technique, and OC through a transverse right subcostal incision, as short as possible.\n Length of hospital stay and the duration of the sick leave were the primary outcome measures. Secondary outcome measures were: postoperative pain evaluated by visual analogue scale (VAS) and the need for opioids; pulmonary function measured by forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak flow velocity (PEFV), and arterial oxygen tension (PaO2), and endocrine stress measured by plasma catecholamines, cortisol and glucose concentrations.\n The median (range) hospital stay was significantly shorter after LC than OC, being 2.0 (1-15) compared with 4.5 (2-19) days p < 0.01. The duration of sick leave was also significantly shorter after LC than OC, being 14 (7-17) compared with 29 (4-34), p < 0.01. Patients had significantly less postoperative pain after LC than OC as reflected by the need for opioids. Pulmonary function and arterial oxygen tension deteriorated significantly less after LC than OC. The stress response was equal. There were three documented complications, one pneumonia after LC and two wound infections after OC.\n LC gives significantly better results in terms of less postoperative pain, better pulmonary function, better arterial oxygenation, and shorter hospital stay and duration of sick leave.", "Laparoscopic cholecystectomy has rapidly become established as the treatment of choice for cholecystolithiasis. There is very little evidence, however, to support the claimed benefit to patients. In the present study 30 consecutive patients below the age of 65 years without acute cholecystitis and with no signs of common bile duct stones were randomized to laparoscopic or conventional open cholecystectomy. Median (interquartile range) intravenous consumption of pethidine with a patient-controlled injection device between 13 and 24 h after surgery was 125 (62-175) mg in patients who underwent the laparoscopic procedure and 200 (150-250) mg in those who had open operation. Urinary adrenaline and cortisol levels as well as those of plasma glucose, C-reactive protein and interleukin 6 were increased after surgery in both groups of patients, but without any significant difference between them. The mean(s.d.) duration of postoperative hospital stay (2.8(0.8) versus 1.8(0.6) days) and sick leave (24.0(4.4) versus 11.7(4.1) days) was significantly longer with open than laparoscopic cholecystectomy. The findings demonstrate obvious advantages of laparoscopic surgery as regards postoperative pain and convalescence, although factors reflecting the magnitude of trauma did not differ.", "To determine the least invasive surgical procedure by comparing the levels of operative stress hormones, response-reactive protein (CRP) and rest energy expenditure (REE) after laparoscopic (LC) and open cholecystectomy (OC).\n Twenty-six consecutive patients with noncomplicated gallstones were randomized for LC (14) and OC (12). Plasma concentrations of somatotropin, insulin, cortisol and CRP were measured. The levels of REE were determined.\n In the third postoperative day, the insulin levels were lower compared to that before operation (P<0.05). In the first postoperative day, the levels of somatotropin and cortisol were higher in OC than those in LC. After operation the parameters of somatotropin, CRP and cortisol increased, compared to those in the preoperative period in the all patients (P<0.05). In the all-postoperative days, the CRP level was higher in OC than that in LC (7.46+/-0.02; 7.38+/-0.01, P<0.05). After operation the REE level all increased in OC and LC (P<0.05). In the all-postoperative days, the REE level was higher in OC than that in LC (1438.5+/-418.5; 1222.3+/-180.8, P<0.05).\n LC results in less prominent stress response and smaller metabolic interference compared to open surgery. These advantages are beneficial to the restoration of stress hormones, the nitrogen balance, and the energy metabolism. However, LC can also induce acidemia and pulmonary hypoperfusion because of the penumoperitonium it uses during surgery.", "To investigate the impairment of pulmonary function and complications after laparoscopic compared with open cholecystectomy through an upper midline incision.\n Prospective randomised trial.\n Teaching hospital, Spain.\n 40 patients, 20 in each group.\n Clinical examination, spirometry, arterial blood gas analysis, and chest radiographs before and after operation.\n 48 hours postoperatively FVC and FEV1 had decreased to 56.7% and 53%, respectively, in the patients who had had open cholecystectomy, compared with 85.3% and 84.8% in the laparoscopic group (p < 0.0001). The mean (SD) postoperative percentage reductions in both PaO2 (86.1 (11.1) compared with 98.3 (11.3)) and SatO2 (98.6 (1.3) compared with 100 (1.5)) were also greater in the open group (p < 0.005 in both cases).\n Laparoscopic cholecystectomy causes less impairment of lung function than cholecystectomy through an upper midline incision.", "Our objective was to determine the least invasive surgical procedure; to do this we compared postoperative pain, duration of ileus, and level of neurohormonal stress response after laparoscopic cholecystectomy (LC) and open cholecystectomy (OC). Postoperative recovery of patients was faster after LC than OC but comparison of the neurohormonal stress response after laparoscopic and open surgical procedures revealed conflicting results. Forty-one consecutive patients with noncomplicated gallstones were randomized for LC (N = 25) and OC (N = 16). The stress level was evaluated in patients before surgery by the Hamilton anxiety scale. Postoperative pain was assessed by a visual analogic scale (VAS) pain score and by the amount of analgesic drugs (propacetamol) administered, while the duration of ileus was determined by the delay between surgery and the time to first passage of flatus as well by the colonic transit time (CTT) measured by radiopaque markers. Plasma concentrations of anti-diuretic hormone (ADH), adrenocorticotropic hormone (ACTH), beta-endorphin (BE), neurotensin (NT), and aldosterone (Ald) were measured before and during surgery as well as 2 and 5 hr after the surgery (D0) and on the day following surgery (D1). Urinary cortisol (uCOR) and urinary catecholamine metabolites were assessed before surgery, during D0, and on D1. Patient characteristics, the duration of surgery, and the doses of anesthetic drugs were not different in LC and OC. In LC patients the VAS pain score and the doses of postoperative antalgics were lower (P < 0.05), the time to first passage of flatus was shorter (P < 0.001), and the CTT tended to be shorter (54 +/- 12 hr vs 81 +/- 17) compared to OC patients. Patients who required the highest doses of postoperative antalgics had the longest delay to first passage of flatus (P < 0.01). During surgery, all neurohormonal parameters increased compared to the preoperative period (P < 0.05), and only plasma NT concentrations were lower during LC than OC (P < 0.05). During the postoperative period, ACTH, BE, Aid, catecholamines, and uCOR concentrations were lower in LC than in OC (P < 0.05). Concentrations of hormonal parameters were higher when the duration of surgery increased (P < 0.05). A greater need for propacetamol to relieve pain was associated with a greater increase in BE, ACTH, and urinary catecholamine levels (P < 0.05-P < 0.005). When the time to first passage of flatus was delayed, levels of BE, ACTH, and catecholamines and NT concentrations were increased (P < 0.05-P < 0.005). In conclusion, LC is less invasive because this surgical procedure induces a shorter neurohormonal stress response than OC, even if the peroperative response is not different. Postoperative pain levels and the duration of ileus are associated with BE, ACTH, and catecholamine levels and NT concentrations, suggesting the importance of hormones in postoperative functional recovery.", "The authors determined the effect of laparoscopic cholecystectomy on protein synthesis in skeletal muscle. In addition to a decrease in muscle protein synthesis, after open cholecystectomy, the authors previously demonstrated a decrease in insulin sensitivity. This study on patients undergoing laparoscopic and open surgery, therefore, included simultaneous measurements of protein synthesis and insulin sensitivity.\n Laparoscopy has become a routine technique for several operations because of postoperative benefits that allow rapid recovery. However, its effect on postoperative protein catabolism has not been characterized. Conventional laparotomy induces a drop in muscle protein synthesis, whereas degradation is unaffected.\n Patients were randomized to laparoscopic or open cholecystectomy, and the rate of protein synthesis in skeletal muscle was determined 24 hours postoperatively by the flooding technique using L-(2H5)phenylalanine, during a hyperinsulinemic normoglycemic clamp to assess insulin sensitivity.\n The protein synthesis rate decreased by 28% (1.77 +/- 0.11%/day vs. 1.26 +/- 0.08%/day, p < 0.01) in the laparoscopic group and by 20% (1.97 +/- 0.15%/day vs. 1.57 +/- 0.15%/day, p < 0.01) in the open cholecystectomy group. In contrast, the fall in insulin sensitivity after surgery was lower with laparoscopic (22 +/- 2%) compared with open surgery (49 +/- 5%).\n Laparoscopic cholecystectomy did not avoid a substantial decline in muscle protein synthesis, despite improved insulin sensitivity. The change in the two parameters occurred independently, indicating different mechanisms controlling insulin sensitivity and muscle protein synthesis.", "In this prospective study the free radical mediated reactions, the changes of endogenous antioxidant defense mechanism and activation of leukocytes were measured from the blood of patients undergoing elective cholecystectomy because of symptomatic cholecystolithiasis. The patients were randomised into two groups. Group one contained 21 patients treated by open cholecystectomy(OC). Group two consisted of 21 patients treated by laparoscopic cholecystectomy (LC). Both groups had similar patient characteristics. Patients with acute cholecystitis, pancreatitis, choledocholithiasis or other disease were excluded. Values from patients in both groups were compared. The measured biochemical parameters are the following: malondialdehyde (MDA) as a marker of the free radical induced lipid peroxidations, reduced and oxidised glutathione (GSH-GSSG), as endogenous scavengers as well as markers of oxidative stress and myeloperoxidase activity (MPO) of leukocytes. The results showed significantly lower values of postoperatively measured MDA, GSH-GSSG, and MPO activity of leukocytes in patients with laparoscopic cholecystectomy, indicating a lesser stress response and tissue trauma in this group of patients. The results correspond to the favourable results of most other trials evaluating clinical aspect of LC." ]

[ "6815756", "4879059", "8072261", "2868029", "3526127", "5340622", "3516608", "7398002", "16714187", "2857803", "7798505", "2865702", "11549300", "5336520", "2647556", "2860740", "4984849", "6401878", "1780077" ]

[ "[Prevention of recurrences of cerebral ischemic vascular accidents by platelet antiaggregants. Results of a 3-year controlled therapeutic trial].", "Dipyridamole: a controlled trial of its effect in acute myocardial infarction.", "Anti-platelet therapy in graft thrombosis: results of a prospective, randomized, double-blind study.", "Persantine-Aspirin Reinfarction Study. Part II. Secondary coronary prevention with persantine and aspirin.", "Treatment of claudication with dipyridamole and aspirin.", "Dipyridamole in the treatment of angina pectoris. A double-blind evaluation.", "Veterans Administration Cooperative Study on antiplatelet agents in diabetic patients after amputation for gangrene: II. Effects of aspirin and dipyridamole on atherosclerotic vascular disease rates.", "Persantine and aspirin in coronary heart disease. The Persantine-Aspirin Reinfarction Study Research Group.", "Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial.", "Drug-induced inhibition of platelet function delays progression of peripheral occlusive arterial disease. A prospective double-blind arteriographically controlled trial.", "Frequent reocclusion of patent infarct-related arteries between 4 weeks and 1 year: effects of antiplatelet therapy.", "[Ischemic cerebrovascular disease: treatment with various anti-platelet aggregation drugs. Clinical follow-up of 80 patients (22-34 months)].", "Dipyridamole in chronic stable angina pectoris; a randomized, double blind, placebo-controlled, parallel group study.", "Treatment of angina pectoris with dipyridamole: a long-term double blind study.", "Effect of aspirin alone and aspirin plus dipyridamole in early diabetic retinopathy. A multicenter randomized controlled clinical trial. The DAMAD Study Group.", "Persantine Aspirin Trial in cerebral ischemia. Part II: Endpoint results. The American-Canadian Co-Operative Study group.", "Treatment of angina pectoris with dipyridamole: a double-blind study.", "\"AICLA\" controlled trial of aspirin and dipyridamole in the secondary prevention of athero-thrombotic cerebral ischemia.", "[Treatment of unstable angina with dipyridamole combined with low doses of aspirin. A multicenter pilot double-blind controlled study]." ]

[ "nan", "A controlled trial of oral dipyridamole in 103 patients with acute myocardial infarction showed no difference in the number of complications or deaths in either the control or the treated groups. It is concluded that dipyridamole has no benefit in acute myocardial infarction.", "Hemodialysis (HD) vascular access thrombosis remains a major cause of morbidity, accounting for 17.4% of all HD patient hospital admissions in 1986. We initiated this prospective, randomized, double-blind, placebo-controlled, parallel group study to examine if dipyridamole and/or aspirin decreased the rate of thrombosis of expanded polytetrafluoroethylene (ePTFE) grafts in HD patients. Two patient groups were studied: Type I--with a new ePTFE graft; and Type II--with thrombectomy and/or revision of a previously placed ePTFE graft. One hundred and seven patients were followed for 18 months or until the first thrombotic episode. Actuarial analysis of Type I patients showed cumulative thrombosis rates (mean +/- SEM) of 21 +/- 9% on dipyridamole alone, compared with 25 +/- 11% on dipyridamole and aspirin combination, 42 +/- 13% on placebo, and 80 +/- 12% on aspirin alone. The relative risk of thrombosis with dipyridamole was 0.35 (P = 0.02) and that for aspirin was 1.99 (P = 0.18). In Type II patients, the rate of thrombosis was high in all study drug and placebo groups (overall 78% thrombosis) and actuarial analysis was not carried out because of the small number of patients enrolled. We conclude that dipyridamole is beneficial in patients with new ePTFE grafts and that aspirin does not improve the risk of thrombosis in ePTFE grafts. Neither dipyridamole nor aspirin has any beneficial effect in patients with prior thrombosis of ePTFE grafts.", "In the Persantine-Aspirin Reinfarction Study, Part II (PARIS II), 3,128 persons who had recovered from myocardial infarction, suffered from 4 weeks to 4 months previously, were randomized into two groups: dipyridamole (Persantine) plus aspirin (n = 1,563) and placebo (n = 1,565). The average length of follow-up was 23.4 months. Prespecified primary end points were coronary incidence (definite nonfatal myocardial infarction plus death due to recent or acute cardiac event), coronary mortality (death due to recent or acute cardiac event) and total mortality, each at 1 year of patient follow-up and at the end of the study. Coronary incidence in the Persantine plus aspirin group was significantly lower than in the placebo group, both at 1 year (30% reduction) and at the end of the study (24% reduction). The statistically significant differences in coronary incidence, at 1 year and at the end of the study, in favor of the combination treatment remained after adjustment for multiple baseline variables and adjustment for multiple testing (three end points for two time periods). Although there were reductions for other end points, these differences were not statistically significant. Coronary mortality was 20% lower in the Persantine plus aspirin group compared with the placebo group at 1 year, and 6% lower overall. Total mortality in the treated group compared with the placebo group was 11% lower at 1 year and 3% lower overall. The reduced rates of coronary incidence largely reflected lower rates of definite nonfatal myocardial infarction in the Persantine plus aspirin group. Several subgroups were defined a priori and at the end of the study. The beneficial effect of Persantine plus aspirin compared with placebo for coronary incidence tended to be greater for the following groups of patients: those who had a non-Q wave infarct; those who were not taking digitalis; those who were receiving beta-receptor blocking drugs at baseline; those who were in New York Heart Association functional class I; those who had had only one myocardial infarction; or those who were enrolled in the study early, that is within 85 days of the qualifying myocardial infarction.", "nan", "nan", "We report the results of a randomized multicenter clinical trial on the effects of aspirin plus dipyridamole versus placebo on major vascular end points in 231 non-insulin-dependent diabetic men with either a recent amputation for gangrene or active gangrene. Primary end points were death from atherosclerotic vascular disease plus amputation of the opposite extremity for gangrene. There were 24 atherosclerotic deaths in the drug treatment group (21.8%) and 23 in the placebo group (19.0%). There were 22 patients in the drug treatment group (20.0%) and 29 patients in the placebo group (24.0%) with opposite-side amputations. Survival curve analyses revealed little difference between these groups for major vascular end points, total mortality, all amputations, or myocardial infarctions. The most noteworthy group difference was observed for cerebrovascular end points (strokes and transient ischemic attacks), with an incidence of 8.2% (9 patients) in the drug treatment group and 19.0% (23 patients) in the placebo group. We conclude from this study that antiplatelet agents have no effect on the primary vascular end points, vascular deaths and/or amputation of the opposite extremity, in this population. Similarly, no effects were seen on secondary vascular end points, except for a suggestion of protection versus strokes and transient ischemic attacks. However, this finding must be interpreted with caution, since it is a secondary end point and was found only after multiple analyses of the data.", "In the Persantine-Aspirin Reinfarction Study (PARIS) trial, 2026 persons who had recovered from myocardial infarction (MI) were randomized into three groups: Persantine plus aspirin (PR/A) (n = 810); aspirin alone (ASA) (n = 810); placebo (PLBO) (n = 406). The average length of follow-up study was 41 months. Results for the three specified primary end points were: total mortality 16% lower in PR/A and 18% lower in ASA compared with PLBO; coronary mortality 24% and 21% lower; incidence of nonfatal MI plus fatal coronary disease 25% and 24% lower. These differences were not satistically significant by the study criterion (Z greater than or equal to 2.6). By life-table analysis, the rates of coronary mortality and coronary incidence were about 50% lower in the PR/A group than in the PLBO group from 8-24 months, and for coronary incidence all Z values were greater than or equal to 2.6; ASA rates were about 30% lower than PLBO rates, and for coronary incidence, Z values were greater than or equal to 2.6 at two points. For these end points, from 8-20 months, PR/A rates were about 30% lower than ASA rates, but all Z values were less than 2.0 PR/A and ASA patients entering within 6 months of last MI showed the largest percentage reductions in mortality; only the difference between PR/A and PLBO groups for 3-year coronary mortality yielded a Z value of 2.6.", "Results of trials of aspirin and dipyridamole combined versus aspirin alone for the secondary prevention of vascular events after ischaemic stroke of presumed arterial origin are inconsistent. Our aim was to resolve this uncertainty.\n We did a randomised controlled trial in which we assigned patients to aspirin (30-325 mg daily) with (n=1363) or without (n=1376) dipyridamole (200 mg twice daily) within 6 months of a transient ischaemic attack or minor stroke of presumed arterial origin. Our primary outcome event was the composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction, or major bleeding complication, whichever happened first. Treatment was open, but auditing of outcome events was blinded. Primary analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN73824458) and with (NCT00161070).\n Mean follow-up was 3.5 years (SD 2.0). Median aspirin dose was 75 mg in both treatment groups (range 30-325); extended-release dipyridamole was used by 83% (n=1131) of patients on the combination regimen. Primary outcome events arose in 173 (13%) patients on aspirin and dipyridamole and in 216 (16%) on aspirin alone (hazard ratio 0.80, 95% CI 0.66-0.98; absolute risk reduction 1.0% per year, 95% CI 0.1-1.8). Addition of the ESPRIT data to the meta-analysis of previous trials resulted in an overall risk ratio for the composite of vascular death, stroke, or myocardial infarction of 0.82 (95% CI 0.74-0.91). Patients on aspirin and dipyridamole discontinued trial medication more often than those on aspirin alone (470 vs 184), mainly because of headache.\n The ESPRIT results, combined with the results of previous trials, provide sufficient evidence to prefer the combination regimen of aspirin plus dipyridamole over aspirin alone as antithrombotic therapy after cerebral ischaemia of arterial origin.", "240 patients were admitted to a double-blind study to determine the effect of long-term treatment with platelet-function inhibiting agents on occlusive arterial disease in the lower extremities. Patients were randomised into 1 of 3 treatment groups: aspirin 330 mg; dipyridamole 75 mg and aspirin 330 mg; or matching placebo 3 times daily. The duration of treatment was 2 years. Arteriography was carried out at the beginning of the study and 2 years later or before if deterioration was observed. 199 patients completed the study according to the trial protocol. The serial arteriograms were assessed in pairs qualitatively, by means of simple comparative viewing, and semiquantitatively with Bollinger's score system. Progression of the disease was most pronounced in the placebo-treated group, less so in the aspirin-treated group, and least of all in the dipyridamole-and-aspirin group. Patients who smoke and those with hypertension may benefit most from treatment with the 2 preparations under investigation.", "This study assessed the effect of the combination of aspirin and dipyridamole on patency of the infarct-related artery between 4 weeks and 1 year after myocardial infarction.\n Patency of the infarct-related artery is an important determinant of prognosis after myocardial infarction. The incidence of late reocclusion and the effects of antiplatelet therapy are unknown.\n To investigate the importance of antiplatelet therapy for the prevention of late reocclusion, 215 patients who had a patent infarct-related artery 4 weeks after myocardial infarction were randomized in a double-blind manner to receive either a combination of 25 mg of aspirin and 200 mg of dipyridamole twice daily or placebo. One hundred fifty-four patients underwent further coronary arteriography 1 year later.\n At 1 year, 38 (25%) of 154 patients had reocclusion of the infarct-related artery; 18 (23%) of 79 patients receiving aspirin and dipyridamole had late reocclusion versus 20 (27%) of 75 who received placebo (p = NS). The rate of reocclusion was related to the severity of the residual coronary artery stenosis at 4 weeks (< 50% stenosis 9.2%; 50% to 69% stenosis 11.6%; 70% to 89% stenosis 30.4%; > or = 90% stenosis 70%, p < 0.01). The majority of reocclusions were silent, and only 17 (45%) of 38 were clinically associated with further infarction. There were no differences for a hierarchic end point of cardiac death, myocardial infarction or revascularization (14.8% aspirin and dipyridamole vs. 17.8% placebo).\n Late reocclusion of the patent infarct-related artery is a frequent event, occurring in 25% of patients. Antiplatelet therapy with the combination of aspirin and dipyridamole does not alter the overall rate of late reocclusion. Other strategies are required to reduce late reocclusion.", "Personal experience in the treatment of Ischaemic Cerebrovascular Disease with platelet suppressant drugs is reported. 80 patients were treated with 5 different protocols: 1) group \"A\": dipyridamol (14 patients); 2) group \"B\": acetylsalicylic acid (ASA) (14 patients); 3) group \"C\": dipyridamol and ASA (22 patients); 4) group \"D\": ditazol (15 patients); 5) group \"E\": isoxsuprine resinate (15 patients) and followed-up for 22-34 months. The evolution of the disease is discussed and recurrences evaluated on the basis of initial clinical features and particular treatment given.", "Oral dipyridamole induces accumulation of endogenous adenosine, which in a hypoxic milieu exerts experimentally an angiogenic effect on coronary collateral circulation. A meta-analysis of 13 randomized placebo-controlled trials published between 1960 and 1992 showed evidence of benefit for dipyridamole in the treatment of angina pectoris, especially with longer duration of treatment. Aim To assess the efficacy and safety of dipyridamole in the treatment of patients with chronic stable angina in a large scale, international, randomized, placebo-controlled, parallel group study.\n Four hundred patients with chronic stable angina pectoris and a positive treadmill exercise test were randomized to receive either modified release dipyridamole (200 mg b.i.d. p.o., n=198) or corresponding placebo (n=202), for 24 weeks as an add-on to conventional antianginal therapy and for 4 additional weeks as monotherapy--the latter after withdrawal of standard treatment with calcium antagonists and/or beta-blockers and/or long-acting (prophylactic) nitrates.\n Of the 198 patients randomized to dipyridamole, 134 completed the add-on and only 12 the monotherapy phase. Of the 202 patients randomized to placebo, 162 reached the add-on and only 12 the monotherapy phase. Serious adverse events occurred in 15 patients with dipyridamole and in 12 with placebo (7.6% vs 6.0, P=0.52). Increase over the baseline treadmill exercise test was similar in the treatment groups at each stage of the trial for all the main efficacy parameters: total treadmill exercise test duration; time to first anginal pain (except for a -13 s difference in favour of placebo at week 24;P=0.040); time to ST segment depression >0.1 mVolt (except for a +21 s difference in favour of dipyridamole at week 8;P=0.024; this latter difference was totally attributable to patients with lower exercise tolerance--Bruce stage II at study entry).\n In patients with chronic stable angina treated with regular antianginal background medication, the use of oral dipyridamole is safe and well tolerated. Antianginal and antiischaemic efficacy, as assessed by exercise testing, is comparable to placebo, except for a beneficial effect on time to ischaemia after 2 months, totally attributable to patients with lower exercise tolerance at study entry.\n Copyright 2001 The European Society of Cardiology.", "nan", "In a double-blind randomized controlled clinical trial conducted in two French and two United Kingdom centers, the effect of antiplatelet agents, i.e., aspirin alone (330 mg 3 times daily) or in combination with dipyridamole (75 mg 3 times daily), was tested versus placebo in 475 patients with early diabetic retinopathy. The assessment of retinopathy was based on change in the number of microaneurysms (MAs) present in the macular field, as seen on fluorescein angiograms, over 3 yr. Forty-one patients did not complete the study. At least three readable initial and yearly angiograms were available on 420 patients (266 treated with insulin and 154 not treated); the results reported are based on these patients. The mean yearly increase in definite MAs was similar in insulin-treated and non-insulin-treated diabetic patients. There was no significant difference between the aspirin-alone group (0.69 +/- 5.1 mean +/- SD, n = 145) and the aspirin-plus-dipyridamole group (0.34 +/- 3.0, n = 142). In the placebo group the mean yearly increase (1.44 +/- 4.5, n = 133) was significantly higher than in the treated group (P = .02, 1-tailed t test). There was a clear relationship between the deterioration in ophthalmological signs and the increase in mean yearly MAs (clinically stable, 0.38 +/- 3.96, n = 293; deteriorating, 1.79 +/- 4.89, n = 127; P = .002, 2-tailed t test). We conclude that aspirin alone and in conjunction with dipyridamole significantly slows the progression of MA evolution in early diabetic retinopathy.", "The Persantine Aspirin Trial focused on the question of whether the administration of the combination of aspirin and dipyridamole (Persantine) would result in a lower incidence of cerebral or retinal infarction or death than the administration of aspirin alone for persons with a history of recent carotid territory transient ischemic attacks (TIAs). Fifteen centers in the United States and Canada participated and 890 individuals were admitted and randomly allocated to either aspirin (325 mg) plus placebo or aspirin (325 mg) plus Persantine (75 mg) four times daily. Ninety eight percent of the subjects were followed for at least one year; many were followed for four to five years. The results of life table analysis indicate that the overall endpoint rates for the \"aspirin only\" and \"aspirin plus Persantine\" groups are identical. Thus, for TIA patients taking aspirin, the addition of Persantine contributes nothing. There was a clustering of stroke endpoints during the first month after randomization. Deaths from all causes were essentially equally divided between the two treatment groups.", "nan", "604 Patients with atherothrombotic cerebral ischemic events (transient, 16%: or completed, 84%) referrable either to the carotid or to the vertebral-basilar circulation were entered into a double blind randomized clinical trial (AICLA) to determine whether aspirin (A) (1 g/day) or aspirin (1 g/day) + Dipyridamole (225 mg/day) (AD) would produce a significant reduction in the subsequent (3 years) occurrence of fatal and nonfatal cerebral infarction. Randomization produced remarkably comparable treatment groups and this good comparability was maintained throughout the study. Adherence to the protocol and drug compliance were excellent. Side effects, particularly symptoms of peptic ulcer and hemorrhagic events were significantly (p less than 0.03) more frequent in the two treatment groups containing aspirin. With the exception of patients who withdrew from the study, each patient was followed for 3 years. At the end of the study, the number of fatal and nonfatal cerebral infarctions was 31 in the placebo (P) group, 17 in the A group and 18 in the AD group. Taking into account the duration of follow-up for each patient, these figures correspond to cumulative rates of 18% in the P group and 10.5% in each of the 2 active treatment groups. Analysis with the Mantel Method showed: 1)--A difference at the 6% level between the 3 groups and between P and AD; 2)--A difference at the 5% level between P and A; 3)--No difference between (A and AD; 4)--A difference at the 2% level between the P group and the two treated groups taken together (A + AD). Among other diseases occurring during the trial, the only significant difference concerned myocardial infarction, which was less frequent in the 2 treated groups (P less than 0.05). Subgroup analysis failed to show a significant sex difference in the efficacy of aspirin. It is concluded that, in patients comparable to those defined in the protocol, Aspirin (1 g) has a significantly beneficial effect in the secondary prevention of atherothrombotic cerebral infarction.", "In order to assess the usefulness of a combination of low-dose aspirin (25 mg b.i.d.) with dipyridamole (200 mg b.i.d.) in the prevention of major coronary events in patients with acute unstable angina, we performed a prospective, double-blind, placebo-controlled study involving 88 consecutive patients admitted to three Hospital Departments of Cardiology. The patients entered the study as soon as possible after hospital admission, and were treated and followed up to one year. There was no appreciable difference in side effects and adverse reactions between the treatment and control group. The incidence of cardiac death and/or nonfatal myocardial infarction during the whole period of observation was 14% (6/44) in the treatment group and 25% (11/44) in the placebo group by \"intention-to-treat\" analysis; 16% (4/25) and 32% (10/31), respectively, by \"drug-efficacy\" analysis (p = 0.21 by Fisher's exact test, non significant difference). However, when considering the only events occurred in the first month (2/44 in the treatment group and 9/44 in the placebo group, amounting to 4.5 and 20 percent, respectively), the combination of dipyridamole with low-dose aspirin reached a statistically significant protective effect (p = 0.04). The results of this pilot study provide strong evidence for a beneficial effect of the regimen tested in patients with acute unstable angina, at least in the first weeks of treatment, while at the same time suggesting a safe alternative for patients with contraindications to higher doses of aspirin." ]

[ "10323814" ]

[ "Effect of preoperative abstinence on poor postoperative outcome in alcohol misusers: randomised controlled trial." ]

[ "To evaluate the influence of preoperative abstinence on postoperative outcome in alcohol misusers with no symptoms who were drinking the equivalent of at least 60 g ethanol/day.\n Randomised controlled trial. Setting: Copenhagen, Denmark.\n 42 alcoholic patients without liver disease admitted for elective colorectal surgery.\n Withdrawal from alcohol consumption for 1 month before operation (disulfiram controlled) compared with continuous drinking.\n Postoperative complications requiring treatment within the first month after surgery. Perioperative immunosuppression measured by delayed type hypersensitivity; myocardial ischaemia and arrhythmias measured by Holter tape recording; episodes of hypoxaemia measured by pulse oximetry. Response to stress during the operation were assessed by heart rate, blood pressure, serum concentration of cortisol, and plasma concentrations of glucose, interleukin 6, and catecholamines.\n The intervention group developed significantly fewer postoperative complications than the continuous drinkers (31% v 74%, P=0.02). Delayed type hypersensitivity responses were better in the intervention group before (37 mm2 v 12 mm2, P=0.04), but not after surgery (3 mm2 v 3 mm2). Development of postoperative myocardial ischaemia (23% v 85%) and arrhythmias (33% v 86%) on the second postoperative day as well as nightly hypoxaemic episodes (4 v 18 on the second postoperative night) occurred significantly less often in the intervention group. Surgical stress responses were lower in the intervention group (P</=0.05).\n One month of preoperative abstinence reduces postoperative morbidity in alcohol abusers. The mechanism is probably reduced preclinical organ dysfunction and reduction of the exaggerated response to surgical stress." ]

[ "15457467", "16298061", "16266355", "18395345", "17060567", "15927394" ]

[ "A double-blind, multicenter trial comparing duloxetine with placebo in the treatment of fibromyalgia patients with or without major depressive disorder.", "A randomized, double-blind, placebo-controlled trial of duloxetine in the treatment of women with fibromyalgia with or without major depressive disorder.", "A double-blind, randomized multicenter trial comparing duloxetine with placebo in the management of diabetic peripheral neuropathic pain.", "Efficacy and safety of duloxetine for treatment of fibromyalgia in patients with or without major depressive disorder: Results from a 6-month, randomized, double-blind, placebo-controlled, fixed-dose trial.", "A randomized controlled trial of duloxetine in diabetic peripheral neuropathic pain.", "Duloxetine vs. placebo in patients with painful diabetic neuropathy." ]

[ "To assess the efficacy and safety of duloxetine, a serotonin and norepinephrine reuptake inhibitor, in subjects with primary fibromyalgia, with or without current major depressive disorder.\n This study was a randomized, double-blind, placebo-controlled trial conducted in 18 outpatient research centers in the US. A total of 207 subjects meeting the American College of Rheumatology criteria for primary fibromyalgia were enrolled (89% female, 87% white, mean age 49 years, 38% with current major depressive disorder). After single-blind placebo treatment for 1 week, subjects were randomly assigned to receive duloxetine 60 mg twice a day (n = 104) or placebo (n = 103) for 12 weeks. Co-primary outcome measures were the Fibromyalgia Impact Questionnaire (FIQ) total score (score range 0-80, with 0 indicating no impact) and FIQ pain score (score range 0-10). Secondary outcome measures included mean tender point pain threshold, number of tender points, FIQ fatigue, tiredness on awakening, and stiffness scores, Clinical Global Impression of Severity (CGI-Severity) scale, Patient Global Impression of Improvement (PGI-Improvement) scale, Brief Pain Inventory (short form), Medical Outcomes Study Short Form 36, Quality of Life in Depression Scale, and Sheehan Disability Scale.\n Compared with placebo-treated subjects, duloxetine-treated subjects improved significantly more (P = 0.027) on the FIQ total score, with a treatment difference of -5.53 (95% confidence interval -10.43, -0.63), but not significantly more on the FIQ pain score (P = 0.130). Compared with placebo-treated subjects, duloxetine-treated subjects had significantly greater reductions in Brief Pain Inventory average pain severity score (P = 0.008), Brief Pain Inventory average interference from pain score (P = 0.004), number of tender points (P = 0.002), and FIQ stiffness score (P = 0.048), and had significantly greater improvement in mean tender point pain threshold (P = 0.002), CGI-Severity (P = 0.048), PGI-Improvement (P = 0.033), and several quality-of-life measures. Duloxetine treatment improved fibromyalgia symptoms and pain severity regardless of baseline status of major depressive disorder. Compared with placebo-treated female subjects (n = 92), duloxetine-treated female subjects (n = 92) demonstrated significantly greater improvement on most efficacy measures, while duloxetine-treated male subjects (n = 12) failed to improve significantly on any efficacy measure. The treatment effect on significant pain reduction in female subjects was independent of the effect on mood or anxiety. Duloxetine was safely administered and well tolerated.\n In this randomized, controlled, 12-week trial (with a 1-week placebo lead-in phase), duloxetine was an effective and safe treatment for many of the symptoms associated with fibromyalgia in subjects with or without major depressive disorder, particularly for women, who had significant improvement across most outcome measures.", "This was a 12-week, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, in 354 female patients with primary fibromyalgia, with or without current major depressive disorder. Patients (90% Caucasian; mean age, 49.6 years; 26% with current major depressive disorder) received duloxetine 60 mg once daily (QD) (N=118), duloxetine 60 mg twice daily (BID) (N=116), or placebo (N=120). The primary outcome was the Brief Pain Inventory average pain severity score. Response to treatment was defined as >or=30% reduction in this score. Compared with placebo, both duloxetine-treated groups improved significantly more (P<0.001) on the Brief Pain Inventory average pain severity score. A significantly higher percentage of duloxetine-treated patients had a decrease of >or=30% in this score (duloxetine 60 mg QD (55%; P<0.001); duloxetine 60 mg BID (54%; P=0.002); placebo (33%)). The treatment effect of duloxetine on pain reduction was independent of the effect on mood and the presence of major depressive disorder. Compared with patients on placebo, patients treated with duloxetine 60 mg QD or duloxetine 60 mg BID had significantly greater improvement in remaining Brief Pain Inventory pain severity and interference scores, Fibromyalgia Impact Questionnaire, Clinical Global Impression of Severity, Patient Global Impression of Improvement, and several quality-of-life measures. Both doses of duloxetine were safely administered and well tolerated. In conclusion, both duloxetine 60 mg QD and duloxetine 60 mg BID were effective and safe in the treatment of fibromyalgia in female patients with or without major depressive disorder.", "Assess efficacy and safety of duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, on the reduction of pain severity, in patients with diabetic peripheral neuropathic pain (DPNP).\n This was a multicenter, parallel, double-blind, randomized, placebo-controlled trial that enrolled 348 patients with pain due to peripheral neuropathy caused by type 1 or type 2 diabetes mellitus. Patients (N = 116 per group) were randomly assigned to receive duloxetine 60 mg once daily (QD), duloxetine 60 mg twice daily (BID), or placebo, for 12 weeks. The primary outcome measure was the weekly mean score of 24-hour average pain severity evaluated on an 11-point Likert scale. Secondary outcome measures and safety were evaluated.\n Compared with placebo-treated patients, both duloxetine-treated groups improved significantly more (P < 0.001) on the 24-hour average pain score. Duloxetine demonstrated superiority to placebo in all secondary analyses of the primary efficacy measure. A significant treatment effect for duloxetine was observed in most secondary measures for pain. Discontinuations due to adverse events were more frequent in the duloxetine 60 mg BID- (12.1%) versus the placebo- (2.6%) treated group. Duloxetine showed no adverse effects on diabetic control, and both doses were safely administered and well tolerated.\n In this clinical trial, duloxetine 60 mg QD and duloxetine 60 mg BID were effective and safe in the management of DPNP.", "The primary objectives of this study were to assess the efficacy and safety of duloxetine for reducing pain severity in fibromyalgia patients with or without current major depressive disorder. This was a 6-month, multicenter, randomized, double-blind, placebo-controlled study. In total, 520 patients meeting American College of Rheumatology criteria for fibromyalgia were randomly assigned to duloxetine (20 mg/day, 60 mg/day, or 120 mg/day) or placebo, administered once daily, for 6 months (after 3 months, the duloxetine 20-mg/day group titrated to 60 mg/day). The co-primary outcome measures were the Brief Pain Inventory (BPI) average pain severity score and Patient Global Impressions of Improvement (PGI-I) score. Safety was assessed via treatment-emergent adverse events, and changes in vital sign, laboratory, and ECG measures. Compared with placebo-treated patients, those patients treated with duloxetine 120 mg/day improved significantly more on the co-primary outcome measures at 3 months (change in BPI score [-2.31 vs -1.39, P<0.001] and PGI-I [2.89 vs 3.39, P=0.004]) and at 6 months (change in BPI [-2.26 vs -1.43, P=0.003] and PGI-I [2.93 vs 3.37, P=0.012]). Compared with placebo, treatment with duloxetine 60 mg/day also significantly improved the co-primary measures at 3 months and BPI at 6 months. Duloxetine was efficacious in patients both with and without major depressive disorder. There were no clinically significant differences between treatment groups in changes in vital signs, laboratory measures, or ECG measures. Study results demonstrated that duloxetine at doses of 60 mg/day and 120 mg/day appears to be safe and efficacious in patients with fibromyalgia.", "Serotonin (5-HT) and norepinephrine (NE) are involved in pain modulation via descending inhibitory pathways in the brain and spinal cord.\n To assess the efficacy of duloxetine, a dual reuptake inhibitor of 5-HT and NE, on the reduction of pain severity, as well as secondary outcome measures in patients with diabetic peripheral neuropathic pain (DPNP).\n In this double-blind study, patients with DPNP and without comorbid depression were randomly assigned to treatment with duloxetine 60 mg once daily (QD), duloxetine 60 mg twice daily (BID), or placebo for 12 weeks. The primary outcome measure was the weekly mean score of 24-hour average pain severity on the 11-point Likert scale. Secondary measures and health outcome measures were also assessed.\n Duloxetine 60 mg QD and 60 mg BID demonstrated improvement in the management of DPNP and showed rapid onset of action, with separation from placebo beginning at week 1 on the 24-hour average pain severity score. For all secondary measures for pain (except allodynia), mean changes showed an advantage of duloxetine over placebo, with no significant difference between 60 mg QD and 60 mg BID. Clinical Global Impression of Severity and Patient's Global Impression of Improvement evaluation demonstrated greater improvement on duloxetine- vs placebo-treated patients. Duloxetine showed no notable interference on diabetic controls, and both doses were safely administered.\n This study confirms previous findings that duloxetine at 60 mg QD and 60 mg BID is effective and safe in the management of diabetic peripheral neuropathic pain.", "The aim of this study was to examine the efficacy and safety of duloxetine, a balanced and potent dual reuptake inhibitor of serotonin and norepinephrine, in the management of diabetic peripheral neuropathic pain. Serotonin and norepinephrine are thought to inhibit pain via descending pain pathways. In a 12-week, multicenter, double-blind study, 457 patients experiencing pain due to polyneuropathy caused by Type 1 or Type 2 diabetes mellitus were randomly assigned to treatment with duloxetine 20 mg/d (20 mg QD), 60 mg/d (60 mg QD), 120 mg/d (60 mg BID), or placebo. The diagnosis was confirmed by a score of at least 3 on the Michigan Neuropathy Screening Instrument. The primary efficacy measure was the weekly mean score of the 24-h Average Pain Score, which was rated on an 11-point (0-10) Likert scale (no pain to worst possible pain) and computed from diary scores between two site visits. Duloxetine 60 and 120 mg/d demonstrated statistically significant greater improvement compared with placebo on the 24-h Average Pain Score, beginning 1 week after randomization and continuing through the 12-week trial. Duloxetine also separated from placebo on nearly all the secondary measures including health-related outcome measures. Significantly more patients in all three active-treatment groups achieved a 50% reduction in the 24-h Average Pain Score compared with placebo. Duloxetine treatment was considered to be safe and well tolerated with less than 20 percent discontinuation due to adverse events. Duloxetine at 60 and 120 mg/d was safe and effective in the management of diabetic peripheral neuropathic pain." ]

[ "4267681", "4204032", "6416259" ]

[ "A controlled trial of gold salt therapy in rheumatoid arthritis.", "Gold salts in the treatment of rheumatoid arthritis. A double-blind study.", "Comparison of auranofin, gold sodium thiomalate, and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial." ]

[ "nan", "nan", "A prospective controlled, double-blind multicenter trial compared placebo, auranofin (an orally administered gold complex), and parenteral gold sodium thiomalate (GST) in patients with active rheumatoid arthritis (RA). Of 193 patients who received any treatment, the only important improvement identified for either auranofin or GST was for pain/tenderness scores. When 161 patients who completed 20 weeks of treatment were examined, both auranofin and GST treatments were superior to placebo as measured by improvement in number of painful and/or tender joints, joint pain/tenderness scores, physician's assessment of disease activity, and decrease in erythrocyte sedimentation rate when elevated at entry. GST was superior to placebo in improvement of joint swelling scores, anemia, thrombocytosis, and rheumatoid factor. No drug-related remissions were observed. The only statistically significant advantages of GST over auranofin for efficacy were an increase in hemoglobin concentration and decrease of thrombocytosis with GST. Withdrawals for adverse effects were 5 times more frequent with GST treatment. Thrombocytopenia, proteinuria, elevated liver enzymes, \"nitritoid\" reactions, and \"gold pneumonitis\" were observed only in the GST treatment group. These results confirm that both parenteral and oral gold may be effective for the treatment of RA, that GST tends to show greater efficacy than auranofin, and that auranofin has fewer significant adverse effects than GST. However, long-term benefits, tolerability, and safety cannot be inferred from this study." ]

[ "19768804" ]

[ "Recombinant human DNase in children with airway malacia and lower respiratory tract infection." ]

[ "Children with airway malacia often have protracted courses of airway infections, because dynamic airway collapse during coughing results in impaired mucociliary clearance. The aim of this study was to determine the effect of the mucolytic drug recombinant human deoxyribonuclease (rhDNase) on the recovery of respiratory symptoms in children with airway malacia and lower respiratory tract infection (LRTI).\n In a randomized double-blind controlled clinical trial, 40 children with airway malacia and LRTI were randomly assigned to receive either 2.5 mg nebulized rhDNase or placebo twice daily for 2 weeks. The primary endpoint was the change in the cough diary score (CDS) (scale 0-5) from baseline to the second week of treatment. Secondary endpoints were VAS symptom scores for cough, dyspnea, and difficulty in expectorating sputum, need for an antibiotic course, and lung function data (FVC, FEV(1), FEF(75), R(int(e))).\n There was no significant difference in the mean change in CDSs from baseline between the rhDNase group and the placebo group (mean difference for daytime 0.19 (95% CI -0.53 to 0.90); for nighttime 0.38 (95% CI -0.30 to 1.05). Proportions of patients requiring antibiotics, and the mean changes in symptom scores and lung function from baseline did not significantly differ between both groups.\n Treatment with 2 weeks of nebulized rhDNase does not enhance recovery or reduce the need for antibiotics in children with airway malacia and LRTI. (Controlled-trials.com number, ISRCTN85366144)." ]

[ "3306943", "3889748", "2782336", "2181689", "8866384", "2181119", "9369820", "8277478", "1385635", "2704510", "8649712", "12839630", "18476152", "4073085", "18475417", "6360038", "1816396", "8925987", "8925979", "453256", "3906971", "1553603", "3329963", "12548209", "7821833", "3415207", "2644594", "3511419", "1442917" ]

[ "Moxalactam versus clindamycin plus tobramycin for the treatment of puerperal infections.", "Aztreonam versus gentamicin, each with clindamycin, in the treatment of endometritis.", "Short course of antibiotic therapy in treatment of postpartum endomyometritis.", "Ampicillin/sulbactam versus clindamycin in the treatment of postpartum endomyometritis.", "Ampicillin/sulbactam vs. clindamycin/gentamicin in the treatment of postpartum endometritis.", "Etiology and treatment of post-cesarean-section endometritis after cephalosporin prophylaxis.", "A randomized, prospective study comparing once-daily gentamicin versus thrice-daily gentamicin in the treatment of puerperal infection.", "Treatment of post-cesarean section endometritis with ampicillin and sulbactam or clindamycin and gentamicin.", "Postcesarean endometritis: a brief review and comparison of three antibiotic regimens.", "Ticarcillin/clavulanic acid versus clindamycin and gentamicin in the treatment of post-cesarean endometritis following antibiotic prophylaxis.", "A comparison of once-daily and 8-hour gentamicin dosing in the treatment of postpartum endometritis.", "Ertapenem once a day versus piperacillin-tazobactam every 6 hours for treatment of acute pelvic infections: a prospective, multicenter, randomized, double-blind study.", "Double-blind, multicenter, prospective randomized study of trospectomycin vs. Clindamycin, both with aztreonam, in non-community acquired obstetric and gynecologic infections.", "Comparative clinical evaluation of ticarcillin plus clavulanic acid versus clindamycin plus gentamicin in treatment of post-cesarean endomyometritis.", "Single-blind, prospective, randomized study of cefmetazole and cefoxitin in the treatment of postcesarean endometritis.", "Randomized comparison of ceftazidime versus clindamycin-tobramycin in the treatment of obstetrical and gynecological infections.", "Ciprofloxacin versus gentamicin/clindamycin for postpartum endometritis.", "[Short-term antibiotic therapy of post-cesarean-section endometritis].", "[Comparison of the therapeutic efficacy of the piperacillin/tazobactame combination vs. ampicillin and gentamycin in in the management of post-cesarean endometritis].", "A comparison of clindamycin-gentamicin and penicillin-gentamicin in the treatment of post-cesarean section endomyometritis.", "Comparative clinical evaluation of ceftizoxime with clindamycin and gentamicin and cefoxitin in the treatment of postcesarean endomyometritis.", "The importance of wound infection in antibiotic failures in the therapy of postpartum endometritis.", "Comparison trial of clindamycin with aztreonam or gentamicin in the treatment of postpartum endometritis.", "Gentamicin and clindamycin therapy in postpartum endometritis: the efficacy of daily dosing versus dosing every 8 hours.", "[Treatment of puerperal endometritis. Evaluation of the efficacy and safety of clindamycin + gentamycin vs. penicillin + chloramphenicol + gentamycin].", "Prospective cost analysis of moxalactam versus clindamycin plus gentamicin for endomyometritis after cesarean section.", "Efficacy of oral antibiotics following parenteral antibiotics for serious infections in obstetrics and gynecology.", "Cefoxitin versus clindamycin and gentamicin in the treatment of postcesarean section infections.", "Randomized, double-blind study of cefotetan and cefoxitin in post-cesarean section endometritis." ]

[ "Sixty women with the diagnosis of puerperal endometritis were randomized to receive either moxalactam (n = 29) or the combination of clindamycin and tobramycin (n = 31) as therapy for their infection. Endometrial bacteriology consisted of mixed flora, both aerobic and anaerobic gram-positive and gram-negative organisms. Clinical cure was achieved in 27 (93%) of the moxalactam-treated patients and 28 (90%) of those given combination therapy. The two failures of moxalactam therapy were associated with enterococcal infection. Failures of clindamycin/tobramycin therapy were due to enterococcal infection, abscess formation, and moderately severe diarrhea. This study indicates that moxalactam is as effective and safe as the combination of clindamycin/tobramycin for the treatment of postpartum endometritis.", "A randomized comparison of aztreonam (2 g intravenously every eight hours) versus gentamicin (1.5 mg/kg intravenously every eight hours), each with clindamycin (600 mg intravenously every six hours), was performed in 119 patients with endometritis after cesarean section. Patients in both groups had similar risk factors. Genital cultures revealed an average of 3.0 isolates per specimen. Eighty-five aerobic gram-negative rods were isolated from 57 (48%) patients. All were susceptible to both aztreonam and gentamicin. Of 133 anaerobic isolates, 131 (98%) were susceptible to clindamycin. The failures in the aztreonam group were associated with a wound abscess and with an enterococcal bacteremia. Of the six failures in the gentamicin group, two were associated with persistent isolation of enteric bacilli. In the other four failures, no explanation was evident. Side effects occurred in four patients, (three diarrhea, one allergic reaction). All were self-limited and appeared to be due to clindamycin. No patient showed nephrotoxicity. When used in combination with clindamycin, aztreonam gave clinical results similar to gentamicin.", "To evaluate the safety and efficacy of an abbreviated course of antibiotic therapy in postpartum endomyometritis, 109 patients with endomyometritis were randomized to three study groups. All were treated with clindamycin and tobramycin until afebrility and clinical signs of disease were absent. Patients in group I received antibiotics for greater than or equal to 24 hours, group II received therapy for greater than or equal to 48 hours, and group III received antibiotic therapy for greater than or equal to 48 hours that preceded a 7-day course of oral Augmentin. The groups were similar in size and in demographic and clinical parameters. Two patients from each group required a third antibiotic, and no patient required rehospitalization. Group III required more days of antibiotic therapy than did group I, 2.9 versus 2.1 days (p less than 0.01), and cost $412.00 more per patient. This data strongly suggest that a short course of antibiotic therapy is efficacious and safe and would result in substantial monetary savings.", "Sixty-eight patients with postpartum endomyometritis were enrolled in this open randomized comparative study. Forty-two patients received ampicillin/sulbactam and 26 received clindamycin. The cure rates were similar in the two groups: 83% in the ampicillin/sulbactam group and 88% in the clindamycin group. The most frequent endometrial bacterial isolates were Bacteroides bivius, Streptococcus faecalis, Escherichia coli, and Ureaplasma urealyticum. Bacteremia was present in 15 of 68 (22%), the most frequent isolates being Mycoplasma (four cases) and B bivius (three cases). Clindamycin-resistant species were S faecalis, E coli, and Proteus mirabilis. There were seven treatment failures in the ampicillin/sulbactam group; only one isolate (an E coli) was resistant to ampicillin/sulbactam. In a significant number of these failures, Mycoplasma was isolated. Ampicillin/sulbactam and clindamycin were found to be equally efficacious in the treatment of postpartum endometritis.", "To evaluate the efficacy and safety of ampicillin/sulbactam with those of clindamycin/gentamicin.\n A prospective, randomized clinical trial of patients with the diagnosis of postpartum endometritis. Intravenous ampicillin, 2.0 g, combined with 1.0 g sulbactam was administered every six hours or intravenous clindamycin, 900 mg, plus gentamicin, 1.5 mg/kg (not to exceed 150 mg unless gentamicin levels were obtained) every eight hours. Endometrial and blood specimens were obtained for culture and antibiotic susceptibility testing.\n One hundred twenty-nine hospitalized women with the diagnosis of endometritis were enrolled. Both treatment regimens were equally effective. At the end of treatment, 42 of 51 (82%) ampicillin/sulbactam-treated patients achieved clinical cure in comparison to 47 of 56 (84%) patients in the clindamycin/gentamicin group. Respective bacterial eradication rates of 86% and 84% for each treatment group were seen. Both antibiotic regimens were well tolerated, with no statistically significant difference in the incidence of adverse experiences.\n The two antibiotic regimens were equally effective for a clinical cure, bacterial eradication and incidence of adverse experiences.", "To describe the microbiologic etiology of post-cesarean endometritis developing after perioperative cephalosporin prophylaxis, endometrial samples were obtained from 27 women with a triple-lumen catheter. The women were assigned in a double-blind, randomized fashion to receive either ticarcillin/clavulanate, 3.1 g, or cefoxitin, 2 g, administered every six hours, until the clinical signs of infection resolved. A total of 149 microorganisms (84 facultative and 65 obligate anaerobes) were recovered from 26 women, for a mean of 5.5 isolates per specimen. One endometrial specimen was sterile. Bacteroides and Peptostreptococcus species were the most frequent isolates, followed by Gardnerella vaginalis, Enterococcus, facultative gram-negative rods and Mycoplasma hominis. Each of the isolates was tested for beta-lactamase activity. At least one beta-lactamase-producing isolate was recovered from 56% of the specimens. Susceptibility testing of endometrial isolates demonstrated that 96% of 118 potential pathogens (Gardnerella, Bacteroides, Peptostreptococcus, enterococci and streptococci) were susceptible to ticarcillin/clavulanate. By comparison, 86% of these isolates were susceptible to cefoxitin in vitro. Women who were treated with ticarcillin/clavulanate were less likely to have a temperature greater than 38 degrees C for two or more days (8% vs. 57%, P = .01). Also, there was a trend toward a decreased duration of uterine tenderness in the ticarcillin/clavulanate group, but it did not attain statistical significance (60% vs. 86%, P = .4). However, the overall clinical success rate with these single-agent treatments was not different for the two groups (77% vs. 79%, P = 1.0).(ABSTRACT TRUNCATED AT 250 WORDS)", "The efficacy, safety, and antibiotic-related charges for once-daily gentamicin with twice-daily clindamycin were compared with those of thrice-daily dosing of these antibiotics.\n Patients with puerperal endometritis or with chorioamnionitis in labor assessed to be at risk for endometritis were randomized to receive gentamicin 4 mg/kg intravenously every 24 hours with clindamycin 1200 mg intravenously every 12 hours (experimental arm) or gentamicin 1.33 mg/kg intravenously and clindamycin 800 mg intravenously every 8 hours (conventional dosing interval arm). Primary outcomes included cure rates, mean length of treatment, antibiotic-related charges, and nephrotoxicity. Multiple logistic regression analysis was used to control for confounding variables.\n There were 135 and 137 patients randomized to the experimental and conventional interval arms, respectively. Cures were obtained in 94.1% and 87.6% of patients in the experimental and conventional arms, respectively (p = 0.06). The experimental arm had mean antibiotic charges of $250.79 versus $442.49 in the conventional arm (p < 0.0001). There was no permanent nephrotoxicity in either group.\n Once-daily gentamicin dosing with twice-daily clindamycin dosing is as efficacious and safe as the thrice-daily dosing of gentamicin and clindamycin for peripartum uterine infection. The experimental regimen results in substantial cost savings. The incidence of nephrotoxicity is low.", "Seventy-seven patients were prospectively enrolled in a randomized clinical trial to compare two antimicrobial regimens for the treatment of post-cesarean section endometritis. The two groups were not significantly different with respect to age, race, gravidity, parity, hours in labor, cesarean section indication, preoperative or postoperative hemoglobin/hematocrit, pretreatment white blood cell count or pretreatment temperature. Pretreatment urine, blood and endometrial cultures were obtained. One or more organisms was recovered from the endometrium in 90% of the patients using a double-lumen sampling device. The most frequent endometrial isolates were Peptostreptococcus and Bacteroides species, followed by Gardnerella vaginalis and enterococci. Thirty (81%) of 37 patients receiving ampicillin/sulbactam and 33 (83%) of 40 receiving gentamicin and clindamycin responded to therapy. There were 14 (18%) treatment failures, 7 in each group. Five (36%) of the 14 clinical failures were due to septic pelvic thrombophlebitis, 2 (14%) of the 14 failures were complications of intraabdominal abscesses, and the remaining 7 patients responded after a change in their antibiotic regimen. We conclude that ampicillin/sulbactam and clindamycin/gentamicin are similarly effective for the treatment of post-cesarean section endometritis.", "Three different antibiotic regimens (trospectomycin plus azteonam, clindamycin plus azteonam, and triple antibiotics-ampicillin plus clindamycin plus gentamicin) were all effective in treating patients with postcesarean endometritis. Patients are frequently cured clinically despite the fact that the offending organisms may be isolated in post-treatment cultures. Treatment of postcesarean endometritis without obtaining endometrial cultures is acceptable gynecologic practice. Obtaining post-treatment cultures is clearly not cost effective nor clinically beneficial. Drug treatment efficacy should be evaluated by clinical response. This communication is the first to report the new antibiotic, trospectomycin, in the treatment of postcesarean endometritis. Further clinical trials are currently underway.", "One hundred fifty-two women who received cefazolin prophylaxis and subsequently developed postpartum endometritis were randomized to treatment with either ticarcillin/clavulanic acid (75) or clindamycin-gentamicin (77). Bacteria isolated from the endometrium were predominantly facultative anaerobic bacteria. The ratio of facultative anaerobes to obligate anaerobes was 3:1. Nineteen percent of the women were bacteremic, with mycoplasma the organism most frequently isolated from venous blood specimens. Cure rates were similar for both groups: ticarcillin/clavulanic acid 85% and clindamycin-gentamicin 81%. The advantages of ticarcillin/clavulanic acid are an increased spectrum of activity against beta-lactamase-producing bacteria, less toxicity, and lower cost.", "To evaluate whether once-daily gentamicin dosing is as effective as the traditional 8-hour regimen for the treatment of postpartum endometritis.\n Postpartum women with endometritis were randomized to receive gentamicin 5 mg/kg as a single daily dose or 1.75 mg/kg every 8 hours. All subjects also received clindamycin. Each participant had a peak serum gentamicin level of at least 5.0 micrograms/mL within the first 24 hours. The dosing regimens were compared by analyzing the number of hours that patients were febrile, the length of hospital stay, occurrence of complications, pharmacy costs, and nursing time required to administer the regimens.\n The study group (n = 62) and the control group (n = 65) were similar in demographic characteristics and the presence of endometritis risk factors. No differences were found between the groups in the number of patients who completed therapy without complications, required changes in antibiotics, or required readmission for endometritis. The groups did not differ in the number of hours that patients remained febrile after the start of therapy or in the length of hospital stay. No patient in the study group had an initial peak serum concentration less than 5.0 micrograms/mL, whereas 24 patients in the control group had initial peak serum concentrations less than 5.0 micrograms/mL and required dose adjustment, a statistically significant difference (P < .001). Pharmacy costs averaged $16.12 +/- 5.68 for the study group and $41.75 +/- 17.41 for the control group, also a significant difference (P < .001). Nurse tasking time averaged 13.62 +/- 2.56 minutes for the study group and 28.06 +/- 8.77 minutes for the control group (P < .001).\n In patients with postpartum endometritis, once-daily gentamicin dosing provides consistently high peak serum levels of gentamicin, requires less nurse tasking time, costs less, and is as effective as the 8-hour dosing regimen.", "To compare ertapenem therapy with piperacillin-tazobactam therapy for the management of acute pelvic infections.\n In a multicenter, double-blind study, 412 women with acute pelvic infection were assigned to one of two strata, namely obstetric/postpartum infection or gynecologic/postoperative infection, and were then randomized to ertapenem, 1 g once a day, or piperacillin-tazobactam, 3.375 g every 6 hours, both administered intravenously.\n In total, 163 patients in the ertapenem group and 153 patients in the piperacillin-tazobactam group were clinically evaluable. The median duration of therapy was 4.0 days in both treatment groups. The most common single pathogen was Escherichia coli. At the primary efficacy endpoint 2-4 weeks post therapy, 93.9% of patients who received ertapenem and 91.5% of those who received piperacillin-tazobactam were cured (95% confidence interval for the difference, adjusting for strata, -4% to 8.8%), indicating that cure rates for both treatment groups were equivalent. Cure rates for both treatment groups were also similar when compared by stratum and severity of infection. The frequency and severity of drug-related adverse events were generally similar in both groups.\n In this study, ertapenem was as effective as piperacillin-tazobactam for the treatment of acute pelvic infection, was generally well tolerated, and had an overall safety profile similar to that of piperacillin-tazobactam.", "Objective: The purpose of this study was to compare the clinical efficacy and safety of trospectomycin sulfate with that of clindamycin phosphate, both with aztreonam, for the treatment of obstetric and gynecologic infections.Methods: In a double-blind, multicenter, prospective randomized study, 579 patients with either endometritis following cesarean delivery or pelvic cellulitis following hysterectomy were enrolled and received medication. Administered was either trospectomycin sulfate 500 mg IV every 8 h or clindamycin phosphate 900 mg IV every 8 h in a 1:1 randomization ratio. Both groups of patients received aztreonam 1 g IV every 8 h. The patients were followed for clinical responses and side effects.Results: The cure rate for the trospectomycin sulfate arm was 91.8% and for clindamycin phosphate arm it was 88.4% (P = 0.218). The adverse events were similar in both groups.Conclusions: Trospectomycin was as effective as clindamycin, when both were combined with aztreonam, in treatment of obstetric and gynecologic infections.", "A new single-antibiotic combination of ticarcillin and clavulanic acid was compared with the standard two-drug regimen of clindamycin and gentamicin in the treatment of post-cesarean endomyometritis. The regimens were as follows: 3 g of ticarcillin plus 100 mg of clavulanic acid intravenously every four hours; or 600 mg of clindamycin intravenously every six hours plus 3 to 5 mg/kg per day of gentamicin intramuscularly. The prospective randomized schedule was calculated such that half the patients were assigned to each treatment group. The diagnosis of endomyometritis was based upon an elevated oral temperature of 100.4 degrees F or higher on any two occasions, excluding the first 24 hours after delivery, uterine tenderness, and the absence of other foci of infection. Lochial discharge was foul in most cases. Forty-seven patients were treated. Treatment was successful in all patients who received clindamycin and gentamicin; ticarcillin plus clavulanic acid failed in two of 23 (9 percent) patients. Patients in whom treatment failed did not appear to be different from those in whom treatment was successful on demographic variables or in terms of risk factors for endomyometritis. The difference between the treatment failure rates was not statistically significant. This study suggests that the single-drug combination of ticarcillin plus clavulanic acid is effective in the treatment of post-cesarean endomyometritis when compared with the standard regimen of clindamycin and gentamicin.", "The purpose of this study was to compare the clinical efficacy and safety of cefmetazole given by IV push with that of parenterally administered cefoxitin for the treatment of endometritis following cesarean delivery.\n In a single-blind, multicenter, prospective, randomized study, 355 patients with endometritis after cesarean delivery were enrolled and received medication. Administered was either cefmetazole sodium, 2 g by IV push over 1 min q 8 h, or cefoxitin sodium, 2 g IV q 6 h in a 2:1 ratio. The patients were followed for clinical responses and side effects.\n The cure rate for cefmetazole was 89% and for cefoxitin it was 79% (P = 0.006). The adverse events were similar in both groups.\n Cefmetazole was significantly more effective than cefoxitin in the treatment of endometritis following cesarean delivery.", "A randomized comparison of ceftazidime versus clindamycin-tobramycin was performed for the treatment of obstetrical and gynecological infections. Entry criteria were an oral temperature of greater than or equal to 38 degrees C and a clinical diagnosis of endometritis, salpingitis, or pelvic cellulitis after hysterectomy. All patients with endometritis had cultures of intrauterine material obtained via a transcervical single-lumen catheter. The patients with pelvic cellulitis had material from the vaginal apex aspirated for culture, and all patients with salpingitis had a culdocentesis for culture of intraperitoneal material. Of 38 patients who received ceftazidime, 34 had endometritis after cesarean section, 3 had endometritis after abortion, and 1 had pelvic cellulitis. Of 39 patients who received clindamycin-tobramycin, 35 had endometritis after cesarean section, 3 had salpingitis, and 1 had pelvic cellulitis. The most common bacterial isolates were Lactobacillus sp., Bacteroides bivius, Escherichia coli, other gram-negative aerobic bacilli, group B streptococci, and other aerobic streptococci. Bacteremia occurred in 9.0% of the patients. Of the patients receiving clindamycin-tobramycin and ceftazidime, 34 (87.2%) and 34 (89.5%), respectively, responded to therapy. All the clinical failures occurred in patients with endometritis after cesarean section. Clinical failures had persistent fever despite 3 or more days of treatment. One of the patients receiving clindamycin-tobramycin developed an urticarial rash after her infection had resolved. No patient in either group developed diarrhea. In these small groups of patients, there were no significant differences in cure rate, side effects, or length of hospital stay.", "An open, randomized, comparative study of intravenous ciprofloxacin versus gentamicin and clindamycin was performed on women with postpartum endometritis. Ciprofloxacin alone successfully eradicated the infections in 35 of 49 patients (71%), while the combination of gentamicin/clindamycin cured 41 of 48 (85%) (P = .15). The microbiology and antibiotic sensitivity of the endometrial isolates confirmed the poor activity of ciprofloxacin against anaerobic bacteria and less-than-optimal activity against Streptococcus faecalis. Ciprofloxacin, when used alone, may not be suitable for the treatment of postpartum endometritis.", "Post-cesarean-section endometritis therapy usually combines an intravenous administered antibiotic followed, once fever has remitted, by an oral or intramuscular course of 7-10 days of the same antibiotic. From November 1993 to May 1994 and trying to reduce the length of the treatment we conducted a randomized, comparative study between the conventional post-C-section endometritis treatment used at the Hospital Central Militar (long course) and a short parenteral treatment with the same antibiotics. Thirty one patients were randomized in the short course group and 32 in the long course group. Only in the long course group there was a patient with persistence of infection after ten days of antibiotic treatment (p > 0.05). The short course regimen brought additional advantages as reduction in treatment days as well as discomfort for the intramuscular administration of antibiotics. This observation suggests that a short course of antibiotics based on the patient's clinical response is a safe and less expensive alternative in the treatment of post-C-section endometritis.", "Traditionally obstetric infections have been treated with combination antimicrobial agents that provide coverage against aerobic and anaerobic bacteria commonly found in these infections. New antibiotics may be a monotherapy alternative for this type of infections. The objective of the study was to compare the efficacy of the agent piperacillin/tazobactam against ampicillin plus gentamicin in the treatment of postcesarean endometritis. By randomized way 14 patients were enrolled in the piperacillin/tazobactam group and 42 in the ampicillin-gentamicin group. A favorable clinical response occurred in 78.6% of piperacillin/tazobactam patients and 88.1% of ampicillin and gentamicin patients (p = NS). There was no statistically significant difference in the times to recovery and days of hospitalization between the two groups. The combination piperacillin/tazobactam did not show advantage towards the standard treatment, so combination antimicrobial agent continue been the optimal approach to the management of obstetric infection.", "A random comparison of clindamycin-gentamicin (C-G) and penicillin-gentamicin was made in 200 women who developed endomyometritis following cesarean section. All pretreatment profiles indicated similar populations. The clinical response was more favorable in the women receiving clindamycin-gentamicin. The implications of these results upon clinical practice is discussed.", "New third generation cephalosporins have been recommended as single agent antibiotic therapy in the treatment of postoperative infections. This study compares the new third generation cephalosporin ceftizoxime with cefoxitin, clindamycin and gentamicin in the treatment of postcesarean section endomyometritis. The results indicate that the clindamycin and gentamicin regimen is more efficacious in the treatment of severe infection after cesarean section than either ceftizoxime or cefoxitin regimens. Therefore, the results of this study suggest caution in substituting single drug antibiotic therapy with cefoxitin or the third generation cephalosporins for the standard clindamycin and gentamicin regimen in the treatment of postcesarean section endomyometritis until more clinical data are available.", "A prospective, randomized, double-blind trial was done to compare the efficacy of cefoxitin (2 grams given intravenously every six hours) with ceftizoxime (2 grams given intravenously every 12 hours) in the treatment of postpartum endometritis. Thirty-eight patients received cefoxitin and 43 received ceftizoxime. Demographic variables (age, gravidity, parity and estimated gestational age) and risk factors (cesarean section, operating time, duration of ruptured membranes and labor, number of vaginal examinations and internal monitoring) were not statistically different in the two antibiotic groups. In the cefoxitin group, eight of 38 patients failed initial antibiotic therapy and six of 43 patients in the ceftizoxime group failed (p = 0.399). In the univariate analysis, abdominal wound infection (p = 0.003) and higher gestational age (p = 0.008) were associated with failure of the antibiotic. With multiple logistic regression, only abdominal wound infection was associated with failure of the antibiotic (p = 0.0002). We conclude that cefoxitin and ceftizoxime are equally effective in the therapy of postpartum endometritis and that abdominal wound infection is primarily responsible for persistent fever and, therefore, failure of the antibiotic in patients with postpartum endometritis.", "Sixty-two patients who had postpartum endometritis were treated with clindamycin in combination with either aztreonam or the aminoglycoside gentamicin. Currently, the combination of clindamycin and an aminoglycoside constitutes a treatment of choice for this condition. Our results suggest that aztreonam can be substituted for an aminoglycoside in the treatment of postpartum endometritis with similar clinical outcomes.", "The objective of the study was to evaluate the efficacy of gentamicin and clindamycin given once daily versus the more common 8-hour dosing regimen for the treatment of postpartum endometritis.\n In a prospective, placebo-controlled, double-blinded study, patients who had postpartum endometritis diagnosed were randomly selected to receive 1.5 mg/kg gentamicin and 900 mg clindamycin phosphate administered every 8 hours versus gentamicin 5 mg/kg and clindamycin phosphate 2700 mg administered as a single-daily dose. The single-dose group received an infusion of gentamicin and clindamycin, followed by an administration of intravenous placebo 8 and 16 hours later to maintain blinding. Treatment success was defined as absence of fever 72 hours after initiation of antibiotic therapy.\n One hundred ten patients were enrolled. The daily-dose group (n = 55) and the thrice-daily dose group (n = 55) were similar with respect to age, gravidity, parity, gestational age, and maternal weight. Clinical characteristics (including maximum temperature, presence of predelivery chorioamnionitis, white blood cell count, and mode of delivery) were also similar. There was no difference in the mean time from initiation of therapy until becoming afebrile in the daily-dose group (27.4 +/- 24.9 hours) compared with the thrice-daily dose group (32.9 +/- 26.3 hours). Forty-five of 56 (82%) patients in the daily-dose group and 38 of 55 (69%) patients in the thrice-daily dose group had treatment success (P =.12).\n Once-daily dosing with gentamicin and clindamycin in women with postpartum endometritis has a similar success rate as the standard every 8-hour dosing schedule.", "This was a prospective, single-blind, comparative study in patients with diagnosis of puerperal endometritis, carried out at the Loayza Hospital in Lima, Peru. The objective of this study was to evaluate the efficacy and safety of clindamycin and gentamicin in the management of endometritis vs. penicillin, chloramphenicol and gentamicin for 10 days. Sixty-five patients were enrolled and 62 were evaluable for efficacy. Both treatment groups were comparable in the pre-treatment period in terms of age, history of pregnancies, controls by gynecologist, days of disease and fever, clinical symptoms like fever, pelvic pain, pulse, uterine size and in laboratory, in hematocrit and leukocytes count. In the culture of endometrium tissue, 27/32 patients (84.4%) in Group A (penicillin + CAF + gentamicin) and 27/30 patients (90%) in Group B (clindamycin + gentamicin) had positive cultures at baseline; 18 and 22 patients showed anaerobes; 8 and 4 patients showed anaerobes plus aerobes and, one patient in each treatment group showed aerobes only. Peptostreptococcus and Bacteroides fragilis were the most frequently isolated pathogens. Improvement in lochia fetidity was more rapid in Group B, it turned transparent and not fetid since day 3. Complete cure was significantly better in Group B 24/30 (80%) in comparison with Group A 16/32 (50%) (p = 0.02). Partial response was found in 15 patients (43.3%) in Group A and 5 patients (16.6%) in Group B. Only one case was considered as bacteriological failure in Group A and only one patient in Group B was considered as failure and required an additional operation due to residual abscess.(ABSTRACT TRUNCATED AT 250 WORDS)", "The direct and indirect costs associated with either moxalactam or clindamycin plus gentamicin as treatment for endomyometritis after emergent cesarean section were compared in an open, randomized prospective trial of 114 patients. A total of 58 patients were assigned to receive moxalactam, 2 g intravenously (i.v.) every 8 h for 5 doses, followed by 2 g every 12 h and prophylactic vitamin K (10 mg) intramuscularly, and 56 patients were assigned to receive clindamycin (600 mg) i.v. every 6 h plus gentamicin (1.5 mg/kg) i.v. every 8 h. Prothrombin times were measured in moxalactam-treated patients, and patients treated with clindamycin plus gentamicin had urinalyses and blood urea nitrogen and serum creatinine determinations performed before and after treatment. Also, gentamicin levels in serum were determined as clinically indicated. A satisfactory treatment response was defined as the resolution of signs and symptoms of endomyometritis within 3 days of the start of antibiotic therapy. Satisfactory responses were demonstrated in 78% of the moxalactam-treated patients and 84% of patients treated with clindamycin plus gentamicin. Mean hospital costs for laboratory tests ($30.30 versus $4.53) and mean patient charges for laboratory tests ($76.39 versus $27.81) and medications ($539.45 versus $421.82) were significantly higher in patients treated with clindamycin plus gentamicin (P less than 0.05), while mean medication costs to the hospital were greater in the moxalactam group ($255.47 versus $195.68; P less than 0.05). However, total patient charges and total hospital drug-associated costs were not significantly different for the two group. In this tudy, moxalactam was similar in efficacy and, despite its higher acquistion cost, was comparable in total hospital costs and patient charges to clindamycin plus gentacmicin in treating endomyometritis.", "Patients with serious soft-tissue infections in obstetrics and gynecology are frequently treated with parenteral antibiotics until afebrile and clinically well for 48-72 hours, and then discharged on a broad-spectrum oral antibiotic. To evaluate the efficacy of this type of management, we designed a prospective, randomized single-blinded study comparing a group of patients who received oral antibiotics after hospital discharge (N = 80) with a group who did not (N = 83). No significant differences in age, race, parity, diagnosis, or pathogen isolated were observed between the patients in the two groups. No significant difference was noted in delayed morbidity between those who did and those who did not take oral antibiotics (P greater than .06). In light of the cost of oral antibiotics and the chance of drug-induced side effects, the data suggest that oral antibiotics after parenteral antibiotics are not indicated.", "Cefoxitin, a cefamycin derivative, has demonstrated activity against a broad spectrum of aerobic and anaerobic bacterial pathogens. The efficacy and safety of cefoxitin were compared with that of the combination of clindamycin and gentamicin in the treatment of postcesarean section infection. Ninety-eight patients were evaluated. Cefoxitin cured 36 of 48 patients (75%); clindamycin/gentamicin cured 38 of 50 (76%) (P greater than .05). Febrile degree hours and length of hospital stay did not differ between the two study groups. No patient experienced abscess formation or septic pelvic thrombophlebitis. Both therapies were well tolerated. In the authors' experience, cefoxitin as a single agent was as effective in the treatment of postoperative pelvic infection as the combination of clindamycin and gentamicin.", "The hypothesis of the study is that cefotetan and cefoxitin will be equally efficacious and safe in the treatment of post-cesarean section endometritis.\n In a double-blind, randomized manner 140 patients with post-cesarean section endometritis were treated with cefotetan, 2 gm intravenously every 12 hours, or cefoxitin, 2 gm intravenously every 6 hours. They were followed prospectively for clinical response and side effects. Cure rates between the two groups were compared with the chi 2 test.\n The cure rates were 83% for cefotetan and 79% for cefoxitin (p = 0.56). No patient required a change in therapy due to adverse effects, and no abnormal bleeding occurred.\n In this study cefotetan and cefoxitin appeared equally effective in treating endometritis with no difference in side effects or complications." ]

[ "2729386", "8335138", "2750828", "9916960", "10759276", "3727190" ]

[ "Comparison of three different surgical procedures for genuine stress incontinence: prospective randomized study.", "Urodynamics in women with stress incontinence before and after surgery.", "Primary stress urinary incontinence and pelvic relaxation: prospective randomized comparison of three different operations.", "A randomized trial of burch retropubic urethropexy and anterior colporrhaphy for stress urinary incontinence.", "Randomised comparison of Burch colposuspension versus anterior colporrhaphy in women with stress urinary incontinence and anterior vaginal wall prolapse.", "Pelvic floor exercise versus surgery for female urinary stress incontinence." ]

[ "One hundred seven consecutive patients with clinical and urodynamic findings of genuine stress incontinence not previously treated were prospectively allocated in a randomized manner to one of three surgical procedures: anterior colporrhaphy, revised Pereyra procedure, or Burch retropubic urethropexy. Randomization included the surgical procedure and choice of surgeon (one of the three authors). Clinical and urodynamic evaluations were repeated at 3 months and 1 year after surgery. Differences in cure rates among the three procedures at the 3-month postoperative evaluation were insignificant (82%, 84%, and 92% for the anterior colporrhaphy, Pereyra, and Burch respectively) but became statistically significant at the 1 year postoperative evaluation (cure rates of 65%, 72%, and 91% for the anterior colporrhaphy, Pereyra, and Burch respectively, p less than 0.05). In our hands the Burch procedure stabilized the urethrovesical junction and prevented its descent during straining (evaluated by a postoperative Q-tip test) more effectively than either the Pereyra or anterior colporrhaphy. No procedure resulted in severe postoperative voiding difficulties. The present prospective randomized study demonstrates that in our hands the abdominal retropubic operation for genuine stress incontinence in patients not previously operated on results in a higher cure rate when compared with anterior colporrhaphy or Pereyra procedure.", "Pad test, cystometry and analysis of micturition were performed in 36 women with stress incontinence before and a year after operation with either retropubic urethrocystopexy (n = 22) or pubococcygeal repair (n = 14). There was no difference in the subjective cure rate between the two groups of women (77% and 79%, respectively). The pad test 1 year after operation showed that 59% of the women in the urethrocystopexy group and 43% of the women in the pubococcygeal repair group had stopped leaking urine. The bladder volume had increased in both groups and the intravesical pressure of the bladder filled to the maximum had increased in the pubococcygeal repair group. The functional length of the urethra, intravesical pressure at maximal urine flow, maximal urine flow rate and urethral conductance were not affected by either operation. Pad test was a more accurate test for an objective evaluation of urine leakage before operation than were the urodynamic investigation or continence tests.", "There were 289 women with clinical and urodynamic diagnosis of primary stress urinary incontinence, stable bladder, and pelvic relaxation who underwent a single-stage surgical procedure because of incontinence and pelvic relaxation. Patients underwent one of three surgical procedures because of stress incontinence--anterior colporrhaphy, revised Pereyra procedure, or Burch retropubic urethropexy. Decisions with regard to the type of bladder neck suspension and the surgeon were made randomly with a randomization table. Each patient had a complete clinical and urodynamic evaluation before surgery and at 3 and 12 months after surgery. Cure rate as defined by strict clinical and urodynamic criteria was not significantly different among the three groups at the 3-month postsurgical evaluations; however, at the 12-month postsurgical evaluations, the cure rate among women who underwent Burch urethropexy (n = 101) was significantly higher than that of either Pereyra or anterior colporrhaphy (cure rates were 87%, 70%, and 69%, respectively; p less than 0.01). The Burch urethropexy was more effective than the Pereyra procedure or anterior colporrhaphy in the stabilization of the bladder base and resulted in a significantly better cure rate in women with primary stress urinary incontinence and pelvic relaxation.", "In a randomized trial, we compared the success of Burch retropubic urethropexy to the modified anterior colporrhaphy for the treatment of genuine stress urinary incontinence.\n Thirty-five patients with stress incontinence were randomly assigned to undergo Burch retropubic urethropexy or modified anterior colporrhaphy. Subjects had preoperative and 1-year postoperative physical examinations, multichannel urodynamic testing, 20-minute pad test, and subjective grading of incontinence severity with questionnaires. Data were evaluated using Fisher exact test, Wilcoxon two-sample test, logistic regression analysis, and analysis of variance.\n Objective cure 1 year postoperatively was significantly greater for the women treated by Burch retropubic urethropexy than by modified anterior colporrhaphy (16 of 18 [89%] versus five of 16 [31%], relative risk .15, 95% confidence interval .04, .59). Patients' subjective ratings of incontinence severity 1 year after surgical treatment were significantly lower in women who had Burch retropubic urethropexy.\n Burch retropubic urethropexy yields a significantly superior objective cure for genuine stress urinary incontinence than the modified anterior colporrhaphy in a randomized trial.", "To compare the Burch colposuspension and the anterior colporrhaphy in women with both stress urinary incontinence and advanced anterior vaginal wall prolapse (cystocele).\n Prospective randomised study.\n Secondary referral centre, Urogynaecology Unit, San Gerardo Hospital, Monza, Italy.\n Seventy-one women undergoing surgery for primary genuine stress incontinence and concurrent grade 2 or 3 cystocele (descending at or outside the vaginal introitus).\n Full urodynamic investigation performed pre-operatively and repeated six months after surgery. Clinical follow up continued for 8 to 17 years.\n Subjective (patient history) and objective (negative stress test result) cure of stress incontinence. Assessment of cystocele recurrence.\n Thirty (86%) of the 35 evaluable women who had the Burch colposuspension and 17 (52%) of the 33 evaluable women who had the anterior colporrhaphy were subjectively cured (OR 5.6, 95% CI 1.6 to 21.6; P = 0.005). Objective cure rates were 74% (26 of 35) and 42% (14 of 33), respectively (OR 3.9, 95% CI 1.3 to 12.5; P = 0.02). A recurrent cystocele of grade 2 or 3 with or without prolapse at other vaginal sites was recorded in 34% (12 of 35) and 3% (1 of 33) of women, respectively (OR 16.7, 95% CI 2.0 to 368.1; P = 0.003).\n The Burch colposuspension was better in controlling stress incontinence but it lead to an unacceptable high rate of prolapse recurrence. The anterior colporrhaphy was more effective in restoring vaginal anatomy but it was accompanied by an unacceptable low cure rate of stress incontinence. Neither of the two operations is recommended for women who are suffering from a combination of stress incontinence and advanced cystocele.", "Fifty consecutive female patients with genuine urinary stress incontinence were randomized either to surgery or to a pelvic floor training program. The operative procedure was chosen according to the type of bladder suspension defect on micturition cystourethrography. The training program was given 5 times in weekly lessons and the patients were guided by trained physiotherapists. Surgery was superior to the pelvic floor training program both subjectively and objectively. However, a significant improvement was found following the training program. Forty-two percent were satisfied with the outcome of the training and did not want operation. We find physiotherapist-guided pelvic floor exercise a realistic alternative to surgery in patients with mild degrees of stress incontinence. Also patients with residual symptoms after surgery are candidates for pelvic floor training." ]

[ "15876944", "10048679", "11214557", "12526069", "9802626", "1909052", "7049959" ]

[ "Role of atypical bacteria and azithromycin therapy for children with recurrent respiratory tract infections.", "Etiology and treatment of community-acquired pneumonia in ambulatory children.", "[Importance of Mycoplasma pneumoniae and Chlamydia pneumoniae in children with community-acquired pneumonia].", "Comparative randomized trial of azithromycin versus erythromycin and amoxicillin for treatment of community-acquired pneumonia in children.", "Safety and efficacy of azithromycin in the treatment of community-acquired pneumonia in children.", "Erythromycin and phenoxymethylpenicillin (penicillin V) in the treatment of respiratory tract infections as related to microbiological findings and serum C-reactive protein.", "[Erythromycin versus amoxicillin for the treatment of pneumonia in children (author's transl)]." ]

[ "The aim of this study of 352 patients, 1-14 years of age, with acute respiratory infections and a history of recurrent respiratory tract infections (RRTIs), and 208 healthy subjects was to evaluate whether Mycoplasma pneumoniae and Chlamydia pneumoniae played a role in causing acute respiratory episodes among children with RRTIs and whether specific antibiotic treatment for these bacteria could improve the acute episodes and reduce recurrences.\n The patients were blindly randomized to receive azithromycin (10 mg/kg/d for 3 days weekly, for 3 weeks) together with symptom-specific agents or symptom-specific agents alone. Acute M. pneumoniae and/or C. pneumoniae infection was diagnosed if the child had a significant antibody response in paired sera and/or if the DNA of the bacteria was detected in nasopharyngeal aspirates.\n Atypical bacterial infections were identified for 190 patients (54.0%) and 8 healthy control subjects (3.8%; P < 0.0001). Short term (1-month) clinical success was significantly more frequent among the patients who had received azithromycin together with symptom-specific agents than among those who had received symptom-specific agents alone, but the difference was significant only for the group of patients with atypical bacteria. In contrast, long term (6-month) clinical success was significantly more frequent among the patients who had received azithromycin in addition to symptom-specific agents, regardless of whether they experienced infections with atypical bacteria or other pathogens, although positive outcomes were significantly more frequent among those with atypical bacteria.\n Atypical bacteria seem to play a role among children with RRTIs, and prolonged azithromycin therapy can significantly improve the acute episodes and reduce the risk of recurrences.", "To determine the etiology of community-acquired pneumonia in ambulatory children and to compare responses to treatment with azithromycin, amoxicillin-clavulanate or erythromycin estolate.\n Ambulatory patients with pneumonia were identified at the Children's Medical Center of Dallas, TX. Children age 6 months to 16 years with radiographic and clinical evidence of pneumonia were enrolled and randomized to receive either azithromycin suspension for 5 days or a 10-day course of amoxicillin-clavulanate for those <5 years or erythromycin estolate suspension for those > or = 5 years. Blood culture was obtained in all patients and we obtained nasopharyngeal and pharyngeal swabs for culture and polymerase chain reaction (PCR) testing for Chlamydia pneumoniae and Mycoplasma pneumoniae and nasopharyngeal swabs for viral direct fluorescent antibody and culture. Acute and convalescent serum specimens were tested for antibodies to C. pneumoniae, M. pneumoniae and Streptococcus pneumoniae. Patients were evaluated 10 to 37 days later when repeat specimens for serology, PCR and culture were obtained. For comparative purposes healthy children attending the well-child clinic had nasopharyngeal and pharyngeal swabs obtained for PCR and culture for C. pneumoniae and M. pneumoniae.\n Between February, 1996, and December, 1997, we enrolled 174 patients, 168 of whom fulfilled protocol criteria for evaluation. There were 55% males and 63% were <5 years of age. All blood cultures were sterile and there was no correlation between the white blood cell and differential counts and etiology of pneumonia. Etiologic agents were identified in 73 (43%) of 168 patients. Infection was attributed to M. pneumoniae in 7% (12 of 168), C. pneumoniae in 6% (10 of 168), S. pneumoniae in 27% (35 of 129) and viruses in 20% (31 of 157). None of the swab specimens from 75 healthy control children was positive for C. pneumoniae or M. pneumoniae. Clinical response to therapy was similar for the three antibiotic regimens evaluated, including those with infection attributed to bacterial agents.\n Although a possible microbial etiology was identified in 43% of the evaluable patients, clinical findings and results of blood cultures, chest radiographs and white blood cell and differential counts did not distinguish patients with a defined etiology from those without a known cause for pneumonia. There were no differences in the clinical responses of patients to the antimicrobial regimens studied.", "To determine the importance of Mycoplasma pneumoniae and Chlamydia pneumoniae in community-acquired pneumonia (CAP) of children from different latitudes and to compare clinical outcome using azithromycin (AZM) versus either amoxicillin-clavulanate (A-C) or erythromycin estolate (EE).\n Ambulatory patients with CAP were identified at either the Children's Medical Center of Dallas, Texas or the Hospital del Niño of Panama City, Panama. Children 6 months to 15 years of age were enrolled and randomized to receive either AZM for 5 days or a 10 day course of either A-C or EE, for those younger or older than 5 years of age, respectively. Mycoplasma pneumoniae and C. pneumoniae were identified by measuring acute and convalescent serum antibody titers and by performing nasopharyngeal (NP) and oropharyngeal (OP) swabs for culture and polymerase chain reaction (PCR) testing.\n Overall 335 patients (168 in Dallas and 167 in Panama) were evaluated from February 1996 through December 1997. Acute M. pneumoniae infection was detected in 12 (7%) patients each in Dallas and Panama. Acute C. pneumoniae infection was observed in 10 (6%) children at each site. Infection caused by these \"atypical\" microorganisms occurred more frequently in children older than 5 years of age (23% vs 9%, P = 0.001, RR 2.5, 95% CI 1.4-4.3). No distinctive pattern of clinical or radiologic abnormalities was seen in relation to etiology. Clinical cure was achieved in 43 of 44 children infected by these bacteria regardless of treatment assignment.\n Mycoplasma pneumoniae and C. pneumoniae are common etiologic agents of CAP in older children from different latitudes. Children with CAP present with similar clinical and radiologic findings to those caused by other etiologic agents. Outcome was excellent for the three treatment regimens studied.", "Our objective was to compare the clinical efficacy of azithromycin vs. erythromycin and amoxicillin in the treatment of presumed bacterial community-acquired pneumonia in ambulatory children, and to evaluate the etiologies of these illnesses. One hundred and ten children, aged 1 month to 14 years, were enrolled between January 1996-January 1999. Children were distributed into two groups according to clinical and radiological patterns: classic or atypical pneumonia. Patients with classic pneumonia were randomly assigned to receive oral amoxicillin 75 mg/kg/day for 7 days, or azithromycin 10 mg/kg/day for 3 days; patients with atypical pneumonia received azithromycin 10 mg/kg/day for 3 days, or erythromycin 50 mg/kg/day for 14 days. Chest X-ray, clinical, and laboratory parameters were obtained on enrollment. Clinic visits were performed on days 3, 7, and 14, and chest X-ray follow-up on days 7 and 14. Microbiological diagnosis of classic pathogens was based on blood and bronchial secretion cultures. The diagnosis of atypical pathogens C. pneumoniae, C. trachomatis, and M. pneumoniae was based on PCR and serologic tests.Forty-seven children met the criteria for classic pneumonia (23 children received azithromycin, and 24 received amoxicillin), and 59 children had atypical pneumonia (33 children were treated with azithromycin, and 26 with erythromycin). Demographic characteristics at enrollment were similar between children with classic pneumonia treated with azithromycin and erythromycin and children treated with azithromycin and erythromycin for atypical pneumonia. However, on day 7, children with classic pneumonia who received azithromycin normalized their chest X-ray more often than those who received amoxicillin (81.0% vs. 60.9%, respectively, P = 0.009). The same was true for children with atypical pneumonia; their chest X-rays had normalized by day 14 (100% in those with azithromycin vs. 81% in those with erythromycin, P = 0.059). Also, children with atypical pneumonia treated with azithromycin had earlier cessation of cough than children treated with erythromycin (3.6 +/- 1.9 vs. 5.5 +/- 3.6 days respectively, P = 0.02). There were only three children with side effects (mild diarrhea, all in the erythromycin group). Etiological agents were identified in 41% of children. In conclusion, azithromycin is an effective therapeutic option for the treatment of community-acquired classic and atypical pneumonia in children.\n Copyright 2003 Wiley-Liss, Inc.", "To compare the safety and efficacy of azithromycin with amoxicillin/clavulanate or erythromycin for the treatment of community-acquired pneumonia, including atypical pneumonia caused by Mycoplasma pneumoniae and Chlamydia pneumoniae.\n Multicenter, parallel group, double blind trial in which patients 6 months to 16 years of age with community-acquired pneumonia were randomized 2:1 to receive either azithromycin for 5 days or conventional therapy for 10 days (amoxicillin/clavulanate if < or =5 years of age or erythromycin estolate if >5 years of age). Patients from 23 geographically diverse sites were evaluated for clinical outcomes and/or adverse events at Days 3 to 5, Days 15 to 19 and 4 to 6 weeks posttherapy. Microbiology (culture or polymerase chain reaction) was done at baseline and Days 15 to 19 for bacteria, Chlamydia pneumoniae and Mycoplasma pneumoniae. Serology for C. pneumoniae and M. pneumoniae was done at baseline and 4 to 6 weeks posttherapy.\n Of 456 patients enrolled during 17 consecutive months, 420 were evaluable. Clinical success at Study Days 15 to 19 was 94.6% in the azithromycin group and 96.2% in the comparative treatment group (P = 0.735) and at 4 to 6 weeks posttherapy 90.6 and 87.1%, respectively (P = 0.330). Evidence of infection was identified in 46% of 420 evaluable patients (1.9% bacteria, 29.5% M. pneumoniae and 15% C. pneumoniae). Microbiologic eradication was 81% for C. pneumoniae and 100% for M. pneumoniae in the azithromycin group vs. 100 and 57%, respectively, in the comparator group. Treatment-related adverse events occurred in 11.3% of the azithromycin group and 31% in the comparator group (P < 0.05).\n Azithromycin used once daily for 5 days produced a satisfactory therapeutic outcome similar to those of amoxicillin/clavulanate or erythromycin given three times a day for 10 days for treatment of community-acquired pneumonia. Azithromycin had significantly fewer side effects than comparator drugs.", "Respiratory tract pathogens (beta-haemolytic streptococci groups A, C and G, Haemophilus influenzae, Branhamella catarrhalis or pneumococci), were isolated from nasopharyngeal and/or throat swabs in 73/138 (53%) patients greater than 10 years of age with a clinical diagnosis of acute sinusitis, acute tonsillitis, purulent nasopharyngitis or acute bronchitis. Serological evidence of a viral infection (influenza A and B, parainfluenza 1, 2 and 3, respiratory syncytial virus, adenovirus) or Mycoplasma pneumoniae infection was found in 10% of the patients. The serum content of C-reactive protein (S-CRP) was increased (greater than 12 mg/l) in 26/33 (79%) patients with streptococci and in 22/59 (37%) patients without respiratory tract bacteria. In patients with a serological evidence of a virus tonsillitis, the S-CRP was also high (32-64 mg/l). At follow-up 10-12 days after the first visit, the clinical effect of erythromycin and penicillin V was judged to be similar (90% clinical effect). Relapse or re-infection with group A streptococci were seen in 7 patients (4 on erythromycin, 3 on penicillin). In another 6 patients (3 on erythromycin, 3 on penicillin), antibiotic treatment was switched owing to persisting symptoms, probably due to H. Influenzae infection in 3 cases. The patients' own estimates of their symptoms suggested treatment with erythromycin to have a more rapid effect than treatment with penicillin.", "Following a study in which the etiology of nearly 70% of 142 cases of pneumonia in children could be determined using a combination of bacteriological and serological methods, the effect of erythromycin ethylsuccinate was compared with that of amoxicillin in a randomized study on 120 cases of pneumonia. We first examined the tracheal secretion microbiologically and determined other serological parameters and clinical data. The tracheal secretion was sterile in only 19% of the cases. We were able to identify the etiology in 64% of the cases using a combination of microbiological and serological methods. A discontinuation of therapy and acceptable side-effects were considerably more frequent with amoxicillin than with erythromycin ethylsuccinate (75 mg/kg body weight). The advantages of erythromycin, especially for the initial therapy of pneumonia, and the improvements in diagnosis resulting from the examination of the tracheal secretion will be discussed." ]

[ "8624291", "2181310", "20074933", "12529345", "10811493" ]

[ "Adjuvant treatment for early epithelial ovarian cancer: results of two randomised clinical trials comparing cisplatin to no further treatment or chromic phosphate (32P). G.I.C.O.G.: Gruppo Interregionale Collaborativo in Ginecologia Oncologica.", "Adjuvant therapy in stage I and stage II epithelial ovarian cancer. Results of two prospective randomized trials.", "Understanding the problem of inadequately staging early ovarian cancer.", "International Collaborative Ovarian Neoplasm trial 1: a randomized trial of adjuvant chemotherapy in women with early-stage ovarian cancer.", "Randomized study on adjuvant chemotherapy in stage I high-risk ovarian cancer with evaluation of DNA-ploidy as prognostic instrument." ]

[ "From 1983 to 1990, 271 consecutive patients with stage I ovarian cancer entered two randomised trials, aimed at assessing the role of adjuvant chemotherapy after radical surgery in early stages of ovarian cancer. Trial I compared cisplatin (50 mg/m2 with repeated courses every 28 days for 6 cycles) to no further therapy in F.I.G.O. stage Ia & b Grade II-III patients; trial II compared cisplatin (same dose and schedule) to 32P in Iaii & bii and Ic patients.\n Both studies were multicentric and centrally randomized. Treatment was allocated by phone and stratified by center. All patients satisfying major eligibility criteria (histological and grade, no previous neoplasms) were analysed according to treatment allocated by randomisation.\n With a median observation time of 76 months, cisplatin significantly reduced the relapse rate by 65% (HR = 0.35; 95% CI = 0.14-0.89, p = 0.028; Cox Model) in trial I and 61% (HR = 0.39; 95% CI = 0.19-0.77, p = 0.007; Cox Model) in trial II. Survival was not significantly different (trial I - Kaplan-Meier overall 5-year survival: cisplatin = 88%, control = 82%, HR = 1.15; 95% CI = 0.44-2.98; p = 0.773; Cox Model); trial II - overall 5-year survival: cisplatin = 81%, 32P = 79%, HR = 0.72; 95% CI = 0.37-1.43; p = 0.354; Cox model). In both studies the risk of dying after relapse increased for patients originally randomized to the cisplatin arms: in trial I, 6 of 7 patients in the cisplatin relapsed arm and died of tumor compared with 8 of 14 patients in the control arm. In trial II 11 of 12 patients on cisplatin, and 18 of 26 on 32P succumbed to tumor recurrence.\n Adjuvant cisplatin treatment in early ovarian cancer significantly prevents relapse in comparison to 32P in stage IC patients or to no immediate treatment in earlier stage women. The impact of cisplatin adjuvant treatment on survival remains, however, unclear.", "About a third of patients with ovarian cancer present with localized disease; despite surgical resection, up to half the tumors recur. Since it has not been established whether adjuvant treatment can benefit such patients, we conducted two prospective, randomized national cooperative trials of adjuvant therapy in patients with localized ovarian carcinoma (International Federation of Gynecology and Obstetrics Stages Ia to IIc). All patients underwent surgical resection plus comprehensive staging and, 18 months later, surgical re-exploration. In the first trial, 81 patients with well-differentiated or moderately well differentiated cancers confined to the ovaries (Stages Iai and Ibi) were assigned to receive either no chemotherapy or melphalan (0.2 mg per kilogram of body weight per day for five days, repeated every four to six weeks for up to 12 cycles). After a median follow-up of more than six years, there were no significant differences between the patients given no chemotherapy and those treated with melphalan with respect to either five-year disease-free survival (91 vs. 98 percent; P = 0.41) or overall survival (94 vs. 98 percent; P = 0.43). In the second trial, 141 patients with poorly differentiated Stage I tumors or with cancer outside the ovaries but limited to the pelvis (Stage II) were randomly assigned to treatment with either melphalan (in the same regimen as above) or a single intraperitoneal dose of 32P (15 mCi) at the time of surgery. In this trial (median follow-up, greater than 6 years) the outcomes for the two treatment groups were similar with respect to five-year disease-free survival (80 percent in both groups) and overall survival (81 percent with melphalan vs. 78 percent with 32P; P = 0.48). We conclude that in patients with localized ovarian cancer, comprehensive staging at the time of surgical resection can serve to identify those patients (as defined by the first trial) who can be followed without adjuvant chemotherapy. The remaining patients with localized ovarian cancer should receive adjuvant therapy, and with adjuvant melphalan or intraperitoneal 32P should have a five-year disease-free survival of about 80 percent.", "Early ovarian cancer patients are often incompletely staged during initial surgery.(1-3) This omission can have serious adverse consequences for the prognosis of patients as the completeness of surgical staging has been identified as an independent prognostic parameter for survival.(4,5) The reasons for the problem of inadequate staging of early ovarian cancer are largely unknown. We have analysed the data of a large randomised trial in early ovarian cancer in which detailed information of the surgical staging procedure was monitored.(5)\n Data of the EORTC Adjuvant ChemoTherapy In Ovarian Neoplasm (ACTION) Trial were used in which 448 early ovarian cancer patients were randomised between postoperative chemotherapy in one arm and observation following surgery in the other. In this trial strict criteria for surgical staging were advised but optimal, complete staging was performed in only 1/3 of patients. Staging characteristics of the incompletely staged patients were analysed and factors that could explain the failure to perform a complete staging were studied.\n Sampling of para-aortic nodes was omitted in 78% of the incompletely staged patients, while 52% of these patients had no pelvic lymph node dissection. Taking blind biopsies from different peritoneal sites was not performed in more than 1/3 of the incompletely staged group. Omission of the staging steps ranged from 3% (infracolic omentectomy) to 55% (biopsy of the right hemi-diaphragm). A significant difference (p=0.04) between the fraction of completely staged patients was found when comparing institutes who entered less than 5 patients (21%) versus those who included more than 20 patients (37%) in the trial.\n Even in a randomised trial in which comprehensive surgical staging was strongly advised in the study protocol the majority of patients (66%) were incompletely staged. Factors relating to a lack of surgical skills attributed most to the number of incompletely staged patients, but insufficient knowledge of the tumour behaviour and routes of spread of ovarian cancer also contributed substantially to this problem. Multicentre trials recruiting patients from many institutes with small volume contribution to the study, run the risk of inadequate adherence to the study protocol.\n Copyright 2009 Elsevier Ltd. All rights reserved.", "The question of whether platinum-based adjuvant chemotherapy can improve outcomes in patients with early-stage epithelial ovarian cancer is an important one. We carried out a multicenter, open randomized trial to determine whether adjuvant chemotherapy would improve overall survival and prolong recurrence-free survival in women with early-stage epithelial ovarian cancer.\n Between August 1991 and January 2000, 477 patients in 84 centers in five countries were randomly assigned to receive either adjuvant chemotherapy immediately following surgery (n = 241) or no adjuvant chemotherapy until clinically indicated (n = 236). Kaplan-Meier curves of overall survival and recurrence-free survival were compared using the Mantel-Cox version of the log-rank test. All statistical tests were two-sided.\n Women who received adjuvant chemotherapy had better overall survival than women who did not (hazard ratio [HR] of 0.66, 95% confidence interval [CI] = 0.45 to 0.97; P =.03). These results translate into 5-year survival figures of 70% for women who did not receive adjuvant chemotherapy and 79% for women who did receive adjuvant chemotherapy, a difference of 9% (95% CI = 1% to 15%). Adjuvant chemotherapy also improved recurrence-free survival (HR = 0.65; 95% CI = 0.46 to 0.91; P =.01). These results translate into 5-year recurrence-free survival figures of 62% for women who did not receive adjuvant chemotherapy and 73% for women who did receive adjuvant chemotherapy, a difference of 11% (95% CI = 3% to 18%).\n These results suggest that platinum-based adjuvant chemotherapy improves survival and delays recurrence in patients with early-stage ovarian cancer.", "Adjuvant chemotherapy versus observation and chemotherapy at progression was evaluated in 162 patients in a prospective randomized multicenter study. We also evaluated DNA-measurements as an additional prognostic factor.\n Patients received adjuvant carboplatin AUC 7 every 28 days for six courses (n = 81) or no adjuvant treatment (n = 81). Eligibility included surgically staged and treated patients with FIGO stage I disease, grade 1 aneuploid or grade 2 or 3 non-clear cell carcinomas or clear cell carcinomas. Disease-free (DFS) and disease-specific (DSS) survival were end-points.\n Median follow-up time was 46 months and progression was observed in 20 patients in the treatment group and 19 in the control group. Estimated five-year DFS and DSS were 70% and 86% in the treatment group and 71% and 85% in the control group. The hazard ratio was 0.98 (95% confidence interval (95% CI): 0.52-1.83) regarding DFS and 0.94 (95% CI: 0.37-2.36) regarding DSS. No significant differences in DFS or DSS could be seen when the log-rank test was stratified for prognostic variables. Therefore, data from both groups were pooled for the analysis of prognostic factors. DNA-ploidy (P = 0.003), extracapsular growth (P = 0.005), tumor rupture (P = 0.04), and WHO histologic grade (P = 0.04) were significant independent prognostic factors for DFS with P < 0.0001 for the model in the multivariate Cox analysis. FIGO substage (P = 0.01), DNA ploidy (P < 0.05), and histologic grade (P = 0.05) were prognostic for DSS with a P-value for the model < 0.0001.\n Due to the small number of patients the study was inconclusive as regards the question of adjuvant chemotherapy. The survival curves were superimposable, but with wide confidence intervals. DNA-ploidy adds objective independent prognostic information regarding both DFS and DSS in early ovarian cancer." ]

[ "9580172" ]

[ "Administration of antibiotics to patients with rupture of membranes at term: a prospective, randomized, multicentric study. Collaborative Group on PROM." ]

[ "To assess whether antibiotic administration changes the rate of materno-fetal infectious morbidity in premature rupture of membranes occurring later than 35 weeks of gestation.\n A prospective, randomized and multicentric study in the Perinatology Units of eleven hospitals in Spain. Women were randomized to either antibiotic administration or control group. All were induced, if labor had not started spontaneously after 12 hours of ruptured membranes. Main outcome measures were maternal infection (chorioamnionitis and endometritis) and neonatal infectious morbidity (neonatal sepsis, meningitis and bronchopneumonia).\n Seven hundred and thirty-three patients were enrolled in the study, 371 in the antibiotics group and 362 in the control group. The incidence of chorioamnionitis and puerperal endometritis were reduced but the differences are statistically nonsignificant. However, the incidence of neonatal sepsis was significantly lower in newborns to mothers who had received antibiotics, 1 vs. 7 cases (Fisher's exact test, p<0.007).\n The study strongly suggests that prophylactic use of antibiotics in premature rupture of membranes occurring at 36 or more weeks of gestation reduces the risk of neonatal sepsis and probably maternal endometritis." ]

[ "9417158" ]

[ "alpha1-Proteinase inhibitor therapy for the prevention of chronic lung disease of prematurity: a randomized, controlled trial." ]

[ "An imbalance between increased neutrophil elastase and a decreased antiprotease shield has been suggested as a factor contributing to the development of chronic lung disease (CLD). We hypothesized that administration of alpha1-proteinase inhibitor (A1PI), also known as alpha1-antitrypsin, to premature neonates would prevent CLD.\n A randomized, placebo-controlled, prospective study of A1PI supplementation was performed. Neonates <24 hours of age with birth weights 600-1000 g on respiratory support, and 1001-1250 g with respiratory distress syndrome (RDS) were eligible. Intravenous A1PI (60 mg/kg) or placebo was infused on days 0, 4, 7, and 14. Primary outcome was CLD in survivors, defined as the need for supplemental oxygen on day 28.\n A total of 106 patients were recruited. There were no significant differences between groups in birth weight or incidence of RDS. The incidence of CLD in survivors was lower in the treated group, but the difference did not reach statistical significance (relative risk [RR], 0.79; confidence interval [CI], 0.60-1.02). This beneficial trend persisted at 36 weeks corrected gestational age (RR, 0.48; CI, 0.23-1.00). The incidence of pulmonary hemorrhage was lower in the treated group (RR, 0.22; CI, 0.05-0.98). Other complications were not significantly different between groups.\n In this, the first trial of a protease inhibitor for the prevention of CLD in premature infants, the infusions were well-tolerated. A1PI therapy may impede the development of CLD and appears to reduce the incidence of pulmonary hemorrhage in some neonates born prematurely." ]

[ "2688355", "3559816", "1586184", "4014092" ]

[ "The effect of caffeine compared with theophylline in the treatment of idiopathic apnea in premature infants.", "Theophylline versus caffeine: comparative effects in treatment of idiopathic apnea in the preterm infant.", "Caffeine or theophylline for neonatal apnoea?", "Comparative efficacy of theophylline and caffeine in the treatment of idiopathic apnea in premature infants." ]

[ "nan", "nan", "Caffeine, in the dose usually recommended (12.5 mg/kg loading dose and 3 mg/kg daily maintenance), and a higher dose regimen (25 mg/kg loading and 6 mg/kg daily maintenance), was compared with theophylline (7.5 mg/kg loading and 3 mg/kg thrice daily maintenance). The study was a randomised controlled trial in the treatment of a group of 44 infants of less than 31 weeks' gestation (mean gestational age 28.3 weeks) who were suffering from frequent apnoeic attacks. All three regimens produced a significant reduction in apnoeic attacks within 24 hours, but only the higher dose caffeine and theophylline groups showed a significant improvement in apnoea within eight hours. The use of caffeine for the treatment of neonatal apnoea is recommended, because a once daily dose is more easily administered, and because it was found that plasma concentrations were more predictable than those of theophylline. If used in very preterm infants, however, its is suggested that a higher dose regimen than that previously recommended be used to achieve a faster response.", "The purpose of our prospective randomized study was to compare the efficacy of theophylline ethylenediamine and caffeine sodium citrate in the treatment of idiopathic apnea in premature infants. Sixteen infants with three or more severe apneic attacks were studied. Twenty-four-hour cardiorespiratory recordings immediately before and after randomization and four days later showed similar significant decreases of the apnea frequency in both theophylline- (group 1, n = 8) and caffeine-treated infants (group 2, n = 8). No undesirable side effects were observed, except for tachycardia in one infant in group 1. We suggest reasons for preferring caffeine to theophylline in the control of idiopathic apnea in premature infants: caffeine is as efficient and easier to administer." ]

[ "16580386", "19890022", "18940877" ]

[ "Simvastatin improves biochemical parameters in women with polycystic ovary syndrome: results of a prospective, randomized trial.", "Comparison of simvastatin and metformin in treatment of polycystic ovary syndrome: prospective randomized trial.", "The effect of atorvastatin in patients with polycystic ovary syndrome: a randomized double-blind placebo-controlled study." ]

[ "To test the hypothesis that statins improve hyperandrogenemia in women with polycystic ovary syndrome (PCOS).\n Prospective, randomized trial.\n Academic medical center.\n Forty-eight women with PCOS.\n Subjects were randomized to a statin group (simvastatin, 20 mg daily plus oral contraceptive pill [OCP]; n = 24) or an OCP group (OCP alone; n = 24).\n Serum T.\n Baseline parameters of both groups were comparable. After 12 weeks of treatment, serum T levels declined by 41% in the statin group and by 14% in the OCP group. In the statin group, there was a greater decrease of LH (43% decrease vs. 9% in the OCP group) and a greater decline of LH/FSH ratio (44% vs. 12%). In the statin group, total cholesterol declined by 10% and low-density lipoprotein (LDL) by 24%. In the OCP group, total cholesterol increased by 8%, and LDL was unchanged.\n This is the first study demonstrating that statin decreases T levels and normalizes gonadotropin levels in women with PCOS. Statin therapy might offer a novel approach, providing endocrine and cardiovascular benefits.", "Polycystic ovary syndrome (PCOS) is characterized by ovarian dysfunction and hyperandrogenism; it is also associated with increased cardiovascular risks such as adverse lipid profile and endothelial dysfunction. Metformin and, more recently, statins have been shown to improve endocrine and metabolic aspects of PCOS.\n The aim of the study was to compare effects of simvastatin and metformin on PCOS.\n In a prospective trial, women with PCOS (n = 136) were randomized to simvastatin (S), metformin (M), or simvastatin plus metformin (SM) groups. Evaluations were performed at baseline and after 3 months.\n The study was conducted at an academic medical center.\n The change of serum total testosterone was measured.\n The study was completed by 113 subjects. Total testosterone decreased significantly and comparably in all groups: by 17.1, 13.6, and 15.1%, respectively, in the S, M, and SM groups. Significant decreases were also observed in all groups with respect to body mass index, C-reactive protein, and soluble vascular cell adhesion molecule-1. DHEAS declined significantly only in the S group. None of the treatments were associated with significant changes in LH or FSH. Total cholesterol and low-density lipoprotein cholesterol significantly declined only in S and SM groups.\n Simvastatin treatment was superior to metformin alone, whereas a combination of simvastatin and metformin was not significantly superior to simvastatin alone.", "Polycystic ovary syndrome (PCOS) is associated with increased risk of cardiovascular morbidity, whereas statins are proven to reduce cardiovascular mortality and morbidity through lipid-lowering and perhaps through their pleiotropic effects. Statins can also reduce testosterone in vitro by inhibiting ovarian theca-interstitial cell proliferation and steroidogenesis and reducing inflammation in vivo.\n Our objective was to assess the effect of atorvastatin on inflammatory markers, insulin resistance, and biochemical hyperandrogenemia in patients with PCOS.\n We conducted a randomized, double-blind, placebo-controlled study at a tertiary care setting in United Kingdom.\n Patients included 40 medication-naive patients with PCOS and biochemical hyperandrogenemia.\n Patients were randomized to either atorvastatin 20 mg daily or placebo.\n The primary endpoint of the study was a change in the inflammatory marker high-sensitivity C-reactive protein. The secondary endpoints were a change in insulin resistance and total testosterone. Results: After 12 wk atorvastatin, there was a significant reduction (mean +/- sem) in total cholesterol (4.6 +/- 0.2 vs. 3.4 +/- 0.2 mmol/liter, P < 0.01), low-density lipoprotein cholesterol (2.9 +/- 0.2 vs. 1.8 +/- 0.2 mmol/liter, P < 0.01), triglycerides (1.34 +/- 0.08 vs. 1.08 +/- 0.13 mmol/liter, P <0.01), high-sensitivity C-reactive protein (4.9 +/- 1.4 vs. 3.4 +/- 1.1 mg/liter, P = 0.04), free androgen index (13.4 +/- 0.6 vs. 8.7 +/- 0.4, P < 0.01), testosterone (4.1 +/- 0.2 vs. 2.9 +/- 0.1 nmol/liter, P < 0.01) and insulin resistance as measured by homeostasis model assessment for insulin resistance (HOMA-IR) (3.3 +/- 0.4 vs. 2.7 +/- 0.4). There was a significant increase in SHBG (31.1 +/- 1.0 vs. 35.3 +/- 1.2 nmol/liter, P < 0.01). There was a positive correlation between the reduction in HOMA-IR in the atorvastatin group with the reduction in triglycerides and the reduction of free androgen index. There was a significant deterioration of HOMA-IR in the placebo group (3.0 +/- 0.4 vs. 3.8 +/- 0.5).\n This study suggests that atorvastatin is effective in reducing inflammation, biochemical hyperandrogenemia, and metabolic parameters in patients with PCOS after a 12-wk period." ]

[ "15042289", "11517199", "12780963", "14595042" ]

[ "Advantages and disadvantages of different nasal CPAP systems in newborns.", "A randomised control study comparing the Infant Flow Driver with nasal continuous positive airway pressure in preterm infants.", "Comparison of two nasal prongs for application of continuous positive airway pressure in neonates.", "A randomized, controlled trial comparing two different continuous positive airway pressure systems for the successful extubation of extremely low birth weight infants." ]

[ "To compare three different systems of continuous positive airway pressure (CPAP): the naso-pharyngeal tube and two-prong systems in newborns, focusing on duration of CPAP, side effects and cost.\n Randomized clinical study.\n Between July 2000 and September 2001 newborns were randomized to three different CPAP systems. Forty infants in two weight groups (>2500 g and 1250-2500 g; 20 patients in each group) were included.\n In the group >2500 g the median duration of CPAP was 1.1 days (range 0.25-14.3 days). The median time on a naso-pharyngeal CPAP was 1 day (range 0.25-14.3 days), on Hudson prongs 1.6 days (range 0.5-3.3 days) and on the Infant Flow system 0.7 days (range 0.3-13.6 days; p>0.05 for comparison between groups, Fisher's exact test). With naso-pharyngeal CPAP, 2 patients developed moderate nasal injuries. On Hudson, 2 patients developed moderate and three mild nasal injuries. One patient on the Infant Flow showed mild and one moderate nasal injuries. In the weight group 1250-2500 g the median duration of CPAP was 1.1 days (range 0.1-7.0 days). The median time on the naso-pharyngeal tube was 0.9 days (range 0.1-7 days), on Hudson prongs 1.1 days (range 0.7-6.6 days) and on the Infant Flow system 1.3 days (range 0.25-5.9 days; p>0.05 for comparison between groups, Fisher's exact test). With a naso-pharyngeal tube, one infant developed mild and one moderate nasal injuries. On Hudson prongs, two had moderate nasal injuries. On Infant Flow, one newborn showed a severe nasal injury and two mild injuries. None of the patients developed a pneumothorax.\n The naso-pharyngeal tube is an easy, safe and economical CPAP system usable with every common ventilator. For very low birth weight newborns, a prong system may have advantages.", "To compare the effectiveness of the Infant Flow Driver (IFD) with single prong nasal continuous positive airway pressure (nCPAP) in preterm neonates affected by respiratory distress syndrome.\n Randomised controlled study.\n Between September 1997 and March 1999, 36 preterm infants who were eligible for CPAP treatment were randomly selected for either nCPAP or IFD and studied prospectively for changes in oxygen requirement and/or respiratory rate. The requirement for mechanical ventilation, complications of treatment, and effects on mid-term outcome were also evaluated.\n Use of the IFD had a significantly beneficial effect on both oxygen requirement and respiratory rate (p < 0.0001) when compared with nCPAP. Moreover, O(2) requirement and respiratory rate were significantly decreased by four hours (p < 0.001 and p < 0.03 respectively). The probability of remaining supplementary oxygen free over the first 48 hours of treatment was significantly higher in patients treated with the IFD than with nCPAP (p < 0.02). IFD treated patients had a higher success (weaning) rate (94% v 72 %) and shorter duration of treatment (49.3 (31) v 56 (29.7) hours respectively; mean (SD)), although the difference was not significant.\n IFD appears to be a feasible device for managing respiratory distress syndrome in preterm infants, and benefits may be had with regard to oxygen requirement and respiratory rate when compared with nCPAP. The trend towards reduced requirement for mechanical ventilation, shorter clinical recovery time, and shorter duration of treatment requires further evaluation in a multicentre randomised clinical trial.", "OBJECTIVE: Few studies have compared the performance of nasal prongs used for applying continuous positive airway pressure. The present study compared the tolerance and efficacy with the Argyle and Hudson nasal prongs. DESIGN: A prospective, randomized clinical study. SETTING: A tertiary neonatal intensive care unit in a university hospital. PATIENTS: A total of 99 preterm infants weighing </=2500 g were assigned to one of three weight categories. They were then randomly assigned to use one of two nasal prong types. The number of times the prongs were out of the nostrils, time on nasal continuous positive airway pressure, respiratory and heart rate, Silverman-Andersen retraction score, blood gases, abdominal distention, nasal hyperemia and bleeding, septum necrosis, pneumothorax, and therapeutic success were documented. MEASUREMENTS AND MAIN RESULTS: The two groups were matched for weight, gestational age, and disease for which the continuous positive airway pressure was used. For patients weighing 1500-2000 g, the Hudson users had a greater gestational age. Both types of nasal prongs reduced the Silverman-Andersen retraction score in all infants 2 hrs after continuous positive airway pressure application, except for patients weighing </=1000 g. The Argyle prong was related to a higher frequency of hyperemia in babies weighing <1500 g (p =.03). There were no cases of septum necrosis or pneumothorax. The frequency of therapeutic success for patients using Hudson prongs and weighing >/=1500 g was significantly higher than for those using the Argyle catheter (p =.03). CONCLUSION: Considering the difference in gestational age for the patients weighing 1500-2500 g, we conclude that the two prongs tested are equally effective for nasal continuous positive airway pressure, but the Argyle prong is more difficult to keep in the nostrils of active patients, and nasal hyperemia, the first sign of tissue aggression, occurs more frequently among infants using this prong.", "To determine whether the use of the Infant Flow continuous positive airway pressure (IF CPAP) system reduces the rate of extubation failure among extremely low birth weight (ELBW) infants (infants with birth weight <1000 g) when compared with conventional CPAP delivered with a conventional ventilator and nasal prongs.\n A prospective, unmasked, randomized, controlled clinical trial was conducted in 162 eligible intubated ELBW infants who were hospitalized in 2 intensive care nurseries in Winston-Salem, North Carolina, between July 1997 and November 2000. Successful extubation was defined as no need for reintubation for any reason for at least 7 days after the first extubation attempt.\n The individual extubation success rates were 61.9% (52 of 84) in the conventional CPAP group and 61.5% (48 of 78) in the IF CPAP group. There were no significant differences in the extubation success rate in any birth weight subset between the 2 cohorts. The most common cause of extubation failure was apnea/bradycardia. Infants who were randomized to IF CPAP had fewer days on supplemental O(2) and shorter hospital stays.\n Extubation failure is a common problem, occurring in nearly 40% of ELBW infants who require mechanical ventilation. IF CPAP was as effective but no more effective than conventional CPAP in preventing extubation failure among ELBW infants. New strategies are needed to identify predictors of extubation success and to treat apnea/bradycardia, the most common cause of extubation failure, thereby reducing the likelihood of prolonged intubation in this high-risk cohort of premature infants." ]

[ "19779589", "12527536", "6875530" ]

[ "Evaluation of a Culturally Tailored Skills Intervention for Latinos with Persistent Psychotic Disorders.", "Functional adaptation skills training (FAST): a pilot psychosocial intervention study in middle-aged and older patients with chronic psychotic disorders.", "Life skills training for chronic schizophrenics." ]

[ "Fifty-nine Latino participants diagnosed with persistent psychotic disorders were assigned to either a culturally tailored skills-training intervention (n = 21), an equivalent non-tailored intervention (n = 15), or a community-based support group (n = 23). Participants completed a number of skills-based performance assessments (e.g., UCSD performance-based skills assessment; UPSA) and a well-being measure prior to and immediately post-treatment. Compared to those in the non-tailored intervention, participants receiving the tailored intervention showed significant improvement in several outcomes. These results indicate that Latino individuals with persistent psychotic disorders benefit from interventions which consider cultural values and mores.", "Developing behavioral interventions to improve functioning of older patients with schizophrenia and other chronic psychoses has the potential to significantly increase the patients' independence and quality of life.\n The authors evaluated a psychosocial intervention designed to improve everyday living skills of middle-aged and older outpatients with very chronic psychotic disorders (mean duration of illness: 21 years). Forty patients who resided in board-and-care facilities were randomly assigned to either a 24-session functional adaptation skills training (FAST) group therapy program targeting problem areas identified in previous work as being problematic for this population (e.g., using public transportation) or treatment-as-usual. Almost all the participants also received antipsychotics.\n Compared with the patients randomized to the treatment-as-usual condition, FAST-treated patients' performance on everyday living skills improved significantly immediately post-intervention and was still significantly better at a 3-month maintenance follow-up period. There was no significant change in psychopathology.\n Results suggest that older patients with longstanding psychotic disorders may benefit from participation in this skills-training program.", "This research evaluates the effectiveness of training chronic schizophrenic patients in interpersonal and instrumental skills for coping adequately in community living situations. The subjects were male, chronic schizophrenic inpatients with histories of multiple rehospitalizations. Twenty-eight volunteers were randomly assigned to either the life skills training or to a traditional Veterans Administration rehabilitation program. The life skills program included 7 weeks of training in interpersonal and instrumental skills considered important for community tenure: interpersonal communication skills, nutrition, health, finance, time management, and utilization of community resources. Acquisition of skills was assessed by means of a Life Skills Inventory (LSI) and five attitudinal and affective measures pretreatment and post-treatment. The results of the comparison of outcome measures showed the treatment group superior to the control in interpersonal skills, finance, health, use of community resources, and total LSI score. They also showed greater improvement on most of the attitudinal and affective measures. Patients are being followed to measure duration of community placement and maintenance of skills." ]

[ "12795585", "17907851", "20181120", "19411074", "17517002", "19766942", "18665688", "17007812", "12873069", "17175410", "18664995", "19968379", "17548850", "17295559", "9661327", "19702662", "16741684", "16643843", "7896672", "19786274", "16551144", "15547059", "11735841", "19968378", "19167144", "20877438", "11068970", "12602420", "19326270", "19490308", "17176380", "18698064", "19491183", "19695776", "15100560", "17074301" ]

[ "The prevention of depressive symptoms in rural school children: a randomized controlled trial.", "Prevention of depressive symptoms in adolescents: a randomized trial of cognitive-behavioral and interpersonal prevention programs.", "Effectiveness of a single-session early psychological intervention for children after road traffic accidents: a randomised controlled trial.", "Prevention of depression among Icelandic adolescents.", "Depressive symptoms in young adults: the influences of the early home environment and early educational child care.", "Evaluation of an intervention program for anxious adolescent boys who are bullied at school.", "Brief cognitive-behavioral depression prevention program for high-risk adolescents outperforms two alternative interventions: a randomized efficacy trial.", "Randomized trial of a brief depression prevention program: an elusive search for a psychosocial placebo control condition.", "Effect of the Teaching Kids to Cope (TKC) program on outcomes of depression and coping among rural adolescents.", "Symptoms of internalizing and externalizing problems: modeling recovery curves after the death of a parent.", "Effectiveness of a school-based group psychotherapy program for war-exposed adolescents: a randomized controlled trial.", "The YouthMood Project: a cluster randomized controlled trial of an online cognitive behavioral program with adolescents.", "Home visiting for adolescent mothers: effects on parenting, maternal life course, and primary care linkage.", "School-based prevention of depressive symptoms: A randomized controlled study of the effectiveness and specificity of the Penn Resiliency Program.", "School-based intervention to promote coping in rural teens.", "School-based prevention of depression: a randomised controlled study of the beyondblue schools research initiative.", "Preventing depression among early adolescents in the primary care setting: a randomized controlled study of the Penn Resiliency Program.", "The prevention of depressive symptoms in low-income, minority children: two-year follow-up.", "Targeted prevention of unipolar depressive disorder in an at-risk sample of high school adolescents: a randomized trial of a group cognitive intervention.", "The prevention of anxiety and depression in children from disadvantaged schools.", "Evaluation of universal, indicated, and combined cognitive-behavioral approaches to the prevention of depression among adolescents.", "The Gatehouse Project: can a multilevel school intervention affect emotional wellbeing and health risk behaviours?", "A randomized trial of a group cognitive intervention for preventing depression in adolescent offspring of depressed parents.", "Randomized controlled trial of a family cognitive-behavioral preventive intervention for children of depressed parents.", "Peer-group support intervention improves the psychosocial well-being of AIDS orphans: cluster randomized trial.", "Clinical Trail Outcomes of the Mexican American Problem Solving Program (MAPS).", "An experimental evaluation of theory-based mother and mother-child programs for children of divorce.", "Preventing adolescent depression: an evaluation of the problem solving for life program.", "Efficacy of a brief school-based program for selective prevention of childhood anxiety.", "'Learn Young, Learn Fair', a stress management program for fifth and sixth graders: longitudinal results from an experimental study.", "Efficacy of Interpersonal Psychotherapy-Adolescent Skills Training: an indicated preventive intervention for depression.", "School-based mental health intervention for children affected by political violence in Indonesia: a cluster randomized trial.", "Prevention of depression in at-risk adolescents: a randomized controlled trial.", "Randomized controlled trial of an Internet-delivered family cognitive-behavioral therapy intervention for children and adolescents with chronic pain.", "A randomized placebo-controlled trial of a school-based depression prevention program.", "Group prevention of depression and anxiety symptoms." ]

[ "A controlled trial was conducted to evaluate a prevention program aimed at reducing depressive and anxious symptoms in rural school children. Seventh-grade children with elevated depression were selected. Nine primary schools (n = 90) were randomly assigned to receive the program, and 9 control schools (n = 99) received their usual health education classes. Children completed questionnaires on depression, anxiety, explanatory style, and social skills. Parents completed the Child Behavior Checklist (T. M. Achenbach, 1991). No intervention effects were found for depression. Intervention group children reported less anxiety than the control group after the program and at 6-month follow-up and more optimistic explanations at postintervention. Intervention group parents reported fewer child internalizing and externalizing symptoms at postintervention only.", "This study evaluated the efficacy of 2 programs for preventing depressive symptoms in adolescents. Participants were 380 high school students randomly assigned to a cognitive-behavioral program (CB), an interpersonal psychotherapy-adolescent skills training program (IPT-AST), or a no-intervention control. The interventions involved eight 90-min weekly sessions run in small groups during wellness classes. At postintervention, students in both the CB and IPT-AST groups reported significantly lower levels of depressive symptoms than did those in the no-intervention group, controlling for baseline depression scores; the 2 intervention groups did not differ significantly from each other. The effect sizes, using Cohen's d, for the CB intervention and the IPT-AST intervention were 0.37 and 0.26, respectively. Differences between control and intervention groups were largest for adolescents with high levels of depressive symptoms at baseline. For a high-risk subgroup, defined as having scored in the top 25th percentile on the baseline depression measure, the effect sizes for the CB and the IPT-AST interventions were 0.89 and 0.84, respectively. For the whole sample, sociotropy and achievement orientation moderated the effect of the interventions. Intervention effects were short term and were not maintained at 6-month follow-up.\n (PsycINFO Database Record (c) 2007 APA, all rights reserved).", "Road traffic accidents (RTAs) are the leading health threat to children in Europe, resulting in 355,000 injuries annually. Because children can suffer significant and long-term mental health problems following RTAs, there is considerable interest in the development of early psychological interventions. To date, the research in this field is scarce, and currently no evidence-based recommendations can be made.\n To evaluate the effectiveness of a single-session early psychological intervention, 99 children age 7-16 were randomly assigned to an intervention or control group. The manualised intervention was provided to the child and at least one parent around 10 days after the child's involvement in an RTA. It included reconstruction of the accident using drawings and accident-related toys, and psychoeducation. All of the children were interviewed at 10 days, 2 months and 6 months after the accident. Parents filled in questionnaires. Standardised instruments were used to assess acute stress disorder (ASD), posttraumatic stress disorder (PTSD), depressive symptoms and behavioural problems.\n The children of the two study groups showed no significant differences concerning posttraumatic symptoms and other outcome variables at 2 or at 6 months. Interestingly, analyses showed a significant intervention x age-group effect, indicating that for preadolescent children the intervention was effective in decreasing depressive symptoms and behavioural problems.\n This study is the first to show a beneficial effect of a single-session early psychological intervention after RTA in preadolescent children. Therefore, an age-specific approach in an early stage after RTAs may be a promising way for further research. Younger children can benefit from the intervention evaluated here. However, these results have to be interpreted with caution, because of small subgroup sizes. Future studies are needed to examine specific approaches for children and adolescents. Also, the intervention evaluated here needs to be studied in other groups of traumatised children.\n Clinical Trial Registry: ClinicalTrials.gov: NCT00296842.", "Major depression and dysthymia are frequent, debilitating, and chronic disorders, whose highest rate of initial onset is during the late adolescent years. The effectiveness of a program designed to prevent an initial episode of major depression or dysthymia among adolescents was investigated. Participants were 171 fourteen-year-old \"at risk\" Icelandic adolescents who were randomly assigned to a prevention program or a treatment-as-usual assessment only control group. They were identified as \"at risk\" by reporting the presence of depressive symptoms or a negative attributional style. The program was based on a developmental psychosocial model of enhancement of resilience to factors associated with the occurrence of mood disorders. The results indicated that the prevention program resulted in a significantly lower rate of major depression and dysthymia than did the control group. The study demonstrated that school personnel in the school setting can implement such prevention programs.", "The relationship between depressive symptoms in young adults, the quality of the early home environment, and early educational child care was investigated in young adults randomly assigned to receive early childhood intervention in the Abecedarian study. Of the original 111 infants enrolled (98% African American), 104 participated in an age-21 follow-up. Those who had early treatment reported fewer depressive symptoms. The protective effects of the early childhood program were further supported by a significant home environment by treatment interaction. Negative effects of lower quality home environments on young adult depressive symptoms were almost entirely offset by preschool treatment, whereas depressive symptoms increased as the quality of the early home environment decreased for those in the control group.", "This study tested the efficacy of an intervention for anxious adolescent boys experiencing bullying at school. The cognitive-behavioral intervention focused on targeting individual factors that appear to increase an adolescent's vulnerability to bullying experiences such as anxiety, low self-esteem, and use of maladaptive coping strategies.\n Adolescent boys reporting anxiety symptoms and the recent experience of being bullied at school (grades 7-10) were randomly assigned by group to intervention (n = 22) or wait-list (n = 24) conditions. Depressive and anxiety symptoms and bullying experiences were measured before and after the intervention, and at a 3-month follow-up for the intervention condition.\n The intervention was effective in significantly reducing adolescent's bullying experiences as well as their anxiety, depression, and the degree of distress associated with being bullied. Intervention gains were maintained at the 3-month follow-up. The intervention was not effective in enhancing adolescent's self-esteem or changing aggressive or avoidant responses to bullying situations.\n This study provides preliminary support for the value of individually focused interventions for boys in the effort to reduce the incidence of bullying within schools.", "In this depression prevention trial, 341 high-risk adolescents (mean age = 15.6 years, SD = 1.2) with elevated depressive symptoms were randomized to a brief group cognitive-behavioral (CB) intervention, group supportive-expressive intervention, bibliotherapy, or assessment-only control condition. CB participants showed significantly greater reductions in depressive symptoms than did supportive-expressive, bibliotherapy, and assessment-only participants at posttest, though only the difference compared with assessment controls was significant at 6-month follow-up. CB participants showed significantly greater improvements in social adjustment and reductions in substance use at posttest and 6-month follow-up than did participants in all 3 other conditions. Supportive-expressive and bibliotherapy participants showed greater reductions in depressive symptoms than did assessment-only controls at certain follow-up assessments but produced no effects for social adjustment and substance use. CB, supportive-expressive, and bibliotherapy participants showed a significantly lower risk for major depression onset over the 6-month follow-up than did assessment-only controls. The evidence that this brief CB intervention reduced risk for future depression onset and outperformed alternative interventions for certain ecologically important outcomes suggests that this intervention may have clinical utility.\n Copyright 2008 APA, all rights reserved.", "This trial compared a brief group cognitive-behavioral (CBT) depression prevention program to a waitlist control condition and four placebo or alternative interventions. High-risk adolescents with elevated depressive symptoms (N=225, M age=18, 70% female) were randomized to CBT, supportive-expressive group intervention, bibliotherapy, expressive writing, journaling, or waitlist conditions and completed assessments at baseline, termination, and 1- and 6-month follow-up. All five active interventions showed significantly greater reductions in depressive symptoms at termination than waitlist controls; effects for CBT and bibliotherapy persisted into follow-up. CBT, supportive-expressive, and bibliotherapy participants also showed significantly greater decreases in depressive symptoms than expressive writing and journaling participants at certain follow-up points. Findings suggest there may be multiple ways to reduce depressive symptoms in high-risk adolescents, although expectancies, demand characteristics, and attention may have contributed to the observed effects.", "Incidence of depressive symptoms and lack of sufficient adaptive coping skills in adolescents.\n A randomized controlled study to test the effectiveness of a group-administered, cognitive-behavioral interventions method, TKC, on rural adolescents (N = 89). Outcomes were measured by changes in the scores on an Adolescent Depression Scale and the Coping Response Inventory pre/post intervention, at 6 and at 12 months.\n Results indicated improvement in depressive symptomatology and certain coping skills. Students in the intervention reported a higher use of cognitive problem-solving coping strategies.\n The role of a psychiatric nurse in the school system providing short-term psychoeducation interventions is a practical and effective mental health practice.", "The death of a parent is a major family disruption that can place children at risk for later depression and other mental health problems.\n Theoretically based randomized controlled trial for parentally bereaved children.\n Two-hundred and forty-four children and adolescents and their caregivers from 156 families were randomly assigned to the Family Bereavement Program (FBP) intervention condition (90 families; 135 children) or to a control condition (66 families; 109 children). Data collection occurred from 1996 to 1998.\n Children and caregivers in the intervention condition met separately for 12 two-hour weekly sessions. Skills targeted by the program for children included positive coping, stress appraisals, control beliefs, and self-esteem. The caregiver program targeted caregiver mental health, life stressors, and improved discipline in the home. Both child and caregiver programs focused on improved quality of the caregiver-child relationship.\n Child and caregiver reports of internalizing and externalizing symptoms.\n Longitudinal growth curve modeling was performed to model symptoms over time from the point of parental death. The rate of recovery for girls in the program condition was significantly different from that of girls in the control condition across all outcomes. Boys in both conditions showed reduced symptoms over time.\n The methodology offers a conceptually unique way of assessing recovery in terms of reduced mental health problems over time after an event and has contributed to further understanding of FBP intervention effects. The intervention program facilitated recovery among girls, who did not show reduction in behavior problems without the program, while boys demonstrated decreased symptoms even without intervention.", "To evaluate the comparative effectiveness of a classroom-based psychoeducation and skills intervention (tier 1) and a school-based trauma- and grief-focused group treatment (tier 2) of a three-tiered mental health program for adolescents exposed to severe war-related trauma, traumatic bereavement, and postwar adversity.\n A total of 127 war-exposed and predominantly ethnic Muslim secondary school students attending 10 schools in central Bosnia who reported severe symptoms of posttraumatic stress disorder (PTSD), depression, or maladaptive grief and significant impairment in school or relationships were randomly assigned to one of two experimental conditions. These included either an active-treatment comparison condition (tier 1), consisting of a classroom-based psychoeducation and skills intervention alone (n = 61, 66% girls, mean age 16.0 years, SD 1.13) or a treatment condition composed of both the classroom-based intervention and a 17-session manual-based group therapy intervention (tier 2), trauma and grief component therapy for adolescents (n = 66, 63% girls, mean age 15.9 years, SD 1.11). Both interventions were implemented throughout the school year. Distressed students who were excluded from the study due to acute risk for harm (n = 9) were referred for community-based mental health services (tier 3).\n Program effectiveness was measured via reductions in symptoms of PTSD, depression, and maladaptive grief assessed at pretreatment, posttreatment, and 4-month follow-up. Analysis of mean-level treatment effects showed significant pre- to posttreatment and posttreatment to 4-month follow-up reductions in PTSD and depression symptoms in both the treatment and comparison conditions. Significant pre- to posttreatment reductions in maladaptive grief reactions were found only in the treatment condition. Analyzed at the individual case level, the percentages of students in the treatment condition who reported significant (p <.05) pre- to posttreatment reductions in PTSD symptoms (58% at posttreatment, 81% at 4-month follow-up) compare favorably to those reported in controlled treatment efficacy trials, whereas the percentages who reported significant reductions in depression symptoms (23% at posttreatment, 61% at follow-up) are comparable to, or higher than, those found in community treatment settings. Lower but substantial percentages of significant symptom reduction were found for PTSD (33% at posttreatment, 48% at follow-up) and depression symptoms (13% at posttreatment; 47% at follow-up) in students in the comparison condition. The odds of significant symptom reduction were higher for PTSD symptoms at both posttreatment and 4-month follow-up and for maladaptive grief at posttreatment (no follow-up was conducted on maladaptive grief). Rates of significantly worsened cases were generally rare in both the treatment and comparison conditions.\n A three-tiered, integrative mental health program composed of schoolwide dissemination of psychoeducation and coping skills (tier 1), specialized trauma- and grief-focused intervention for severely traumatized and traumatically bereaved youths (tier 2), and referral of youths at acute risk for community-based mental health services (tier 3) constitutes an effective and efficient method for promoting adolescent recovery in postwar settings.", "The aim in the current study was to investigate the effectiveness of an online, self-directed cognitive-behavioral therapy program (MoodGYM) in preventing and reducing the symptoms of anxiety and depression in an adolescent school-based population. A cluster randomized controlled trial was conducted with 30 schools (N = 1,477) from across Australia, with each school randomly allocated to the intervention or wait-list control condition. At postintervention and 6-month follow-up, participants in the intervention condition had significantly lower levels of anxiety than did participants in the wait-list control condition (Cohen's d = 0.15-0.25). The effects of the MoodGYM program on depressive symptoms were less strong, with only male participants in the intervention condition exhibiting significant reductions in depressive symptoms at postintervention and 6-month follow-up (Cohen's d = 0.27-0.43). Although small to moderate, the effects obtained in the current study provide support for the utility of universal prevention programs in schools. The effectiveness of booster sessions should be explored in future research.", "Adolescent mothers are at risk for rapidly becoming pregnant again and for depression, school dropout, and poor parenting. We evaluated the impact of a community-based home-visiting program on these outcomes and on linking the adolescents with primary care.\n Pregnant adolescents aged 12 to 18 years, predominantly with low incomes and of African American race, were recruited from urban prenatal care sites and randomly assigned to home visiting or usual care. Trained home visitors, recruited from local communities, were paired with each adolescent and provided services through the child's second birthday. They delivered a parenting curriculum, encouraged contraceptive use, connected the teen with primary care, and promoted school continuation. Research assistants collected data via structured interviews at baseline and at 1 and 2 years of follow-up using validated instruments to measure parenting (Adult-Adolescent Parenting Inventory) and depression (Center for Epidemiologic Studies Depression). School status and repeat pregnancy were self-reported. We measured program impact over time with intention-to-treat analyses using generalized estimating equations (GEE).\n Of 122 eligible pregnant adolescents, 84 consented, completed baseline assessments, and were randomized to a home-visited group (n = 44) or a control group (n = 40). Eighty-three percent completed year 1 or year 2 follow-up assessments, or both. With GEE, controlling for baseline differences, follow-up parenting scores for home-visited teens were 5.5 points higher than those for control teens (95% confidence interval, 0.5-10.4 points; P = .03) and their adjusted odds of school continuation were 3.5 times greater (95% confidence interval, 1.1-11.8; P <.05). The program did not have any impact on repeat pregnancy, depression, or linkage with primary care.\n This community-based home-visiting program improved adolescent mothers' parenting attitudes and school continuation, but it did not reduce their odds of repeat pregnancy or depression or achieve coordination with primary care. Coordinated care may require explicit mechanisms to promote communication between the community program and primary care.", "The authors investigated the effectiveness and specificity of the Penn Resiliency Program (PRP; J. E. Gillham, L. H. Jaycox, K. J. Reivich, M. E. P. Seligman, & T. Silver, 1990), a cognitive-behavioral depression prevention program. Children (N = 697) from 3 middle schools were randomly assigned to PRP, Control (CON), or the Penn Enhancement Program (PEP; K. J. Reivich, 1996; A. J. Shatté, 1997), an alternate intervention that controls for nonspecific intervention ingredients. Children's depressive symptoms were assessed through 3 years of follow-up. There was no intervention effect on average levels of depressive symptoms in the full sample. Findings varied by school. In 2 schools, PRP significantly reduced depressive symptoms across the follow-up relative to both CON and PEP. In the 3rd school, PRP did not prevent depressive symptoms. The authors discuss the findings in relation to previous research on PRP and the dissemination of prevention programs.\n Copyright 2007 APA, all rights reserved.", "To evaluate a program designed to help high school students with depressive symptomology to effectively cope.\n Two-phase experimental study.\n Rural high school students (N = 222), ages 14 through 19 years, were surveyed to identify teens with depressive symptomatology, identify stressful life events and coping styles of at-risk subjects, and evaluate a cognitive-behavioral group intervention to enhance students' coping and affect levels of depression. Students with depressive symptomatology were randomized into control (n = 18) or intervention (n = 23) groups. Intervention subjects were treated with a nurse-led, 8-week cognitive skills group, conducted at school.\n On posttesting, the intervention groups demonstrated reduced depressive symptoms in females and a wider range of coping compared with controls.\n School-based nurses are in an ideal position to provide assessment, referral, and intervention programs in the natural setting of the school. Results of this study indicate that such programs can be implemented successfully in schools and have the potential to promote mental health in teenagers.", "Depressive disorders are experienced by 3-5% of the adolescent population at any point of time. They adversely affect adolescent development in a range of areas and greatly increase risk for suicide. The present study investigated the effectiveness of a universal intervention designed to reduce depressive symptoms among students commencing high school.\n Twenty-five pairs of secondary schools matched on socio-economic status were randomly assigned to either an intervention or a comparison group (n = 5,634 Year 8 students). The intervention extended over a 3-year period and utilised a comprehensive classroom curriculum programme, enhancements to the school climate, improvements in care pathways, and community forums. A range of measures completed by students, average age at baseline = 13.1 years (SD = .5), and teachers was used to assess changes in depressive symptoms, risk and protective factors relevant to depression, and the quality of the school environment.\n Changes in the level of depressive symptoms and in the levels of risk and protective factors experienced by students in the two groups did not differ significantly over the 3 years of the study. Furthermore, statistically significant differences in the ratings of school climate across this time period were found only for staff-rated assessments.\n Despite using an extensive, structured programme, based on best evidence to increase protective factors and reduce risk factors at the individual and school levels, the intervention did not reduce levels of depressive symptoms among participating adolescents. The results draw attention to the difficulties faced when implementing large-scale, school-based, universal preventive interventions. These include the need to develop methods to effectively train teachers across large geographical regions to deliver new interventions with fidelity, the difficulty of engaging young adolescents with prevention programmes, and the long period of time required to implement policy and practice changes at 'whole-school' levels.", "This study evaluated the Penn Resiliency Program's effectiveness in preventing depression when delivered by therapists in a primary care setting. Two-hundred and seventy-one 11- and 12-year-olds, with elevated depressive symptoms, were randomized to PRP or usual care. Over the 2-year follow-up, PRP improved explanatory style for positive events. PRP's effects on depressive symptoms and explanatory style for negative events were moderated by sex, with girls benefiting more than boys. Stronger effects were seen in high-fidelity groups than low-fidelity groups. PRP did not significantly prevent depressive disorders but significantly prevented depression, anxiety, and adjustment disorders (when combined) among high-symptom participants. Findings are discussed in relation to previous PRP studies and research on the dissemination of psychological interventions.", "We present 2-year follow-up data on the efficacy of the Penn Resiliency Program (PRP), a school-based depression prevention program, with low-income, racial/ethnic minority children. This program taught cognitive and social problem-solving skills to 168 Latino and African American middle school children who were at-risk for developing depressive symptoms by virtue of their low-income status. We had previously reported beneficial effects of the PRP up to 6 months after the conclusion of the program for the Latino children, but no clear effect for the African American children. In this paper, we extend the analyses to 24 months after the conclusion of the PRP. We continue to find some beneficial effects for the Latino children and no differentially beneficial effect for the African American children. Implications of findings and future research directions are discussed.", "This investigation attempted to prevent unipolar depressive episodes in a sample of high school adolescents with an elevated risk of depressive disorder.\n Adolescents at risk for future depressive disorder by virtue of having elevated depressive symptomatology were selected with a two-stage case-finding procedure. The Center for Epidemiologic Studies-Depression Scale (CES-D) was administered to 1,652 students; adolescents with elevated CES-D scores were interviewed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children. Subjects with current affective diagnoses were referred to nonexperimental services. The remaining 150 consenting subjects were considered at risk for future depression and randomized to either a 15-session cognitive group prevention intervention or an \"usual care\" control condition. Subjects were reassessed for DSM-III-R diagnostic status after the intervention and at 6- and 12-month follow-up points.\n Survival analyses indicated a significant 12-month advantage for the prevention program, with affective disorder total incidence rates of 14.5% for the active intervention, versus 25.7% for the control condition. No differences were detected for nonaffective disorders across the study period.\n Depressive disorder can be successfully prevented among adolescents with an elevated future risk.", "A randomised controlled trial evaluated the Aussie Optimism Program in preventing anxiety and depression. Grade 7 students (n = 496) from disadvantaged government schools in Perth Western Australia, participated. Six schools were randomly assigned to Aussie Optimism and six schools received their usual health education lessons. Students completed questionnaires on depression, anxiety, attribution style, and social skills. Parents completed the Child Behavior Checklist. No significant group effects were found for student-reported data. Parents of intervention group only students reported reductions in internalizing problems at post-test. No follow-up group effects were significant. Students and teachers found the program acceptable.\n Crown Copyright 2009. Published by Elsevier Ltd. All rights reserved.", "A cluster, stratified randomized design was used to evaluate the impact of universal, indicated, and combined universal plus indicated cognitive- behavioral approaches to the prevention of depression among 13- to 15-year-olds initially reporting elevated symptoms of depression. None of the intervention approaches differed significantly from a no-intervention condition or from each other on changes in depressive symptoms, anxiety, externalizing problems, coping skills, and social adjustment. All high-symptom students, irrespective of condition, showed a significant decline in depressive symptoms and improvement in emotional well-being over time although they still demonstrated elevated levels of psychopathology compared with the general population of peers at 12-month follow-up. There were also no significant intervention effects for the universal intervention in comparison with no intervention for the total sample of students in those conditions.\n Copyright (c) 2006 APA, all rights reserved.", "The aim of this study was to determine the effect of a multilevel school based intervention on adolescents' emotional wellbeing and health risk behaviours.\n School based cluster randomised controlled trial. Students were surveyed using laptop computers, twice in the first year of intervention and annually thereafter for a further two years.\n Secondary schools.\n 2678 year 8 students (74%) participated in the first wave of data collection. Attrition across the waves was less than 3%, 8%, and 10% respectively with no differential response rate between intervention and control groups at the subsequent waves (98% v 96%; 92% v 92%, and 90% v 89% respectively).\n A comparatively consistent 3% to 5% risk difference was found between intervention and control students for any drinking, any and regular smoking, and friends' alcohol and tobacco use across the three waves of follow up. The largest effect was a reduction in the reporting of regular smoking by those in the intervention group (OR 0.57, 0.62, and 0.72 at waves 2, 3, and 4 respectively). There was no significant effect of the intervention on depressive symptoms, and social and school relationships.\n While further research is required to determine fully the processes of change, this study shows that a focus on general cognitive skills and positive changes to the social environment of the school can have a substantial impact on important health risk behaviours.", "Adolescent offspring of depressed parents are at high risk for development of depression. Cognitive restructuring therapy holds promise for preventing progression to depressive episodes.\n A randomized, controlled trial was conducted to prevent depressive episodes in at-risk offspring (aged 13-18 years) of adults treated for depression in a health maintenance organization (HMO). Potential adult cases were found by reviewing the HMO pharmacy records for dispensation of antidepressant medication and the mental health appointment system. Medical charts were reviewed for a depression diagnosis. Recruitment letters signed by treating physicians were mailed to adults. Eligible offspring had subdiagnostic depressive symptoms insufficient to meet full DSM-III-R criteria for affective disorder and/or a past mood disorder. These youth were randomized to usual HMO care (n = 49) or usual care plus a 15-session group cognitive therapy prevention program (n = 45).\n We detected significant treatment-by-time (program) effects for the Center for Epidemiological Studies Depression Scale (P=.005) and the Global Assessment of Functioning scores (P =.04). Survival analysis of incident major depressive episodes during a median 15-month follow-up found a significant advantage (P =.003) for the experimental condition (9.3% cumulative major depression incidence) compared with the usual-care control condition (28.8%).\n A brief, group cognitive therapy prevention program can reduce the risk for depression in the adolescent offspring of parents with a history of depression.", "A family cognitive-behavioral preventive intervention for parents with a history of depression and their 9-15-year-old children was compared with a self-study written information condition in a randomized clinical trial (n = 111 families). Outcomes were assessed at postintervention (2 months), after completion of 4 monthly booster sessions (6 months), and at 12-month follow-up. Children were assessed by child reports on depressive symptoms, internalizing problems, and externalizing problems; by parent reports on internalizing and externalizing problems; and by child and parent reports on a standardized diagnostic interview. Parent depressive symptoms and parent episodes of major depression also were assessed. Evidence emerged for significant differences favoring the family group intervention on both child and parent outcomes; strongest effects for child outcomes were found at the 12-month assessment with medium effect sizes on most measures. Implications for the prevention of adverse outcomes in children of depressed parents are highlighted.", "Accumulating evidence suggests that AIDS orphanhood status is accompanied by increased levels of psychological distress such as anxiety, depression, intense guilt, shame, and anger. However, few studies have examined the possible reduction of psychological distress in AIDS orphans through the help of interventions that promote well-being. The objective of the study was to evaluate the effects of a school-based peer-group support intervention combined with periodic somatic health assessments and treatment on the psychosocial well-being of AIDS orphans in the Mbarara District of southwestern Uganda. In a cluster randomized controlled design, 326 AIDS orphans aged 10-15 years were assigned to either peer-group support intervention combined with monthly somatic healthcare (n=159) or control group (n=167) for follow-up assessment. Baseline and 10 week follow-up psychological assessments were conducted in both groups using self-administered Beck Youth Inventories. Complete data were available for 298 orphans. After adjusting for baseline scores, follow-up scores for the intervention group in comparison with controls showed significant improvement in depression, anger, and anxiety but not for self-concept. This study demonstrated that peer-group support intervention decreased psychological distress, particularly symptoms of depression, anxiety and anger. Thus, the use of peer-group support interventions should be incorporated into existing school health programs.", "Depression among Mexican immigrant women and children exceeds national prevalence rates. Given the influence of maternal depression on children, a clinical trial testing the effects of the Mexican American Problem Solving (MAPS) program was designed to address depression symptoms of Mexican immigrant women and their fourth and fifth grade children (302 dyads) through a linked home visiting and after school program compared to peers in a control group. Schools were randomized to intervention and control groups. There were statistically significant improvements in the children's health conceptions and family problem solving communication, factors predictive of mental health. Improvements in children's depression symptoms in the intervention group approached statistical significance. These promising results suggest that refined school based nursing interventions be included in community strategies to address the serious mental health problems that Mexican immigrants face.", "This study evaluated the efficacy of 2 theory-based preventive interventions for divorced families: a program for mothers and a dual component mother-child program. The mother program targeted mother-child relationship quality, discipline, interparental conflict, and the father-child relationship. The child program targeted active coping, avoidant coping, appraisals of divorce stressors, and mother-child relationship quality. Families with a 9- to 12-year-old child (N = 240) were randomly assigned to the mother, dual-component, or self-study program. Postintervention comparisons showed significant positive program effects of the mother program versus self-study condition on relationship quality, discipline, attitude toward father-child contact, and adjustment problems. For several outcomes, more positive effects occurred in families with poorer initial functioning. Program effects on externalizing problems were maintained at 6-month follow-up. A few additive effects of the dual-component program occurred for the putative mediators; none occurred for adjustment problems.", "This study evaluated the effectiveness of the Problem Solving For Life program as a universal approach to the prevention of adolescent depression. Short-term results indicated that participants with initially elevated depressions scores (high risk) who received the intervention showed a significantly greater decrease in depressive symptoms and increase in life problem-solving scores from pre- to postintervention compared with a high-risk control group. Low-risk participants who received the intervention reported a small but significant decrease in depression scores over the intervention period, whereas the low-risk controls reported an increase in depression scores. The low-risk group reported a significantly greater increase in problem-solving scores over the intervention period compared with low-risk controls. These results were not maintained, however, at 12-month follow-up.", "Anxiety sensitivity (AS) is recognized as an early risk factor for the development of anxiety disorders. This study evaluates whether a brief school-based selective prevention program reduces AS and anxious and depressive symptoms in children and youth. Participants scoring high in AS but without any current psychopathological disorder were selected from a sample of 613 individuals (61% female, 11-17 years old) and randomly assigned to the prevention program (n=47) or to a waiting-list control (WLC) (n=45) group. A normal control (NC) group (n=53) was also included. After treatment, a significant decrease in AS and in anxiety and depressive symptoms were observed in both prevention and WLC groups. Differences between experimental conditions only emerged, partially, at six-month follow-up (FU) with the prevention group (PG) exhibiting significantly lower AS (p<.05), and equalling NCs. Although the magnitude of change in the PG is comparable to that reported in previous studies with longer and more complex prevention programs, a parallel reduction in the WLCs suggests that the observed decrease in the short term could be mostly time-linked. Despite this, our results encourage research into brief preventive interventions at an individual level.", "This study examined the effects of a universal stress management program (Learn Young, Learn Fair) on stress, coping, anxiety and depression in fifth and sixth grade children.\n Fifty-two schools (1467 children) participated in a clustered randomized controlled trial. Data was collected in the fall of 2002, the spring of 2003, and the winter of 2004. Given the nested structure of the design mixed (multilevel) regression analyses were applied.\n Positive effects were found for emotion-focused coping at posttest (p < .01) and increased stress awareness at both time points. At posttest a decrease in problem solving was found (p < .01). After correcting for mediation by stress awareness the results showed that the program significantly reduced stress symptoms (p = .05) and anxiety (p = .01) at posttest. Effect sizes varied from small to large.\n Universal prevention programs that address stress and coping in children are warranted given the high prevalence of stress in children and the relationship between stress, on the one hand, and health complaints and pathology, on the other. Such programs are expected to be particularly salient for children with an increased sensitivity to stress and inadequate coping styles (e.g., diathesis-stress model). The results indicate that the school-based program 'Learn Young, Learn Fair' may be a valuable program for reducing stress in children.", "Indicated interventions for adolescents with elevated depressive symptoms may help decrease rates of depression. The current study reports on the efficacy of Interpersonal Psychotherapy-Adolescent Skills Training (IPT-AST), a group indicated preventive intervention.\n Forty-one adolescents with elevated depression symptoms were randomized to receive either IPT-AST or school counseling (SC) as delivered by guidance counselors and social workers. Adolescents in the two intervention conditions were compared on depression symptoms, overall functioning, and depression diagnoses post-intervention and at 3-month and 6-month follow-up.\n Adolescents who received IPT-AST had significantly fewer depression symptoms and better overall functioning post-intervention and at follow-up. Adolescents in IPT-AST also reported fewer depression diagnoses than adolescents in usual care.\n These results provide preliminary evidence of the efficacy of IPT-AST as an intervention for adolescents with subthreshold depression. Future research is needed to confirm the efficacy of IPT-AST in a larger and more diverse sample and to determine its long-term impact on depression symptoms and depression diagnoses.", "Little is known about the efficacy of mental health interventions for children exposed to armed conflicts in low- and middle-income settings. Childhood mental health problems are difficult to address in situations of ongoing poverty and political instability.\n To assess the efficacy of a school-based intervention designed for conflict-exposed children, implemented in a low-income setting.\n A cluster randomized trial involving 495 children (81.4% inclusion rate) who were a mean (SD) age of 9.9 (1.3) years, were attending randomly selected schools in political violence-affected communities in Poso, Indonesia, and were screened for exposure (> or = 1 events), posttraumatic stress disorder, and anxiety symptoms compared with a wait-listed control group. Nonblinded assessment took place before, 1 week after, and 6 months after treatment between March and December 2006.\n Fifteen sessions, over 5 weeks, of a manualized, school-based group intervention, including trauma-processing activities, cooperative play, and creative-expressive elements, implemented by locally trained paraprofessionals.\n We assessed psychiatric symptoms using the Child Posttraumatic Stress Scale, Depression Self-Rating Scale, the Self-Report for Anxiety Related Disorders 5-item version, and the Children's Hope Scale, and assessed function impairment as treatment outcomes using standardized symptom checklists and locally developed rating scales.\n Correcting for clustering of participants within schools, we found significantly more improvement in posttraumatic stress disorder symptoms (mean change difference, 2.78; 95% confidence interval [CI], 1.02 to 4.53) and maintained hope (mean change difference, -2.21; 95% CI, -3.52 to -0.91) in the treatment group than in the wait-listed group. Changes in traumatic idioms (stress-related physical symptoms) (mean change difference, 0.50; 95% CI, -0.12 to 1.11), depressive symptoms (mean change difference, 0.70; 95% CI, -0.08 to 1.49), anxiety (mean change difference, 0.12; 95% CI, -0.31 to 0.56), and functioning (mean change difference, 0.52; 95% CI, -0.43 to 1.46) were not different between the treatment and wait-listed groups.\n In this study of children in violence-affected communities, a school-based intervention reduced posttraumatic stress symptoms and helped maintain hope, but did not reduce traumatic-stress related symptoms, depressive symptoms, anxiety symptoms, or functional impairment.\n isrctn.org Identifier: ISRCTN25172408.", "Adolescent offspring of depressed parents are at markedly increased risk of developing depressive disorders. Although some smaller targeted prevention trials have found that depression risk can be reduced, these results have yet to be replicated and extended to large-scale, at-risk populations in different settings.\n To determine the effects of a group cognitive behavioral (CB) prevention program compared with usual care in preventing the onset of depression.\n A multicenter randomized controlled trial conducted in 4 US cities in which 316 adolescent (aged 13-17 years) offspring of parents with current or prior depressive disorders were recruited from August 2003 through February 2006. Adolescents had a past history of depression, current elevated but subdiagnostic depressive symptoms, or both. Assessments were conducted at baseline, after the 8-week intervention, and after the 6-month continuation phase.\n Adolescents were randomly assigned to the CB prevention program consisting of 8 weekly, 90-minute group sessions followed by 6 monthly continuation sessions or assigned to receive usual care alone.\n Rate and hazard ratio (HR) of a probable or definite depressive episode (ie, depressive symptom rating score of > or = 4) for at least 2 weeks as diagnosed by clinical interviewers.\n Through the postcontinuation session follow-up, the rate and HR of incident depressive episodes were lower for those in the CB prevention program than for those in usual care (21.4% vs 32.7%; HR, 0.63; 95% confidence interval [CI], 0.40-0.98). Adolescents in the CB prevention program also showed significantly greater improvement in self-reported depressive symptoms than those in usual care (coefficient, -1.1; z = -2.2; P = .03). Current parental depression at baseline moderated intervention effects (HR, 5.98; 95% CI, 2.29-15.58; P = .001). Among adolescents whose parents were not depressed at baseline, the CB prevention program was more effective in preventing onset of depression than usual care (11.7% vs 40.5%; HR, 0.24; 95% CI, 0.11-0.50), whereas for adolescents with a currently depressed parent, the CB prevention program was not more effective than usual care in preventing incident depression (31.2% vs 24.3%; HR, 1.43; 95% CI, 0.76-2.67).\n The CB prevention program had a significant prevention effect through the 9-month follow-up period based on both clinical diagnoses and self-reported depressive symptoms, but this effect was not evident for adolescents with a currently depressed parent.\n clinicaltrials.gov Identifier: NCT00073671.", "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.", "To conduct a placebo-controlled study of the effectiveness of a universal school-based depression prevention program.\n Three hundred ninety-two students age 13 to 15 from two schools were randomized to intervention (RAP-Kiwi) and placebo programs run by teachers. RAP-Kiwi was an 11-session manual-based program derived from cognitive-behavioral therapy. The placebo was similar but with cognitive components removed. Outcomes were self-rated depression scales, the Reynolds Adolescent Depression Scale (RADS), and the Beck Depression Inventory II (BDI-II). Follow-up was to 18 months. Analysis was done on an intent-to-treat basis.\n Immediately after the intervention, depression scores were reduced significantly more by RAP-Kiwi than by placebo, with a mean difference in change from baseline between groups of 1.5 on BDI-II (CI > 0.38, p =.01) and 2.24 on RADS (CI > 0.22, p =.04). Categorical analysis confirmed significant clinical benefit with an absolute risk reduction of 3% (95% CI, 1-11%, McNemar chi, p =.03), with the \"number needed to treat\" for short-term benefit of 33. Group differences in depression scores averaged across time to 18 months were significant on RADS but not on BDI-II. Retention rates were 91% at 6 months and 72% at 18 months.\n The RAP-Kiwi program is a potentially effective public health measure. Confirmation of effectiveness measuring episodes of depressive illness and broader measures of adjustment is warranted.", "To prevent depression and anxiety, we delivered a brief, classroom-based cognitive-behavioral workshop along with ongoing Web-based materials and e-mail coaching to college students at risk for depression. At risk was defined as having mild to moderate depressive symptoms on a self-report measure of depression. Two hundred forty students were randomized into either an eight-week workshop that met in groups of 10, once per week for 2 h or into an assessment-only control group. We plan to track participants for 3 years after the workshop and here we report the 6 month preventive effects on depression and anxiety. The workshop group had significantly fewer depressive symptoms and anxiety symptoms than the control group, but there was no significant difference between the conditions on depression or anxiety episodes at 6 month follow up. The workshop group had significantly better well being than the control group, and the workshop group had significantly greater improvement in optimistic explanatory style than the control group. Improved explanatory style was a significant mediator of the prevention effects from pre- to post-workshop for depressive and anxiety symptoms, as well as for improved well being." ]

[ "10370679", "17030175", "9860409", "8228122", "12499786", "9647029", "12455806", "16148557", "7859964", "8855179", "17043424", "3873389", "1397884", "14999693", "8020902" ]

[ "Prevention of infectious complications after transjugular intrahepatic portosystemic shunt in cirrhotic patients with a single dose of ceftriaxone.", "Norfloxacin vs ceftriaxone in the prophylaxis of infections in patients with advanced cirrhosis and hemorrhage.", "Parenteral antibiotic prophylaxis of bacterial infections does not improve cost-efficacy of oral norfloxacin in cirrhotic patients with gastrointestinal bleeding.", "Infectious sequelae after endoscopic sclerotherapy of oesophageal varices: role of antibiotic prophylaxis.", "[Prospective randomized trial of intravenous ciprofloxacin for prevention of bacterial infection in cirrhotic patients with esophageal variceal bleeding].", "The effect of ciprofloxacin in the prevention of bacterial infection in patients with cirrhosis after upper gastrointestinal bleeding.", "Prophylactic antibiotics in cirrhotics with upper gastrointestinal hemorrhage: a prospective, controlled trial.", "Variceal bleeding in portal hypertension: bacterial infection and comparison of efficacy of intravenous and per-oral application of antibiotics--a randomized trial.", "Bacteremia and bacterascites after endoscopic sclerotherapy for bleeding esophageal varices and prevention by intravenous cefotaxime: a randomized trial.", "Systemic antibiotic prophylaxis after gastrointestinal hemorrhage in cirrhotic patients with a high risk of infection.", "Antibiotic prophylaxis using third generation cephalosporins can reduce the risk of early rebleeding in the first acute gastroesophageal variceal hemorrhage: a prospective randomized study.", "Oral, nonabsorbable antibiotics prevent infection in cirrhotics with gastrointestinal hemorrhage.", "Norfloxacin prevents bacterial infection in cirrhotics with gastrointestinal hemorrhage.", "Antibiotic prophylaxis after endoscopic therapy prevents rebleeding in acute variceal hemorrhage: a randomized trial.", "Systemic antibiotic therapy prevents bacterial infection in cirrhotic patients with gastrointestinal hemorrhage." ]

[ "Patients with cirrhosis of the liver are prone to bacterial infections. Therapeutic interventions such as endoscopic sclerotherapy increase the risk of bacterial infections in these patients. Following insertion of a transjugular intrahepatic portosystemic shunt (TIPS), the incidence of severe bacterial infections was recently shown to be 20% after elective procedures. This finding suggests antibiotic prophylaxis with the TIPS procedure. Antibiotic prophylaxis using cefotiam or cefotaxime/ampicillin did not significantly reduce infectious complications. The aim of the present study was therefore to investigate the efficacy of two different doses of a long-acting cephalosporin in prevention of bacterial infection after TIPS.\n Eighty-two patients with cirrhosis (age: 52 +/- 2 years) who underwent elective TIPS were randomized to receive a single i.v. dose of either 1 g or 2 g Ceftriaxone 1 hour before the intervention. Patients with evidence of or suspected infections and patients on antibiotic therapy within 7 days prior to TIPS were excluded. Body temperature was monitored t.i.d. for 1 week and white blood count (WBC) and C-reactive protein (CRP) were determined before TIPS and 1 day and 1 week after TIPS.\n Only 2 of 82 patients (2.6%) showed signs of infection following TIPS insertion: One of 40 patients receiving 1 g Ceftriaxone and 1 of 42 patients receiving 2 g Ceftriaxone prior to TIPS developed temperature > 38.5 degrees C. In the latter patient this was due to pneumonia. This patient received antibiotic treatment with imipenem for 10 days. Temperature in the other patient normalized within 12 hours and he did not require antibiotic treatment. No significant differences in temperature, WBC and CRP between the different doses of Ceftriaxone were observed.\n Prophylactic treatment with Ceftriaxone reduces the reported incidence of bacterial infections after TIPS in patients with cirrhosis of the liver. Prophylaxis with 1 g Ceftriaxone seems as efficacious as 2 g.", "Oral norfloxacin is the standard of therapy in the prophylaxis of bacterial infections in cirrhotic patients with gastrointestinal hemorrhage. However, during the last years, the epidemiology of bacterial infections in cirrhosis has changed, with a higher incidence of infections caused by quinolone-resistant bacteria. This randomized controlled trial was aimed to compare oral norfloxacin vs intravenous ceftriaxone in the prophylaxis of bacterial infection in cirrhotic patients with gastrointestinal bleeding.\n One hundred eleven patients with advanced cirrhosis (at least 2 of the following: ascites, severe malnutrition, encephalopathy, or bilirubin >3 mg/dL) and gastrointestinal hemorrhage were randomly treated with oral norfloxacin (400 mg twice daily; n = 57) or intravenous ceftriaxone (1 g/day; n = 54) for 7 days. The end point of the trial was the prevention of bacterial infections within 10 days after inclusion.\n Clinical data were comparable between groups. The probability of developing proved or possible infections, proved infections, and spontaneous bacteremia or spontaneous bacterial peritonitis was significantly higher in patients receiving norfloxacin (33% vs 11%, P = .003; 26% vs 11%, P = .03; and 12% vs 2%, P = .03, respectively). The type of antibiotic used (norfloxacin), transfusion requirements at inclusion, and failure to control bleeding were independent predictors of infection. Seven gram-negative bacilli were isolated in the norfloxacin group, and 6 were quinolone resistant. Non-enterococcal streptococci were only isolated in the norfloxacin group. No difference in hospital mortality was observed between groups.\n Intravenous ceftriaxone is more effective than oral norfloxacin in the prophylaxis of bacterial infections in patients with advanced cirrhosis and hemorrhage.", "Selective intestinal decontamination with norfloxacin is useful in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding. However, bleeding cirrhotic patients with ascites, encephalopathy, or shock are at high risk to develop bacterial infections in spite of prophylactic norfloxacin. The aim of this study was to assess whether the addition of intravenous ceftriaxone could improve the efficacy of prophylaxis with norfloxacin in these patients.\n Fifty-six cirrhotic patients with gastrointestinal hemorrhage and ascites, encephalopathy, or shock were randomized into two groups: Group 1 (n = 28) received oral norfloxacin 400 mg/12 h for 7 days, and group 2 (n = 28) received norfloxacin plus intravenous ceftriaxone 2 g daily during the first 3 days of admission.\n Ten patients were excluded because of community-acquired infection, surgery, or death within the first 24 h. The incidence of bacterial infections during hospitalization was 18.1% in group 1 and 12.5% in group 2 (p = NS). The incidence of severe infections (spontaneous bacterial peritonitis, bacteremia, or pneumonia) was also similar in both groups: 9% in group 1 versus 8.3% in group 2 (p = NS). There were no statistical differences between the two groups with respect to duration of hospitalization or mortality. The cost of antibiotic therapy (including prophylaxis and treatment of infections) was significantly higher in group 2.\n These results suggest that the addition of intravenous ceftriaxone during the first 3 days of hospitalization does not improve the cost-efficacy of oral norfloxacin in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding and high risk of infection.", "In order to determine the incidence of infection following sclerotherapy and the role of antimicrobial prophylaxis, a prospective randomized control study was performed comparing i.v. imipenem/cilastatin, with an infusion of dextrose-saline as a control group. One hundred patients with bleeding esophageal varices were included. All episodes of infection were documented during admission to the unit. Ninety-seven patients were evaluable. Post-sclerotherapy bacteremia developed in six (5.6%) of 107 sclerotherapy sessions in the control group and one (1.1%) of the 88 sclerotherapy sessions in the imipenem/cilastatin group (P < or = 0.1, NS): six of these seven post-sclerotherapy bacteremias occurred after emergency sclerotherapy. Infection within 7 days of the procedure was documented after 43 (22.1%) of the 195 sclerotherapy sessions, 18 (20.5%) in the imipenem/cilastatin group and 25 (23.4%) in the control group (P = NS). These infections were significantly more common after emergency sclerotherapy, 40 (34.8%) of 115 sessions, than after elective sclerotherapy, three (3.8%) of 80 sessions (P < or = 0.0001). A short prophylactic antibiotic regime does not reduce the risk of early bacteremia or the frequency of infection after sclerotherapy. The higher risk of infection after emergency sclerotherapy may be therefore related more to the gastrointestinal hemorrhage and its associated effects than to sclerotherapy.", "In cirrhotic patients with esophageal variceal bleeding, bacterial infections are a frequent complication. Oral antibiotic prophylaxis decreases the incidence of bacterial infections. The administration of oral antibiotics, however, may be difficult in some cirrhotic patients with active bleeding. The purpose of this study was to assess the efficacy of prophylactic intravenous antibiotics for the prevention of bacterial infections in cirrhotic patients with esophageal variceal bleeding.\n From December 1998 to September 2001, a total of 40 consecutive cirrhotic patients with Child-Pugh class B or C were enrolled after emergent endoscopic esophageal variceal ligation (EVL) was taken because of esophageal variceal bleeding. Enrolled patients were randomized into a treatment group and a control group. The treatment group (n=20) received the intravenous ciprofloxacin 200mg IV q 12 hours for 3 days while the control group(n=20) didn,t.\n Bacterial infection developed in nine patients (45%) of the control group and only two patients (10%) in the treatment group. The incidence of bacterial infections was significantly lower in the treatment group than the control group (p < 0.005). The hospital cost and length of hospital stay decreased in the treatment group compared with the control group (p < 0.001). There were no differences in the hospital course and mortality within 30 days between the two groups.\n In cirrhotic patients with variceal bleeding and with Child-Pugh class B or C, the use of intravenous ciprofloxacin for 3 days after EVL was not only effective in the prevention of bacterial infections but also cost-effective.", "Cirrhotic patients with upper gastrointestinal bleeding are prone to bacterial infection. The aim of this study was to investigate the efficacy of prophylactic intestinal decontamination with oral ciprofloxacin for the prevention of bacterial infections in cirrhotic patients with upper gastrointestinal bleeding.\n A total of 120 cirrhotic patients with acute upper gastrointestinal bleeding were enrolled. Sixty patients received ciprofloxacin 500 mg twice daily given orally or through nasogastric tube immediately after upper gastrointestinal endoscopic examination; drug administration continued for 7 days. The remaining 60 patients, who received placebo, served as controls.\n The incidence of proven bacterial infection in the ciprofloxacin-treated group was significantly lower than that of placebo group (10% vs 45%, p < 0.001). The incidences of bacteremia, spontaneous bacterial peritonitis, and urinary tract infection in the ciprofloxacin-treated group were significantly lower than those in the placebo group (0% vs 23%, 3.3% vs 13%, and 5% vs 18%, respectively; p < 0.05, respectively). Multivariate logistic regression analysis showed that a lack of prophylactic treatment with ciprofloxacin and severity of cirrhosis were the independent significant predictors for cirrhotic patients with acute gastrointestinal bleeding with infection.\n Prophylactic intestinal decontamination with oral ciprofloxacin is effective in the prevention of bacterial infections in patients with cirrhosis who were suffering from acute upper gastrointestinal hemorrhage.", "Infections are a frequent complication in cirrhotics, and gastrointestinal bleeding may increase the infection rate. Nonabsorbable antibiotics or quinolone have been employed to decrease the incidence of infection. Since most of these studies were performed in western countries, it is still unclear whether this holds true in our Taiwan cirrhotic patients. Thus we conducted this study using a different formula of antibiotics to evaluate the efficacy of reducing infection rates in cirrhotics with upper gastrointestinal bleeding.\n From July 1999 to August 2000, all cirrhotic in-patients presenting with upper gastrointestinal bleeding but without infection were enrolled. The patients should not have received antibiotics within 2 weeks before admission and should have expected life expectance more than 7 days. Eligible patients who had received endoscopy within 12 hours of hospitalization were randomly allocated into 2 groups. Group A received intravenous cefazolin 1 gm every 8 hours started before endoscopy. After 3 days of prophylactic parenteral antibiotics, antibiotics were shifted to oral cephalexin of 500 mg every 6 hours for 4 days. Group B served as control subjects. All patients received chest X-ray, blood and urine cultures, and ascites culture and sputum culture if ascites and sputum were found. Patients were excluded when initial blood, urine or ascites culture was positive for bacterial growth.\n Ninety-seven patients were included. Group A was comprised of 47 patients and Group B comprised of 50 patients. There was no significant difference in age, sex, Child-Pugh's score or initial hemoglobin between the 2 groups. Proved infection developed in 6 patients of Group B. By contrast, no proved infection was found in Group A. Three organisms belonged to gram-negative bacilli and 3 organisms were gram-positive cocci. The incidence of proved infection during hospitalization was 0% in Group A and 12.0% in Group B (p = 0.027). If possible infection cases (patient's body temperature more than 38 degrees C for more than 2 days) were included, the infection rate was 6.4% in Group A and 26% in Group B (p = 0.013). Infection-related mortality occurred in 2 patients in Group B, but none in Group A.\n Our prophylactic antibiotic treatment proved safe and effective in reducing the infection rate in cirrhotics with upper gastrointestinal bleeding.", "To determine the prevalence of bacterial infection in patients admitted to hospital with variceal bleeding in comparison with patients with liver cirrhosis admitted because of another reason. To compare the effect of orally administered antibiotics vs. intravenous antibiotics.\n Bacteriological investigation of blood culture, urine, throat smear, perianal smear and ascites (polymorphonuclear count as well in ascites) was made in 46 cirrhotic patients admitted to hospital with variceal bleeding and 48 cirrhotic patients admitted because of another reason. Bleeders were treated endoscopically (sclerotization) and pharmacologically (terlipressin 1 mg every 4 h for 5 days), and were randomly allocated to the treatment with oral norfloxacin (25 patients) or intravenous ampicillin/sulbactam (21 patients). Early and late mortalities were evaluated.\n The incidence of infection was high in both groups (63.0% bleeders vs. 54.2% controls), but bleeding patients more often had positive blood culture (17.3% vs. 8.6%) and statistically significantly more positive findings in the throat smears (36.9% vs. 17.3%, P=0.04), which gives the evidence of increased pathological colonization in these patients. No difference in survival was seen in patients with per-oral or intravenous administration of antibiotics.\n Bacterial infection was demonstrated in high percentage in patients with liver cirrhosis admitted to hospital. The administration of antibiotics is indicated in these patients. Intravenous application is probably of the same efficacy as per-oral one.", "Thirty-one patients were randomized during 39 episodes of bleeding to receive either 1 g of intravenous cefotaxime (19 patients) or no antibiotic (20 patients) immediately before emergency endoscopic sclerotherapy. Blood was obtained for culture before and at 5 minutes, 4 hours, and 24 hours after the procedure. Specimens for culture were taken from the endoscope tip and channel, water bottle, and injection needle after sclerotherapy. When ascites was present (5 patients in the antibiotic group, 7 in the control group), fluid was obtained by paracentesis before endoscopy and at 4 and 24 hours. Bacteremia occurred in 1 of 19 patients in the antibiotic group (5.3%), compared with 6 of 19 in the control group (31.6%; p = .04). The cultured organisms were oral flora and usually also contaminated the endoscope and needle. No bacteria were cultured from ascitic fluid in any patient nor was the ascitic fluid white cell count elevated. Clinical infection attributable to sclerotherapy did not develop in any patient. In conclusion, the frequency of bacteremia after endoscopic sclerotherapy for bleeding esophageal varices can be reduced by prophylactic administration of intravenous cefotaxime. However, this may not be clinically relevant, given the absence of bacterascites and infection in this study. These findings do not support the routine use of antibiotics before sclerotherapy.", "In cirrhotic patients with gastrointestinal hemorrhage, bacterial infections are frequent and play a significant role in mortality. We have previously found that patients with a Child-Pugh's class C or a rebleeding are a subgroup of cirrhotic patients with a high risk of infection. The aims of the study were (1) to validate these indicators and (2) to assess the effectiveness of a systemic antibiotic treatment in preventing bacterial infections in bleeding cirrhotics with a high risk of infection. One hundred and nineteen bleeding cirrhotic patients were divided into 3 groups. Patients with a Child-Pugh's class A-B and no rebleeding (i.e., with a low risk of infection) constituted group 1 (n = 55). Patients with a high risk of infection were randomly allocated to serve as controls (group 2, n = 34) or to receive the ciprofloxacin and a combination of amoxicillin and clavulanic acid for 3 days after hemorrhage (group 3, n = 30). This antibiotic prophylaxis was administered first intravenously and then orally when the bleeding was controlled. The study period was defined as 10 days after hemorrhage. Incidence of bacterial infections was significantly higher in patients from group 2 than in patients from group 1 (52.9% vs. 18.2%; P < .001). Moreover, infections were more severe in group 2: a sepsis syndrome or a septic shock developed in 66.7% of infected patients from this group, but in only 20% of infected patients from group 1. Incidence of bacterial infections was much lower in patients from group 3 than in those from group 2 (13.3% vs. 52.9%; P < .001). Eight patients from group 2 (23.5%) and 4 patients from group 3 (13.3%) died during the first four weeks (P-not significant). Septic shock was the cause of death in 3 patients from group 2 and in only 1 patient from group 3. The cost of antibiotic therapy, including antibiotic prophylaxis in group 3, was $208 +/- $63 per patient in group 2 and $167 +/- $42 per patient in group 3 (P < .05). We conclude that (1) patients with a Child-Pugh's class C and/or a rebleeding are a subgroup of cirrhotic patients with a high risk of infection after gastrointestinal hemorrhage and that (2) in these patients, a prophylactic treatment with systemic antibiotics is very effective in preventing bacterial infections.", "Bacterial infection may be a critical trigger for variceal bleeding. Antibiotic prophylaxis can prevent rebleeding in patients with acute gastroesophageal variceal bleeding (GEVB). The aim of the study was to compare prophylactic third generation cephalosporins with on-demand antibiotics for the prevention of gastroesophageal variceal rebleeding. In a prospective trial, patients with the first acute GEVB were randomly assigned to receive prophylactic antibiotics (intravenous cefotaxime 2 g q 8 hr for 7 days, prophylactic antibiotics group) or to receive the same antibiotics only when infection became evident (on-demand group). Sixty-two patients in the prophylactic group and 58 patients in the on-demand group were included for analysis. Antibiotic prophylaxis decreased infection (3.2% vs. 15.5%, p=0.026). The actuarial rebleeding rate in the prophylactic group was significantly lower than that in the on-demand group (33.9% vs. 62.1%, p=0.004). The difference of rebleeding rate was mostly due to early rebleeding within 6 weeks (4.8% vs. 20.7%, p=0.012). On multivariate analysis, antibiotic prophylaxis (relative hazard: 0.248, 95% confidence interval (CI): 0.067-0.919, p=0.037) and bacterial infection (relative hazard: 3.901, 95% CI: 1.053-14.448, p=0.042) were two independent determinants of early rebleeding. In conclusion, antibiotic prophylaxis using third generation cephalosporins can prevent bacterial infection and early rebleeding in patients with the first acute GEVB.", "To investigate if oral, nonabsorbable antibiotics prevent bacterial infections in cirrhotics with gastrointestinal hemorrhage, 140 consecutive patients were randomly allocated into two groups: 68 patients (Group I) were given oral, non absorbable antibiotics (gentamicin + vancomycin + nystatin or neomycin + colistin + nystatin) from the inclusion into the trial up to 48 hr after cessation of the hemorrhage, or until emergency surgery or death in those cases who continued bleeding; and 72 patients (Group II) did not receive oral, nonabsorbable antibiotics. Both groups were similar in relation to clinical and laboratory data and characteristics of the hemorrhage. The incidence of infection was significantly lower in Group I than in Group II (11 patients in Group I and 25 in Group II developed proved infections; p less than 0.025). This difference was due to the fact that spontaneous bacteremia and peritonitis and urinary tract infection caused by enteric bacteria occurred almost exclusively in Group II. Two patients of Group I and 10 of Group II developed spontaneous bacteremia and/or peritonitis caused by enteric bacteria (p less than 0.025). These results indicate that prophylactic administration of oral, nonabsorbable antibiotics markedly reduces the incidence of infections caused by enteric bacteria in cirrhotic patients with gastrointestinal hemorrhage.", "To assess the efficacy of selective intestinal decontamination with norfloxacin in the prevention of bacterial infections in cirrhotic patients with gastrointestinal hemorrhage, 119 patients were included in a prospective randomized study. Group 1 (n = 60) received norfloxacin orally or through a nasogastric tube, 400 mg twice daily for 7 days beginning immediately after emergency gastroscopy; group 2 (n = 59) was the control group. We found a significantly lower incidence of infections (10% vs. 37.2%; P = 0.001), bacteremia and/or spontaneous bacterial peritonitis (3.3% vs. 16.9%; P less than 0.05), and urinary infections (0% vs. 18.6%; P = 0.001) in patients receiving norfloxacin, as a consequence of decrease in the incidence of infections caused by aerobic gram-negative bacilli. The decrease in mortality observed in the treated group (6.6% vs. 11.8%) did not reach statistical significance. The cost for antibiotic treatment showed a 62% reduction in the treated group compared with the control group. The results show that selective intestinal decontamination with norfloxacin is useful in preventing bacterial infections in cirrhotics with gastrointestinal hemorrhage.", "Bacterial infection may adversely affect the hemostasis of patients with gastroesophageal variceal bleeding (GEVB). Antibiotic prophylaxis can prevent bacterial infection in such patients, but its role in preventing rebleeding is unclear. Over a 25-month period, patients with acute GEVB but without evidence of bacterial infection were randomized to receive prophylactic antibiotics (ofloxacin 200 mg i.v. q12h for 2 days followed by oral ofloxacin 200 mg q12h for 5 days) or receive antibiotics only when infection became evident (on-demand group). Endoscopic therapy for the GEVB was performed immediately after infection work-up and randomization. Fifty-nine patients in the prophylactic group and 61 patients in the on-demand group were analyzed. Clinical and endoscopic characteristics of the gastroesophageal varices, time to endoscopic treatment, and period of follow-up were not different between the two groups. Antibiotic prophylaxis decreased infections (2/59 vs. 16/61; P <.002). The actuarial probability of rebleeding was higher in patients without prophylactic antibiotics (P =.0029). The difference of rebleeding was mostly due to early rebleeding within 7 days (4/12 vs. 21/27, P =.0221). The relative hazard of rebleeding within 7 days was 5.078 (95% CI: 1.854-13.908, P <.0001). The multivariate Cox regression indicated bacterial infection (relative hazard: 3.85, 95% CI: 1.85-13.90) and association with hepatocellular carcinoma (relative hazard: 2.46, 95% CI: 1.30-4.63) as independent factors predictive of rebleeding. Blood transfusion for rebleeding was also reduced in the prophylactic group (1.40 +/- 0.89 vs. 2.81 +/- 2.29 units, P <.05). There was no difference in survival between the two groups. In conclusion, antibiotic prophylaxis can prevent infection and rebleeding as well as decrease the amount of blood transfused for patients with acute GEVB following endoscopic treatment.", "This randomized prospective study was aimed at assessing the efficiency of a systemic antibiotic therapy for the prevention of bacterial infections in cirrhotic patients with gastrointestinal hemorrhage by ruptured esophageal varices. For 15 mo, all patients hospitalized with no infection on admission, were included in the study. Starting on admission day, patients in group A received ofloxacin (400 mg/day) for 10 days, first intravenously then orally. They also received an intravenous bolus of amoxicillin plus clavulanic acid (1 g) before each endoscopy performed during hemorrhage. Patients in group B received antibiotic therapy only in cases of established or suspected infection. Chest X-ray, blood culture, urine culture and sputum and ascitic fluid culture were performed every day for 7 days, then every other day for the next 7 days. A bronchial sampling was performed with the Wimberley technique on patients with endotracheal intubation. Ninety-one patients (55 men, 54 +/- 11 years, 78% Child Pugh class C) were included in the study (46 in group A, 45 in group B). Group A showed a lower incidence of bacterial infections than group B (20% vs. 66%; p < 0.001). Breakdown of positive bacteriological sampling was as follows: blood (6 vs. 17), ascites (3 vs. 7), lungs (2 vs. 18), urine (1 vs. 10). The 2-wk mortality rate was 24% in group A and 35% in group B." ]

[ "16253973", "10527991", "15575055", "15618254", "11527895", "8034082" ]

[ "In unselected patients, elective single embryo transfer prevents all multiples, but results in significantly lower pregnancy rates compared with double embryo transfer: a randomized controlled trial.", "Prevention of twin pregnancy after in-vitro fertilization or intracytoplasmic sperm injection based on strict embryo criteria: a prospective randomized clinical trial.", "Elective single-embryo transfer versus double-embryo transfer in in vitro fertilization.", "Two cycles with single embryo transfer versus one cycle with double embryo transfer: a randomized controlled trial.", "One versus two embryo transfer after IVF and ICSI: a randomized study.", "How many embryos should be transferred in in vitro fertilization? A prospective randomized study." ]

[ "Elective single embryo transfer (eSET) in a selected group of patients (i.e. young patients with at least one good quality embryo) reduces the number of multiple pregnancies in an IVF programme. However, the reduced overall multiple pregnancy rate (PR) is still unacceptably high. Therefore, a randomized controlled trial (RCT) was conducted comparing eSET and double embryo transfer (DET) in an unselected group of patients (i.e. irrespective of the woman's age or embryo quality).\n Consenting unselected patients were randomized between eSET (RCT-eSET) (n = 154) or DET (RCT-DET) (n = 154). Randomization was performed just prior to the first embryo transfer, provided that at least two 2PN zygotes were available. Non-participants received our standard transfer policy [SP-eSET in a selected group of patients (n = 100), otherwise SP-DET (n = 122)].\n The ongoing PR after RCT-eSET was significantly lower as compared with RCT-DET (21.4 versus 40.3%) and the twin PR was reduced from 21.0% after RCT-DET to 0% after RCT-eSET. The ongoing PRs after SP-eSET and SP-DET did not differ significantly (33.0 versus 30.3%), with an overall twin PR of 12.9%.\n To avoid twin pregnancies resulting from an IVF treatment, eSET should be applied in all patients. The consequence would be a halving of the ongoing PR as compared with applying a DET policy in all patients. The transfer of one embryo in a selected group of good prognosis patients leads to a less drastic reduction in PR but maintains a twin PR of 12.9%.", "A prospective randomized study comparing single embryo transfer with double embryo transfer after in-vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) was carried out. First, top quality embryo characteristics were delineated by retrospectively analysing embryos resulting in ongoing twins after double embryo transfer. A top quality embryo was characterized by the presence of 4 or 5 blastomeres at day 2 and at least 7 blastomeres on day 3 after insemination, the absence of multinucleated blastomeres and <20% cellular fragments on day 2 and day 3 after fertilization. Using these criteria, a prospective study was conducted in women <34 years of age, who started their first IVF/ICSI cycle. Of 194 eligible patients, 110 agreed to participate of whom 53 produced at least two top quality embryos and were prospectively randomized. In all, 26 single embryo transfers resulted in 17 conceptions, 14 clinical and 10 ongoing pregnancies [implantation rate (IR) = 42.3%; ongoing pregnancy rate (OPR) = 38.5%] with one monozygotic twin; 27 double embryo transfers resulted in 20 ongoing conceptions with six (30%) twins (IR = 48.1%; OPR = 74%). We conclude that by using single embryo transfer and strict embryo criteria, an OPR similar to that in normal fertile couples can be achieved after IVF/ICSI, while limiting the dizygotic twin pregnancy rate to its natural incidence of <1% of all ongoing pregnancies.", "The risks of premature birth and perinatal death are increased after in vitro fertilization. These risks are mainly due to the high incidence of multiple births, which relates to the number of embryos transferred.\n We performed a randomized, multicenter trial to assess the equivalence of two approaches to in vitro fertilization with respect to the rates of pregnancy that result in at least one live birth and to compare associated rates of multiple gestation. Women less than 36 years of age who had at least two good-quality embryos were randomly assigned either to undergo transfer of a single fresh embryo and, if there was no live birth, subsequent transfer of a single frozen-and-thawed embryo, or to undergo a single transfer of two fresh embryos. Equivalence was defined as a difference of no more than 10 percentage points in the rates of pregnancy resulting in at least one live birth.\n Pregnancy resulting in at least one live birth occurred in 142 of 331 women (42.9 percent) in the double-embryo-transfer group as compared with 128 of 330 women (38.8 percent) in the single-embryo-transfer group (difference, 4.1 percentage points; 95 percent confidence interval, -3.4 to 11.6 percentage points); rates of multiple births were 33.1 percent and 0.8 percent, respectively (P<0.001). These results do not demonstrate equivalence of the two approaches in rates of live births, but they do indicate that any reduction in the rate of live births with the transfer of single embryos is unlikely to exceed 11.6 percentage points.\n In women under 36 years of age, transferring one fresh embryo and then, if needed, one frozen-and-thawed embryo dramatically reduces the rate of multiple births while achieving a rate of live births that is not substantially lower than the rate that is achievable with a double-embryo transfer.\n Copyright 2004 Massachusetts Medical Society.", "With the aim of reducing the number of multiple pregnancies after IVF we investigated the effectiveness of two cycles with single embryo transfer (SET) and one cycle with double embryo transfer (DET) after IVF and calculated the cost-effectiveness of both strategies. Methods: A randomized controlled trial was performed in 107 women, aged <35 years, in their first IVF cycle, with at least one good quality embryo. They were randomized to the SET (n = 54) or DET (n = 53) group using a computer-generated random block number table, stratified for primary or secondary infertility.\n The cumulative live birth rates per woman randomized of two consecutive cycles of SET [41%; 95% confidence interval (CI) 27-54] versus one cycle of DET (36%; 95% CI 23-49) were comparable, whereas the multiple pregnancy rate was significantly higher: 37% (95% CI 15-59) in the DET and 0% in the in the SET group (P = 0.002). Combining the medical costs of the IVF treatments (where 1.5 more SET cycles were required to achieve each live birth) and of pregnancies up to 6 weeks after delivery, the total medical costs of DET per live birth were 13,680 and 13,438 for SET.\n Two cycles with SET were equally effective as one cycle with DET, and the medical costs per live birth up to 6 weeks after delivery were the same. However, if lifetime costs for severe handicaps are included, more than 7000 per live birth will be saved after implementing SET. Because of the high probability of multiple pregnancies in this group of IVF patients, only SET should be performed.", "The main reason for adverse treatment outcome in assisted reproduction is the high rate of multiple pregnancies. The only strategy to avoid dizygotic twins is to transfer one embryo at a time.\n A total of 144 women, who had had at least four good quality embryos available after IVF/intracytoplasmic sperm injection (ICSI) and who had no more than one previous failed treatment cycle, were randomized to have either one or two embryos transferred. The treatment outcomes including those after frozen embryo transfer were compared between these groups.\n The clinical pregnancy rate per transfer was 32.4% in the one embryo transfer group and 47.1% in the two embryo transfer group, the difference being not significant. Eleven twin deliveries (n = 39) occurred in the two embryo transfer group and there was one pair of monozygotic twins in the one embryo transfer group. The cumulative pregnancy rate per patient after transfer of fresh and frozen embryos was 47.3% in the one embryo transfer group and 58.6% in the two embryo transfer group.\n Our results indicate that among women who have good quality embryos in their first IVF/ICSI, good treatment results can be achieved. They support the idea of changing embryo transfer policy towards one embryo transfer without any remarkable decrease in the success rate, while dizygotic twins can be avoided.", "To maintain the rate of pregnancy, while suppressing high rank multiple pregnancies by limiting the number of fresh embryos transferred after IVF, in a population selected for potential success.\n A prospective, randomized study.\n Département de Gynécologie Obstétrique, Centre Hospitalo Universitaire, Paris VI, France.\n There were two groups of 28 couples. Women were < or = 35 years of age, with > or = 70% cleavage rate and at least four morphologically regular embryos.\n On the day of ET, either four fresh embryos were transferred (group 1) or two fresh embryos were transferred and two were frozen for later transfer (group 2).\n Pregnancy rate and multiple pregnancy.\n The pregnancy rate was the same in the two groups with one-third of the high rank pregnancies in group 1 and no pregnancies in group 2.\n Only two fresh embryos need to be transferred in this selected population." ]

[ "8033499" ]

[ "Mecamylamine combined with nicotine skin patch facilitates smoking cessation beyond nicotine patch treatment alone." ]

[ "To evaluate concurrent administration of mecamylamine (nicotine antagonist) with nicotine skin patch treatment for smoking cessation.\n This was a randomized, double-blind, placebo-controlled trial. Forty-eight healthy smokers who smoked at least one pack per day were studied at an outpatient smoking cessation research clinic. The subjects ranged in age from 20 to 40 years. Intervention with the nicotine skin patch (6 to 8 weeks) plus oral mecamylamine (2.5 to 5 mg twice a day for 5 weeks) was compared to nicotine patch plus placebo. Mecamylamine treatment began 2 weeks before smoking cessation. The primary outcome was continuous abstinence through 7 weeks after cessation (1 week after treatment), confirmed by expired air carbon monoxide measurements. Secondary measures included point abstinence at 7 weeks, continuous abstinence at 6- and 12-month follow-up, and self-reported withdrawal symptoms.\n The continuous abstinence rate at 7 weeks was three times higher in the mecamylamine condition: 50% versus 16.7%, p = 0.015. Point abstinence at 7 weeks was 58% for mecamylamine versus 29% for placebo, p = 0.044. At follow-up, continuous abstinence remained higher for mecamylamine: 37.5% versus 12.5% at 6 months (p = 0.046) and 37.5% versus 4.2% at 12 months (p = 0.004). Mecamylamine also significantly reduced craving for cigarettes, negative affect, and appetite.\n Agonist-antagonist therapy, consisting of the nicotine patch with oral mecamylamine, may substantially improve current smoking cessation treatment." ]

[ "11089633", "9871887", "9366579", "10703807", "15614717", "12960834" ]

[ "Effect of short-course of antiretroviral agents on serum triglycerides of healthy individuals.", "Occupational exposure to HIV: experience at a tertiary care center.", "A case-control study of HIV seroconversion in health care workers after percutaneous exposure. Centers for Disease Control and Prevention Needlestick Surveillance Group.", "Tolerability and side-effects of post-exposure prophylaxis for HIV infection.", "Postexposure HIV prophylaxis regimen.", "Drug-induced aminotransferase alterations during antiretroviral HIV post-exposure prophylaxis." ]

[ "nan", "We examined our hospital-based occupational health clinic's experience with combination antiretroviral therapy for postexposure prophylaxis for human immunodeficiency virus (HIV). Over a 12-month period, 68 workers started postexposure prophylaxis: 23 with zidovudine and lamivudine and 45 with zidovudine, lamivudine, and indinavir. Fifty-one (75%) of the 68 workers starting postexposure prophylaxis reported one or more side effects. Side effects were more common among those taking three drugs. Many workers failed to complete the recommended 28-day regimen because of the side effects of the various treatments. The estimated mean cost for evaluations, prophylaxis, and monitoring of exposed workers was $669 per reported exposure. In our experience, major challenges in carrying out the current HIV postexposure prophylaxis guidelines include expeditious source testing, improved staff education and prevention measures, and scrupulous monitoring of workers taking combination antiretroviral drugs for postexposure prophylaxis, with consideration of alternate regimens for intolerant workers.", "The average risk of human immunodeficiency virus (HIV) infection after percutaneous exposure to HIV-infected blood is 0.3 percent, but the factors that influence this risk are not well understood.\n We conducted a case-control study of health care workers with occupational, percutaneous exposure to HIV-infected blood. The case patients were those who became seropositive after exposure to HIV, as reported by national surveillance systems in France, Italy, the United Kingdom, and the United States. The controls were health care workers in a prospective surveillance project who were exposed to HIV but did not seroconvert.\n Logistic-regression analysis based on 33 case patients and 665 controls showed that significant risk factors for seroconversion were deep injury (odds ratio= 15; 95 percent confidence interval, 6.0 to 41), injury with a device that was visibly contaminated with the source patient's blood (odds ratio= 6.2; 95 percent confidence interval, 2.2 to 21), a procedure involving a needle placed in the source patient's artery or vein (odds ratio=4.3; 95 percent confidence interval, 1.7 to 12), and exposure to a source patient who died of the acquired immunodeficiency syndrome within two months afterward (odds ratio=5.6; 95 percent confidence interval, 2.0 to 16). The case patients were significantly less likely than the controls to have taken zidovudine after the exposure (odds ratio=0.19; 95 percent confidence interval, 0.06 to 0.52).\n The risk of HIV infection after percutaneous exposure increases with a larger volume of blood and, probably, a higher titer of HIV in the source patient's blood. Postexposure prophylaxis with zidovudine appears to be protective.", "A study of HIV post-exposure prophylaxis in 28 recipients showed that indinavir-containing regimens were poorly tolerated. This finding has implications for compliance and efficacy of the currently recommended combinations.", "nan", "In 655 individuals receiving HIV postexposure prophylaxis (PEP), drug-induced aminotransferase alterations were frequent and severe in the nevirapine-including regimen, rare and mild-to-moderate in other combinations, and always reversible. Grade 3-4 incidence in protease inhibitor or nevirapine PEP was 0.5 and 25.0 per 100 person-months, respectively. Apart from nevirapine, continuing PEP appears to be safe even in the case of aminotransferase alterations. The usefulness of routine monitoring of liver function during PEP could be re-considered." ]

[ "12269760", "18538701", "9052110" ]

[ "Changing knowledge, behavior, and practice related to universal precautions among hospital nurses in China.", "Three successful interventions in health care workers that improve compliance with hand hygiene: is sustained replication possible?", "The use of a ward-based educational teaching package to enhance nurses' compliance with infection control procedures." ]

[ "To evaluate the effect of an educational training program for hospital nurses on universal precautions in Changsha, Hunan Province, People's Republic of China.\n Using a quasi-experimental design, 50 of 100 randomly selected hospital nurses were randomly assigned to receive an educational intervention. Questionnaires were administered to the 100 nurses prior to and 4 months after the training.\n Knowledge, practice, and behaviors related to universal precautions and the prevalence of hepatitis B immunization improved among nurses in the group who received training. No significant change in the frequency of glove use was found. Underreporting of sharps injuries to hospital authorities continued in both groups.\n Although educational training significantly improved Chinese nurses' knowledge, practice, and behavior related to universal precautions, there remains room for improvement in glove use and needlestick injury reporting.", "Hand hygiene (HH) compliance by health care workers has been universally disappointing. Two major programs (Washington and Geneva) have demonstrated interventions that induce sustained improvement. The introduction of alcohol-based hand rub (AHR) together with education also has been reported to improve compliance.\n These interventions were replicated concurrently for 2 years in selected wards of an 800-bed university teaching hospital, with compliance assessed only within, not between, programs.\n No significant improvement in HH compliance was observed after the introduction of AHR (incidence rate ratio [IRR] = 1.11; 95% confidence interval [CI] = 0.93 to 1.33; P = .238) or substitution of AHR for a similar product (IRR = 1.10; 95% CI = 0.91 to 1.32; P = .328) with concomitant education. The Washington program achieved a 48% (IRR = 1.48, 95% CI = 1.20 to 1.81; P < .001) improvement in compliance, sustained over 2 years. The Geneva program failed to induce a significant increase in HH compliance in 3 wards, but achieved a 56% (IRR = 1.56; 95% CI = 1.29 to 1.89; P < .001) improvement over the already high HH rate in 1 ward (infectious disease unit).\n The Washington program demonstrated effectiveness in achieving sustained improved HH compliance, whereas the effect of the Geneva program was limited in those wards without strong medical leadership. Introduction of AHR without an associated behavioral modification program proved ineffective.", "Obtaining study leave is becoming difficult for clinical nurses in the current economic climate, but the need to develop new clinical skills and to maintain existing good practice remains of prime importance to patient care and will become mandatory with the advent of post-registration education and practice (PREP) in the UK. The ward is widely acknowledged as the best venue for learning clinical skills by nurse educationalists and for many nurses is the preferred learning environment. The feasibility of using a ward-based teaching package to enhance nurses' compliance with key infection control precautions (hand decontamination, the use of gloves and the safe handling and disposal of sharp instruments) was tested in a quasi-experimental research study conducted on matched surgical wards in a teaching hospital, controlling for variables likely to influence performance (knowledge, availability of resources to perform infection control, previous opportunity to develop infection control expertise and nursing workload). Nurses on two wards received the intervention (experimental group). The remaining wards, which received no intervention, operated as controls. The ward-based sessions consisted of a carefully planned sequence of theory and practical demonstration delivered to qualified nurses in the clinical environment at convenient times selected by the ward managers. Performance of infection control precautions was audited before the intervention and 3 months afterwards. The sessions were well evaluated and the clinical environment was considered suitable for teaching by the nurses, but heavy and unpredictable workload prevented the teaching programme from being implemented as planned. The analysis of covariance failed to detect any changes in performance between nurses in the control and experimental groups. The implications of the study findings are discussed to help develop creative new ways of strengthening ward-based educational programmes." ]

[ "17124017", "15592281", "11084540", "19530004", "15970816" ]

[ "Fetal pulse oximetry and cesarean delivery.", "Intrapartum management of nonreassuring fetal heart rate patterns: a randomized controlled trial of fetal pulse oximetry.", "A multicenter controlled trial of fetal pulse oximetry in the intrapartum management of nonreassuring fetal heart rate patterns.", "Reduction in caesarean delivery with fetal heart rate monitoring and intermittent pulse oximetry after induction of labour with misoprostol.", "Use of fetal pulse oximetry among high-risk women in labor: a randomized clinical trial." ]

[ "Knowledge of fetal oxygen saturation, as an adjunct to electronic fetal monitoring, may be associated with a significant change in the rate of cesarean deliveries or the infant's condition at birth.\n We randomly assigned 5341 nulliparous women who were at term and in early labor to either \"open\" or \"masked\" fetal pulse oximetry. In the open group, fetal oxygen saturation values were displayed to the clinician. In the masked group, the fetal oxygen sensor was inserted and the values were recorded by computer, but the data were hidden. Labor complicated by a nonreassuring fetal heart rate before randomization was documented for subsequent analysis.\n There was no significant difference in the overall rates of cesarean delivery between the open and masked groups (26.3% and 27.5%, respectively; P=0.31). The rates of cesarean delivery associated with the separate indications of a nonreassuring fetal heart rate (7.1% and 7.9%, respectively; P=0.30) and dystocia (18.6% and 19.2%, respectively; P=0.59) were similar between the two groups. Similar findings were observed in the subgroup of 2168 women in whom a nonreassuring fetal heart rate was detected before randomization. The condition of the infants at birth did not differ significantly between the two groups.\n Knowledge of the fetal oxygen saturation is not associated with a reduction in the rate of cesarean delivery or with improvement in the condition of the newborn. (ClinicalTrials.gov number, NCT00098709 [ClinicalTrials.gov].).\n Copyright 2006 Massachusetts Medical Society.", "We tested if fetal pulse oximetry in addition to electronic fetal monitoring (CTG) and scalp blood sampling improves the accuracy of fetal assessment and allows safe reduction of operative deliveries (-50%) and scalp blood sampling (-50%) performed because of nonreassuring fetal status. Study design A randomized controlled trial was conducted in 146 patients with term pregnancies in active labor and abnormal fetal heart rate patterns: 73 had electronic fetal heart rate monitoring (CTG) and fetal scalp blood sampling (control group), 73 had CTG, fetal scalp blood sampling, and continuous fetal pulse oximetry (study group).\n There was a reduction of -50% in operative deliveries and fetal scalp blood sampling performed because of nonreassuring fetal status in the study group: operative deliveries, study versus control 25/49 (P </= .001); fetal scalp sampling, study versus control 32/64 (P </= .001). An increase in cesarean sections because of dystocia in the study group did not change the net number of operative deliveries. There was no difference between the 2 groups in adverse maternal or neonatal outcomes, as well as for the end points of metabolic acidosis and need for resuscitation.\n There was a safe reduction in operative deliveries (-50%) and scalp blood sampling (-50%) performed because of nonreassuring fetal status. The increase in cesarean sections because of dystocia in the study group was a well-documented arrest of labor, but it did not change the total number of operative deliveries in this group.", "Recent developments permit the use of pulse oximetry to evaluate fetal oxygenation in labor. We tested the hypothesis that the addition of fetal pulse oximetry in the evaluation of abnormal fetal heart rate patterns in labor improves the accuracy of fetal assessment and allows safe reduction of cesarean deliveries performed because of nonreassuring fetal status.\n A randomized, controlled trial was conducted concurrently in 9 centers. The patients had term pregnancies and were in active labor when abnormal fetal heart rate patterns developed. The patients were randomized to electronic fetal heart rate monitoring alone (control group) or to the combination of electronic fetal monitoring and continuous fetal pulse oximetry (study group). The primary outcome was a reduction in cesarean deliveries for nonreassuring fetal status as a measure of improved accuracy of assessment of fetal oxygenation.\n A total of 1010 patients were randomized, 502 to the control group and 508 to the study group. There was a reduction of >50% in the number of cesarean deliveries performed because of nonreassuring fetal status in the study group (study, 4. 5%; vs. control, 10.2%; P =.007). However, there was no net difference in overall cesarean delivery rates (study, n = 147 [29%]; vs. control, 130 [26%]; P = .49) because of an increase in cesarean deliveries performed because of dystocia in the study group. In a blinded partogram analysis 89% of the study patients and 91% of the control patients who had a cesarean delivery because of dystocia met defined criteria for actual dystocia. There was no difference between the 2 groups in adverse maternal or neonatal outcomes. In terms of the operative intervention for nonreassuring fetal status, there was an improvement in both the sensitivity and the specificity for the study group compared with the control group for the end points of metabolic acidosis and need for resuscitation.\n The study confirmed its primary hypothesis of a safe reduction in cesarean deliveries performed because of nonreassuring fetal status. However, the addition of fetal pulse oximetry did not result in an overall reduction in cesarean deliveries. The increase in cesarean deliveries because of dystocia in the study group did appear to result from a well-documented arrest of labor. Fetal pulse oximetry improved the obstetrician's ability to more appropriately intervene by cesarean or operative vaginal delivery for fetuses who were actually depressed and acidotic. The unexpected increase in operative delivery for dystocia in the study group is of concern and remains to be explained.", "To integrate intermittent fetal pulse oximetry (FPO) to intrapartum fetal assessment and reduce the rate of caesarean sections.\n A randomised controlled trial using 37 weeks as a restriction point was conducted in 230 women induced with misoprostol. One hundred-fourteen were assessed with intermittent FPO plus fetal heart rate (FHR) monitoring (study group) and 116 were assessed with FHR monitoring alone (control group). The primary outcome measure was caesarean delivery rates. Secondary outcome measures included induction to delivery interval, number of emergency caesarean deliveries performed for fetal non-reassuring FHR patterns and neonatal outcomes.\n There was a reduction both in the overall caesarean deliveries (study n = 18, (15.7%); vs. control n = 31 (26.7%); p = 0.04), and the rate of caesarean deliveries performed for non-reassuring fetal status in the study group (study n = 11, (9.6%); vs. control n = 23 (19.8%); p = 0.03). Induction to delivery interval was similar in between the groups (759 +/- 481 min in group 1; vs. 735 +/- 453 min in group 2 respectively; p = 0.69).\n Intermittent FPO in misoprostol induced deliveries decreases both total caesarean rate and the caesarean rate due to non-reassuring FHR patterns.", "The purpose of this study was to determine the clinical role of fetal pulse oximetry to reduce cesarean delivery for a nonreassuring fetal heart rate tracing.\n Singletons > or =28 weeks were randomized to fetal pulse oximetry plus electronic fetal heart rate monitoring (monitoring + fetal pulse oximetry) or monitoring alone.\n Overall, 360 women in labor were recruited: 150 cases with monitoring+fetal pulse oximetry and 177 cases with monitoring alone were analyzed. Most demographic, obstetric, and neonatal characteristics were similar. Specifically, the gestational age, cervical dilation, and station of the fetal head were not differential factors. In addition, cesarean delivery for nonreassuring fetal heart rate tracing was not different between the group with monitoring+fetal pulse oximetry (29%) and the group with monitoring alone (32%; relative risk, 0.95; 95% CI, 0.75, 1.22). Likewise, cesarean delivery for arrest disorder was similar between the group with monitoring+fetal pulse oximetry (22%) and the group with monitoring alone (23%; relative risk, 1.05; 95% CI, 0.79, 1.44). However, the decision-to-incision time was shorter for the group with monitoring+fetal pulse oximetry (17.8 +/- 8.2 min) than for the group with monitoring alone (27.7 +/- 13.9 min; P < .0001).\n The use of fetal pulse oximetry with electronic fetal heart rate monitoring does not decrease the rate of cesarean delivery, although it does alter the decision-to-incision time." ]