Datasets:

allenai

/

cochrane_sparse_oracle

like 0

[ "6813921", "6773113", "4631743", "15998652", "6808169", "6429406", "6783809", "17492348" ]

[ "[Parenteral nutrition and \"hypermetabolic\" acute renal failure].", "[Parenteral nutrition in septic patients with acute renal failure in polyuric phase].", "Improved survival from acute renal failure after treatment with intravenous essential L-amino acids and glucose. Results of a prospective, double-blind study.", "Effects of different energy intakes on nitrogen balance in patients with acute renal failure: a pilot study.", "A comparison of essential and general amino acid infusions in the nutritional support of patients with compromised renal function.", "Total parenteral nutrition with high or low nitrogen intakes in patients with acute renal failure.", "Clinical and metabolic responses to parenteral nutrition in acute renal failure. A controlled double-blind study.", "High-dose amino acid infusion preserves diuresis and improves nitrogen balance in non-oliguric acute renal failure." ]

[ "nan", "nan", "nan", "Thus far, there have been no controlled studies to examine optimal levels of energy provision in critically ill patients with acute renal failure (ARF) receiving artificial nutrition.\n After a 24 h nitrogen-free regimen (20% dextrose), we assigned during an open-label, AB/BA-crossover-trial, 10 ARF patients receiving both total parenteral nutrition (TPN) and renal replacement therapy (seven males; mean age 72 years, range 60-83; mean APACHE II score 27.1, range 23-34, mechanical ventilation 8/10) to a lower calorie-TPN regimen (30 kcal/kg/day) and to a higher calorie-TPN regimen (40 kcal/kg/day), each for 3 days. Nitrogen intake was 0.25 g/kg/day for both regimens. We estimated nitrogen balance, protein catabolic rate and urea generation rate by urea kinetic methods based on both timed blood samples of serum urea and direct urea quantification from dialysis fluid.\n Two patients were excluded from the analysis (due to death and serum triglycerides above 5.1 mmol/l, respectively). Compared with the lower calorie-TPN, the higher calorie-TPN regimen did not improve estimated nitrogen balance [+1.55 g/day (95% confidence interval: -0.95 to +4.05, P = 0.18)], protein catabolic rate [-0.10 g/kg/day (-0.33 to +0.14, P = 0.35)], or urea generation rate [-1.3 mg/min (-5.2 to +2.7, P = 0.46)], whereas it increased serum triglycerides [+1.36 mmol/l (+0.53 to +2.19, P = 0.007)], glucose [+1.15 mmol/l (+0.07 to +2.24, P = 0.041)], insulin need [+20.4 U/day (+8.3 to +32.6, P = 0.006)] and nutritional fluid administration [+468 ml/day (+370 to +566, P<0.001)].\n The present study, conducted in a small group of subjects, shows that in critically ill patients with ARF on a nitrogen intake of 0.25 g/kg/day, an energy provision of 40 kcal/kg/day does not improve nitrogen balance estimates compared with a 30 kcal/kg/day intake; instead, it may increase the risk of artificial nutrition-related side-effects.", "nan", "This study was undertaken to assess the clinical and metabolic responses to total parenteral nutrition (TPN) in patients with acute renal failure who could not be nourished adequately through the enteral tract. The TPN provided either about 21 g/day of essential amino acids (EAA) or a larger quantity of essential and nonessential amino acids (ENAA); the ratio of essential to nonessential amino acids in the latter preparation was 1.0:1.0. Attempts were made to give sufficient ENAA nitrogen to equal or slightly exceed the urea nitrogen appearance (UNA). Five patients were randomly assigned to receive TPN with EAA (2.3 g of nitrogen per day) and six patients to receive ENAA (11.3 g of nitrogen per day). Hypotension with trauma or infarcted intestine was the cause of acute renal failure in 10 of the 11 patients. Three of the five patients receiving EAA recovered renal function, and two survived. In the patients receiving ENAA, as compared with those given EAA, UNA was significantly greater (14 +/- 7.4 [SD] vs. 7.5 +/- 3.0 g/day; P less than 0.01), and nitrogen balance, estimated from the difference between intake nitrogen and UNA was slightly, but not significantly, less negative (-3.0 +/- 4.0 vs. -5.2 +/- 2.9 g of nitrogen per day). These preliminary findings suggest that in comparison to TPN with EAA, there is no advantage to larger amounts of ENAA (76 +/- 13 g/day). Studies are indicated to assess whether a multifaced approach using TPN with ENAA and possibly a larger proportion of the branched-chain amino acids, higher energy intakes, anabolic agents, and continuous arterio-venous hemofiltration will improve morbidity and mortality in patients with acute renal failure.", "1. Thirty patients with acute renal failure who were unable to eat adequately were evaluated while they received parenteral nutrition with glucose alone (n = 7), glucose and 21 g/day essential amino acids (EAA, n = 11) or glucose, 21 g/day essential and 21 g/day nonessential amino acids (ENAA, n = 12). Energy intake did not differ with the three treatments. Patients were studied in a prospective double blind fashion. 2. Thirteen patients recovered renal function and 11 survived to leave the hospital. Those in whom renal failure was attributed to hypotension and/or sepsis had a poorer recovery of renal function (17%) and survival (17%). Recovery of renal function and survival was greater in patients on the medical service as compared to the surgical service and in those who received more energy. Recovery of renal function was worse in those treated with dialysis. There were no differences in recovery of renal function of survival among the three treatment groups. 3. Many patients were markedly catabolic as indicated by nitrogen balances, urea in nitrogen appearance rates (UNA), serum protein concentrations, and plasma amino acid levels. There was no correlation between the degree of catabolism and recovery of renal function or survival. Mean UNA in individual patients also correlated with body weight. Among the three groups, however, UNA was significantly less with the group receiving EAA as compared to ENAA. 4. Serum protein concentrations were lower than normal in all treatment groups. Serum albumin fell significantly during the treatment in the more catabolic patients. Plasma amino acid levels tended to fall in all three groups and concentrations at the end of the treatment were frequently lower than normal. 5. These data suggest that acute renal failure patients who are unable to eat adequately are often hypercatabolic and have a high mortality, particularly if hypotension or sepsis is the cause of renal failure. The improved survival in those with higher energy intakes, the high rate of net protein breakdown, the low serum protein levels and the reduced plasma concentrations of both essential and nonessential amino acids suggest that greater quantities of energy and both essential and nonessential amino acids may be beneficial to such patients.", "The effects of protein-enriched diets on glomerular filtration have been described in normal subjects and in patients with chronic renal failure. In acute renal failure, the effects of administration of high rates of protein on renal function and nitrogen balance have not been studied in critically ill patients. The present study examines the effects of large doses of amino acids on the glomerular filtration rate and nitrogen balance in critically ill patients with acute renal failure.\n Fourteen critically ill patients with a creatinine clearance below 50 ml/min and conserved diuresis above 2,000 ml/day received 2000 non-protein kcal/day and either 75 g (Group 1) or 150 g (Group 2) of amino acids parenterally. Renal function tests, fluid balance, sodium and nitrogen balances, and furosemide administration were assessed on day 1 (baseline day when dextrose 5% was administered) and days 2, 3 and 4.\n The two groups were comparable in terms of severity indices, sex and creatinine clearance. Group 2 was significantly older (p < 0.05). Blood urea nitrogen increased significantly in Group 1 but not in Group 2; creatinine clearance remained unchanged in the two groups. Group 2 patients had a significantly more positive cumulative nitrogen balance (-10.5 +/- 17 g/day vs. 9 +/- 8.3 g/day) (p < 0.01), less positive fluid balance (2003 +/- 1336 ml vs. -2407 +/- 1990 ml) and lower furosemide requirement (1003 +/- 288 mg vs. 649 +/- 293 mg) (p < 0.05).\n A high amino acid regimen administered as a part of parenteral nutrition improves nitrogen balance, reduces furosemide requirements and ameliorates water balance in acute renal failure patients with conserved diuresis." ]

[ "2405864", "7978695", "8350329", "11710708", "8507221", "2132565" ]

[ "The effect of folic acid supplementation on the toxicity of low-dose methotrexate in patients with rheumatoid arthritis.", "Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial.", "Low dose leucovorin does not interfere with the efficacy of methotrexate in rheumatoid arthritis: an 8 week randomized placebo controlled trial.", "The C677T mutation in the methylenetetrahydrofolate reductase gene: a genetic risk factor for methotrexate-related elevation of liver enzymes in rheumatoid arthritis patients.", "Low-dose methotrexate with leucovorin (folinic acid) in the management of rheumatoid arthritis. Results of a multicenter randomized, double-blind, placebo-controlled trial.", "Administration of folinic acid after low dose methotrexate in patients with rheumatoid arthritis." ]

[ "Thirty-two patients with rheumatoid arthritis completed a 24-week, placebo-controlled, double-blind trial of folic acid (FA) supplementation during low-dose methotrexate (MTX) therapy. Administration of the daily FA supplement significantly lowered toxicity scores without affecting efficacy, as measured by joint counts, joint indices, and patient and physician evaluation of disease activity. Fifteen patients experienced some sort of toxicity; 67% were in the placebo group, and 33% were in the FA supplement group. Four patients in the placebo group had toxicity levels serious enough to require discontinuation of the MTX, while no patients in the FA supplement group discontinued MTX because of toxicity. Low-normal initial plasma and red blood cell folate levels were predictive of future toxicity with MTX therapy. We conclude that a daily supplement of 1 mg of FA during low-dose MTX therapy (median dose 7.5 mg/week [16.4 mumoles]) is usefull in lessening toxicity without altering efficacy during the first 6 months of treatment.", "To determine the effect of two different weekly doses of folic acid on the toxicity and efficacy of low-dose methotrexate therapy for rheumatoid arthritis.\n Randomized, double-blind, placebo-controlled study.\n 79 persons between 19 and 78 years of age who fulfilled the American Rheumatism Association's criteria for rheumatoid arthritis.\n Participants were randomly assigned to visually identical placebo or to 5 mg or 27.5 mg of folic acid each week.\n Duration, intensity, and clinical severity of toxic events; efficacy (indices of joint tenderness and swelling and grip strength); plasma and erythrocyte folate levels; and other laboratory variables.\n Folic acid supplementation at either dose did not affect the efficacy of methotrexate therapy as judged by joint indices and patient and physician assessments of disease. Patients given folic acid supplements had lower toxicity scores than did participants given placebo (P < or = 0.001). Low blood folate levels and increased mean corpuscular volumes were associated with substantial methotrexate toxicity, whereas daily dietary intakes of more than 900 nmol (400 micrograms) of folic acid were associated with little methotrexate toxicity.\n Folic acid, an inexpensive vitamin, is safe in a broad range of doses and protects patients with rheumatoid arthritis who are taking methotrexate from toxicity while preserving the efficacy of methotrexate.", "To determine if simultaneously administered low dose leucovorin interferes with the efficacy of methotrexate (MTX).\n An 8-week double blind placebo controlled study of leucovorin (1 mg) in 16 patients with rheumatoid arthritis receiving chronic MTX was performed at a single academic center.\n A flare of disease activity was not observed. Clinical variables of arthritis activity did not change in the leucovorin treated population.\n Low dose leucovorin when taken simultaneously with MTX did not interfere with the efficacy of MTX in a short term 8 week trial.", "To study the possible relationship between the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and the toxicity and efficacy of treatment with methotrexate (MTX) in patients with rheumatoid arthritis (RA).\n Genotype analysis of the MTHFR gene was done in 236 patients who started MTX treatment with (n = 157) or without (n = 79) folic or folinic acid supplementation. Outcomes were parameters of efficacy of MTX treatment, patient withdrawal due to adverse events, discontinuation of MTX treatment because of elevated liver enzyme levels, and the total occurrence of elevated liver enzyme levels during the study. Multivariate logistic regression analysis was used to study the relationship between the presence of the MTHFR C677T mutation and toxicity outcomes of MTX treatment.\n Forty-eight percent of the patients showed the homozygous (T/T) or heterozygous (T/C) mutation. The presence of the C677CT or C677TT genotypes was associated with an increased risk of discontinuing MTX treatment because of adverse events (relative risk 2.01; 95% confidence interval 1.09, 3.70), mainly due to an increased risk of elevated liver enzyme levels (relative risk 2.38; 95% confidence interval 1.06, 5.34). Efficacy parameters were not significantly different between the patients with and those without the mutation.\n The C677T mutation is the first identified genetic risk factor for elevated alanine aminotransferase values during MTX treatment in patients with RA. We postulate that the incidence of clinically important elevation of liver enzyme levels during MTX treatment is mediated by homocysteine metabolism. Supplementation with folic or folinic acid reduced the risk of toxicity-related discontinuation of MTX treatment both in patients with and in patients without the mutation.", "To determine whether the side effects of methotrexate can be decreased by the concurrent use of leucovorin, without affecting the efficacy of the methotrexate.\n We conducted a multicenter randomized, double-blind, placebo-controlled trial of leucovorin administration, 2.5-5.0 mg orally, to be given 24 hours after the single, weekly, oral dose of methotrexate. Every 3 weeks for 52 weeks, patients were evaluated for rheumatic disease activity and side effects. Dosage adjustments for both methotrexate and leucovorin were made as needed, according to a defined protocol. The primary outcome evaluated was the frequency of study withdrawals because of side effects and/or inefficacy. Secondary outcomes evaluated included the frequency of side effects and the relative efficacy of methotrexate in the leucovorin and placebo treatment groups.\n Ninety-two evaluable patients were analyzed (44 took leucovorin and 48 placebo). Twenty-two patients withdrew early because of side effects unresponsive to our protocol, and 1 because of inefficacy; 17 had been taking placebo and 6 had been taking leucovorin (35% versus 14%, P < 0.02). The number of visits during which side effects were reported was reduced by almost 50% in the leucovorin treatment group (P < 0.001). There were significant reductions in the frequencies of all common side effects. At 52 weeks, disease activity was similar in both patient groups.\n The methotrexate-leucovorin protocol used significantly reduces common side effects of methotrexate therapy without significantly altering efficacy.", "Folinic acid (leucovorin) supplementation has been suggested as a possible means of treating the short term side effects that occur with low dose methotrexate (MTX). However, it has not been established whether leucovorin will abrogate the antiarthritic effect of MTX. We entered 20 patients with rheumatoid arthritis treated with MTX into a 48 week randomized, double blind, crossover trial of folinic acid vs placebo. The dose of folinic acid was equal to the dose of MTX and it was given orally 4 h following the single, weekly MTX administration. Under these conditions, leucovorin did not decrease the therapeutic effect of MTX. While the incidence of stomatitis and gastrointestinal toxicity were lower during leucovorin treatment, our study lacked sufficient power to establish a statistically significant difference." ]

[ "8275622", "8219431", "3367452", "3056540" ]

[ "Smoking cessation, clonidine, and vulnerability to nicotine among dependent smokers.", "Randomized, controlled trial of transdermal clonidine for smoking cessation.", "Heavy smokers, smoking cessation, and clonidine. Results of a double-blind, randomized trial.", "Effect of clonidine on cigarette cessation and in the alleviation of withdrawal symptoms." ]

[ "This study examines the efficacy of clonidine in smoking cessation and the influence of gender, history of major depression, and measures of nicotine dependence.\n The study was designed as a 10-week double-blind randomized comparison stratified for gender and major depression. Three hundred subjects who smoked cigarettes heavily were enrolled in the study. Abstinence from smoking was evaluated by self-report and verified by serum cotinine levels.\n Gender, major depression recurrent type, and measures of nicotine addiction were risk factors for treatment failure. There was no clonidine effect in men, but there was a modest effect in women (odds ratio, 2.01; 95% confidence interval, 1.00 to 4.10) that was most pronounced (odds ratio, 8.5; 95% confidence interval, 1.67 to 43.62) among women with the highest risks.\n Measures of addiction and major depression predict treatment failure. Together they are stronger predictors of outcome than drug. Clonidine is a limited aid in cessation, and drug effects come primarily from women at high risk for treatment failure. An increased risk for psychiatric complications after smoking cessation was apparent among smokers with histories of major depression, particularly bipolar disease.", "To determine the efficacy and safety of clonidine versus placebo in smoking cessation.\n Single-center, randomized, double-blind, parallel-design comparison of transdermal clonidine with behavior modification, transdermal clonidine without behavior modification, placebo with behavior modification, and placebo without behavior modification.\n Outpatient, university-based ambulatory care facility.\n One hundred fifty generally healthy, highly nicotine-dependent cigarette smokers.\n Clonidine was given as the transdermal patch initiated 72 hours prior to smoking-cessation attempts and continued for six weeks thereafter. Clonidine was given at a dose of 0.2 mg/d for patients weighing more than 150 pounds (> 67.5 kg) and at a dose of 0.1 mg/d for patients weighing less than 150 pounds (< 67.5 kg). Behavior modification consisted of a total of 12 one-hour structured group training sessions. Patients not receiving behavior modification received printed material, which included the \"Help Quit Kit\" and the \"I Quit Kit\" from the American Cancer Society.\n Smoking-cessation rates were assessed at 6, 12, 24, and 52 weeks of follow-up. In addition, adverse reactions to clonidine or placebo were evaluated.\n Clonidine with behavior modification was statistically superior to the other three treatment groups but only at 6 weeks of follow-up. There were no differences in smoking-cessation rates among any of the treatment groups at any other follow-up intervals. Patients receiving behavior modification, regardless of whether they received clonidine, had better quit rates than patients not receiving behavior modification at all follow-up times except 52 weeks. Women receiving clonidine had significantly better quit rates than men receiving clonidine at all follow-up visits. Clonidine was associated with a significantly higher incidence of adverse effects than placebo (52 vs. 11 percent). However, the number of smokers withdrawing from the study was not greater with clonidine compared with placebo (9 vs. 7 percent, respectively).\n Clonidine is probably not effective as a pharmacologic adjunct to behavior modification in smoking cessation. It may have a potential role in women smokers who do not respond to or cannot tolerate more traditional smoking-cessation therapies.", "Seventy-one heavy smokers who had failed in previous attempts to stop smoking participated in a randomized clinical trial to test the efficacy of clonidine as an aid in smoking cessation. The success rate in clonidine-treated subjects (verified by serum cotinine concentration) was more than twice that in the placebo-treated subjects. When the data were stratified by gender, a strong effect present in women was not apparent in men. After six months, cessation rates remained significantly higher among smokers treated with clonidine than those receiving placebo. The data also revealed an unexpectedly high prevalence (61%) of a history of major depression in this sample and a significant negative effect of such a history on cessation regardless of treatment. These findings, highly suggestive of an important role of clonidine in smoking cessation, warrant further studies to establish the long-term (greater than or equal to 12 months) efficacy of this drug and to replicate the association between nicotine dependence and depression.", "nan" ]

[ "18208636", "3285637", "16280447", "16753014", "15230999", "16278262" ]

[ "Effect of vitamin D supplementation on bone and vitamin D status among Pakistani immigrants in Denmark: a randomised double-blinded placebo-controlled intervention study.", "Double blind study on the need for vitamin D supplementation in prepubertal children.", "Effects of calcium, dairy product, and vitamin D supplementation on bone mass accrual and body composition in 10-12-y-old girls: a 2-y randomized trial.", "A positive dose-response effect of vitamin D supplementation on site-specific bone mineral augmentation in adolescent girls: a double-blinded randomized placebo-controlled 1-year intervention.", "School-milk intervention trial enhances growth and bone mineral accretion in Chinese girls aged 10-12 years in Beijing.", "Effect of vitamin D replacement on musculoskeletal parameters in school children: a randomized controlled trial." ]

[ "Severe vitamin D deficiency is common among Muslim immigrants. The dose necessary to correct the deficiency and its consequence for bone health are not known for immigrants. The aim was to assess the effect of relatively low dosages of supplemental vitamin D on vitamin D and bone status in Pakistani immigrants. This 1-year-long randomised double-blinded placebo-controlled intervention with vitamin D3 (10 and 20 microg/d) included girls (10.1-14.7 years), women (18.1-52.7 years) and men (17.9-63.5 years) of Pakistani origin living in Denmark. The main endpoints were serum 25-hydroxyvitamin D (S-25OHD), parathyroid hormone, bone turnover markers and bone mass. The study showed that supplementation with 10 and 20 microg vitamin D3 per d increased S-25OHD concentrations similarly in vitamin D-deficient Pakistani women (4-fold), and that 10 microg increased S-25OHD concentrations 2-fold and 20 microg 3-fold in Pakistani men. S-25OHD concentrations increased at 6 months and were stable thereafter. Baseline S-25OHD concentrations tended to be lower in girls and women than in men; females achieved about 46 nmol/l and men 55 nmol/l after supplementation. Serum intact parathyroid hormone concentrations decreased at 6 months, but there was no significant effect of the intervention on bone turnover markers and dual-energy X-ray absorptiometry measurements of the whole body and lumbar spine.", "Fifty-one healthy prepubertal schoolchildren were followed for 13 months in a double blind study. Twenty-four of them were supplemented with 400 IU of vitamin D2 5-7 times weekly, while 27 received a placebo. The children were examined in winter both at the beginning and at the end of the study, and in the middle of the study in autumn. Mean 25-hydroxyvitamin D levels in the supplemented group were significantly higher than those in the placebo group both in autumn and in winter, when the study ended. The vitamin D supplementation did not, however, affect other vitamin D metabolites, serum calcium, albumin, inorganic phosphorus, parathyroid hormone concentrations or alkaline phosphatase activity. Moreover, the supplementation caused no alterations in the weight or height gain or bone mineral content of the distal radius of the children, and thus subclinical rickets could not be shown.", "Little is known about the relative effectiveness of calcium supplementation from food or pills with or without vitamin D supplementation for bone mass accrual during the rapid growth period.\n The purpose was to examine the effects of both food-based and pill supplements of calcium and vitamin D on bone mass and body composition in girls aged 10-12 y.\n This placebo-controlled intervention trial randomly assigned 195 healthy girls at Tanner stage I-II, aged 10-12 y, with dietary calcium intakes <900 mg/d to 1 of 4 groups: calcium (1000 mg) + vitamin D3 (200 IU), calcium (1000 mg), cheese (1000 mg calcium), and placebo. Primary outcomes were bone indexes of the hip, spine, and whole body by dual-energy X-ray absorptiometry and of the radius and tibia by peripheral quantitative computed tomography.\n With the use of intention-to-treat or efficacy analysis, calcium supplementation with cheese resulted in a higher percentage change in cortical thickness of the tibia than did placebo, calcium, or calcium + vitamin D treatment (P = 0.01, 0.038, and 0.004, respectively) and in higher whole-body bone mineral density than did placebo treatment (P = 0.044) when compliance was >50%. With the use of a hierarchical linear model with random effects to control for growth velocity, these differences disappeared.\n Increasing calcium intake by consuming cheese appears to be more beneficial for cortical bone mass accrual than the consumption of tablets containing a similar amount of calcium. Diverse patterns of growth velocity may mask the efficacy of supplementation in a short-term trial of children transiting through puberty.", "The effect of vitamin D supplementation on bone mineral augmentation in 212 adolescent girls with adequate calcium intake was studied in a randomized placebo-controlled setting. Bone mineral augmentation determined by DXA increased with supplementation both in the femur and the lumbar vertebrae in a dose-responsive manner. Supplementation decreased the urinary excretion of resorption markers, but had no impact on formation markers.\n Adequate vitamin D intake protects the elderly against osteoporosis, but there exists no indisputable evidence that vitamin D supplementation would benefit bone mineral augmentation. The aim of this 1-year study was to determine in a randomized double-blinded trial the effect of 5 and 10 microg vitamin D3 supplementation on bone mineral augmentation in adolescent girls with adequate dietary calcium intake.\n Altogether, 228 girls (mean age, 11.4 +/- 0.4 years) participated. Their BMC was measured by DXA from the femur and lumbar spine. Serum 25-hydroxyvitamin D [S-25(OH)D], intact PTH (S-iPTH), osteocalcin (S-OC), and urinary pyridinoline (U-Pyr) and deoxypyridinoline (U-Dpyr) were measured. Statistical analysis was performed both with the intention-to-treat (IT) and compliance-based (CB) method.\n In the CB analysis, vitamin D supplementation increased femoral BMC augmentation by 14.3% with 5 microg and by 17.2% with 10 microg compared with the placebo group (ANCOVA, p = 0.012). A dose-response effect was observed in the vertebrae (ANCOVA, p = 0.039), although only with the highest dose. The mean concentration of S-25(OH)D increased (p < 0.001) in the 5-microg group by 5.7 +/- 15.7 nM and in the 10-microg group by 12.4 +/- 13.7 nM, whereas it decreased by 6.7 +/- 11.3 nM in the placebo group. Supplementation had no effect on S-iPTH or S-OC, but it decreased U-DPyr (p = 0.042).\n Bone mineral augmentation in the femur was 14.3% and 17.2% higher in the groups receiving 5 and 10 microg of vitamin D, respectively, compared with the placebo group, but only 10 mug increased lumbar spine BMC augmentation significantly. Vitamin D supplementation decreased the concentration of bone resorption markers, but had no impact on bone formation markers, thus explaining increased bone mineral augmentation. However, the positive effects were noted with the CB method but not with IT.", "A 2-year milk intervention trial was carried out with 757 girls, aged 10 years, from nine primary schools in Beijing (April 1999 - March 2001). Schools were randomised into three groups: group 1, 238 girls consumed a carton of 330 ml milk fortified with Ca on school days over the study period; group 2, 260 girls received the same quantity of milk additionally fortified with 5 or 8 microg cholecalciferol; group 3, 259 control girls. Anthropometric and bone mineralisation measurements, as well as dietary, health and physical-activity data, were collected at baseline and after 12 and 24 months of the trial. Over the 2-year period the consumption of this milk, with or without added cholecalciferol, led to significant increases in the changes in height (> or =0.6 %), sitting height (> or =0.8 %), body weight (> or 2.9 %), and (size-adjusted) total-body bone mineral content (> or =1.2 %) and bone mineral density (> or =3.2 %). Those subjects receiving additional cholecalciferol compared with those receiving the milk without added 25-hydoxycholecalciferol had significantly greater increases in the change in (size-adjusted) total-body bone mineral content (2.4 v. 1.2 %) and bone mineral density (5.5 v. 3.2 %). The milk fortified with cholecalciferol significantly improved vitamin D status at the end of the trial compared with the milk alone or control groups. It is concluded that an increase in milk consumption, e.g. by means of school milk programmes, would improve bone growth during adolescence, particularly when Ca intake and vitamin D status are low.", "Despite the high prevalence of hypovitaminosis D in children and adolescents worldwide, the impact of vitamin D deficiency on skeletal health is unclear.\n One hundred seventy-nine girls, ages 10-17 yr, were randomly assigned to receive weekly oral vitamin D doses of 1,400 IU (equivalent to 200 IU/d) or 14,000 IU (equivalent to 2,000 IU/d) in a double-blind, placebo-controlled, 1-yr protocol. Areal bone mineral density (BMD) and bone mineral content (BMC) at the lumbar spine, hip, forearm, total body, and body composition were measured at baseline and 1 yr. Serum calcium, phosphorus, alkaline phosphatase, and vitamin D metabolites were measured during the study.\n In the overall group of girls, lean mass increased significantly in both treatment groups (P < or = 0.05); bone area and total hip BMC increased in the high-dose group (P < 0.02). In premenarcheal girls, lean mass increased significantly in both treatment groups, and there were consistent trends for increments in BMD and/or BMC at several skeletal sites, reaching significance at lumbar spine BMD in the low-dose group and at the trochanter BMC in both treatment groups. There was no significant change in lean mass, BMD, or BMC in postmenarcheal girls.\n Vitamin D replacement had a positive impact on musculoskeletal parameters in girls, especially during the premenarcheal period." ]

[ "10700492", "9186381", "18032739", "2389831", "14641799", "7491044", "15731473" ]

[ "Abciximab in acute ischemic stroke. A randomized, double-blind, placebo-controlled, dose-escalation study.", "CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group.", "Emergency administration of abciximab for treatment of patients with acute ischemic stroke: results of an international phase III trial: Abciximab in Emergency Treatment of Stroke Trial (AbESTT-II).", "Effects of ticlopidine on the neurologic outcome and the hemorheologic pattern in the postacute phase of ischemic stroke: a pilot study.", "Aspirin in the prevention of progressing stroke: a randomized controlled study.", "Randomised controlled trial of streptokinase, aspirin, and combination of both in treatment of acute ischaemic stroke. Multicentre Acute Stroke Trial--Italy (MAST-I) Group.", "Emergency administration of abciximab for treatment of patients with acute ischemic stroke: results of a randomized phase 2 trial." ]

[ "Abciximab is a potent parenterally administered platelet glycoprotein IIb/IIIa antagonist. Because this agent has been shown to improve outcomes in coronary artery disease, there is interest to evaluate whether it could improve cerebral perfusion and outcomes after ischemic stroke. This study was designed to evaluate the safety of abciximab in acute ischemic stroke and to obtain pilot efficacy data.\n We conducted a randomized, double-blind, placebo-controlled, dose-escalation trial. Seventy-four eligible and consenting patients presenting within 24 hours after ischemic stroke onset at 38 study sites were randomly allocated to receive either an escalating dose of abciximab (54 patients) or placebo (20 patients) in a ratio of 3:1. We studied 4 escalating doses of abciximab. Patients underwent a scheduled follow-up head CT scan 24 to 36 hours after the completion of study agent administration to monitor for bleeding complications and were evaluated through 3 months.\n There were no cases of major intracranial hemorrhage. Asymptomatic parenchymal hemorrhages were detected on post-study agent CT in 4 of 54 abciximab patients (7%) and in 1 of 20 placebo patients (5%). Six additional abciximab patients had asymptomatic hemorrhagic lesions detected by unscheduled brain imaging during their follow-up period. Nine of 11 patients with asymptomatic hemorrhage had a baseline National Institutes of Health Stroke Scale score >14. At 3 months, there was a trend toward a higher rate of minimal residual disability (Barthel Index > or =95 or modified Rankin scale < or =1) among abciximab patients compared with those who received placebo.\n Abciximab appears to be safe when administered up to 24 hours after stroke onset, and it might improve functional outcome.", "Aspirin is effective in the treatment of acute myocardial infarction and in the long-term prevention of serious vascular events in survivors of stroke and myocardial infarction. There is, however, no reliable evidence on the effectiveness of early aspirin use in acute ischaemic stroke.\n The Chinese Acute Stroke Trial (CAST) was a large randomised, placebo-controlled trial of the effects in hospital of aspirin treatment (160 mg/day) started within 48 h of the onset of suspected acute ischaemic stroke and continued in hospital for up to 4 weeks. The primary endpoints were death from any cause during the 4-week treatment period and death or dependence at discharge, and the analyses were by intention to treat. 21,106 patients with acute ischaemic stroke were enrolled in 413 Chinese hospitals at a mean of 25 h after the onset of symptoms (10,554 aspirin, 10,552 placebo). 87% had a CT scan before randomisation. It was prospectively planned that the results would be analysed in parallel with those of the concurrent. International Stroke Trial (IST) of 20,000 patients with acute stroke from other countries.\n There was a significant 14% (SD 7) proportional reduction in mortality during the scheduled treatment period (343 [3.3%] deaths among aspirin-allocated patients vs 398 [3.9%] deaths among placebo-allocated patients; 2p = 0.04). There were significantly fewer recurrent ischaemic strokes in the aspirin-allocated than in the placebo-allocated group (167 [1.6%] vs 215 [2.1%]; 2p = 0.01) but slightly more haemorrhagic strokes (115 [1.1%] vs 93 [0.9%]; 2p > 0.1). For the combined in-hospital endpoint of death or non-fatal stroke at 4 weeks, there was a 12% (6) proportional risk reduction with aspirin (545 [5.3%] vs 614 [5.9%]; 2p = 0.03), an absolute difference of 6.8 (3.2) fewer cases per 1000. At discharge, 3153 (30.5%) aspirin-allocated patients and 3266 (31.6%) placebo-allocated patients were dead or dependent, corresponding to 11.4 (6.4) fewer per 1000 in favour of aspirin (2p = 0.08).\n There are two major trials of aspirin in acute ischaemic stroke. Taken together, CAST and the similarly large IST show reliably that aspirin started early in hospital produces a small but definite net benefit, with about 9 (SD 3) fewer deaths or non-fatal strokes per 1000 in the first few weeks (2p = 0.001), and with 13 (5) fewer dead or dependent per 1000 after some weeks or months of follow-up (2p < 0.01).", "A previous randomized, placebo-controlled, double-blind study suggested that abciximab may be safe and effective in treatment of acute ischemic stroke. The current phase 3 study was planned to test the relative efficacy and safety of abciximab in patients with acute ischemic stroke with planned treatment within 5 hours since symptoms onset.\n An international, randomized, placebo-controlled, double-blind phase 3 trial tested intravenous administration of abciximab in 2 study cohorts using stratification variables of time since onset and stroke severity. The planned enrollment was 1800 patients. The primary cohort enrolled those patients who could be treated within 5 hours of onset of stroke. A companion cohort enrolled patients that were treated 5 to 6 hours after stroke as well as a smaller cohort of patients who could be treated within 3 hours of stroke present on awakening. The primary efficacy measure was the dichotomous modified Rankin Scale score at 3 months as adjusted to the baseline severity of stroke among subjects in the primary cohort. The primary safety outcome was the rate of symptomatic or fatal intracranial hemorrhage that occurred within 5 days of stroke.\n The trial was terminated prematurely after 808 patients in all cohorts were enrolled by recommendation of an independent safety and efficacy monitoring board due to an unfavorable benefit-risk profile. At 3 months, approximately 33% of patients assigned placebo (72/218) and 32% of patients assigned abciximab (71/221; P=0.944) in the primary cohort were judged to have a favorable response to treatment. The distributions of outcomes on the modified Rankin Scale were similar between the treated and control groups. Within 5 days of enrollment, approximately 5.5% of abciximab-treated and 0.5% of placebo-treated patients in the primary cohort had symptomatic or fatal intracranial hemorrhage (P=0.002). The trial also did not demonstrate an improvement in outcomes with abciximab among patients in the companion and wake-up cohorts. Although the number of patients was small, an increased rate of hemorrhage was noted within 5 days among patients in the wake-up population who received abciximab (13.6% versus 5% for placebo).\n This trial did not demonstrate either safety or efficacy of intravenous administration of abciximab for the treatment of patients with acute ischemic stroke regardless of end point or population studied. There was an increased rate of symptomatic or fatal intracranial hemorrhage in the primary and wake-up cohorts.", "This double-blind pilot study observed the effects of a twenty-one day oral ticlopidine treatment (250 mg/twice daily) on the neurologic outcome and the hemorheologic pattern of 15 patients and 15 placebo-treated controls. Patients and controls (age range sixty-six to eighty-six years) were included in the study within twelve hours of the onset of ischemic stroke, confirmed clinically and by computerized tomography. Scores on Hachinski's Scale and the following hemorheologic parameters were monitored weekly for twenty-one days: fibrinogen levels, the whole blood, unfractionated white and red blood cell filterability rates (through 5-micron-pore-diameter filters using a constant-flow positive-pressure system), and the leukocyte count and activation (by microscopic observation). The results showed treatment with ticlopidine improved the neurologic outcome (Hachinski's Score +36%, p less than 0.03) slightly but significantly (p less than 0.001) increased the average values of the whole blood (+19%) and red cell (+17%) filterability rates and decreased fibrinogen levels (-17%).", "In acute stroke, progression has a severe impact on patient outcome and no effective treatment is known. The main objective was to evaluate the efficacy of aspirin for prevention of stroke progression thereby improving outcome.\n The trial was randomized, double-blind and placebo-controlled.\n The patients were treated in stroke units of four hospitals in Sweden.\n Patients with ischaemic stroke but not complete paresis were included. No antiplatelet drugs were allowed within the last 72 h before onset. Delay until first trial dosage was maximized to 48 h. The trial was designed to detect a 20% reduction of the rate of stroke progression, which was estimated to take place in 20% of cases. Totally, 441 patients (220 aspirin, 221 placebo) completed the trial. Baseline comparisons between the groups showed no differences.\n Aspirin (325 mg) or placebo was given once daily for five consecutive days.\n Neurological assessments were carried out three times daily during the treatment period to detect progression of at least two points in the Scandinavian Stroke Supervision Scale. Patient outcome was followed up at discharge and at 3 months.\n Aspirin treatment did not significantly reduce the frequency of stroke progression. Amongst aspirin-treated patients, stroke progression occurred in 15.9% as compared with 16.7% in the placebo group, which is less frequent than expected. The relative risk was 0.95 (95% CI 0.62-1.45) in the treatment group. As regards patient outcome at discharge and after 3 months, aspirin treatment did not show any difference.\n No positive effect of aspirin, of the expected size, could be shown on the frequency of stroke progression or patient outcome.", "In ischaemic stroke, thrombolytic drugs speed the recanalisation of intracerebral arteries. The effects of aspirin are not known. A trial was conducted to determine whether, separately or together, streptokinase and aspirin have clinical benefits in acute ischaemic stroke similar to those in acute myocardial infarction. 622 patients with acute ischaemic stroke within 6 hours of symptom onset were randomised with a 2 x 2 factorial design to (i) a 1-hour intravenous infusion of 1.5 MU streptokinase, (ii) 300 mg/day buffered aspirin for 10 days, (iii) both active treatments, or (iv) neither. Early results raised a question whether the trial should be continued. Streptokinase (alone or with aspirin) was associated with an excess of 10-day case fatality (odds ratio 2.7; 95% confidence interval 1.7-4.3; 2p < 0.00001). Of the four groups randomised, only patients allocated to streptokinase plus aspirin had a significantly higher risk of early death than those given neither streptokinase nor aspirin (odds ratio 3.5; 95% CI 1.9-6.5; 2p < 0.00001). Streptokinase (alone or with aspirin) and aspirin (alone or with streptokinase) reduced, albeit not significantly, the incidence of combined six-month case fatality and severe disability: odds ratio for streptokinase 0.9 (95% CI 0.7-1.3) and odds ratio for aspirin 0.9 (95% CI 0.6-1.3). The risk of early death with thrombolytic treatments should be weighed against the potential benefit of a marginal reduction of severe disability after the first six months.", "Because of its success in treatment of acute cardiac ischemia, there is interest in the use of abciximab for treating patients with acute ischemic stroke. A previous dose-escalation study determined that abciximab could be given safely in a regimen of 0.25 mg/kg intravenous bolus followed by a 12-hour infusion at 0.125 microg/kg per minute (maximum 10 microg/min). This study was performed to obtain more information about the safety and potential efficacy of abciximab in patients with stroke.\n An international randomized, double-blind, placebo-controlled phase 2 trial enrolled 400 patients within 6 hours of onset of ischemic stroke. The primary safety outcome was the rate of symptomatic hemorrhage that occurred during the first 5 days after stroke. The primary efficacy measure was the distribution of outcomes at 3 months after stroke using the modified Rankin Scale (mRS) based on an ordinal regression model of outcomes, adjusting for baseline severity of stroke, age, and interval from stroke.\n Symptomatic intracranial hemorrhage within 5 days was diagnosed in 7 of 195 (3.6%) patients treated with abciximab and 2 of 199 (1%) patients given placebo (odds ratio [OR], 3.7; P=0.09; 95% confidence interval [CI], 0.7 to 25.9). Asymptomatic hemorrhagic transformation was detected by brain imaging in 24 patients administered abciximab and 33 patients receiving placebo (OR, 0.74; P=0.25; 95% CI, 0.4 to 1.3). Treatment with abciximab showed a nonsignificant shift in favorable outcomes as measured by mRS scores at 3 months (OR, 1.20; P=0.33; 95% CI, 0.84 to 1.70).\n Intravenously administered abciximab can be given to patients with a reasonable degree of safety. The trial also suggests that abciximab could improve outcomes at 3 months after stroke. A larger randomized, double-blind, placebo-controlled trial is necessary to test the efficacy of abciximab." ]

[ "17998507", "17101999" ]

[ "Improved vision-related function after ranibizumab treatment of neovascular age-related macular degeneration: results of a randomized clinical trial.", "Ranibizumab combined with verteporfin photodynamic therapy in neovascular age-related macular degeneration: year 1 results of the FOCUS Study." ]

[ "To examine the effects of ranibizumab on patient-reported visual function using the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) in patients with neovascular age-related macular degeneration (AMD).\n In MARINA, a randomized, double-masked clinical trial, 716 patients with AMD with recent disease progression and minimally classic or occult with no classic lesion component were randomized 1:1:1 to monthly intravitreal ranibizumab (0.3 or 0.5 mg) or sham injections. The NEI VFQ-25 was administered at 0, 1, 2, 3, 6, 9, 12, 18, and 24 months. Main Outcome Measure Mean change from baseline in NEI VFQ-25 scores at 12 and 24 months.\n At 12 months, ranibizumab-treated patients (0.3 mg [n = 238] and 0.5 mg [n = 240]) had mean improvements in NEI VFQ-25 composite scores of +5.2 (95% confidence interval [CI], 3.5 to 6.9) and +5.6 (95% CI, 3.9 to 7.4), respectively; sham-injected patients (n = 238) had a mean decline of -2.8 (95% CI, -4.6 to -1.1; P < .001 vs each dose). Ranibizumab-treated patients were more likely to improve in near activities, distance activities, and vision-specific dependency through 24 months.\n In MARINA, ranibizumab-treated patients were more likely than sham-treated patients to report visual function improvements at 12 and 24 months.\n Treatment of neovascular AMD with ranibizumab can improve patient-reported visual function in a meaningful way compared with sham treatments.\n clinicaltrials.gov Identifier: NCT00056836.", "To investigate the safety and efficacy of intravitreal ranibizumab treatment combined with verteporfin photodynamic therapy (PDT) in patients with predominantly classic choroidal neovascularization secondary to age-related macular degeneration.\n In this 2-year, phase I/II, multicenter, randomized, single-masked, controlled study, patients received monthly ranibizumab (0.5 mg) (n = 106) or sham (n = 56) injections. The PDT was performed 7 days before initial ranibizumab or sham treatment and then quarterly as needed.\n Proportion of patients losing fewer than 15 letters from baseline visual acuity at 12 months (primary efficacy outcome) and the incidence and severity of adverse events.\n At 12 months, 90.5% of the ranibizumab-treated patients and 67.9% of the control patients had lost fewer than 15 letters (P<.001). The most frequent ranibizumab-associated serious ocular adverse events were intraocular inflammation (11.4%) and endophthalmitis (1.9%; 4.8% if including presumed cases). On average, patients with serious inflammation had better visual acuity outcomes at 12 months than did controls. Key serious nonocular adverse events included myocardial infarctions in the PDT-alone group (3.6%) and cerebrovascular accidents in the ranibizumab-treated group (3.8%). CONCLUSION/APPLICATION TO CLINICAL PRACTICE: Ranibizumab + PDT was more efficacious than PDT alone for treating neovascular age-related macular degeneration. Although ranibizumab treatment increased the risk of serious intraocular inflammation, affected patients, on average, still experienced visual acuity benefit." ]

[ "3002720", "2161308", "14990402", "10362151", "3329078", "3297482" ]

[ "A comparative study of Neo Sampoon, Ortho Vaginal Tablets and Emko Vaginal Tablets in Accra, Ghana.", "A comparative study of the safety, effectiveness and acceptability of two foaming vaginal tablets (nonoxynol-9 versus menfegol) in Thai women.", "Contraceptive effectiveness and safety of five nonoxynol-9 spermicides: a randomized trial.", "Contraceptive effectiveness of two spermicides: a randomized trial.", "Clinical acceptability, use-patterns and use-effectiveness of the vaginal contraceptive sponge and Neo Sampoon tablets--an international multi-center randomized clinical trial.", "A clinical trial of Neo Sampoon vaginal tablets and Emko foam in Alexandria, Egypt." ]

[ "Neo Sampoon is an effervescent contraceptive vaginal tablet manufactured in Japan that contains 60 mg of the spermicide menfegol. Ortho Vaginal Tablets (OVT) and Emko Vaginal Tablets (EVT), both containing 100 mg of the spermicide nonoxynol-9, were manufactured in the USA. The three products were compared in a randomized clinical trial conducted at the family planning clinics of the Korle-Bu Teaching Hospital and the Kotobaabi Polyclinic in Accra, Ghana. Three-hundred volunteers participated. At 12 months, the life-table pregnancy rates were 9.6, 11.3 and 12.5 per 100 women in the Neo Sampoon, OVT and EVT groups, respectively (p greater than 0.10). More EVT than Neo Sampoon or OVT users discontinued because of discomfort as well as for other product-related reasons (p less than 0.01). The most common reason for discontinuation was the temporary absence of sexual partner, with more than 40% of the women overall terminating for this reason. The 12-month life-table continuation rates per 100 women were higher for the Neo Sampoon group (62.4) than the OVT group (48.6) or the EVT group (38.5) (p less than 0.01). The effectiveness of the three products seems to be similar, but Neo Sampoon and OVT appear to be more acceptable than EVT in this Ghanaian population.", "Two foaming vaginal tablets containing nonoxynol-9 (OVT-n) or menfegol (OVT-m) were studied to evaluate safety, effectiveness and acceptability. The study was conducted at the Chulalongkorn University, Institute of Health Research, Bangkok, Thailand. One-hundred-two women randomly assigned to one of the two types of tablets were scheduled for follow-up visits at 1, 3, 6 and 12 months. Although there were differences between the two groups in the gross cumulative 12-month life table rates and 12-month continuation rates, these differences were not statistically significant. Twelve-month discontinuation rates for accidental pregnancy were 31.7 per 100 women for OVT-n group and 25.3 per 100 women for the OVT-m group. Seventeen of the total 22 pregnancies occurred due to use failure. This study indicates that the regular and proper use of OVT-n or OVT-m tablets are comparable and are a safe means of birth control. Although a few product-related (burning) or medical complaints were reported by both groups of tablet users, it seems that the vaginal contraceptive is an acceptable method for fertility control in a suitable population who will use it regularly and properly.", "To estimate and compare the effectiveness and safety of 5 spermicides over 6 and 7 months of use, respectively. The spermicides included 3 gels containing 52.5 mg, 100 mg, and 150 mg of nonoxynol-9 per dose and a film and a suppository, each containing 100 mg of nonoxynol-9 per dose.\n Women wishing to use only spermicide for contraception for 7 months were randomly assigned to use 1 of the 5 spermicides with emergency contraception backup. Participants were followed up for up to 30 weeks after admission.\n Of 1,536 women enrolled, 868 (57%) either relied on the spermicide for 6 months or became pregnant. The probability of pregnancy during 6 months of typical use of the spermicide was 22% (95% confidence limits 16%, 28%) in the 52.5-mg gel group, 16% (10%, 21%) in the 100-mg gel group, 14% (9%, 19%) in the 150-mg gel group, 12% (7%, 17%) in the film group, and 10% (6%, 15%) in the suppository group. The pregnancy risk in the 52.5-mg gel group was significantly different (P <.05) from that in either of the other gel groups. The pregnancy risks in the three 100-mg product groups were not significantly different (P =.35). No significant differences among groups were found in the 7-month probability of specified urogenital conditions.\n The gel with the lowest amount of nonoxynol-9 was less effective than the 2 higher-dose gels. Among 3 products containing 100 mg of nonoxynol-9, formulation did not significantly affect pregnancy risk. All products were safe.\n I", "We conducted a multinational randomized trial to determine whether a spermicidal film containing 72 mg of nonoxynol-9 per film was at least as effective in preventing pregnancy as a foaming tablet containing 100 mg of nonoxynol-9 per tablet.\n Between September 1995 and July 1997, 765 women aged 18-35 years who had no evidence of subfecundity were randomly assigned to use one of the two spermicides as their only contraceptive method at every coital act for 28 weeks. Participants were asked to keep coital diaries throughout the study period. Pregnancy tests were performed on a scheduled basis. Each participant was followed for 28 weeks or until she stopped considering the spermicide as her primary method of contraception.\n The Kaplan-Meier estimate of the 6-month probability of pregnancy during typical use of the spermicide was 28.0% in the tablet group and 24.9% in the film group (P = .78, one-tailed test). The study had nearly 75% power to have detected a difference of seven percentage points between groups. Results were almost identical when the analysis included only months when the participants reported use of the spermicide during every coital act. Reported levels of sexual activity and compliance with use of the spermicide were high in both groups.\n The contraceptive effectiveness of these two spermicidal products appeared similar. Both products were associated with a fairly high risk of pregnancy in this young, highly sexually active population.", "This paper describes the results from a randomized clinical trial comparing the Collatex vaginal contraceptive sponge (a predecessor of the Today sponge) and Neo Sampoon foaming vaginal contraceptive tablets; the trial was conducted from 1979 to 1983 in four centers located in three countries (two in Yugoslavia and one each in Taiwan and Bangladesh). The sponge was associated with more insertion and retention problems than the tablet, especially in the two Asian centers. More Neo Sampoon users complained of a burning or stinging sensation. This complaint, however, seemed to be well-tolerated and was not a frequent reason for irregular use and/or discontinuation of use of the tablets. Clinically significant medical complications were rarely reported for either method. Sponge users were more likely to report irregular use than tablet users, primarily due to inconvenience of use. Rates of discontinuation at six months of use were also consistently higher among sponge users than Neo Sampoon users in the four centers. Life-table pregnancy rates at 12 months of use ranged from 3.8 to 18.2 per 100 sponge users and 6.2 to 29.9 per 100 Neo Sampoon users, based on data from the two Yugoslavian centers and the Taiwan center (data from the Bangladesh center were excluded from analysis of pregnancy rates). Practical implications of these findings are discussed.", "Results are reported for a comparative 12-month study of Neo Sampoon foaming vaginal tablets containing 60 mg of the spermicide, menfegol, and Emko vaginal foam containing an 8.0% concentration of the spermicide, nonoxynol-9. Conducted in cooperation with the Family Planning Association in Alexandria, Egypt, the trial included 349 women who were randomly allocated to use one of the two contraceptive products. The twelve-month cumulative life-table rate for accidental pregnancy (per 100 women) was 2.8 for Neo Sampoon tablet users and 2.1 for Emko foam users. The 12-month continuation rates were 77.6 and 77.2 per 100 women for the tablet and foam groups, respectively. In both groups, the majority of discontinuations from the study were for personal reasons, including lack of confidence in the method, messiness, partner's objection and a burning sensation. Few women reported a product-related complaint while using their assigned contraceptive method. The most commonly reported complaint for both methods was that use of the product led to an uncomfortable burning sensation for the woman and/or her partner. This complaint, however, was cited by less than 5% of the women in each group. Thus, a combination of low pregnancy rates, few complications and complaints and high continuation rates confirm the relative acceptability, effectiveness and short-term safety of these methods of contraception among this sample of Egyptian women." ]

[ "3943262", "10197569", "9341413", "6897478", "7035046" ]

[ "Effect of water supplementation of full-term newborns on arrival of milk in the nursing mother.", "Age of introduction of complementary foods and growth of term, low-birth-weight, breast-fed infants: a randomized intervention study in Honduras.", "The effect of feeding glucose water to breastfeeding newborns on weight, body temperature, blood glucose, and breastfeeding duration.", "Supplementary feeding and jaundice in newborns.", "The effect of early initiation of colostrum feeding on proliferation of intestinal bacteria in neonates." ]

[ "It has been suggested that water supplementation of breast-fed newborns may delay the arrival of true milk. A total of 136 healthy term neonates were divided into two groups. Seventy-eight nursed exclusively on demand, and 58 received in addition supplemental water ad lib. Mean time for arrival of milk in the unsupplemented group was 54.9 hours and in the supplemented group 56.6 hours. This difference was not significant, indicating that water supplementation to the normal term newborn does not affect or disrupt the establishment of lactation.", "The optimal age at which to introduce complementary foods is a topic of considerable debate.\n This study was designed to evaluate this issue in a nutritionally vulnerable population in Honduras.\n Mothers of low-birth-weight (1500-2500 g) term (ie, small-for-gestational-age) infants were recruited in the hospital and assisted with exclusive breast-feeding during the first 4 mo. At 4 mo, mothers were randomly assigned to either continue exclusive breast-feeding to 6 mo (EBF; n = 59) or to feed complementary solid foods (jarred rice cereal, chicken, and fruit and vegetables) twice daily from 4 to 6 mo while continuing to breast-feed at their initial frequency (SF; n = 60). At 4 and 6 mo, breast milk and total energy intake were measured for a nonrandom subsample (those who could stay overnight in a central unit: 32 EBF and 31 SF).\n At 4 mo, breast milk intake in the subsample was not significantly different between groups (EBF: 729 +/- 135 g/d; SF: 683 +/- 151 g/d: P >0.2); from 4 to 6 mo it increased (by 28 g/d) in the EBF group but decreased (by 39 g/d) in the SF group (P < 0.005). Nonetheless, total energy intake (including solid foods) increased more from 4 to 6 mo in the SF than in the EBF group. However, there were no significant differences between groups in weight or length gain during the intervention or subsequently (6-12 mo).\n There was no growth advantage of complementary feeding of small-for-gestational-age, breast-fed infants between 4 and 6 mo of age.", "In order to determine the effect of feeding glucose water on breastfeeding newborns, we randomly distributed 180 normal newborns into two groups: a glucose water group (GW), fed 5% glucose solution during the first 3 days of life in addition to being breastfed; and an exclusively breastfed nonglucose water group (NGW). The following data were evaluated: weight at 6, 12, 24, 48, and 72 hours of life; temperature during the first 72 hours of life; serum glucose level at 6, 12, 24, and 48 hours; total duration of breastfeeding and age at introduction of infant formulas. In the NGW, there was a greater weight loss at 48 hours but not at 72 hours, temperatures higher than 37.5 degrees C were more frequent, and the mean serum glucose levels at 6, 12, and 24 hours were lower. This group also had more serum glucose level determinations under 2.2 mmol/l (40 mg/dL). However, no infants exhibited hypoglycemic symptoms. Infants in the GW received twice as many formulas during the first month and had a shorter duration of any breastfeeding. Our results suggest that the suppression of feedings with glucose water in the first days of life increases the probability of successful breastfeeding. However, infants who do not receive glucose water in the first few days of life may require greater supervision and close monitoring of blood glucose and body temperature, particularly in the first 24 hours of life.", "In a survey it was found that the majority of full-term breast fed infants receive supplementary feeds of water, dextrose solution or infant formula during the first few days of life. Breast fed babies receiving water or dextrose supplements had higher plasma bilirubins on the sixth day of life than bottle fed infants. Supplementation with water or dextrose did not reduce the hyperbilirubinaemia of term, breast fed infants. Since it may prejudice the establishment of breast feeding, we suggest that the practice is abandoned.", "One hundred eighty normal neonates with an average weight above 2.50 kg and having no feeding difficulties were divided into two groups and randomly assigned to either colostrum or to glucose water feeding regimens during the 3-day stay at the maternity ward. The effects of the feeding regimens on intestinal colonization were studied by examining the stools of the neonates. All bacteria recovered were identified quantitatively and biochemically. Of the 180 mothers, 105 complied with the instructions on feeding regimens. The majority of the neonates receiving colostrum had significantly lower bacterial counts than those on glucose water (p less than 0.001). The results of the preliminary study indicated that early initiation of colostrum feeding to neonates where potable water is not readily available will suppress the proliferation of bacteria in the neonates." ]

[ "8211584", "683658", "10492101", "9800929" ]

[ "Blood loss at time of cesarean section by method of placental removal and exteriorization versus in situ repair of the uterine incision.", "Extraabdominal uterine exteriorization at cesarean section.", "A randomised, controlled study of uterine exteriorisation and repair at caesarean section.", "Uterine exteriorisation at caesarean section: influence on maternal morbidity." ]

[ "The current study was undertaken to determine if blood loss at the time of cesarean section is affected by method of placental removal (spontaneous versus extracted) or uterine position for repair (in situ versus exteriorized). This prospective randomized study involved 100 women who were undergoing a cesarean section. The patients were placed into one of four groups--1, spontaneous placenta detachment, in situ uterine repair; 2, spontaneous placental detachment, exteriorized uterine repair; 3, manual placental removal, in situ uterine repair, and 4, manual placental removal, exteriorized uterine repair. Patients with spontaneous placental separation (groups 1 and 2) compared with manual removal (groups 3 and 4) revealed a significant decrease in blood loss (p < 0.001). Uterine position did not significantly affect blood loss in the spontaneous group (1 and 2; p = 0.971) or the manual placental removal groups (3 and 4; p = 0.061). The hematocrit values for all groups were similar preoperatively, but postoperatively, were significantly lower in the manual removal groups when compared with the spontaneous placental separation groups (p < 0.001). The method of placental removal and not the position of the uterus at the time of its repair has a significant role in blood loss during cesarean birth.", "A series of 386 consecutive cesarean sections is presented in which postpartum uteri were randomly exteriorized or left in situ for suturing the hysterotomy incision in an attempt to evaluate differences in morbidity. Both groups were shown to be similar with respect to overall morbidity, although a high-morbidity subgroup exhibiting increased blood loss was defined and included significantly more patients in the noneventrated group. Emesis occurred in 4 (3.4%) patients in the eventrated group and was directly related to fundal traction under regional anesthesia. Although a larger prospective series is needed to evaluate more serious morbidity, the data presented suggest that uterine eventration at cesarean section is not to be condemned.", "To determine the surgical and anaesthetic benefits and problems associated with the practice of routine exteriorisation of the uterus to facilitate repair at caesarean section.\n A randomised controlled study of women undergoing caesarean section. After establishment of anaesthesia, women were randomised to either exteriorisation and uterine repair or suture of the uterus in the abdomen.\n A maternity hospital in the United Kingdom.\n Peri-operative haemoglobin change, duration of operation, maternal morbidity and length of hospital stay. Intra-operative pain, nausea, vomiting, pulling or tugging sensations were secondary outcome measures.\n Three hundred and sixteen women were randomised, of whom 288 were subsequently analysed (139 women in whom the uterus was exteriorised and 149 where the uterus was not exteriorised). Exteriorisation of the uterus, an elective caesarean section and a spinal or general anaesthesia each had a statistically significant association with reduced blood loss (P < 0.05). There were no statistically significant differences between the two groups with regard to intra-operative complications or pain, nor were there any statistically significant difference in post-operative wound sepsis, pyrexia, deep vein thrombosis, blood transfusion or length of hospital stay.\n With effective anaesthesia, exteriorisation of the uterus for repair following caesarean delivery is not associated with significant problems and is associated with less blood loss.", "To compare the influence on caesarean section morbidity of uterine exteriorisation or in situ repair.\n Randomised controlled trial.\n Princess Anne Maternity Unit of the Royal Bolton Hospital, UK.\n One hundred and ninety-four women undergoing delivery by caesarean section.\n Two intra-operative readings of arterial pulse rate, mean arterial blood pressure, and arterial haemoglobin oxygen saturation were obtained. Pre-operative and day-3 haemoglobin concentrations were determined. Intra- and post-operative complications, puerperal pain scores, and febrile and infectious morbidity were assessed. A postal questionnaire was used to assess morbidity six weeks after delivery.\n Intra-operative changes in pulse rate, mean arterial blood pressure and oxygen saturation; peri-operative changes in haemoglobin concentration; incidence of intraoperative vomiting, pain, intra- and post-operative complications, and febrile and infectious morbidity; immediate and late puerperal pain scores; satisfaction with the operation.\n No clinically significant differences between uterine exteriorisation and in situ repair were found in pulse rate, mean arterial pressure, oxygen saturation and haemoglobin changes. Likewise, the incidence of vomiting and pain was similar. Vomiting occurred in 10% of all the women, and 57% of all pain complaints occurred at the initial skin incision. There was a trend towards higher immediate and late pain scores in the exteriorisation group, reaching statistical significance on day 3. Overall, pain scores averaged 6/10 on day 1 despite patient-controlled analgesia, and three-quarters of all women reported persisting pain on day 42. Intra- and post-operative complications, febrile and infectious morbidity, and duration of hospital stay were similar in both groups.\n We have demonstrated that uterine exteriorisation and in situ repair have similar effects on peri-operative caesarean section morbidity. Intra-operative pain reflected adequacy of anaesthesia, while vomiting reflected adequacy of pre-operative preparation of patients. Exteriorising the uterus at caesarean section is a valid option." ]

[ "1393034", "8959160", "18723709", "12517545", "9404792", "10207461", "16953529", "11103723" ]

[ "Safety of early pain relief for acute abdominal pain.", "Intravenous morphine for early pain relief in patients with acute abdominal pain.", "Morphine analgesia in patients with acute appendicitis: a randomised double-blind clinical trial.", "Effects of morphine analgesia on diagnostic accuracy in Emergency Department patients with abdominal pain: a prospective, randomized trial.", "The use of analgesics in patients with acute abdominal pain.", "Acute appendicitis: influence of early pain relief on the accuracy of clinical and US findings in the decision to operate--a randomized trial.", "Randomized clinical trial of morphine in acute abdominal pain.", "Prospective randomized study of analgesic use for ED patients with right lower quadrant abdominal pain." ]

[ "(a) to determine the efficacy of papaveretum in treating pain when administered early to patients presenting with acute abdominal pain and (b) to assess its effect on subsequent diagnosis and management.\n Prospective, randomised, placebo controlled study.\n Walsgrave Hospital, Coventry.\n 100 consecutive patients with clinically significant abdominal pain who were admitted as emergencies to a surgical firm.\n Intramuscular injection of up to 20 mg papaveretum or an equivalent volume of saline.\n Pain and tenderness scores, assessment of patient comfort, accuracy of diagnosis, and management decisions.\n Median pain and tenderness scores were lower after papaveretum (pain score 8.3 in control group and 3.1 in treatment group, p < 0.0001; tenderness score 8.1 in control group and 5.1 in treatment group, p < 0.0001). Forty eight patients were deemed to be comfortable after papaveretum compared with nine after saline. Incorrect diagnoses and management decisions applied to two patients after papaveretum compared with nine patients after saline.\n Early administration of opiate analgesia to patients with acute abdominal pain can greatly reduce their pain. This does not interfere with diagnosis, which may even be facilitated despite a reduction in the severity of physical signs. These patients should not be denied effective treatment.", "To determine whether morphine affects evaluation or outcome for patients with acute abdominal pain.\n Prospective, double-blind, placebo-controlled administration of morphine sulfate (MS) or normal saline (NS) in the setting of acute abdominal pain. The study was performed at a military ED with an annual census of 60,000 visits. Patients > or = 18 years old who had abdominal pain for < or = 48 hours were included. Patients who were allergic to MS or who had systolic blood pressures < 90 mm Hg were excluded. The physicians indicated a provisional diagnosis, a differential diagnosis, and a provisional disposition. Study solution was titrated to the patient's assessment of adequate analgesia (up to a volume equivalent of 20 mg of MS); pain response was monitored using a visual analog scale (VAS). The patients were followed until diagnosis occurred or symptoms resolved.\n Of 75 patients enrolled, 71 completed the study; 35 patients received MS and 36 received NS. More than half (44; 62%) of the patients were admitted from the ED; 28 patients underwent surgery. The VAS pain level improved more for the MS group, 3.9 +/- 2.8 cm, than it did for the NS group, 0.8 +/- 1.5 cm (p < 0.01). Study solution dose was less in the MS group than it was in the NS group, 1.5 +/- 0.5 mL vs 1.8 +/- 0.4 mL (p < 0.01). There was no difference between the groups when comparing accuracy of provisional or differential diagnosis with that of final diagnosis. Differences between provisional and actual dispositions were the same in all groups. There were 3 diagnostic or management errors in each group.\n When compared with saline placebo, the administration of MS to patients with acute abdominal pain effectively relieved pain and did not alter the ability of physicians to accurately evaluate and treat patients.", "The administration of analgesics to patients with acute abdominal pain due to acute appendicitis is controversial. A study was undertaken to assess the analgesic effect of morphine in patients with acute appendicitis.\n A randomised double-blind clinical trial was conducted in Sina hospital, a general teaching hospital, from January 2004 to March 2005. Patients scheduled for appendectomy were randomised to receive 0.1 mg/kg morphine sulfate or saline (0.9%) to a maximum dose of 10 mg over a 5 min period. Patients were examined by surgeons not involved in their care before and after drug administration and their pain intensity and signs were recorded at each visit. The physicians were also asked to indicate their own treatment plan. The main outcome measures were pain intensity using a visual analogue scale (VAS) and signs of acute appendicitis. A favourable reduction in VAS score was defined as a change of >13 mm.\n Of the 71 patients enrolled in the study, 35 were allocated to receive morphine and 36 to receive placebo. One patient left the hospital before receiving morphine. No significant differences were seen between the two groups with regard to age, sex and initial VAS score. A more favourable change in VAS score was reported in the morphine group with a significantly greater reduction in the median VAS score than in the placebo group. Morphine administration did not cause significant changes in patients' signs or in the physicians' plans or diagnoses. No adverse events were seen in either group.\n Morphine can reduce pain in patients with acute appendicitis without affecting diagnostic accuracy. Trial registration number: NCT00477061.", "Because of concerns about masking important physical findings, there is controversy surrounding whether it is safe to provide analgesia to patients with undifferentiated abdominal pain. The purpose of this study was to address the effects of analgesia on the physical examination and diagnostic accuracy for patients with abdominal pain.\n The study was a prospective, double-blind clinical trial in which adult Emergency Department (ED) patients with undifferentiated abdominal pain were randomized to receive placebo (control group, n = 36) or morphine sulphate (MS group, n = 38). Diagnostic and physical examination assessments were recorded before and after a 60-minute period during which study medication was titrated. Diagnostic accuracy and physical examination changes were compared between groups using univariate statistical analyses.\n There were no differences between control and MS groups with respect to changes in physical or diagnostic accuracy. The overall likelihood of change in severity of tenderness was similar in MS (37.7%) as compared with control (35.3%) patients (risk ratio [RR] 1.07, 95% confidence interval [CI] 0.64-1.78). MS patients were no more likely than controls to have a change in pain location (34.0% versus 41.2%, RR 0.82, 95% CI 0.50-1.36). Diagnostic accuracy did not differ between MS and control groups (64.2% versus 66.7%, RR 0.96, 95% CI 0.73-1.27). There were no differences between groups with respect to likelihood of any change occurring in the diagnostic list (37.7% versus 31.4%, RR 1.20, 95% CI 0.71-2.05). Correlation with clinical course and final diagnosis revealed no instance of masking of physical examination findings.\n Results of this study support a practice of early provision of analgesia to patients with undifferentiated abdominal pain.\n Copyright 2003 by the American College of Surgeons", "Analgesics in patients with acute abdominal pain are often withheld for fear that they may change physical examination findings and thus may be unsafe. We conducted a randomized, prospective, placebo-controlled trial to investigate changes in physical examination following the administration of placebo, 5 mg, or 10 mg of morphine to 49 patients with acute abdominal pain. One patient was withdrawn secondary to inadequate documentation. Of the 48 patients who completed the trial, a statistically significant change in physical examination was noted in both groups receiving analgesics, but not in the placebo group. No adverse events or delays in diagnosis were attributed to the administration of analgesics. We conclude that physical examination does change after the administration of analgesics in patients with acute abdominal pain and that a larger study is needed to evaluate analgesic safety in this subpopulation of emergency department patients.", "To determine the influence of early pain relief on the diagnostic performance of ultrasonography (US) and on the appropriateness of the surgical decision.\n A prospective randomized, double-blind placebo-controlled trial with morphine was conducted. A visual analog scale was used to evaluate pain in 340 patients aged 16 years or older. US was performed with a standardized protocol. Diagnosis was confirmed at histologic analysis or, in the patients released without surgery, at follow-up.\n One hundred seventy-five patients were injected with morphine, and 165 were injected with the placebo. Pain relief was stronger in the morphine group. In the morphine group, US had lower (71.1%) sensitivity (difference, -9.5%; 95% CI, -18.5%, -0.5%) and higher (65.2%) specificity (difference, 11.4%; 95% CI, 1.0%, 21.8%). This group had also a higher positive predictive value (64.6%) and a lower negative predictive value (71.4%), but the differences between this group and the placebo group were not statistically significant. Among female patients, the decision to operate was appropriate more often in the morphine group (75.8%), but the difference between this group and the placebo group was not statistically significant (5.1%; 95% CI, -7.4%, 17.6%). In male patients and overall, opiate analgesia did not influence the appropriateness of the decision. The appropriateness to discharge patients without surgery was 100% in all groups.\n Morphine does not improve US-based diagnosis of appendicitis.", "Administration of analgesia to patients with acute abdominal pain is controversial. We test the hypothesis that morphine given to emergency department (ED) patients with acute abdominal pain will reduce discomfort and improve clinically important diagnostic accuracy.\n Pain was measured with a standard 0- to 100-mm visual analog scale. ED patients with acute abdominal pain were randomized in a double-blind fashion to 0.1 mg/kg intravenous morphine or placebo. The primary endpoint was the difference between the 2 study arms in clinically important diagnostic accuracy. Clinically important diagnostic accuracy was defined a priori by its complement, clinically important diagnostic error, using 2 independent, blinded investigators to identify any discordance between the provisional and final diagnoses that might adversely affect the patient's health status. The provisional diagnosis was provided by an ED attending physician, who examined the patient only once, 15 minutes after administration of the study agent. The final diagnosis was obtained through follow-up at least 6 weeks after the index ED visit.\n We randomized 160 patients, of whom 153 patients were available for analysis, 78 patients in the morphine group and 75 patients in the placebo group. Baseline features were similar in both groups, including initial median visual analog scale scores of 98 mm and 99 mm. The median decrease in visual analog scale score at 15 minutes was 33 mm in the morphine group and 2 mm in the placebo group. There were 11 instances of diagnostic discordance in each group, for a clinically important diagnostic accuracy of 86% (67/78) in the morphine group and 85% (64/75) in the placebo group. The difference in clinically important diagnostic accuracy between the 2 groups was 1% (95% confidence interval [CI] -11% to 12%). Analysis by efficacy and intention to treat yielded similar results. Kappa for interobserver concordance in classification of clinically important diagnostic accuracy was 0.94 (95% CI 0.79 to 1.00). No patients required naloxone.\n Although administration of intravenous morphine to adult ED patients with acute abdominal pain could lead to as much as a 12% difference in diagnostic accuracy, equally favoring opioid or placebo, our data are most consistent with the inference that morphine safely provides analgesia without impairing clinically important diagnostic accuracy.", "Giving an analgesic to patients with right lower quadrant (RLQ) pain causes greater alteration of abdominal signs predictive of appendicitis than placebo. A randomized double-blinded controlled trial of 68 patients who received either tramadol or placebo. Absence or presence of seven abdominal signs (tenderness on light and deep palpation, tenderness in the RLQ and elsewhere, rebound, cough, and percussion tenderness) and pain (100 mm Visual Analog Scale [VAS]) at 0 and 30 minutes were recorded. The predictive value of each physical finding (PF) was measured using an 11-point PF score weighted by likelihood ratios. There was significant reduction in mean VAS of 14.2 mm (95% CI 5.6 to 22.8) in analgesic group versus 6.5 mm (95% CI 1.6 to 11.4) in placebo group. The analgesic group had less normalization of signs as measured by the PF score in all patients [32 of 154 (20.8%) versus 40 of 121 (33.1 %) (P = .031)] and in those with proven appendicitis [4 of 33 (12.1%) versus 10/22 (45.5%) (P = .014)]. Parenteral use of tramadol in emergency department patients with RLQ pain resulted in significant levels of pain reduction without concurrent normalisation of abdominal examination findings indicative of acute appendicitis." ]

[ "9236422", "9316514", "11827923", "16169344", "12934762", "8615305", "11052840", "12766743" ]

[ "Randomized comparison of angioplasty of complex coronary lesions at a single center. Excimer Laser, Rotational Atherectomy, and Balloon Angioplasty Comparison (ERBAC) Study.", "Angioscopic evaluation of rotational atherectomy followed by additional balloon angioplasty versus balloon angioplasty alone in coronary artery disease: a prospective, randomized study.", "Rotational atherectomy does not reduce recurrent in-stent restenosis: results of the angioplasty versus rotational atherectomy for treatment of diffuse in-stent restenosis trial (ARTIST).", "Comparison of angiographic and clinical outcomes between rotational atherectomy and cutting balloon angioplasty followed by radiation therapy with a rhenium 188-mercaptoacetyltriglycine-filled balloon in the treatment of diffuse in-stent restenosis.", "Coronary stenting after rotational atherectomy in diffuse lesions of the small coronary artery: comparison with balloon angioplasty before stenting.", "Rotational atherectomy with adjunctive balloon angioplasty versus conventional percutaneous transluminal coronary angioplasty in type B2 lesions: results of a randomized study.", "A randomized comparison of balloon angioplasty versus rotational atherectomy in complex coronary lesions (COBRA study).", "Comparison of rotational atherectomy with conventional balloon angioplasty in the prevention of restenosis of small coronary arteries: results of the Dilatation vs Ablation Revascularization Trial Targeting Restenosis (DART)." ]

[ "The purpose of this study was to test whether coronary revascularization with ablation of either excimer laser or rotational atherectomy can improve the initial angiographic and clinical outcomes compared with dilatation (balloon angioplasty) alone.\n At a single center, a total of 685 patients with symptomatic coronary disease warranting elective percutaneous revascularization for a complex lesion were randomly assigned to balloon angioplasty (n = 222), excimer laser angioplasty (n = 232), or rotational atherectomy (n = 231). The primary end point was procedural success (diameter stenosis < 50%, absence of death, Q-wave myocardial infarction, or coronary artery bypass surgery). The patients who underwent rotational atherectomy had a higher rate of procedural success than those who underwent excimer laser angioplasty or conventional balloon angioplasty (89% versus 77% and 80%, P = .0019), but no difference was observed in major in-hospital complications (3.2% versus 4.3% versus 3.1%, P = .71). At the 6-month follow-up, revascularization of the original target lesion was performed more frequently in the rotational atherectomy group (42.4%) and the excimer laser group (46.0%) than in the angioplasty group (31.9%, P = .013).\n Procedural success of rotational atherectomy is superior to laser angioplasty and balloon angioplasty; however, it does not result in better late outcomes. The role of plaque debulking before balloon dilatation in percutaneous coronary revascularization remains to be fully defined.", "This study sought to compare, by angioscopy, the morphologic changes induced by rotational atherectomy, followed by additional angioplasty, with those observed after balloon angioplasty alone.\n Rotational atherectomy and balloon angioplasty act by different mechanisms, which could explain the difference in morphologic changes induced by these two techniques.\n The study group included 50 patients with 50 lesions who were randomly assigned to undergo rotational atherectomy (n = 24) or balloon angioplasty (n = 26). Rotational atherectomy with a single burr (approximately equal to 70% of coronary diameter) was systematically followed by additional balloon angioplasty. Angioscopy was performed immediately after the procedure. Abnormal angioscopic findings were 1) flaps, graded from 1 to 3 (1 = intimal flap; 2 = flap protruding into < 50% of the lumen; 3 = flap protruding into > or = 50% of the lumen); 2) thrombi, graded from 1 to 3 (1 = flat deposits; 2 = protruding but nonocclusive thrombus; 3 = occlusive thrombus); 3) subintimal hemorrhage; 4) longitudinal dissection. The two groups were comparable for clinical and angiographic baseline data.\n On angioscopy, flaps were observed less frequently after rotational atherectomy followed by additional balloon angioplasty (8 [33%] of 24 lesions) than after balloon angioplasty alone (14 [54%] of 26 lesions, p = 0.08) and were also less severe (grade 1 in 6 lesions, grade 2 in 2 and grade 3 in none vs. grade 1 in 4 lesions, grade 2 in 5 and grade 3 in 5). Longitudinal dissections were also significantly less frequent: one versus six (p = 0.05). There was no difference in the incidence of angioscopic thrombi (p = 0.16) or subintimal hemorrhage (p = 0.15), but the power to detect a significant difference was low for these variables (37% and 26%, respectively).\n Rotational atherectomy followed by additional balloon angioplasty leads to fewer angioscopic dissections and a trend toward fewer intimal flaps than balloon angioplasty alone. However, our angioscopic differences did not lead to an outcome difference between the two groups.", "Aim of this trial was to compare rotational atherectomy followed by balloon angioplasty (rotablation [ROTA] group) with balloon angioplasty (percutaneous transluminal coronary angioplasty [PTCA] group) alone in patients with diffuse in-stent restenosis.\n The ARTIST study is a multicenter, randomized, prospective European trial with 298 patients with in-stent restenosis>70% (mean lesion length, 14 +/- 8 mm) in stents, implanted in coronary arteries for >/= 3 months. In the PTCA group, angioplasty was performed at the discretion of the local investigator, and rotablation was performed by using a stepped-burr approach followed by adjunctive PTCA with low (</= 6 atm) inflation pressure. Intravascular ultrasound during the intervention and at follow-up was used in a substudy in 86 patients (45 PTCA, 41 ROTA). Angiography demonstrated no difference regarding the short-term outcome, with equivalent procedural success rates defined as remaining stenosis <30% (89% PTCA, 88% ROTA). However, the results showed that, in the long term, PTCA was a significantly better strategy than ROTA. Mean net gain in minimal lumen diameter was 0.67 mm and 0.45 mm for PTCA and ROTA, respectively (P=0.0019). Mean gain in diameter stenosis was 25% and 17% (P=0.002), resulting in restenosis (>/= 50%) rates of 51% (PTCA) and 65% (ROTA) (P=0.039). By intravascular ultrasound, the major difference was the missing stent over-expansion during PTCA after ROTA. Six-month event-free survival was significantly higher after PTCA (91.3%) compared with ROTA (79.6%, P=0.0052).\n In terms of the primary objective of the study, PTCA produced a significantly better long-term outcome than ROTA followed by adjunctive low-pressure PTCA.", "Rotational atherectomy (RA) and cutting balloon angioplasty (CBA) have been shown to effectively dilate in-stent restenosis (ISR). It is not known, however, which of these technique, when followed by beta-radiation, is more effective. Therefore, we performed a prospective randomized study comparing RA and CBA before beta-radiation therapy for diffuse ISR.\n Patients with diffuse ISR were randomly assigned to receive RA (group 1, n = 58) or CBA (group 2, n = 55) before beta-radiation therapy with a rhenium 188-mercaptoacetyltriglycine-filled balloon, with the radiation dose being 18 Gy at a depth of 1.0 mm into the vessel wall. The primary end point was angiographic restenosis at 6 months, and the secondary end point was major adverse cardiac events (myocardial infarction, death, target lesion revascularization) at 9 months.\n The 2 groups were similar in baseline characteristics. Mean lesion length was 21.0 +/- 11.2 mm in group 1 and 20.8 +/- 10.2 mm in group 2 (P = .77). Radiation was delivered successfully to all patients. We obtained 6-month angiographic follow-up in 90 patients (80%). The rates of angiographic restenosis were 14.9% (7 of 47) in group 1 and 14.0% (6 of 43) in group 2 (P = .89). No patient experienced myocardial infarction or death during the 9-month follow-up period. Rates of target lesion revascularization or major adverse cardiac events were 3.4% in group 1 and 3.6% in group 2 (P = .94) during the 9-month follow-up.\n Either RA or CBA, followed by beta-radiation using a rhenium 188-mercaptoacetyltriglycine-filled balloon, is equally safe and effective for diffuse ISR in 6-month angiographic and 9-month clinical outcomes.", "The purpose of this randomized trial was to evaluate the role of debulking and balloon predilation on acute and long-term results of stent implantation in diffuse stenosis of small vessels. Patients with symptomatic diffuse stenosis of the native left anterior descending coronary artery between 2 and 2.9 mm in size were randomly assigned to rotational atherectomy (group I, n = 21) or balloon dilation (group II, n = 20) before stenting. The primary end point of the study was the incidence of angiographic restenosis at follow-up; adverse clinical events, such as death, myocardial infarction, stroke, or target vessel revascularization, were assessed as secondary end points. Acute gain was significantly greater in group I than in group II (p = 0.038), but net gain at follow-up was similar in both groups (p = 0.24). There was no significant difference in angiographic restenosis rate (33.3% vs 31.3%, p = 0.80), target vessel revascularization (23.8% vs 15%, p = 0.21) or 1-year event-free survival rate (72.8% vs 84.6%, p = 0.28). In conclusion, rotational atherectomy before stenting showed no additional benefit over balloon dilation with stenting in the management of diffuse lesions in small coronary vessels.", "A randomized pilot study was performed comparing conventional balloon angioplasty (percutaneous transluminal coronary angioplasty [PTCA] group) and rotational atherectomy (RA) with a medium size burr (50% to 70% burr/artery ratio) with systematic adjunctive balloon angioplasty (RA group) in type B2 stenosis. A total of 64 patients were included. Primary success was 93.7% in the RA group and 87.5% in the PTCA group (p = NS). Technical failure with no complication occurred once in each group. Acute complications occurred in three patients in the PTCA group and in one in the RA group. Angiographic restenosis rates were similar (RA group: 39%, PTCA group: 42%, p = NS) with a follow-up rate of 93%. In type B2 lesions, when compared with conventional angioplasty, RA with systematic balloon angioplasty does not seem to increase procedural success, and the restenosis rate remains comparable. However, these results must be confirmed in a larger series of patients.", "Rotablation is a widely used technique for the treatment of complex coronary artery lesions but is so far only poorly supported by controlled studies. The Comparison of Balloon-Angioplasty versus Rotational Atherectomy study (COBRA) is a multicentre, prospective, randomized trial to compare short- and long-term effects of percutaneous transluminal coronary angioplasty (PTCA) and rotablation in patients with angiographically pre-defined complex coronary artery lesions.\n At seven clinical sites 502 patients with pre-defined complex coronary artery lesions were assigned to either PTCA (n=250) or rotablation (n=252). Primary end-points were procedural success, 6-month restenosis rates in the treated segments, and major cardiac events during follow-up. Procedural success was achieved in 78% (PTCA), and 85% (rotablation) (P=0.038) of cases. Crossover from PTCA to rotablation was 4% and 10% vice versa (P=0.019). There was no difference between PTCA and rotablation with respect to procedure-related complications such as Q wave infarctions (2.4% each), emergency bypass surgery (1.2% versus 2.4%), and death (1.6% versus 0.4%). However, more stents were required after PTCA (14.9% versus 6.4%, P<0.002), predominantly for bailout or unsatisfactory results. Including bail-out stents as an end-point, the procedural success rates were 73% for angioplasty and 84% for rotablation (P=0.006). At 6 months, symptomatic outcome, target vessel reinterventions and restenosis rates (PTCA 51% versus rotablation 49%, P=0.33) were not different.\n Complex coronary artery lesions can be treated with a high level of success and low complication rates either by PTCA with adjunctive stenting or rotablation. The long-term clinical and angiographic outcome is comparable.", "The optimum treatment of obstructive coronary disease in small (<3.0 mm diameter) arteries remains unknown. Rotational atherectomy is an approved treatment that might reduce the vascular injury during percutaneous coronary intervention compared with angioplasty. We report on a multicenter, randomized, blinded end point trial comparing rotational atherectomy with balloon angioplasty in the prevention of restenosis of obstructed small coronary arteries.\n A total of 446 patients with myocardial ischemia associated with an angiographic stenosis in a native coronary artery 2 to 3 mm in diameter and < or =20 mm in length without severe calcification were randomly assigned to receive rotational atherectomy (n = 227) or balloon angioplasty (n = 219). The primary end point was target vessel failure at 12 months (defined as the composite of death, Q-wave myocardial infarction, and clinically driven repeat revascularization of the target vessel).\n The mean reference vessel diameter was 2.46 +/- 0.40 mm, the mean lesion length was 9.97 +/- 5.59 mm, and the prevalence of diabetes mellitus was 32%. Acute procedural success (91.6% for rotational atherectomy, 94.1% for balloon angioplasty, P =.36) and target vessel failure at 12 months were not significantly different (30.5% vs 31.2%, P =.98). At 8 months, there were no significant differences in minimum lumen diameter (1.28 +/- 0.63 mm vs 1.19 +/- 0.54 mm, P =.26), percent diameter stenosis (28% +/- 12% vs 29% +/- 15%, P =.59), binary restenosis rate (50.5% vs 50.5%, P = 1.0), or late loss index (0.57 vs 0.62, P =.7). No Q-wave myocardial infarctions occurred in either arm of the study, and non-Q-wave myocardial infarctions (defined as creatine kinase level >2 times normal with an elevated creatine kinase-myocardial band isoenzyme level) occurred in 2.2% and 1.4% of the patients in the rotational atherectomy and balloon angioplasty groups, respectively (P =.72).\n Rotational atherectomy was found to be safe in the treatment of obstructed small arteries, but lower rates of target vessel failure were not achieved compared with balloon angioplasty. Because the acute gain and loss index ratios of the 2 treatments were similar, there was no evident beneficial antirestenosis mechanism seen for rotational atherectomy." ]

[ "11720460", "9346455", "11164322", "10390003", "12024545", "12464832", "8186168", "14966078", "8788351", "2373065", "10302610", "11304773", "9190093", "10723618", "10334612", "8652254", "1861939", "2373656", "14528573", "16707508", "14729297", "7603933", "15653255", "3977198", "346537", "12048339", "12727038", "8917146", "3049968", "12781926" ]

[ "Promoting patient participation and shortening cancer consultations: a randomised trial.", "Effects of a self-administered previsit questionnaire to enhance awareness of patients' concerns in primary care.", "A checklist to improve patient education in a cardiology outpatient setting.", "Promoting patient participation in the cancer consultation: evaluation of a prompt sheet and coaching in question-asking.", "The effects of communication skills training on patients' participation during medical interviews.", "Feasibility of using a computer-assisted intervention to enhance the way women with breast cancer communicate with their physicians.", "Patient participation in the cancer consultation: evaluation of a question prompt sheet.", "Randomised controlled trial of effect of leaflets to empower patients in consultations in primary care.", "Empowering the patient in the consultation: a pilot study.", "Patient-oriented interventions to improve communication in a medical office visit.", "Encouraging patient question-asking: a clinical trial.", "Individualized patient education and coaching to improve pain control among cancer outpatients.", "Empowerment of men newly diagnosed with prostate cancer.", "Empowering older patients to communicate more effectively in the medical encounter.", "A randomized controlled trial of facilitating information giving to patients with chronic medical conditions: effects on outcomes of care.", "The influence of audiotapes on patient participation in the cancer consultation.", "Increasing patient knowledge, satisfaction, and involvement: randomized trial of a communication intervention.", "Promoting parent-provider interaction during young children's health-supervision visits.", "Encouraging out-patients to make the most of their first hospital appointment: to what extent can a written prompt help patients get the information they want?", "Effect of patient completed agenda forms and doctors' education about the agenda on the outcome of consultations: randomised controlled trial.", "Promoting patient participation in consultations: a randomised controlled trial to evaluate the effectiveness of three patient-focused interventions.", "Evaluation of a patient education leaflet designed to improve communication in medical consultations.", "Long-term efficacy of a checklist to improve patient education in cardiology.", "Expanding patient involvement in care. Effects on patient outcomes.", "Patient participation in the patient-provider interaction: the effects of patient question asking on the quality of interaction, satisfaction and compliance.", "Strengthening patient-provider relationships.", "Breast cancer patient perception of the helpfulness of a prompt sheet versus a general information sheet during outpatient consultation: a randomized, controlled trial.", "Patient-initiated prevention discussions. Two interventions to stimulate patients to initiate prevention discussions.", "Patients' participation in medical care: effects on blood sugar control and quality of life in diabetes.", "Increasing patient participation in reproductive health consultations: an evaluation of \"Smart Patient\" coaching in Indonesia." ]

[ "Patient participation in medical consultations has been demonstrated to benefit their subsequent psychological well being. Question asking is one way in which patients can be active. We investigated 2 means of promoting cancer patient question asking. One was the provision of a question prompt sheet to patients prior to their initial consultation with their oncologist. The second was the active endorsement and systematic review of the question prompt sheet by their oncologist. 318 patients with heterogeneous cancers, seeing one of 5 medical and 4 radiation oncologists for the first time, were randomised to either receive or not receive a question prompt sheet. Doctors were randomised to either proactively address or passively respond to the question prompt sheet in the subsequent consultation. Anxiety was assessed prior to the consultation. Consultations were audiotaped and content analysed. Anxiety was assessed again immediately following the consultation. Within the next 10 days patients completed questionnaires assessing information needs, anxiety and satisfaction and were given a structured telephone interview assessing information recall. Patients provided with a question prompt sheet asked more questions about prognosis compared with controls and oncologists gave significantly more prognostic information to these patients. Provision of the question prompt sheet prolonged consultations and increased patient anxiety; however, when oncologists specifically addressed the prompt sheet, anxiety levels were significantly reduced, consultation duration was decreased and recall was significantly improved. A patient question prompt sheet, used proactively by the doctor, is a powerful addition to the oncology consultation.\n Copyright 2001 Cancer Research Campaign", "To determine if a self-administered previsit questionnaire designed to increase awareness of patients' concerns alters the visit duration, content of the discussion, and patient and physician satisfaction.\n A balanced, two-arm trial in which physicians were randomized.\n Two primary-care clinics affiliated with a university hospital.\n Ten physicians and 201 continuity-care patients.\n In intervention visits, patients completed a previsit questionnaire asking about the desire for medical information, psychosocial assistance, therapeutic listening, general health advice, and biomedical treatment. Physicians reviewed questionnaires with patients during the visit.\n We used audiotapes of encounters to quantify the duration of the encounter and measured the number and type of diagnoses discussed in the visit, and patient and physician satisfaction with the encounter. Intervention visits were 34% longer (increase of 6.8 minutes; 95% confidence interval [CI] 0.4, 13.2) than control visits with most of the additional time spent in discussion of biomedical diagnoses (3.35 minutes; 95% CI 0.00, 6.72) and in the performance of the physical examination (2.7 minutes; 95% CI 0.5, 4.9). The number of diagnoses discussed per visit was 30% higher in intervention visits (increase of 1.7 diagnoses per visit; 95% CI 0.3, 3.2), but patients' satisfaction with these visits tended to be lower.\n Using a previsit questionnaire to increase awareness of the patients' concerns may entail a trade-off between conflicting goals: trying to respond to patient concerns while not significantly increasing the cost per visit. A future challenge is to develop and refine techniques with sufficient efficacy to justify the expense of implementing the intervention and the longer visit needed to respond adequately to patients' concerns.", "A randomised controlled trial with process evaluation was conducted (n=103) to study the use and impact of a Frequently Asked Questions checklist as a means to prepare coronary outpatients for a regular visit to their cardiologist. It was hypothesised that use of the checklist would result in better patient-doctor communication, lower state anxiety and higher knowledge scores among patients, resulting in greater patient satisfaction. The patients in the experimental group (n=53) received the checklist, with written instructions in addition to a brochure from the Dutch Heart Foundation, at home to prepare for their visit. The control patients only received the brochure. State anxiety immediately before the visit was significantly lower among experimental patients. No significant differences in patient satisfaction or knowledge were found. Using the checklist did not result in longer patient-doctor consultations. Experimental patients regarded the checklist as a useful tool to prepare for their visits to the clinic. We conclude that the checklist may be a useful tool for cardiac patients to prepare for their visits to their cardiologist.", "Active participation in the medical consultation has been demonstrated to benefit aspects of patients' subsequent psychological well-being. We investigated two interventions promoting patient question-asking behaviour. The first was a question prompt sheet provided before the consultation, which was endorsed and worked through by the clinician. The second was a face to face coaching session exploring the benefits of, and barriers to, question-asking, followed by coaching in question-asking behaviour employing rehearsal techniques. Sixty patients with heterogeneous cancers, seeing two medical oncologists for the first time, were randomly assigned to one of three groups: two intervention groups and one control group. Sociodemographic variables and anxiety were assessed prior to the intervention which preceded the consultation. The consultations were audiotaped and subsequently analysed for question-asking behaviour. Anxiety was assessed again immediately following the consultation. Questionnaires to assess patient satisfaction, anxiety and psychological adjustment were sent by mail 2 weeks following the consultation. Presentation and discussion of the prompt sheet significantly increased the total number of questions asked and the number of questions asked regarding tests and treatment. Coaching did not add significantly to the effects of the prompt sheet. Psychological outcomes were not different among the groups. We conclude that a question prompt sheet addressed by the doctor is a simple, inexpensive and effective means of promoting patient question asking in the cancer consultation.", "Recent models of physician-patient communication emphasize information exchange in promoting partnership. Although considerable attention has been given to physicians' information exchange, little research has examined patients' communication contributions. The purpose of this research was to test the effectiveness of a training booklet designed to enhance patients' communication skills in information exchange. A nested design was used, such that 25 physicians each saw six patients, two patients in each of three communication skills interventions (i.e. trained, informed, control). The dependent variables included several discourse categories designed to assess patients' information seeking, provision, and verifying. Results indicate that trained patients engaged in more effective and efficient information seeking, provided physicians with more detailed information about their medical condition, and used more summarizing utterances to verify information they received from physicians. Additionally, dyads consisting of trained patients demonstrated a more patient-controlled style of communication than did dyads consisting of informed or untrained patients.", "This study was conducted to evaluate the feasibility of using a computer intervention to enhance communication between healthcare professionals and women with breast cancer. Additional aims were to measure the extent to which women achieved their preferred decisional roles and satisfaction with the clinical medical appointment. This two-arm randomized clinical trial design included a convenience sample of 749 women with breast cancer attending 3 urban Canadian outpatient oncology clinics. Most women were older than 50 years and had a high school diploma or greater (57%). Women in the control group completed measures of decision preference before their clinic appointments. Women in the intervention group were encouraged to use the information and decision preference profiles generated by the computer program at their clinic appointments. Levels of involvement in decision making and satisfaction were measured after the clinic appointments. Results showed that although the majority of women in both groups did assume their preferred roles in decision making, a significantly higher proportion of women in the intervention group reported playing a more passive role than originally planned. Both groups reported high satisfaction levels. Future research is required to study how this computer intervention could be used by clinicians to provide information and decision support to these women.", "Active participation and asking questions are important ways in which patients can ensure they understand what the doctor has said. This study evaluated a question prompt sheet designed to encourage patients to ask questions in the cancer consultation.\n Patients (n = 142) were randomised to receive (i) a question prompt sheet or (ii) a general sheet informing patients of services available through the regional Cancer Council. Recall of information was assessed in a structured interview 4-20 days after the consultation. Questionnaires to assess patient satisfaction and adjustment to cancer were sent by mail.\n The question prompt sheet had a significant effect in one content area: prognosis. Thirty-five percent of patients who received the question handout asked questions about prognosis compared to 16% of those receiving the information handout. The prompt sheet did not increase the mean number of questions asked overall. Age, in/out-patient status, gender and involvement preference were predictive of both number and duration of patient questions.\n A question prompt sheet has a limited but important effect on patient question asking behaviour in the cancer consultation.", "To assess the impact of leaflets encouraging patients to raise concerns and to discuss symptoms or other health related issues in the consultation.\n Randomised controlled trial.\n Five general practices in three settings in the United Kingdom.\n 636 consecutive patients, aged 16-80 years, randomised to receive a general leaflet, a depression leaflet, both, or neither.\n Mean item score on the medical interview satisfaction scale, consultation time, prescribing, referral, and investigation.\n The general leaflet increased patient satisfaction and was more effective with shorter consultations (leaflet 0.64, 95% confidence interval 0.19 to 1.08; time 0.31, 0.0 to 0.06; interaction between both -0.045, -0.08 to-0.009), with similar results for subscales related to the different aspects of communication. Thus for a 10 minute consultation the leaflet increased satisfaction by 7% (seven centile points) and for a five minute consultation by 14%. The leaflet overall caused a small non-significant increase in consultation time (0.36 minutes, -0.54 to 1.26). Although there was no change in prescribing or referral, a general leaflet increased the numbers of investigations (odds ratio 1.43, 1.00 to 2.05), which persisted when controlling for the major potential confounders of perceived medical need and patient preference (1.87, 1.10 to 3.19). Most of excess investigations were not thought strongly needed by the doctor or the patient. The depression leaflet had no significant effect on any outcome.\n Encouraging patients to raise issues and to discuss symptoms and other health related issues in the consultation improves their satisfaction and perceptions of communication, particularly in short consultations. Doctors do, however, need to elicit expectations to prevent needless investigations.", "This study examined the efficacy of a brief written intervention for primary care patients, designed to increase their level of participation in the consultation. Patients given the intervention leaflet (N = 59) were compared with those given a control leaflet (N = 61) on various consultation process and outcome measures. Psychological and sociodemographic data were also obtained to determine whether these influenced the effects of the intervention. The results showed that the intervention group had significantly longer consultations and asked more questions than the controls. Younger patients and those from social classes 1 and 2 were more likely to benefit from the intervention, but locus of control and self-efficacy scores were not particularly helpful in predicting outcomes. No differences in patient satisfaction were found nor were any negative effects on the doctor observed. A number of explanations are explored and some directions for future research are discussed.", "Examined a simple intervention to improve the patient's contribution to communication in a medical office visit. In the first study, women awaiting a medical appointment were randomly assigned either to a group that was asked to list three questions to ask their physician or to a control group. Women who listed questions asked more questions in the visit and reported being less anxious. In the second study, a third group that received a message from their physician encouraging question asking was added. Both experimental groups asked more of the questions they had wished to, had greater feelings of control, and were more satisfied with the visit in general and with the information they received. The two experimental groups did not differ significantly, suggesting that the effect may be attributed either to thinking one's questions out ahead of time or to the perception that one's physician is open to questions.", "Increases in patient participation in medical interactions have been achieved to date using structured waiting-room interviews. In this pilot study, a printed intervention was tested as an inexpensive alternative with potential for wider dissemination. Sixty-seven family medicine patients were assigned randomly to one to two educational conditions just prior to their medical visit: a treatment booklet stressing the importance of recognizing information needs and encouraging patients to ask questions; or a placebo education booklet similar in format but not in content. The patient-physician interactions were audiotaped to determine the number of questions patients asked, and a questionnaire was administered after each encounter to assess patient satisfaction with care. The mean numbers of questions asked in the experimental and control groups were 7.46 and 5.63, respectively; the mean difference of 1.83 questions was statistically non-significant (P greater than 0.05). Question-asking did not correlate with reported satisfaction. Suggestions for modification to this research approach are presented.", "An estimated 42% of cancer patients suffer from poorly controlled pain, in part because of patient-related barriers to pain control. The objective of this study was to evaluate the effect of an individualized education and coaching intervention on pain outcomes and pain-related knowledge among outpatients with cancer-related pain.\n English-speaking cancer patients (18 to 75 years old) with moderate pain over the past 2 weeks were randomly assigned to the experimental (n = 34) or control group (n = 33). Experimental patients received a 20-minute individualized education and coaching session to increase knowledge of pain self-management, to redress personal misconceptions about pain treatment, and to rehearse an individually scripted patient-physician dialog about pain control. The control group received standardized instruction on controlling pain. Data on average pain, functional impairment as a result of pain, pain frequency, and pain-related knowledge were collected at enrollment and 2-week follow-up.\n At baseline, there were no significant differences between experimental and control groups in terms of average pain, functional impairment as a result of pain, pain frequency, or pain-related knowledge. At follow-up, average pain severity improved significantly more among experimental group patients than among control patients (P =.014). The intervention had no statistically significant impact on functional impairment as a result of pain, pain frequency, or pain-related knowledge.\n Compared with provision of standard educational materials and counseling, a brief individualized education and coaching intervention for outpatients with cancer-related pain was associated with improvement in average pain levels. Larger studies are needed to validate these effects and elucidate their mechanisms.", "The purpose of this study was to explore the hypothesis that assisting men with prostate cancer to obtain information would enable them to assume a more active role in treatment decision making and decrease their levels of anxiety and depression. Respondents were recruited from one community urology clinic in Winnipeg, Manitoba. Sixty newly diagnosed men were randomly assigned to receive either a self-efficacy information intervention that consisted of a written information package with discussion, a list of questions they could ask their physician, and an audiotape of the medical consultation (n = 30), or a written information package alone (n = 30). Men completed measures of preferred decisional role as the pretest; anxiety and depression before the intervention, and at 6 weeks post-intervention; and assumed decisional role at 6 weeks post-intervention. Results demonstrated that men in the intervention group assumed a significantly more active role in treatment decision making, and had lower state anxiety levels at 6 weeks. Levels of depression were similar for both groups at 6 weeks. This group of older men do want to be informed and participate in medical decisions. Further efforts are required to evaluate the efficacy of such an intervention in other community urology clinics.", "Active involvement of patients in medical encounters has been associated with several desirable outcomes, including greater satisfaction, increased adherence to treatment, and positive treatment outcomes. Older patients, particularly the very old and less well educated, are more likely to place physicians in a dominant role and themselves in a submissive role. Intervention trials to increase patient involvement have shown positive results. Activation interventions with older patients to increase a sense of control and self-efficacy are promising. Most of the attention to improving doctor-patient interaction has been directed toward physicians. The results of these few intervention trials support increased attention to patient behaviors.", "The purpose of this study was to assess the impact of an intervention to facilitate information giving to patients with chronic medical conditions on outcomes of care.\n A consecutive sample of 276 eligible patients with chronic medical conditions at a family medicine clinic was randomized to control and experimental interventions. A total of 205 completed the study. Experimental group patients received copies of their medical record progress notes, and they completed question lists for physician review, while control group patients received health education sheets and completed suggestion lists for improving clinic care. Self-reported physical functioning, global health, and patient satisfaction and adherence were measured at enrollment and after the interventions. Visit lengths and patient response to medical record sharing after the interventions were also measured.\n After the intervention, experimental group patients reported 3.7% better overall physical functioning than did control patients (mean = 83.6, standard deviation [SD] = 17.6 vs mean = 79.9, SD = 25.3; P = .005 after adjusting for covariates). The experimental group was more satisfied with their physician's care (mean = 31.4, SD = 4.6 vs mean = 31.3, SD = 5.2; P = .045 after adjusting for covariates). They were also more interested in seeing their medical records than were control patients (mean = 12.0, SD = 2.8 vs mean = 11.2, SD = 2.8; P = .002 after adjusting for covariates). Experimental group patients also reported an 8.3% improvement in overall health status (postintervention mean = 3.0, SD = 1.1) compared with their pre-intervention health status (mean = 2.8, SD = 1.0; P =.001). Visit lengths for patients in the experimental group did not differ from those of the control group.\n A simple patient-centered intervention to facilitate information giving in the primary health care of patients with chronic medical conditions can improve self-reported health, physical functioning, and satisfaction with care.", "This study examined the effect of providing patients with an audiotape of a previous consultation on their level of participation during a subsequent consultation. 117 newly referred medical oncology patients randomised to receive a tape (n = 63) or not (n = 54) had two linked consultations which were both audiotaped. A content analysis revealed no significant differences between tape and control group in the mean number of questions asked during the second consultation. However, significantly more tape group patients (77%) asked for clarification of at least one piece of information compared to the control group (57%) (P = 0.04). A larger number of control group patients (61%) made at least one request for facts already provided in their first consultation compared to tape group patients (39%) (P = 0.05). Audiotapes appear to facilitate patients' requests for the clarification of previously given information and permit the re-absorption of complex information given when patients may have been too distressed for it to be assimilated.", "A brief educational intervention to promote effective communication between physicians, children, and parents during pediatric office visits was designed and tested. A randomized clinical trial involving 141 children (5- to 15-year-olds) tested the effectiveness of the intervention to improve the process and outcome of medical care. The intervention was contained in three brief videotapes (one each for parents, physicians, and patients) and in accompanying written materials. Materials were designed to build skills and motivation for increased child competence and participation during pediatric medical visits. Control subjects saw health education videotapes and received materials comparable in length with those of experimental subjects. Postintervention medical visit process was analyzed using videotapes of visits. Visit outcomes, assessed with standardized instruments and interviews, included children's rapport with physicians, children's anxiety, children's preference for an active health role, children's recall of information, parents' satisfaction with the medical visit, and physician satisfaction. Results indicated that physicians in the intervention group, compared with their counterparts in the control group, more often included children in discussions of medical recommendations (50% vs 29%, t = 2.39, P less than .05); that children in the intervention group, compared with control children, recalled more medication recommendations (77% vs 47%, P less than .01) and reported greater satisfaction and preference for an active health role; and that the intervention and control groups did not differ in parent satisfaction, physician satisfaction, or child anxiety. The results suggest that a brief educational intervention administered during waiting room time can positively impact physician-child rapport and children's preference for an active role in health and their acquisition of medical information.", "We prompted parents to increase their interactions with health-care providers during their children's health-supervision visits. Before scheduled appointments we asked parents of 32 infants and young children if they had specific child health questions or concerns. Sixteen parents randomly assigned to the prompted group were then prompted to initiate discussions of their concerns. Sixteen control parents discussed unrelated topics before their appoitments. Prompted parents initiated significantly more interactions with health-care providers and more health and behavioral topics were discussed during their appointments. Both parent groups reported satisfaction with health-care services. Further research is needed to determine the clinical significance of outcomes associated with enhanced parent-provider interaction during children's health-supervision visits. These visits are ideal settings for behavioral research on improving health care for children and their families.", "A randomised controlled study in which a written prompt was sent to new patients to help them make the most of their consultation was conducted amongst patients referred to the dermatology, gynaecology and orthopaedic out-patients clinics at the Royal Free Hospital, London. The impact of the help card on patients' expectations, preparation for and experience of their out-patient consultation are discussed. A help card and letter were sent to a random sample of patients before their appointment to encourage them to prepare and prioritize questions to ask the doctor at the consultation. After their consultation, patients were sent a postal questionnaire to complete at home. Analysis of the questionnaires provided quantitative and qualitative data about patients' information requirements and whether they were fulfilled. The results highlight the difficulties out-patients have in asking questions and discussing topics fully at their initial consultation, even when they have thought of questions in advance. Half the patients who were sent a help card said they got more out of their consultation as a result, yet few statistically significant differences between the help card group and the other patients were found.", "To assess the effect of patient completed agenda forms for the consultation and doctors' education on identifying patients' agendas on the outcome of consultations.\n Randomised controlled trial.\n General practices in Leicestershire and Nottinghamshire, United Kingdom.\n 46 general practitioners and 976 patients.\n Education for general practitioners, with an embedded clustered randomised controlled trial of a patient agenda form.\n Number of problems identified, time required to manage each problem, duration of consultations, number of problems raised after the doctor considered the consultation finished (\"by the way\" questions), and patient satisfaction.\n Data were available from 45 doctors (98%) and 857 patients (88%). The number of problems identified in each consultation increased by 0.2 (95% confidence interval 0.1 to 0.4) with the agenda form, by 0.3 (0.1 to 0.6) with education, and by 0.5 (0.3 to 0.7) with both interventions. The time required to manage each problem was not affected. The duration of consultations with the agenda form was increased by 0.9 minutes (0.3 to 1.5 minutes) and with the combined intervention by 1.9 minutes (1.0 to 2.8 minutes). Patient satisfaction with the depth of the doctor-patient relationship was increased with the agenda form. The occurrence of \"by the way\" presentations did not change.\n A patient completed agenda form before the consultation or general practitioner education about the agenda form, or both, enabled the identification of more problems in consultations even though consultations were longer.", "The aim of this experimental study was to evaluate the effectiveness of three patient-focused interventions designed to increase patient question asking in clinical consultations. Patients were randomly allocated to one of five conditions to receive either one of three interventions or to serve as an attention control group or a control group. The primary outcome measure was question asking by the patient of their physician. Participants in the intervention groups did not ask more questions than participants in the control groups. Immediately after the consultation participants in the intervention groups had higher levels of self-efficacy in asking questions. Three months after the index visit patients in the intervention groups were significantly more likely to be satisfied to some degree than patients in the control group. There was no difference in diabetic control. These results suggest that simple brief patient-focused interventions do not change patient behaviour in medical outpatient consultations.", "It is important for patients to provide relevant information to the doctor in consultation and to make their own information requirements known. This requires patients to actively participate in the process, something they appear to be reluctant to do. Earlier patient intervention studies have successfully manipulated patient involvement and question asking, although, the latter has tended to be accompanied by increased tension and negative impact. The present study uses a patient education leaflet which uses a wide definition of patient activation. It emphasizes the role of the 'good' patient as a provider of information extending beyond the recitation of symptoms to include insights to interpretation and meaning. Results showed that patients responded positively to the leaflet and a comparison of doctor ratings of communication quality showed the experimental group performed better than the controls. The findings are considered in terms of improved information exchange and the impact of making the 'rules' of consultation explicit is also discussed.", "In a randomised controlled trial a Frequently Asked Questions (FAQ) checklist intended to prepare coronary artery disease (CAD) outpatients for a medical check-up visit at the cardiologist was evaluated. The checklist was mailed to patients in preparation to their visits after 1, 4 and 10 months following patients' discharge from hospitalisation for CAD. It was hypothesised that the intervention would result in lower state anxiety, better patient-doctor communication, more knowledge of CAD and greater patient satisfaction, while it would not result in longer visits. Repeated measurements analyses of covariance showed that experimental patients (N = 46) were less anxious before the first visit. This visit was shorter than in the controls, though the third visit was longer. Control patients (N = 59) showed more CAD knowledge than experimental patients at the first and third visit. Experimental patients found the checklist useful, though its value diminished at subsequent visits. Using the checklist thus decreased anxiety prior to the first visit and the duration of that visit, while negatively affecting knowledge. No conclusions about long-term effects could be drawn, due to the likelihood of type II and type III errors. Process evaluation indicated that the approach used is not sufficiently stimulating for patients to use as a preparation to every visit.", "An intervention was developed to increase patient involvement in care. Using a treatment algorithm as a guide, patients were helped to read their medical record and coached to ask questions and negotiate medical decisions with their physicians during a 20-minute session before their regularly scheduled visit. In a randomized controlled trial we compared this intervention with a standard educational session of equal length in a clinic for patients with ulcer disease. Six to eight weeks after the trial, patients in the experimental group reported fewer limitations in physical and role-related activities (p less than 0.05), preferred a more active role in medical decision-making, and were as satisfied with their care as the control group. Analysis of audiotapes of physician-patient interactions showed that patients in the experimental group were twice as effective as control patients in obtaining information from physicians (p less than 0.05). Results of the intervention included increased involvement in the interaction with the physician, fewer limitations imposed by the disease on patients' functional ability, and increased preference for active involvement in medical decision-making.", "The purpose of this study was to investigate the effectiveness, dynamics, and consequences of a health education intervention designed to increase patient question asking during the patient's medical visit. Data were collected at a Baltimore family and community health center which provides outpatient services to a low income, predominantly black and female population. The majority of the study participants were, in addition, elderly and chronically ill. A total of 294 patients and 3 providers took part in the study. The study design included random assignment of patients to experimental and placebo groups with two non-equivalent (non-randomized) control groups. Findings included: (1) The experimental group patients asked more direct questions and fewer indirect questions than did placebo group patients. (2) The experimental group patient-provider interaction was characterized by negative affect, anxiety, and anger, while the placebo group patient-provider interaction was characterized as mutually sympathetic. (3) The experimental group patients were less satisfied with care received in the clinic on the day of their visit than were placebo patients. (4) The experimental group patients demonstrated higher appointment-keeping ratios (an average number of appointments kept divided by an average number of appointments made) during a four-month prospective monitoring period.", "In support of the Veterans Health Administration commitment to the promotion of shared decision-making between providers and patients, this study investigated the relationship between the provision of a patient appointment guidebook, designed to promote and support patient participation in the health care visit, and patient perceptions of primary care visit effectiveness. This study compared perceptions among 277 randomly selected patients randomly assigned to one of two groups. Patients assigned to an intervention group received a patient appointment guidebook along with the standard appointment reminder letter prior to the scheduled routine visit. Patients assigned to a control group received only the standard appointment reminder letter. Patient perceptions were assessed with a follow-up questionnaire designed to measure patient agreement with six statements pertaining to primary care visit effectiveness. No significant differences were noted in the proportion of patients in the two groups that agreed with any of the six statements pertaining to primary care visit effectiveness. Significant differences were noted, however, in the proportion of patients in the groups who received preventive health care interventions of influenza vaccination, pneumococcal vaccination, and gender-specific cancer screening. Approximately 37% of the patients in the intervention group provided positive comments about the patient appointment guidebook, while only 7% provided negative comments. Although statistically inconclusive, the narrative comments indicate that a patient appointment guidebook may assist veterans in preparing for primary care appointments. The lack of significant difference between the two groups on the measures of primary care visit effectiveness may be due, in part, to positive perceptions among the sample in general, as reflected by high levels of agreement and predominantly positive comments for both control and intervention groups.", "The purpose of this study was to determine the helpfulness of a prompt sheet versus a general information sheet for patient communication with physicians. Sixty women with breast cancer attending their first outpatient consultation with a breast medical oncologist were randomized to receive either a prompt sheet (PS) or a general information (GI) sheet regarding breast cancer. Analysis of the results found that helpfulness of the written material was rated higher in the PS group (8.5 +/- 2) than the GI group (6.2 +/- 3.6), P = 0.005. The mean score of helpfulness in communicating with physicians was 7.9 +/- 2.4 and 5.7 +/- 3.8, respectively, P = 0.01. There were no significant differences between the groups in the average total number of questions asked by the patients or average physician or patient speaking time. We conclude that a disease-specific prompt sheet provided before medical encounters may assist in communication between patients and physicians.", "When patients are active participants in discussions, comprehension and compliance are likely to improve. This study examines the use of two interventions to aid patients in initiating such discussions in the area of health maintenance.\n The study was a randomized controlled trial of adult patients. The first intervention used two cards that listed seven core health maintenance concerns. The second intervention used a brief session with a nurse to help patients identify their health risks and develop a plan for seeking any desired information about these risks. An exit questionnaire and a telephone interview 4 to 6 weeks later assessed the extent to which (1) information seeking by patients was stimulated; (2) patients recalled the information obtained; (3) patients used the information to effect lifestyle changes; and (4) patients felt they participated in the decision to discuss health maintenance.\n Both interventions stimulated patients to request health maintenance information (both P < .05); the second intervention significantly increased patient recall (P = .018). Neither intervention, however, had a significant impact on lifestyle change or sense of participation in the decision to initiate discussion. Analysis of the second intervention did show that both increasing patients' recall of information (P = .008) and sense of involvement in the decision to discuss health maintenance (P = .003) significantly increases the likelihood of lifestyle change.\n Two interventions have been developed that are relatively simple and inexpensive methods to stimulate patients to seek health maintenance, and quite probably other health-related information. The blunted impact of these two interventions, however, raises the question of whether such simple and relatively inexpensive interventions are strong enough to stimulate patients to use this information to initiate change when one seeks to address a wide range of risks.", "To maximize disease control, patients must participate effectively in their medical care. The authors developed an intervention designed to increase the involvement of patients in medical decision making. In a 20-minute session just before the regular visit to a physician, a clinic assistant reviewed the medical record of each experimental patient with him/her, guided by a diabetes algorithm. Using systematic prompts, the assistant encouraged patients to use the information gained to negotiate medical decisions with the doctor. A randomized trial was conducted in two university hospital clinics to compare this intervention with standard educational materials in sessions of equal length. The mean pre-intervention glycosylated hemoglobin (HbA1) values were 10.6 +/- 2.1% for 33 experimental patients and 10.3 +/- 2.0% for 26 controls. After the intervention the mean levels were 9.1 +/- 1.9% in the experimental group (p less than 0.01) and 10.6 +/- 2.22% for controls. Analysis of audiotapes of the visits to the physician showed the experimental patients were twice as effective as controls in eliciting information from the physician. Experimental patients reported significantly fewer function limitations. The authors conclude that the intervention is feasible and that it changes patient behavior, improves blood sugar control, and decreases functional limitations.", "Paternalistic models of health care, social distance between patients and providers, and cultural norms discourage patients from playing an active role in health consultations. This study tested whether individual coaching can give family planning patients the confidence and communication skills to talk more openly and more vigorously with providers. Educators met with 384 Indonesian women in clinic waiting rooms and coached them on asking questions, expressing concerns, and seeking clarification. An analysis of audiotaped consultations found that patients who received coaching articulated significantly more questions and concerns than others. Coaching narrowed differentials in active communication by patient type, age, and assertiveness, but it widened differentials by patient education and socioeconomic class. The discontinuation rate at 8 months was lower in the intervention than the control condition, but the difference was only marginally significant." ]

[ "11496070", "15624051", "12239902", "12113422", "15868256", "14669314", "15791369", "9109247", "11241922", "11052484", "15457380", "12432295", "11089583", "8252346", "9153173", "8269230", "7660266", "10411441", "11727078", "15920688", "11793255", "11961595", "10872622", "15821617", "12673746", "15069719", "12473889", "9189777", "9221851", "12874687", "15931488", "10749610", "10653240", "10460907", "12854115", "15081650", "11928022", "12163970", "16222464", "12907898", "9189099", "12616116" ]

[ "Hybrid laparoscopic flexure takedown and open procedure for rectal resection is associated with significantly shorter length of stay than equivalent open resection.", "Laparoscopic vs open total mesorectal excision for rectal cancer: an evaluation of the mesorectum's macroscopic quality.", "Results of laparoscopic versus open resections for non-early rectal cancer in patients with a minimum follow-up of four years.", "Laparoscopic total mesorectum excision.", "Laparoscopic resection for rectal cancer: outcomes in 194 patients and review of the literature.", "Comparative evaluation of immune response after laparoscopical and open total mesorectal excisions with anal sphincter preservation in patients with rectal cancer.", "Laparoscopic-assisted approach in rectal cancer patients: lessons learned from >200 patients.", "Abdominoperineal resection: laparoscopic versus conventional.", "Laparoscopic total mesorectal excision with autonomic nerve preservation.", "Laparoscopic ultralow anterior resection combined with per anum intersphincteric rectal dissection for lower rectal cancer.", "Laparoscopic versus open total mesorectal excision with anal sphincter preservation for low rectal cancer.", "Does laparoscopic abdominoperineal resection of the rectum compromise long-term survival?", "Laparoscopic abdominoperineal resection: early postoperative results of a prospective study involving 116 patients. The Laparoscopic Colorectal Surgery Study Group.", "Prospective comparison of laparoscopic and conventional anterior resection.", "Early experience with laparoscopic abdominoperineal resection.", "Laparoscopic assisted abdominoperineal resection.", "Laparoscopic abdominoperineal excision of the rectum.", "Laparoscopic vs. open abdominoperineal resection for cancer.", "Laparoscopic-assisted total mesorectal excision and colonic J pouch reconstruction in the treatment of rectal cancer.", "The oncological safety of laparoscopic total mesorectal excision with sphincter preservation for rectal carcinoma.", "A comparison between open versus laparoscopic assisted colonic pouches for rectal cancer.", "Laparoscopic abdominoperineal resection and anterior resection with curative intent for carcinoma of the rectum.", "Laparoscopic low anterior resection using a triple stapling technique.", "Safety of laparoscopic intracorporeal rectal transection with double-stapling technique anastomosis.", "Laparoscopic intersphincteric resection with coloplasty and coloanal anastomosis for mid and low rectal cancer.", "Laparoscopic versus conventional open resection of rectal carcinoma: A clinical comparative study.", "Prospective evaluation of laparoscopic surgery for rectosigmoidal and rectal carcinoma.", "A preliminary comparison of a consecutive series of open versus laparoscopic abdomino-perineal resection for rectal adenocarcinoma.", "Early postoperative results of a prospective series of laparoscopic vs. Open anterior resections for rectosigmoid cancers.", "Long-term results of laparoscopic versus open resections for rectal cancer for 124 unselected patients.", "Early outcomes of 100 patients with laparoscopic resection for rectal neoplasm.", "Systemic cytokine response after laparoscopic-assisted resection of rectosigmoid carcinoma: A prospective randomized trial.", "Laparoscopic-assisted abdominoperineal resection for low rectal adenocarcinoma.", "A case-control-study comparing laparoscopic versus open surgery for rectosigmoidal and rectal cancer.", "Prospective evaluation of laparoscopic total mesorectal excision with colonic J-pouch reconstruction for mid and low rectal cancers.", "Laparoscopic resection of rectosigmoid carcinoma: prospective randomised trial.", "Hand-assisted laparoscopic low anterior resection: initial experience with a new procedure.", "Local recurrence and survival after laparoscopic mesorectal resection forrectal adenocarcinoma.", "Laparoscopic rectal resection with anal sphincter preservation for rectal cancer: long-term outcome.", "Outcome of laparoscopic surgery for rectal cancer in 101 patients.", "Laparoscopic resection of the colon and rectum for cancer.", "Laparoscopic total mesorectal excision: a consecutive series of 100 patients." ]

[ "Laparoscopic-assisted, sphincter-saving resection (largest incision < 7 cm) of the middle and distal rectum is technically very difficult and, with regard to cancers, has not been demonstrated to be oncologically safe. The hypothesis of this retrospective study is that a hybrid operation that combines laparoscopic and open methods would be associated with short-term outcome benefits compared with open surgery results for patients undergoing sphincter-saving proctectomy.\n A total of 31 hybrid and 25 fully open rectal resection patients were compared in this retrospective review. All patients had splenic flexure takedown and rectal anastomosis. The hybrid approach consisted of laparoscopic splenic flexure takedown (with or without partial rectal mobilization and devascularization) followed by completion of the procedure via infraumbilical midline laparotomy. The indication was neoplasm in 87 percent of hybrid patients and in 68 percent of open patients. The majority of tumors were located between 4 and 10 cm from the dentate line.\n Fifty-eight percent of hybrid and 68 percent of open patients had low anterior or coloanal resections, and 48 percent of hybrid and 64 percent of open patients underwent temporary diversion via ileostomy. The mean hybrid midline incision length was 11 cm compared with 24 cm for open patients (P < 0.0001). The neoplastic specimens were similar with regard to margins and lymph node harvest. Similar complication rates were noted in both groups. Nonsignificant benefits for hybrid patients (0.9-1.2 days) were seen with regard to length of time until toleration of liquid or solid diet and first flatus. Hybrid patients experienced their first bowel movements 4.1 days vs. 5.7 days for the open group (P = 0.03). Mean length of stay was significantly shorter for hybrid patients (6.1. days) than for open patients (11.1 days; P = 0.0006).\n This preliminary retrospective study suggests that a combined hybrid laparoscopic and open approach to sphincter-saving proctectomy permits a similar resection as open methods and may be associated with a length-of-stay benefit and more rapid return of bowel function. Prospective studies will be needed before any firm conclusions can be drawn.", "Next to surgical margins, yield of lymph nodes, and length of bowel resected, macroscopic completeness of mesorectal excision may serve as another quality control of total mesorectal excision (TME). In this study, the macroscopic completeness of laparoscopic TME was evaluated.\n A series of 25 patients with rectal cancer were managed laparoscopically (LTME) and included in this study. The pathologic specimens of the LTME group were prospectively examined and matched with a historical group of resection specimens from patients who had undergone open TME (OTME). The two groups were matched for gender and type of resection (low anterior or abdominoperineal resection). Special care was given to the macroscopic judgment concerning the completeness of the mesorectum.\n A three-grade scoring system showed no differences between the LTME and OTME groups.\n The current study supports the hypothesis that oncologic resection using laparoscopic TME is feasible and adequate.", "Laparoscopic rectal resection for malignancy is still debated. Concern has been expressed regarding the lack of significant data from larger patient series with longer periods of follow-up. The aims of this study were to compare long-term outcome with a minimum follow-up of four years in unselected patients undergoing either laparoscopic rectal resection or open rectal resection for cancer.\n From May 1992 to August 1997 all electively admitted patients with rectal cancer were included in a prospective non-randomized study. Written information was submitted to each patient and the location in each group (laparoscopic or open) was related to the patient's choice. The inclusion protocol criteria excluded T1 tumors. All 68 T2-T4 patients underwent preoperative radiotherapy (5.040 cGy), completed with chemotherapy in selected cases (patients below 70 years of age). Long-term results were compared between the two groups. Follow-up time of both groups ranged between 48 and 96 months (mean, 49.4 months).\n Excluding patients who underwent a palliative resection or conversion to open surgery and deaths not related to cancer, 53 pts (29 laparoscopic rectal resection, 24 open rectal resection) out of 68 are available and are the object of this study. No patient was lost to follow-up. No wound recurrence was observed. The local recurrence rate after laparoscopic rectal resection was 24.1% vs. 25% after open rectal resection (P = 0.799). Distant metastases occurred in 20.7% of patients in the LLR group (laparoscopic rectal resection) vs. 25% in the ORR group (open rectal resection) (P = 0.980). Cumulative survival probability after laparoscopic rectal resection and open rectal resection was 0.690 and 0.625 (P = 0.492), respectively. Cumulative survival probability for Duke's stage A, B and C in the LRR group vs. the ORR group was 1.000 vs. 0.900 (P = 0.585), 0.667 vs. 0.636 (P = 0.496) and 0.429 vs. 0.445 (P = 0.501), respectively. Sixteen laparoscopic rectal resection patients (55.2%) and 12 open rectal resection patients (50%) are presently disease free (P = 0.979).\n Long-term results after laparoscopic resection of rectal cancer were comparable to those after conventional resection, with a trend in favor of the laparoscopic approach that does not reach a statistically significant difference, possibly due to the limited size of the sample.", "The main controversy of colon-rectal laparoscopic surgery comes from its use as a cancer treatment. Two points deserve special attention: the incidence of port-site tumor implantation and the possibility of performing radical cancer surgery, such as total mesorectum excision. Once these points are addressed, the laparoscopic approach will be used routinely to treat rectal cancer. To clarify these points, 32 patients with cancer of the lower rectum participated in a special protocol that included preoperative radiotherapy and laparoscopic total mesorectum excision. All data were recorded. At the same time, all data recorded from the experience of a multicenter laparoscopic group (Brazilian Colorectal Laparoscopic Surgeons - 130 patients with tumor of the lower rectum) were analyzed and compared with the data provided by our patients. Analysis of the results suggests that a laparoscopic approach allows the same effective resection as that of conventional surgery and that preoperative irradiation does not influence the incidence of intraoperative complications. The extent of lymph nodal excision is similar to that obtained with open surgery, with an average of 12.3 lymph nodes dissected per specimen. The rate of local recurrence was 3.12%. No port site implantation of tumor was noted in this series of patients with cancer of the lower rectum.", "There are few reports on laparoscopic rectum resection demonstrating its feasibility and efficacy in patients with rectal cancer. Most patient series are small, and results must be considered preliminary and medium-term. Our large prospective conducted study aimed to assess the effectiveness of a totally laparoscopic resection for rectum carcinoma with emphasis on perioperative and long-term oncological outcomes.\n Between November 1992 and July 2003, 194 unselected patients were resected laparoscopically for rectal carcinoma. Patients with locally advanced rectum carcinoma (uT3/uT4) and no evidence of distant metastases were candidates for neoadjuvant chemoradiation. Adjuvant treatment was administered to patients with UICC stage II/III disease. All patients were followed up prospectively to evaluate complications and late outcomes. Survival probability analysis was performed using the Kaplan-Meier method. Study selection was made by Medline search using the following key words: rectal cancer, rectal neoplasms, laparoscopy, and resection. Single case reports and abstracts were excluded. When surgical series were reported more than once, only the most recent reports were considered and listed.\n The most common procedures were low anterior resection with total mesorectum excision in 65.5% of patients and high anterior resection in 25.3%. Average operative time was 174 min. Average number of lymph nodes removed was 25.4 and length of specimen resected was 27.6 cm. Resection was curative in 145 patients and palliative in 49 cases. UICC tumor stages were as follows: stage I: 25.2%, stage II: 27.3%, stage III: 30.4%, and stage IV: 17%. Intraoperative complications were <1% for lesions of the ureter, urinary bladder, and deferent duct. Conversion to conventional surgery was necessary in two cases (1%). The most common postoperative complication was anastomotic leakage in 13.5% of patients. There was no postoperative mortality. Follow-up evaluation ranged from 1 to 128 months with a mean of 46.1 months. The most common late complication was incisional hernia in 3.6% of patients. Port-site metastases occurred in one patient (0.5%). Tumor recurrence developed in 23 of the 145 curative resected patients (11.7% distant metastases and 4.1% local recurrence). Overall local recurrence rate was 6.7% (4.1% after curative resection and 14.3% after palliative resection). Overall survival rate was 90.6% at 1 year, 74.5% at 3 years, and 66.3% at 5 years. Overall 5-year survival rate was 76.9% after curative resection and 31.8% after palliative resection. Cancer-related survival rate was 94% at 1 year, 82.4% at 3 years, and 78.9% at 5 years. At 5 years it was 87.7% after curative resection and 48.5% after palliative resection. At 5 years, the survival rate was 100% for stage I, 94.4% for stage II, 66.6% for stage III, and 44.6% for stage IV.\n Our results and the literature review clearly demonstrate that laparoscopic resection for rectal cancer is not associated with higher morbidity and mortality. Established oncological and surgical principles are respected and long-term outcomes are at least as good as those after open surgery.", "The study of immune response of open versus laparoscopical total mesorectal excision with anal sphincter preservation in patients with rectal cancer has not been reported yet. The dissected retroperitoneal area that contacts directly with carbon dioxide is extensive in laparoscopic total mesorectal excision with anal sphincter preservation surgery. It is important to clarify whether the immune response of laparoscopic total mesorectal excision with anal sphincter preservation (LTME with ASP) in patients with rectal cancer is suppressed more severely than that of open surgery (OTME with ASP). This study was designed to compare the immune functions after laparoscopic and open total mesorectal excision with anal sphincter preservation for rectal cancer.\n This study involved 45 patients undergoing laparoscopic (n=20) and open (n=25) total mesorectal excisions with anal sphincter preservation for rectal cancer. Serum interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha) were assayed preoperatively and on days 1 and 5 postoperatively. CD3+ and CD56+ T lymphocyte count, CD3- and CD56+ natural killer cell (NK) count and immunoglobulin (IgG/IgM/IgA) were assayed preoperatively and on day 5 postoperatively. The numbers of CD3+ and CD56+ T lymphocytes and CD3- and CD56+ NK cells were counted using flow cytometry. An enzyme-linked immunosorbent assay (ELISA) was used for IL-2, IL-6 and TNFalpha determination. And IgG, IgM, and IgA were assayed using immunonephelometry.\n The demographic data of the two groups had no difference. The preoperative levels of CD3+ and CD56+ T lymphocyte count, CD3- and CD56+ NK count, serum IgG, IgM, IgA, IL-2, IL-6 and TNFalpha also had no significant difference in the two groups (P>0.05). The CD3+ and CD56+ T lymphocyte counts had no obvious changes after surgery in laparoscopic (d=-0.79 +/- 3.83%) and open (d=0.42 +/- 2.09%) groups. The CD3- and CD56+ NK counts were decreased postoperatively in both laparoscopic (d=-7.23 +/- 11.33%) and open (d=-9.21 +/- 13.93%) groups. The differences of the determined values of serum IgG, IgM and IgA on the fifth day after operation subtracted those before operation were -2.56 +/- 2.14 g/L, -252.35 +/- 392.94 mg/L, -506.15 +/- 912.24 mg/L in laparoscopic group, and -1.81 +/- 2.10 g/L, -282.72 +/- 356.75 mg/L, -252.20 +/- 396.28 mg/L in open group, respectively. The levels of IL-2 were decreased after operation in both groups. However, the levels of IL-6 were decreased after laparoscopic surgery (d1=-23.14 +/- 263.97 ng/L and d5=-40.08 +/- 272.03 ng/L), and increased after open surgery (d1=27.38 +/- 129.14 ng/L and d5=21.67 +/- 234.31 ng/L). The TNFalpha levels were not elevated after surgery in both groups. There were no significant differences in the numbers of CD3+ and CD56+ T lymphocytes and CD3- and CD56+ NK cells, the levels of IgG, IgM, IgA, IL-2, IL-6 and TNFalpha between the two groups (P>0.05).\n There are no differences in immune responses between the patients having laparoscopic total mesorectal excision with anal sphincter preservation and those undergone open surgery for rectal cancer.", "The applicability of laparoscopic surgery in the treatment of colorectal diseases is still controversial. Early reports on laparoscopic-assisted colectomy in patients with colon cancer suggested that it minimizes surgical trauma, decreases perioperative complications, and leads to a more rapid recovery. To our knowledge, no previous studies have compared the laparoscopic vs the open approach in rectal cancer. The aim of this paper was to assess the results of laparoscopic techniques in patients with rectal cancer.\n From March 1998 to February 2003, all patients admitted to our unit with adenocarcinoma of the rectum were evaluated for surgery by the laparoscopic approach.\n A total of 220 patients with a mean age of 67.3 years were included in the study. One hundred thirty patients (59%) were treated with neoadjuvant chemoradiotherapy. In >75% of the patients, a surgical procedure with sphincter preservation was performed. The rate of conversion to the open approach was 20%. Ten patients had intraoperative complications. Fifty-eight patients (26.3%) developed postoperative complications. The length of hospital stay was 6.8 days. The distribution of tumor stages was as follows: stage I, 16.81%; stage II, 33.6%; stage III, 26.36%; stage IV, 19.09%. The mean number of lymph nodes was 13.8. The incidence of local relapse was 5.3%, with a follow-up of 18 months.\n Laparoscopic surgery can be safely performed in patients with adenocarcinoma of the rectum with good short-term results. Randomized controlled trials are needed to confirm these results.", "A prospective comparison of laparoscopic (Group 1 = 18 patients) and conventional (Group 2 = 18 patients) abdominoperineal resection in patients with low rectal cancer was carried out. Parameters studied included the length of the procedure, ileus, and hospitalization; the rate of conversion; and the morbidity and mortality rates. The mean (SD) operating time was slightly longer for laparoscopic than for standard surgery: 229 (SD = 56) versus 208 (SD = 45) min; p = 0.47. Moreover, the mean (SD) time to reintroduction of diet of 2.5 (SD = 1.1) days versus 3.8 (SD = 2.1, p < 0.005) and the length of hospital stay of 7.4 (SD = 4.1) days versus 12.9 (SD = 3.9, p < 0.005) were statistically lower in Group 1. Histopathological examination of the resection specimens (length of specimen, lateral margins, and number of lymph nodes retrieved) showed similar results in the two groups. Major complications were few and occurred in a similar proportion in the two groups (4 x 3). The conversion rate was 10% (2/20). One death (5.5%) and two reoperations (11.1%) occurred in group 2. Local recurrence was also similar (1 x 3). There were no port sites or abdominal incisions recurrences. This clinical study indicates that oncologic laparoscopic abdominoperineal resection is not only technically feasible and safe but also provides better postoperative recovery and the same rate of early recurrence and survival as the open technique.", "Laparoscopy has greatly influenced abdominal surgery. We hypothesize that the benefits of minimally invasive surgery are applicable to rectal cancer. A cadaver model of laparoscopic rectal resection with total mesorectal excision (TME) and autonomic nerve preservation was utilized to explore this hypothesis. The principles of TME were followed, including high vascular ligation, sharp mesorectal dissection, and identification and preservation of the autonomic pelvic nerves. After proving feasibility in the cadaver model, a clinical study was performed on patients with mid to low rectal cancers. We observed acceptable morbidity with this minimally invasive technique of rectal resection and TME. We conclude that there is growing evidence that laparoscopic methods can be applied to patients with rectal cancer.", "Rectal resection with total mesorectal excision is perhaps the most technically challenging of laparoscopic procedures, and the purpose of this study was to show that laparoscopic ultralow anterior resection is feasible for lower rectal cancer. Seven patients with lower rectal cancer were treated in this way with a satisfactory outcome in each case, and on the basis of this limited study, we suggest that extension of laparoscopy to the treatment of very low rectal lesions may be of advantage.", "The Laparoscopic approach has been applied to colorectal surgery for many years; however, there are only a few reports on laparoscopic low and ultralow anterior resection with construction of coloanal anastomosis. This study compares open versus laparoscopic low and ultralow anterior resections, assesses the feasibility and efficacy of the laparoscopic approach of total mesorectal excision (TME) with anal sphincter preservation (ASP), and analyzes the short-term results of patients with low rectal cancer.\n We analyzed our experience via a prospective, randomized control trail. From June 2001 to September 2002, 171 patients with low rectal cancer underwent TME with ASP, 82 by the laparoscopic procedure and 89 by the open technique. The lowest margin of tumors was below peritoneal reflection and 1.5-8 cm above the dentate line (1.5-4.9 cm in 104 cases and 5-8 cm in 67 cases). The grouping was randomized.\n Results of operation, postoperative recovery, and short-term oncological follow-up were compared between 82 laparoscopic procedures and 89 controls who underwent open surgery during the same period. In the laparoscopic group, 30 patients in whom low anterior resection was performed had the anastomosis below peritoneal reflection and more than 2 cm above the dentate line, 27 patients in whom ultralow anterior resection was performed had anastomotic height within 2 cm of the dentate line, and 25 patients in whom coloanal anastomosis was performed had the anastomosis at or below the dentate line. In the open group, the numbers were 35, 27, and 27, respectively. There was no statistical difference in operation time, administration of parenteral analgesics, start of food intake, and mortality rate between the two groups. However, blood loss was less, bowel function recovered earlier, and hospitalization time was shorter in the laparoscopic group.\n Totally laparoscopic TME with ASP is feasible, and it is a minimally invasive technique with the benefits of much less blood loss during operation, earlier return of bowel function, and shorter hospitalization.", "Laparoscopic techniques for bowel resection have not enjoyed widespread popularity. Of concern is that long-term follow-up data of cancer specific outcomes is not yet available. The aim of our study was to examine the long-term outcome of abdominoperineal resection for cancer done laparoscopically compared with a similar cohort who underwent open surgery.\n A retrospective review was performed of all abdominoperineal resections done in our center between 1992 and 2000, comparing the cancer-specific outcomes of the laparoscopic cohort with the open cohort. The analysis was performed on an intention-to-treat basis and survival analysis was calculated by the techniques of Kaplan-Meier.\n Eighty-nine patients were reviewed. Twenty-eight operations were done laparoscopically, and 61 were open. The two groups were matched for age and stage of disease. There was no difference in mean length of overall survival (open = 30.3 months; laparoscopic = 40.8 months; P = 0.355 log rank). No difference in overall recurrence rate, isolated recurrence rate, or distant recurrence rates was seen nor was there any difference in the disease-free period. There was no difference in the number of lymph nodes harvested from the resected specimens, and the distance to the lateral margins or involvement of tumor in the lateral margins between the two groups was the same. The laparoscopic cohort did have a significantly shorter length of stay (mean, 13 days) compared with the open cohort (mean, 18 days), P = 0.008 Mann-Whitney U test.\n Laparoscopic abdominoperineal resection of the rectum for cancer does not compromise cancer-specific survival outcomes. The patients avoid a large abdominal wound, which improves cosmesis and presumably is responsible for the significantly shorter length of stay.", "Although laparoscopic colorectal surgery is attracting ever more attention, its use for curative treatment of colorectal carcinoma in particular continues to be controversial. The present study was an attempt to analyze the results of the perioperative course, oncologic quality, and preliminary long-term results.\n The data considered here were collected within the framework of a prospective, observational study initiated on August 1, 1995, and involving a total of 18 institutions in Germany and Austria. At the end of three years, the results are now being presented selectively, i.e., focusing only on abdominoperineal resection.\n A total of 116 patients underwent laparoscopic abdominoperineal resections, 98 (84.5 percent) of which were performed with curative intent. The mean operating time was 226 (confidence interval, 140-365) minutes. Seven patients (6 percent) experienced an intraoperative complication, which in more than one-half of the cases was a vascular injury involving the presacral venous plexus; the conversion rate was 3.4 percent. Postoperatively, 40 patients developed 97 complications--including those of a very minor nature--giving an overall morbidity rate of 34.4 percent. Reoperation in six patients (5.2 percent) had to be performed for an afterbleed in one-half of the cases and ileus in the other one-half. Postoperative mortality was a low 1.7 percent. In most of the curative resections, an oncologically radical operation with high transection of the inferior mesenteric artery and a complete dissection of the pelvis down to the floor was performed. The median number of lymph nodes investigated was 11.5, and there was wide fluctuation in the numbers among the individual institutions. Tumor cell dissemination occurred intraoperatively in five patients. In the meantime, 79 patients (81 percent) underwent at least one follow-up examination, the mean follow-up period being 491 days. Seven patients developed a local recurrence, and a further six patients developed distant metastases. For recurrence-free survival rate, the Kaplan-Meier estimation calculated a probability of 71 percent.\n Not all of the reservations about laparoscopic abdominoperineal resection, in particular with regard to resection with curative intent, have yet been eliminated. The present study does, however, show that a laparoscopic approach can in principle meet oncologic requirements of radicality and, with regard to the postoperative course, is associated with considerable benefits to the patient.", "A prospective comparison of laparoscopically assisted (n = 11) and conventional (n = 14) anterior resection in patients with sigmoid colon or upper rectal cancer was carried out. Patients were not randomized; age and the presence of metastases determined the type of surgery. Laparoscopic assistance was used to mobilize the tumour and minimize the abdominal incision. This was achieved in all patients and six of the 11 required only a muscle-splitting incision. The mean(s.d.) operating time was longer for laparoscopic than conventional surgery (205(31) versus 123(26) min, P = 0.01). The mean(s.d.) time to reintroduction of normal diet (2.5(0.2) versus 3.6(0.3) days, P = 0.01), postoperative analgesia requirement (2.6(0.4) versus 7.4(2.1) doses of pethidine, P = 0.01) and length of hospital stay (12.3(3) versus 14.3(6) days, P = 0.08) were less in the laparoscopic group. Histopathological examination of the resection specimens showed similar results for the two procedures. Major complications were few and occurred in a similar proportion of patients treated laparoscopically or conventionally. Laparoscopically assisted anterior resection is technically feasible, adequate tumour excision can be achieved and recovery after operation is enhanced.", "Laparoscopic abdominoperineal resection (LAPR) has not been fully evaluated as a technique in the treatment of rectal and anal cancer or inflammatory bowel disease. The purpose of our study was to evaluate the early experience with laparoscopic abdominoperineal resection at Washington University Medical Center.\n A prospective analysis was performed on the first 21 patients undergoing the procedure at Washington University Medical Center. Indications for surgery included rectal cancer (14 patients), anal squamous cell cancer (four patients), inflammatory bowel disease (two patients), and anal melanoma (one patient).\n The procedure was converted to open procedure in four patients (19%). The mean (+/-SEM) operative time and blood loss for completed and converted LAPR were 239 +/- 11 min and 424 +/- 43 ml, respectively. Postoperative hematocrit dropped a mean of 8.3% +/- 1.2% SEM; five patients required blood transfusion (24%). Wound complication occurred in four patients (19%; three perineal, one trocar site). Bowel function returned after a mean of 3 days, and mean postoperative hospital stay for the completed LAPR group was 5 days. Mild pain was experienced by 81% of patients (17/21) while 19% (4/21) noted moderate pain, usually of the perineal wound. The mean duration of patient-controlled analgesia use was 2 days. During the 1-44-month follow-up, six patients (29%) died from cancer (stage III or IV at operation) and only one patient developed local recurrence in the pelvis (5%). There were no trocar-site implants of cancer. Furthermore, there was no relationship between prior abdominal operations, the amount of blood loss, postoperative drop of hematocrit, or blood transfusion requirement and the length of hospitalization or complication rates.\n Laparoscopic abdominoperineal resection is a feasible alternative to the conventional open technique in both cancer and colitis patients.", "A technique is described for laparoscopic abdominoperineal resection (APR). Three of four such cases could be successfully completed laparoscopically. One major complication was directly related to the laparoscopic approach, an enterotomy caused by the Babcock clamp, which was discovered at the time of conversion to laparotomy for bleeding. A minor complication related to the laparoscopic procedure, subcutaneous emphysema, required no treatment. There was one postoperative death unrelated to the laparoscopic technique. The intraoperative advantage was enhanced visualization; the intraoperative disadvantages were increased operative time and cost. Postoperative advantages were earlier mobilization, oral intake, and discharge; decreased pain; and improved cosmesis. Laparoscopic APR is both feasible and safe and with more experience should prove to be cost effective.", "In laparoscopic abdominoperineal resection of the rectum (LAP-AP) an abdominal incision is completely avoided as the tumor is delivered through the perineal incision. It is our belief that the view provided in the pelvis by laparoscopy is significantly better than at laparotomy and allows excellent anatomical definition and meticulous dissection. In this study we compared the adequacy of excision of the first 12 patients undergoing LAP-AP to the last 16 patients undergoing open abdominoperineal resection (OP-AP). In all patients the procedure was carried with curative intent for adenocarcinoma and the Dukes staging and Jass score's were similar in both groups. [table: see text] The data demonstrate similar nodal harvest in both groups as well as extent of radial excision. However, two patients in the open group had microscopic radial margin involvement despite being microscopically clear at surgery. We conclude that although long-term follow-up is required to address the issue of local cancer recurrence, laparoscopic rectal dissection appears as good as open surgery and may allow a more precise assessment of excision margins.", "The aim of this study was to compare the safety and efficacy of laparoscopic abdominoperineal resection and open abdominoperineal resection for cancer.\n Records of 194 patients who underwent laparoscopic abdominoperineal resection (42 patients) or open abdominoperineal resection (152 patients) at three institutions between 1991 and 1997 were reviewed. Follow-up was through office charts, American College of Surgeons cancer registry, or telephone contact. Tumors included (laparoscopic abdominoperineal resection and open abdominoperineal resection, respectively) adenocarcinoma (86 and 92 percent), squamous (12 and 7 percent), and gastrointestinal stromal (2 and 1.4 percent) types; Stages I (17 and 26 percent), II (24 and 33 percent), III (43 and 32 percent), and IV (14 and 9 percent); and those with invasion of pelvic structures (14 and 16 percent).\n Laparoscopic abdominoperineal resection was converted to open abdominoperineal resection in 21 percent because of vessel injury (33 percent), poor exposure (22 percent), adhesions (22 percent), inguinal hernia (11 percent), or radiation fibrosis (11 percent). Perineal infections occurred more often in the laparoscopic abdominoperineal resection group (24 vs. 8 percent; P=0.02). Late stoma complications were similar. Mean hospital stay was shorter after laparoscopic abdominoperineal resection (7 vs. 12 days). Radial margins were positive in 12 percent of laparoscopic abdominoperineal resection and 12.5 percent of open abdominoperineal resection specimens. Tumor recurrence was similar for both local (19 and 14 percent) and distant (38 and 26 percent) recurrence. Survival rates were similar by Kaplan-Meier curves, with median follow-up of 19 and 24 months, respectively (P=0.22; log rank).\n Laparoscopic abdominoperineal resection can be performed safely and results in a shorter hospital stay. A randomized, prospective trial is needed to determine the long-term outcome of cancer treatment.", "Total mesorectal excision (TME) and colonic J pouch reconstruction has been widely practiced for mid- or low-rectal cancer. However, the laparoscopic version of TME has never been described.\n Five patients suffering from newly diagnosed mid- to low-rectal cancer were seen between March and July 1999. These five patients were selected for laparoscopic TME and colonic J pouch reconstruction because preoperative investigations revealed resectable tumor without extrarectal disease.\n There were three men and two women with a mean age of 61 years. The average body weight was 69 kg (range, 57-80). None of the patients had had previous abdominal operations. In all five patients, the tumor was located within 9 cm from anal verge. The average size of the main incision was 5 cm. All patients had a covering ileostomy at the end of the procedure. The mean operating time was 208 min; average blood loss was 158 ml; and mean hospital stay was 10.6 days. Three patients had Dukes' B disease and two had Dukes' C disease. The resection margins (proximal, circumferential, and distal) were all clear. There were no deaths or major complications. Two patients suffered from transient urinary retention. After ileostomy closure, the median frequency of bowel motion was twice per day at 6-month follow-up. Neither incontinence nor nocturnal soiling was reported.\n To the best of our knowledge, this is the first published series of such an operation. With good patient selection, laparoscopic-assisted TME and colonic J pouch-anal anastomosis is safe and feasible.", "Although experience of laparoscopic treatment of rectal carcinoma has been reported, there is no evidence of its oncological safety because most procedures included partial mesorectal excision or abdominoperineal excision and quality of surgery is lacking. The aim of this study was to assess the oncological results of laparoscopic total mesorectal excision with sphincter preservation for rectal carcinoma.\n From 2000 to 2003, 144 patients underwent laparoscopic total mesorectal excision with low colorectal or coloanal anastomosis for mid and low rectal adenocarcinoma. There were 88 men and 56 women, with a median age of 65 years. The tumor was located at 5.5 cm (range 1-12) from the anal verge and was classified uT1T2 in 25 cases and uT3 in 119 cases. One hundred twenty patients received preoperative radiotherapy.\n Postoperative mortality and morbidity were 1% and 34% respectively. Conversion was 14% (n = 20). Macroscopic assessment of the specimen (n = 92) showed an intact mesorectum in 88% of the cases. The distal margin and the circumferential margin were safe in 98% and 94% of the cases, respectively. A complete microscopic excision, i.e., R0 resection, was achieved in 134 cases (93%). Pathological data were similar to those of an open match group. With a median follow-up of 18 months, there was no port-site recurrence and two patients had local recurrence (1.4%). The 3-year overall and disease- free survival rates were 89% and 77%, respectively.\n A high quality of surgical excision can be achieved by the laparoscopic dissection, suggesting that this approach in treatment of rectal carcinoma is oncologically safe.", "The aim of this prospective study was to compare the surgical outcomes in patients undergoing laparoscopic assisted vs. open ultralow anterior resection (ULAR) with the creation of a colonic pouch-anal anastomosis. Patients undergoing ULAR with creation of a colonic pouch and who either had conventional open (CO) or laparoscopic assisted (LA) surgery in colorectal cancer were studied and compared. There were 33 patients, 22 in CO group and 11 in LA group. The groups were comparable for age, sex, tumour and anastomotic heights from anal verge, stage of disease, length of specimen removed and duration of surgery. Incisions were significantly shorter in the LA group (median, 9 cm vs. 16 cm, p = 0.01). Less parenteral analgesia was required in the LA group (2 days vs. 3 days, p = 0.05), but there were no significant differences in the time to passage of flatus, commencement of oral fluids or solid foods and length of hospital stay. There was no difference in morbidity or mortality. With regards to patients with Dukes A to C disease only, at a median of 12 months of follow-up, there was no patient with local or port site recurrence in the LA group. In the CO group, there was one local recurrence and two with distal metastases. In conclusion, laparoscopic assisted ULAR with colonic J pouch anal anastomosis is feasible, easy to perform and safe. It s advantages include significantly shorter incision and lower analgesic requirements postoperatively. Return of bowel function and length of hospital stay, however, are comparable to those of conventional open surgery.", "Within a 5-year period, 380 rectal carcinoma patients undergoing laparoscopic abdominoperineal excision or laparoscopic anterior resection were recruited to a multicenter study by 23 institutions in Germany and Austria. This study was initiated by the Laparoscopic Colorectal Surgery Study Group.\n One hundred forty-nine patients (39.2%) underwent abdominoperineal resection (APR), and 231 patients (60.8%) were treated by anterior resection (AR). The mean operating time was 208 min, and the conversion rate was 6.1%. Intraoperative complications, mostly vascular or bowel injuries, were observed in 22 patients (5.8%). Overall, a total of 257 postoperative complications and problems occurred in 143 patients, resulting in a morbidity rate of 37.6%. In the AR group, the anastomotic leakage rate increased as the distance of the tumor from the anal verge decreased. The perioperative mortality rate was low (6/1.6%). Most of the patients received a high transsection of the inferior mesenteric artery with radical lymph node dissection (342/90.0%); the mean number of recovered lymph nodes was 13.0, with considerable variation among the individual institutions. Intraoperative tumor cell spillage was reported in 12 patients (3.2%). Sufficient follow-up findings are available for 288 (77%) patients. To date, 19 patients have sustained a local recurrence (6.6%), and 30 (10.4%) have developed distant metastases. Within the (admittedly limited) mean follow-up of 24.8 months, the overall survival rate is 86.6%, the disease-free survival (freedom from both local recurrence and distant metastases) rate is 62.4% for APR, with the corresponding rates for AR being 71.7 and 54.8%, respectively, as established by the Kaplan-Meier function. These data show no alarmingly high recurrence rates at this time.\n In principle, laparoscopic anterior resection with curative intent generates considerably more reservations than laparoscopic abdominoperineal resection, which is technically much easier to perform.", "Laparoscopic low anterior resections using a triple stapling technique in five patients with rectal cancers (four Dukes A and one Dukes C) were performed. The location of the tumors was between 5 and 18 cm from the anal verge. For easy maneuverability, a 33-mm suprapubic port was used. In this technique, the Endo TA (the first stapler) is applied at the distal margin of the rectum to occlude the bowel. The bowel is irrigated with povidone-iodine solution and transected by an endolinear (the second) stapler. Anastomosis is completed by firing the circular (the third) stapler. The operative time was 177 +/- 28.0 minutes, estimated blood loss was 41.7 +/- 28.6 g, and flatus appeared 1.8 +/- 0.8 days after surgery. Follow-up studies have showed no local recurrence or distant metastasis. This procedure is safe and useful for performing laparoscopic low anterior resection.", "To assess the feasibility and analyze the short-term outcomes of laparoscopic intracorporeal rectal transection with double-stapling technique anastomosis, a review was performed of a prospective registry of 67 patients who underwent laparoscopic sigmoidectomy and anterior resection with intracorporeal rectal transection and double-stapling technique anastomosis between July 2001 and January 2004. Patients were divided into 3 groups: sigmoid colon/rectosigmoid carcinoma, upper rectal carcinoma, and middle/lower rectal carcinoma. A comparison was made of the short-term outcomes among the groups. The number of cartridges required in bowel transection was significantly increased in patients with middle/lower rectal carcinoma, and significant differences were observed in the length of the first stapler cartridge fired for rectal transection. Furthermore, mean operative time and blood loss were also significantly greater in the middle/lower rectum group; however, complication rates and postoperative course were similar among the 3 groups. No anastomotic leakage was observed. Laparoscopic intracorporeal rectal transection with double-stapling technique anastomosis can be performed safely without increased morbidity or mortality.", "The feasibility of laparoscopic rectal resection in patients with mid or low rectal cancer was studied prospectively with regard to quality of mesorectal excision, autonomic pelvic nerve preservation and anal sphincter preservation.\n Laparoscopic rectal excision was performed in 32 patients (21 men) with rectal carcinoma located 5 cm from the anal verge. Most patients had T3 disease and received preoperative radiotherapy. The surgical procedure was performed 6 weeks after radiotherapy and included total mesorectal excision, intersphincteric resection, transanal coloanal anastomosis with coloplasty and loop ileostomy.\n Three patients needed conversion to a laparotomy. Postoperative morbidity occurred in ten patients, related mainly to coloplasty. Macroscopic evaluation showed an intact mesorectal excision in 29 of 32 excised specimens; microscopically, 30 of the 32 resections were R0. Sphincter preservation was achieved in 31 patients. The hypogastric nerves and pelvic plexuses were identified and preserved in 24 of the 32 patients. Sexual function was preserved in ten of 18 evaluable men.\n A laparoscopic approach can be considered in most patients with mid or low rectal cancer.\n Copyright 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.", "To evaluate the feasibility of laparoscopic resection of rectal carcinoma and to compare the short-term outcome of laparoscopic procedure with conventional open surgery for rectal cancer.\n Thirty-eight patients with rectal cancer were included in a prospective non-randomized study. The patients were assigned to laparoscopic (n=18) or open (n=18) colorectal resection. Case selection, surgical technique, and clinical and pathological results were reviewed.\n The operative time was longer in laparoscopic resection group (LAP) than in open resection group (189+/-18 min vs 146+/-22 min, P<0.05). Intraoperative blood loss and postoperative complications were less in LAP resection group than in open resection group. An earlier return of bowel motility was observed after laparoscopic surgery. The overall postoperative morbidity was 5.6% in the LAP resection group and 27.8% in open resection group (P<0.05). No anastomotic leakage was found in both groups. The pathologic examination showed that the length of the resected specimen, the mean number of harvested lymph nodes in laparoscopic resection group were comparable to those in open resection group.\n Laparoscopic total mesorectal excision (TME) for rectal cancer is a feasible but technically demanding procedure. The present study demonstrates the safety of the procedure, while oncologic results are comparable to the open surgery, with a favorable short-term outcome.", "This study was designed to examine the short-term results of laparoscopy in the treatment of curative cases of rectosigmoidal and rectal carcinoma.\n A review was performed of a prospective registry of 70 patients who underwent curative laparoscopic resection for rectosigmoidal and rectal carcinoma between July 1993 and April 2001. Before 1997, only patients with early (Tis or T1) cancers located in the rectosigmoid and upper rectum that required bowel resection were candidates for laparoscopy. In 1997, we expanded the application of laparoscopy to include T2 cancers located anywhere in the rectum. Mesorectal transection was performed at least 5 cm below the tumor for rectosigmoidal and upper rectal lesions, and total mesorectal excision was performed for lower tumors. Primary anastomosis was performed by a double-stapling technique, or a handsewn coloanal anastomosis was performed. Patient demographics and outcomes were recorded prospectively.\n The median follow-up was 23 months. An anastomosis was performed in 92.9 percent of the operations. Oral intake was started on median postoperative Day 1, and the median length of hospitalization was 8 days. Two patients needed conversion to conventional open surgery. A total of 15 postoperative complications occurred in 13 patients (18.6 percent), including anastomotic leakage in 6 (8.6 percent) and bowel obstruction in 3 (4.3 percent). Reoperation was required in six patients. Two patients developed recurrence of cancer at the anastomotic site. The expected 5-year survival and disease-free survival rates were 100 and 92.1 percent, respectively.\n The findings of the present study demonstrate the feasibility and safety of laparoscopic surgery for selected patients with rectal carcinoma. Morbidity and mortality rates and oncologic outcome appear to be comparable with conventional surgery.", "To compare a consecutive series of patients who underwent laparoscopic abdomino-perineal resection (LAPR) versus conventional open abdomino-perineal resection (CAPR).\n Sixteen patients (8 females) and 11 patients (4 females) underwent LAPR and CAPR respectively.\n The median operative time was 110 (65-210) mins and 100 (80-185) mins for LAPR and CAPR respectively (P = 0.43). The median amount of blood loss were 200 (100-1000) mls and 100 (60-800) mls for LAPR and CAPR respectively. There was no significant difference in the need for post operative analgesics and time to first stoma function but the LAPR group showed significant improvement in starting fluids, diet, ambulation and discharge from hospital.\n The laparoscopic technique may be an acceptable alternative to conventional abdomino-perineal resection for the patient requiring anal resection for rectal cancer.", "This study was undertaken to compare postoperatively laparoscopic (LAR) with open (OAR) anterior resection in patients with rectosigmoid cancers.\n Forty consecutive patients were divided into two groups: 20 patients (9 males) were allocated to LAR and 20 patients (6 males) to OAR.\n Median age in the LAR group was 62 (range, 39-77) years, and in the OAR group, it was 61 (range, 43-84) years (P = 0.9). Median lengths of the distal margin of clearance beyond the tumor were 4 (range, 2-8) cm and 4.5 (range, 3-7.5) cm in the LAR and OAR groups, respectively (P = 0.35). Median numbers of lymph nodes harvested were 20 (range, 7-49) and 19 (range, 7-97) for the LAR and OAR groups, respectively (P = 0.44). Median operating times were 90 (range, 55-185) minutes and 73 (range, 40-140) minutes in the LAR and OAR groups, respectively (P = 0.08). Blood losses were 50 (range, 50-800) ml and 50 (range, 50-1,500) ml in the LAR and OAR groups, respectively. There was no intraoperative complication in either group, and no laparoscopic patient was converted to an open procedure. Median length of extraction site incision in the LAR group was 5.5 (4-13) cm, and length of incision in the OAR group was 18 (8-25) cm (P < 0.002).\n There were no significant differences between the two groups with regard to duration of parenteral analgesia, starting of fluid and solid diet after surgery, or time to first bowel movement and time to discharge from the hospital.", "Controversy continues to surround laparoscopic rectal resection for malignancy. A longer follow-up period is required to evaluate the long-term efficacy of the procedure and its impact on survival. Furthermore, no data from ongoing randomized controlled trials are yet available. The aims of this study were to compare long-term outcomes for unselected patients undergoing either laparoscopic or open rectal resection for cancer.\n A series of 124 unselected consecutive patients with rectal cancer, who underwent surgery by the same surgical team, have been included in this study. Patients with T1N0 tumors underwent local excision, and emergency cases were excluded from the study. Written consent was submitted by each patient, and inclusion in either group (laparoscopic or open) was left to the patient's choice. The laparoscopic approach was chosen by 81 patients, and 43 patients chose open surgery. All the patients underwent preoperative radiotherapy (5,040 cGy), performed in selected cases with chemotherapy (for patients younger than 70 years). The following parameters were compared between the two groups: length of the surgical specimen, clearance of the margins of the specimen, number of lymph nodes identified, local recurrence rate, incidence of distant metastases, and survival probability analysis. The mean follow-up period for both groups was 43.8 months (range, l-9 years).\n We performed 60 laparoscopic and 27 open anterior resections, as well as 21 laparoscopic and 16 open abdomino perineal resections, respectively. No mortality occurred in either group. The mean length of the resected specimens was 24.3 cm in the laparoscopic group and 23.8 cm in the open group ( p = 0.47). The mean tumor-free margin was 3.0 cm in the laparoscopic group and 2.8 cm in the open group ( p = 0.57), and the mean number of lymph nodes identified was 10.3 in the laparoscopic group and 9.8 in the open group ( p = 0.63). Of the 124 patients, 86 (52 laparoscopic and 34 open) were included in out study. We excluded patients who underwent a palliative resection (6 laparoscopic and 6 open patients) or conversion to open surgery ( n = 10) and patients who had undergone surgery in the past year ( n = 16). One laparoscopic patient was lost to follow-up evaluation, whereas three laparoscopic patients and one open patient died of causes not related to cancer. No wound recurrence was observed. The local recurrence rate after laparoscopic resection was 20.8%, as compared with 16.6% after open resection ( p = 0.687). Distant metastases occurred in 18.2% of the patients in the laparoscopic group, as compared with 21.2% in the open group ( p = 0.528). Cumulative survival probability was 0.709 after laparoscopic resection after LR and 0.606 after open resection ( p = 0.162), whereas for Dukes' stages A, B, and C in the laparoscopic group versus the open group, it was 0.875 vs 0.889 ( p = 0.392), 0.722 vs 0.584 ( p = 0.199), and 0.500 vs 0.417 ( p = 0.320), respectively. At this writing 20 laparoscopic patients (62.5%) and 20 open patients (60.6%) are disease free ( p = 0.623).\n Oncologic surgical principles were respected. Long-term outcome after laparoscopic resection of rectal cancer was comparable with that after conventional resection. We should wait to draw conclusive scientific statements until the completion of ongoing international randomized controlled trials.", "Laparoscopic resection has been shown to be a feasible option in patients with colorectal diseases. However, there have been only a few studies on laparoscopic resection for rectal neoplasm. This report aimed to evaluate the early outcomes of patients treated by laparoscopic rectal resection for neoplasm.\n From May 2000 to April 2003, 100 patients underwent laparoscopic resection for rectal neoplasm with mesorectal excision. Data on the patients' demographics, operative details, and outcomes were collected prospectively. In those with successful laparoscopic resection, comparison was made between patients with predominantly intracorporeal surgery (ICS) and those with anterior resection performed with extracorporeal rectal transection and anastomosis following intracorporeal bowel mobilization and vessel ligation (IECS).\n Sixty-six men and 34 women (median age, 69 years; range, 40-85) were included. Operations included 91 anterior resections, eight abdominoperineal resections, and one Hartmann's procedure. Conversion was required in 15 patients and no conversion was needed in patients treated by laparoscopic abdominoperineal resection. One patient died 30 days after surgery because of liver failure. Postoperative complications occurred in 31 patients. Among them, three had anastomotic leakage and all of them could be treated conservatively. Reoperation was required in one patient with intestinal obstruction. Patients with conversion were found to have significantly more blood loss, longer time to resume diet, a longer hospital stay, and a higher morbidity rate when compared to those with successful laparoscopic surgery. Among those with successful laparoscopic procedures, no difference was observed between patients with ICS (n = 57) and those with IECS (n = 28), except that a shorter incision and less blood loss were found in patients in the former group.\n Laparoscopic rectal resection with mesorectal dissection is feasible. The operating mortality and reoperation rates were low. Conversion was associated with an increased morbidity rate, leading to a longer hospital stay. Laparoscopically assisted anterior resection with rectal transection by a transverse stapler through the abdominal incision produced similar results when compared to a procedure that was predominantly intracorporeally performed.", "To compare the systemic cytokine response in patients after laparoscopic-assisted resection with those after open resection of rectosigmoid carcinoma.\n Laparoscopic resection of colorectal carcinoma is technically feasible, but objective evidence of its benefit is scarce. Systemic cytokines are accepted as markers of postoperative tissue trauma and mediators of the host immune response.\n Thirty-four patients with rectosigmoid carcinoma, without evidence of metastatic disease and suitable for laparoscopic resection, were randomized to undergo either laparoscopic (n = 17) or conventional open (n = 17) resection of the tumor. Clinical parameters were recorded. Sera were collected before surgery and at appropriate time points afterward and assayed for interleukin-1beta, tumor necrosis factor-alpha, interleukin-6, and C-reactive protein. The primary end points were the cytokine and C-reactive protein levels. Data were analyzed by intention to treat.\n The demographic data of the two groups were comparable. The clinical outcome of both groups was satisfactory, with no surgical deaths and a reasonable complication rate. Both interleukin-1beta and interleukin-6 levels peaked 2 hours after surgery, with the responses in the laparoscopic group significantly less than those in the open group. C-reactive protein levels peaked at 48 hours, and the difference was also statistically significant. Levels of tumor necrosis factor-alpha were not elevated after surgery, and there was no difference between the groups.\n Tissue trauma, as reflected by systemic cytokine response, was less after laparoscopic resection than after open resection of rectosigmoid carcinoma. The difference in the systemic cytokine response may have implications on the long-term survival.", "Laparoscopic-assisted resection for colorectal lesions is feasible, but most reported series are heterogeneous and noncomparative. The aim of this study was to investigate whether laparoscopic-assisted resection was better than open abdominoperineal resection for low rectal adenocarcinoma.\n Twenty-five (study group) of 59 consecutive patients who were considered suitable were selected for laparoscopic-assisted abdominoperineal resection based on the availability of informed consent, laparoscopic instruments, and experienced surgeons. The results in these patients were compared with the other 34 patients operated on by the open method (control group).\n The median follow-up times for the study and control groups were 30.1 and 28.3 months, respectively. The operation time was significantly longer (t-test, p < 0.001), while operative blood loss (Mann-Whitney U test, p = 0.02), postoperative analgesic requirement (Mann-Whitney U test, p = 0.02), time to resume normal diet (Mann-Whitney U test, p = 0.04), and total hospital stay (Mann-Whitney U test, p = 0.02) were significantly less in the study than in the control group. The oncological clearance, complication rate, disease-free interval, and survival were comparable in the two groups.\n Laparoscopic-assisted abdominoperineal resection allowed earlier postoperative recovery, with equal oncological clearance, morbidity, mortality, disease-free interval, and survival.", "This study compared laparoscopic with open surgery for the cure of cancer of the rectosigmoid and rectum. Results of surgery, postoperative recovery, and oncological follow-up were compared between 32 laparoscopic curative procedures (19 laparoscopic-assisted anterior resections for cancer of the rectosigmoid or upper rectum and 13 laparoscopic abdominoperineal resections for low rectal cancer) and 32 controls matched for age, UICC stage, tumor site, and type of resection who underwent open surgery during the same observation period. Morbidity was identical after laparoscopic and open resection (31.3%). Surgery was equally radical in the two groups regarding yield of lymph nodes and lateral and distal margins. Survival, recurrence, and cancer-related mortality showed no statistical differences. There was no port-site recurrence. The benefits of laparoscopic surgery were shown with a reduction in perioperative blood transfusion and earlier return of bowel function. However, the operative time was significantly increased in the laparoscopic group. This study shows that laparoscopic surgery for the cure of colorectal cancer is technically feasible, and that oncological short-term outcome does not differ from the results achieved by open techniques. However, prospective randomized trials are mandatory to evaluate the definite role of laparoscopic surgery for malignancy.", "Results of laparoscopic sphincter-preserving total mesorectal excision and colonic J-pouch reconstruction are few. The aim of this study was to examine outcomes after this procedure.\n Patients with mid or low rectal cancer underwent laparoscopic total mesorectal excision with construction of a colonic J pouch, performed by a single surgeon. The patients were evaluated prospectively.\n From March 1999 to January 2002, 44 patients underwent laparoscopic total mesorectal excision with colonic J-pouch reconstruction. There were 21 men and 23 women of median age 65.5 years. The median operating time was 180 min and median blood loss 80 ml. There was no conversion to an open procedure. The median distance of the anastomosis from the anal verge was 4 cm. No procedure-related death occurred. Four patients developed significant complications that required reoperation. With a median follow-up period of 15 months, no port-site recurrence was noted. Five patients developed distant metastases, and two had local recurrence in the pelvis. Bowel function was satisfactory at 6, 12 and 18 months after ileostomy closure.\n Laparoscopic total mesorectal excision with colonic J-pouch reconstruction is safe, with a reasonable operating time. Early results suggest satisfactory oncological control and functional outcomes.\n Copyright 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.", "Although laparoscopic resection of colorectal carcinoma improves post-operative recovery, long-term survival and disease control are the determining factors for its application. We aimed to test the null hypothesis that there was no difference in survival after laparoscopic and open resection for rectosigmoid cancer.\n From Sept 21, 1993, to Oct 21, 2002, 403 patients with rectosigmoid carcinoma were randomised to receive either laparoscopic assisted (n=203) or conventional open (n=200) resection of the tumour. Survival and disease-free interval were the main endpoints. Patients were last followed-up in March, 2003. Perioperative data were recorded and direct cost of operation estimated. Data were analysed by intention to treat.\n The demographic data of the two groups were similar. After curative resection, the probabilities of survival at 5 years of the laparoscopic and open resection groups were 76.1% (SE 3.7%) and 72.9% (4.0%) respectively. The probabilities of being disease free at 5 years were 75.3% (3.7%) and 78.3% (3.7%), respectively. The operative time of the laparoscopic group was significantly longer, whereas postoperative recovery was significantly better than for the open resection group, but these benefits were at the expense of higher direct cost. The distal margin, the number of lymph nodes found in the resected specimen, overall morbidity and operative mortality did not differ between groups.\n Laparoscopic resection of rectosigmoid carcinoma does not jeopardise survival and disease control of patients. The justification for adoption of laparoscopic technique would depend on the perceived value of its effectiveness in improving short-term post-operative outcomes.", "Laparoscopic low anterior resection for rectal cancer has never gained wide acceptance among general surgeons, mainly due to the technical difficulties encountered during pelvic dissection. It has therefore been stated that these patients should undergo open rather than laparoscopic surgery. Hand-assisted laparoscopic surgery (HALS) is a new technique that has the potential to overcome many of the existing limitations of pure laparoscopy. In the treatment of rectal cancer, HALS could reproduce an operative setting similar to that of the open approach.\n To assess the technical feasibility of hand-assisted laparoscopic low anterior resection for rectal cancer and evaluate potential benefits and drawbacks of this new procedure, a pilot study was conducted at a university hospital on 16 consecutive patients during a 12-month period. Only patients with extraperitoneal rectal cancer were included in this series. Patients' clinical data, operative time, conversion rate, complications, and early outcome measures were prospectively examined.\n There were 9 men and 7 women. The average +/- SD operation time was 238 +/- 38 min. Conversion to open surgery was never required. Ten of 16 patients were off pain medication on the third postoperative day. Eight were able to walk the day after surgery. Three minor postoperative complications were recorded. Mean postoperative stay for patients without complications was 5.6 +/- 1.4 days.\n From a technical standpoint, the reported hand-assisted procedure makes pelvic dissection during laparoscopic low anterior resection almost equivalent to the laparotomic operation. The incision for hand access that is needed with this technique does not seem to compromise the quick recovery of patients undergoing purely laparoscopic procedures.", "Laparoscopic resection for rectal cancer is controversial. Actuarial survival and local recurrence rates have not been determined.\n A prospective database containing 80 consecutive unselected laparoscopic resections of rectal cancers performed between November 1991 and 1999 was reviewed. Local recurrence was defined as any detectable local disease at follow-up assessment occurring either alone or in conjunction with generalized recurrence. The tumor node metastases (TNM) classification for colorectal cancers and the Kaplan-Meier method were used to determine staging and survival curves. The mesorectal excision technique was used during surgery.\n The median follow-up period was 31 months for patients with stages I, II, and III cancer, and 15.5 months for patients with stage IV cancer. The overall 5-year survival rate was 65.1% for all cancer stages and 72.1% for stages I, II, and III cancer. No trocar-site recurrence was observed. The overall local recurrence rate was 3.75% (3/80) for all cancer stages, and 4.3% (3/70) for stages I, II, and III cancer.\n The survival and local recurrence rates for patients with rectal cancer treated by laparoscopic mesorectal excision do not differ negatively from those in the literature for open mesorectal excision. Further validation is needed.", "Total mesorectal excision (TME) is the surgical gold standard treatment for middle and low third rectal carcinoma. Laparoscopy has gradually become accepted for the treatment of colorectal malignancy after a long period of questions regarding its safety. The purposes of this study were to examine prospectively our experience with laparoscopic TME and high rectal resections, to evaluate the surgical outcomes and oncologic adequacy, and to discuss the role of this procedure in the treatment of rectal cancer.\n Between December 1992 and December 2004, all patients who underwent elective laparoscopic sphincter preserving rectal resection for rectal cancer were enrolled prospectively in this study. Data collection included preoperative, operative, postoperative and oncologic results with long-term follow-up.\n A total of 218 patients were operated on during the study period: 142 patients underwent laparoscopic TME and 76 patients underwent anterior resection. Of the TME patients, 122 patients were operated using the double-stapling technique, and 20 patients underwent colo-anal anastomosis with hand-sewn sutures. Mean operative time was 138 min (range, 107-205), and mean blood loss was 120 ml (range, 30-350). Conversion to open surgery occurred in 26 cases (12%). Mortality rate during the first 30 days was 1%. Anastomotic leaks were observed in 10.5% of the patients. Of these, 61.9% needed reoperation and diverting stoma, and the rest were treated conservatively. Three patients had postoperative bleeding requiring relaparoscopy. Other minor complications (infection and urinary retention) occurred in 9.1% of patients. Mean ambulation time and mean hospital stay were 1.6 days (range, 1-5) and 6.4 days (range, 3-28) , respectively. Patients were followed for a mean period of 57 months. No port site metastases were observed during follow-up. The recurrence rate was 6.8 %. Overall survival rate was 67% after 5 years and 53.5% after 10 years.\n Laparoscopic anterior resection and TME with anal sphincter preservation for rectal cancer is feasible and safe. The short- and long-term outcomes reported in this series are comparable with those of conventional surgery.", "This study was conducted to investigate the feasibility of laparoscopic resection of rectal cancer and to compare early outcome data with the results of the conventional technique.\n From January 1996 to March 2002, 435 patients with primary rectal cancer were operated on at our institution. Low-risk, small rectal tumors treatable by local excision, rectal cancer recurrences, and emergency cases were excluded from the analysis. Three hundred thirty-four patients were operated on by the conventional open approach. One hundred one selected patients underwent surgery by the laparoscopic technique.\n Because of the selection process, significantly more patients with early tumor stages were operated on by laparoscopy. There were no differences in mean operation time, morbidity, mortality, or the anastomotic leakage rate; however, the need for intraoperative transfusion, mean stay in the intensive care unit, and length of hospital stay were reduced significantly.\n In terms of the intraoperative and early postoperative course, the laparoscopic resection of rectal cancer in a selected cohort of patients compares favorably with the open technique. Because follow-up time is limited to date, only very preliminary information can be given on tumor-related outcome data. However, these preliminary data appear to suggest that rectal cancer resection can be performed by laparoscopy in accordance with established principles of cancer therapy and that port-site metastases are not a relevant clinical problem. Prospective, randomized trials are required to determine whether the laparoscopic approach will play a significant role in the treatment of rectal cancer in the future.", "Laparoscopically-assisted resection for large bowel cancer is technically feasible. Sixty-six patients who had resection of the colon or rectum for cancer have been audited prospectively.\n Clinical and pathological data were collected prospectively as part of the ongoing Concord Hospital colorectal cancer project. Patients were followed up for a median of 29 months.\n In 57 of 66 patients in whom laparoscopic resection was attempted the operation was completed laparoscopically. Three patients died from perioperative myocardial infarction. The median postoperative stay was 14 days. There was a high incidence of postoperative respiratory and cardiac complications. One patient developed a port-site metastasis.\n There was no obvious benefit from laparoscopically-assisted resection of large bowel cancer in these patients.", "To analyze total mesorectal excision (TME) for rectal cancer by the laparoscopic approach during a prospective nonrandomized trial.\n Improved local control and survival rates in the treatment of rectal cancer have been reported after TME.\n The authors conducted a prospective consecutive series of 100 laparoscopic TMEs for low and mid-rectal tumors. All patients had a sphincter-saving procedure. Case selection, surgical technique, and clinical and oncologic results were reviewed.\n The distal limit of rectal neoplasm was on average 6.1 (range 3-12) cm from the anal verge. The mean operative time was 250 (range 110-540) minutes. The conversion rate was 12%. Excluding the patient who stayed 104 days after a severe fistula and reoperation, the mean postoperative stay was 12.05 (range 5-53) days. The 30-day mortality was 2% and the overall postoperative morbidity was 36%, including 17 anastomotic leaks. Of 87 malignant cases, 70 (80.4%) had a minimum follow-up of 12 months, with a median follow-up of 45.7 (range 12-72) months. During this period 18.5% (13/70) died of cancer and 8.5% (6/70) are alive with metastatic disease. The port-site metastasis rate was 1.4% (1/70): a rectal cancer stage IV presented with a parietal recurrence at 17 months after surgery. The locoregional pelvic recurrence rate was 4.2% (3/70): three rectal cancers stage III at 19, 13, and 7 postoperative months.\n Laparoscopic TME is a feasible but technically demanding procedure (12% conversion rate). This series confirms the safety of the procedure, while oncologic results are at present comparable to the open published series with the limitation of a short follow-up period. Further studies and possibly randomized series will be necessary to evaluate long-term clinical outcome in cancer patients." ]

[ "10064663", "3300570", "1599300", "11396814", "2805024", "9360203", "2061776" ]

[ "Cisapride in the control of symptoms in infants with gastroesophageal reflux: A randomized, double-blind, placebo-controlled trial.", "Cisapride for gastro-oesophageal reflux and peptic oesophagitis.", "Gaviscon and Carobel compared with cisapride in gastro-oesophageal reflux.", "Does cisapride influence cardiac rhythm? Results of a United States multicenter, double-blind, placebo-controlled pediatric study.", "Effect of cisapride on excessive regurgitation in infants.", "Cisapride in pediatric gastroesophageal reflux.", "Cisapride decreases prolonged episodes of reflux in infants." ]

[ "To evaluate the efficacy of cisapride in the treatment of uncomplicated gastroesophageal reflux in children younger than 36 months of age.\n A total of 95 patients satisfied the entry criteria and were randomly assigned to double-blind treatment with either cisapride (n = 50), 0.2 mg/kg 4 times daily, or placebo (n = 45) for 2 weeks. At the end of the 2-week treatment period, symptom diary and parental evaluation with repeat 24-hour pH study were performed.\n Sixty-eight patients completed the trial (38 in the cisapride group and 30 in the placebo group). There were no significant differences in the symptoms of crying, vomiting, or gagging; the overall symptom intensity score; or parental global evaluations. There was a significant difference (P <.03) in the percent time pH <4, the number of reflux episodes lasting more than 5 minutes, and the duration of the longest episode. No significant difference was demonstrated for the number of episodes with pH <4 or the reflux score.\n Cisapride was no better than placebo for relief of symptoms in children with uncomplicated gastroesophageal reflux. A beneficial effect was demonstrated in the cisapride group in relation to the measured parameters for esophageal acid exposure time.", "Twenty children (age range 75 days-47 months) with reflux oesophagitis entered a random double blind trial in which they received either Cisapride (Janssen Pharmaceutical Ltd), a new prokinetic agent, or an identical placebo syrup. Diagnosis of gastro-oesophageal reflux was made by measurement of intraluminal oesophageal pH combined with manometry. Oesophagitis was assessed in all patients by histological examination of mucosal specimens taken during oesophagogastroduodenoscopy. Manometry, pH test, and endoscopy with biopsy examination were repeated at the end of the treatment period. Seventeen patients completed the trial, eight of whom were taking the drug and nine the placebo. Mean total clinical score and post-prandial reflux time (% of reflux) significantly improved in patients in the group given Cisapride but not in the group given placebo. Furthermore, there was a significant improvement of the histological oesophagitis score only in the children in the group given Cisapride, whereas placebo was ineffective. It is concluded that Cisapride is a useful agent both for the relief of symptoms of gastro-oesophageal reflux and for the healing of peptic oesophagitis in infancy.", "We compared the efficacy of the prokinetic agent cisapride with that of Gaviscon (an alginate/alkaline compound) plus Carobel (carob seed flour) in the treatment of gastrooesophageal reflux (GOR). Fifty infants with confirmed GOR received either oral cisapride (0.8 mg/kg/day) or Gaviscon plus Carobel for one month in a randomised, parallel group study. Parental evaluations, diary scores, and 24 hour lower oesophageal pH recordings before and at the end of each treatment were compared. In the cisapride group 14/26 (53%) were considered better by their parents compared with 19/24 (79%) of those who received Gaviscon plus Carobel. Diary scores, range (0.00-1.00), improved in both groups with the median change being greater in the Gaviscon plus Carobel group (-0.21) than the cisapride group (-0.15). Five of 17 pH variables had significantly improved from baseline in infants who had received cisapride compared with 11/17 in those receiving Gaviscon plus Carobel. However, unpaired analysis of diary and pH data showed no significant differences between the two groups. We conclude that first line treatment of GOR with cisapride is no more effective than conventional treatment with Gaviscon plus Carobel.", "Major concerns about serious cardiac side effects underlie the recent decision by the FDA and Janssen Pharmaceutica (Titusville, NJ) to make cisapride available only through a limited access program. Concerns have grown despite the fact that most instances of prolonged QTc and other ventricular arrhythmias occurred while the drug was used concomitantly with contraindicated drugs. This study sought to analyze electrocardiograms (ECGs) from a multicenter pediatric study and to identify abnormalities in QTc interval associated with cisapride use.\n Children between 6 months and 4 years of age were enrolled if they manifested symptoms of gastroesophageal reflux not responding to medical therapy for at least 6 weeks. In 49 subjects, ECGs obtained before and after randomization to receive 0.2 mg/kg dose three times daily or placebo were reviewed independently and blindly by two pediatric cardiologists. Placebo and active drug groups were compared for QTc and for change in QTc from baseline values after 3 to 8 weeks of treatment.\n Mean QTc among patients taking the drug was 408+/-18 ms. None was higher than 450 ms. Change between baseline and subsequent QTc at 3 to 8 weeks of treatment was 2+/-20 ms.\n In our study group of children without underlying cardiac disease or electrolyte imbalance, cisapride was found to have no significant effect on cardiac electrical function compared with placebo. These results are consistent with the drug's record of exceedingly infrequent cardiac events. Because the availability of this prokinetic is threatened, its safety and the safety and efficacy of alternative treatment options (including surgery) should be studied further.", "The relevance of the upper gastrointestinal motility-stimulating effects of cisapride for the treatment of excessive regurgitation and vomiting in infants was studied in 137 patients aged less than 1 year. They were treated with placebo or with cisapride, 0.1 to 0.2 mg/kg three times daily, for up to four weeks. In a dose-dependent fashion, cisapride significantly reduced the frequency and severity of regurgitation: after four weeks of treatment at 0.15 to 0.2 mg/kg, only about 20% of infants still had moderate or severe regurgitation, compared with about two thirds of those treated with placebo. Although only a few patients were followed up, the duration of treatment (four weeks) appeared to be long enough to minimize relapse. Side effects were limited to phenomena indicative of stimulated bowel motility.", "Gastroesophageal reflux is a common condition that in infants may lead to serious complication. This study assessed the efficacy and safety of oral cisapride suspension in the treatment of children 6 weeks to 2 years old with daily regurgitant reflux.\n A randomized, prospective, double-blind, placebo-controlled clinical trial was conducted at three study sites. After a 1 week baseline assessment, 45 infants 6 weeks to 2 years old were randomized to a double-blind trial in which they received a 6 week course of cisapride (0.2 mg/kg q6h) or a placebo suspension. Efficacy was assessed with 24 hour esophageal pH monitoring, esophageal manometry, and esophageal biopsy before and after the treatment period. A diary of regurgitation frequency and severity was kept by the parents. Safety was assessed by adverse event monitoring and standard laboratory measurements.\n Compared with placebo, cisapride significantly (p < 0.05) reduced the mean duration of upright and supine reflux episodes. Compared to baseline, cisapride significantly reduced the mean duration of the longest reflux episode, and placebo increased the mean number of reflux episodes longer than 5 minutes. Cisapride was not significantly different from placebo for the following mean measurements: percent of total time pH < 4, number of reflux episodes, lower esophageal sphincter pressure, swallow pressure, regurgitation frequency or global evaluation scores.\n Cisapride is a safe, well tolerated prokinetic agent that improves the esophageal clearance of refluxed gastric acid in children under the age of 2 years.", "Twenty-nine infants (2-4 months old), with pathological gastroesophageal reflux assessed by 24-h esophageal pH monitoring, were studied. Cisapride or placebo was randomly added to positional treatment, prone-antiTrendelenburg position, which was applied to all infants. The pH monitoring was repeated after 13-16 days of treatment and revealed a significant improvement in both groups for most parameters. But the number of reflux episodes lasting longer than 5 min and the total number of reflux episodes had not decreased significantly in the placebo group. Only in the number of reflux episodes lasting longer than 5 min was improvement during treatment significantly greater in the cisapride group. This suggests cisapride both prevented reflux and improved esophageal clearance. These results suggest that in addition to other therapeutic measurements, such as positional treatment (which was previously demonstrated to be effective in this age group), cisapride might be of benefit in the treatment of gastroesophageal reflux disease." ]

[ "2799743", "1984988", "6844410", "10669276", "9062568" ]

[ "Physiotherapy after coronary artery surgery: are breathing exercises necessary?", "Comparison of incentive spirometry and intermittent positive pressure breathing after coronary artery bypass graft.", "Are maximal inspiratory breathing exercises or incentive spirometry better than early mobilization after cardiopulmonary bypass?", "Effects of conventional physiotherapy, continuous positive airway pressure and non-invasive ventilatory support with bilevel positive airway pressure after coronary artery bypass grafting.", "The effectiveness of incentive spirometry with physical therapy for high-risk patients after coronary artery bypass surgery." ]

[ "One hundred and ten men undergoing coronary artery bypass grafting took part in a prospective randomised study comparing three physiotherapy protocols. All patients were taught self supported huffing and coughing by a physiotherapist and encouraged to move about. This comprised the sole treatment for the 37 control patients (group 3). Additional physiotherapy included breathing exercises for the 35 patients in group 1 and use of an incentive spirometer for the 38 patients in group 2. Functional residual capacity (FRC) was measured daily at the bedside until the fifth postoperative day and arterial blood gas tensions were measured on the second and fourth postoperative days. After surgery patients developed a severe restrictive ventilatory defect and profound arterial hypoxaemia. There were no differences between the three groups. Mean FRC on day 2 was 1.90 litres (61% of the preoperative value), increasing to 2.32 1 by day 5 (76% of the preoperative value). The mean arterial oxygen tension was 7.37 kPa on day 2 and 8.58 kPa on day 4. Four patients in group 1, two in group 2, and five in group 3 developed a chest infection. It is concluded that the addition of breathing exercises or incentive spirometry to a regimen of early mobilisation and huffing and coughing confers no extra benefit after uncomplicated coronary artery bypass grafting.", "Fifty-two patients were randomized to receive either incentive spirometry (IS) or intermittent positive pressure breathing (IPPB) in addition to conventional chest physical therapy following coronary artery bypass grafting. Slow vital capacity and peak expiratory flow readings decreased rapidly and to an equal extent in both groups after surgery, and partly recovered by the sixth postoperative day (POP). Arterial PO2 values were similar for the groups on the first three POPs. On the POPs 2, 3, and 6, the number of chest films showing atelectases as well as the number of individual patients having atelectases revealed no statistically significant differences between the two groups. Based on the three variables studied, we consider both devices equal in efficiency after coronary surgery.", "Forty-nine adults who had undergone cardiopulmonary bypass surgery were randomly assigned to one of three exercise programs to determine if either maximal inspiratory breathing exercises or incentive spirometry offered a therapeutic advantage over early mobilization alone. After extubation, the patients started their assigned exercise programs. A physical examination and pulmonary function tests were performed preoperatively, at the start of the exercise program, and 24 and 48 hours after the start of the program. The results showed a significant decrease (approximately 50%) in lung volumes but no airflow obstruction in patients who had coronary artery bypass graft. In those patients who had valve replacement, lung volumes fell, and in addition, mild airflow obstruction occurred. A majority of patients had postoperative pulmonary complications. There were no significant differences among the exercise programs in improving lung volumes and airflow or in preventing postoperative complications. We conclude that maximal inspiratory breathing exercises or incentive spirometry, when used in addition to early mobilization, offers no therapeutic advantage over early mobilization alone after cardiopulmonary bypass surgery.", "Coronary artery bypass graft (CABG) surgery with the use of mammary arteries is associated with severe alteration of lung function parameters. The purpose of the present study was to compare the effect on lung function tests of conventional physiotherapy using incentive spirometry (IS) with non-invasive ventilation on continuous positive airway pressure (CPAP) and with non-invasive ventilation on bilevel positive airway pressure (BiPAP or NIV-2P), METHODS: Ninety-six patients were randomly assigned to 1 of 3 groups: NIV-2P (1 h/3 h), CPAP (1 h/3 h) and IS (20/2 h). Pulmonary function tests and arterial blood gases analyses were obtained before surgery. On the 1st and 2nd postoperative days, these parameters were collected together with cardiac output and calculation of venous admixture.\n For the 3 groups a severe restrictive pulmonary defect was observed during the 1st postoperative day. On the 2nd postoperative day, in opposition to IS, intensive use of CPAP and NIV-2P reduced significantly the venous admixture (P<0.001) and improved VC, FEV1 and PaO2 (P<0.01).\n We conclude that preventive use of NIV can be considered as an effective means to decrease the negative effect of coronary surgery on pulmonary function.", "The purpose of this study was to determine whether the addition of incentive spirometry (IS) to postoperative pulmonary physical therapy is more effective than physical therapy alone in reducing postoperative pulmonary complications in high-risk patients after coronary artery bypass grafting (CABG). Patients were given the spirometer and instructed in its use, as often occurs in clinical settings.\n Patients with chronic airflow limitation following CABG (N = 185) participated.\n Subjects were randomly assigned to receive either postoperative pulmonary physical therapy (breathing exercises, secretion removal, mobility) or physical therapy combined with IS.\n No difference was found between the two groups in atelectasis, spirometry, oxygen saturation, pulmonary infection, or hospital stay.\n Incentive spirometry combined with physical therapy is no more effective than postoperative physical therapy alone in reducing atelectasis for this population. Use of the spirometer, however, was not monitored, and although the study mimicked practice as it often occurs, the effectiveness of the spirometer cannot be fully evaluated." ]

[ "2205286" ]

[ "The implications of introducing the symphyseal-fundal height-measurement. A prospective randomized controlled trial." ]

[ "A total of 1639 women attending the antenatal clinic of Gentofte University Hospital, Copenhagen, during 1986-1987 was randomized into a symphyseal fundal (SF)-group and a control group. The women in the SF-group had their fundal height measured from the 29th week until delivery. The measurements were used along with the other usual screening procedures. The SF-measurements were not found helpful in the prediction of small-for-gestational-age infants and no significant differences were found between the two groups regarding the number of interventions, additional diagnostic procedures, or the condition of the newborns." ]

[ "17321948", "6208312", "20869187", "21410332", "14551000", "16626610" ]

[ "Intervening with couples: assessing contraceptive outcomes in a randomized pregnancy and HIV/STD risk reduction intervention trial.", "The efficacy of personalized audiovisual patient-education materials.", "Structured contraceptive counseling--a randomized controlled trial.", "A randomized controlled trial to promote long-term contraceptive use among HIV-serodiscordant and concordant positive couples in Zambia.", "Understanding risk: a randomized controlled trial of communicating contraceptive effectiveness.", "Communicating contraceptive effectiveness: A randomized controlled trial to inform a World Health Organization family planning handbook." ]

[ "This study assessed the contraceptive outcomes of the Partners Against Risk-Taking: A Networking, Evaluation and Research Study (PARTNERS). The PARTNERS project developed and evaluated a 3-session intervention to help young women and their male partners reduce their risk for unintended pregnancies, and HIV and other STDs.\n Participating couples were randomly assigned to the 3-session intervention or a 1-session information session for couples. Changes in psychosocial factors related to women's motivation to use contraception and relationship factors were assessed using analysis of variance with repeated measures. Changes in contraceptive outcomes were assessed using logistic regression with generalized estimating equations.\n Comparison of changes from baseline to 6 months among women who participated in the 3-session intervention with those who participated in the information session showed no significant intervention effect on reports of contraceptive use. Instead, contraceptive use increased in both conditions. Both groups exhibited similar changes in the psychosocial variable measuring the importance of avoiding pregnancy and in the relationship variable measuring women's participation in contraceptive decision making. Members of the intervention group, however, showed greater improvement in the psychosocial variable measuring positive expectations pertaining to partner's support for contraception.\n These findings raise questions for further investigation to better understand couples behavior, and whether and how to intervene with couples.", "Patient education is considered an important component of primary care medicine. The traditional methods of patient education have been physician-patient dialogue and printed handouts. This study compares the relative efficacy of pamphlets, one-to-one dialogue, and audiovisual presentations. The results indicate that the slide and sound presentation was most effective in conveying patient information.", "To evaluate the addition of structured contraceptive counseling to usual care on choice, initiation, and continuation of very effective contraception after uterine aspiration.\n We conducted a RCT of a version of the WHO Decision-Making Tool for Family Planning Clients and Providers with women having a procedure for a spontaneous or induced abortion. Our intervention provided structured, standardized counseling. We randomized women to usual care or usual care with structured counseling. Our outcomes included choosing a very effective contraceptive method and 3 months continuation.\n Fifty-four percent of all participants chose a very effective method. Women in the intervention group were no more likely to choose a very effective method (OR 0.74, 95% CI 0.44, 1.26) or to initiate their method compared to the usual care group (OR 0.65, 95% CI 0.31, 1.34). In multivariate models, structured counseling was not associated with using a very effective method at 3 months (AOR 1.06, 95% CI 0.53, 2.14).\n In this setting, structured counseling had little impact on contraceptive method choice, initiation, or continuation.\n Adding structured counseling did not increase the proportion choosing or initiating very effective contraception in a practice setting where physicians already provide individualized counseling.\n Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.", "Countries facing high HIV prevalence often also experience high levels of fertility and low contraceptive use, suggesting high levels of unmet need for contraceptive services. In particular, the unique needs of couples with one or both partners HIV positive are largely missing from many current family planning efforts, which focus on the prevention of pregnancies in the absence of reduction of the risk of HIV and other sexually transmitted infections (STIs).\n This article presents an examination of contraceptive method uptake among a cohort of HIV serodiscordant and concordant positive study participants in Zambia.\n Baseline contraceptive use was low; however, exposure to a video-based intervention that provided information on contraceptive methods and modeled desirable future planning behaviors dramatically increased the uptake of modern contraceptive methods.\n Including information on family planning in voluntary counseling and testing (VCT) services in addition to tailoring the delivery of family planning information to meet the needs and concerns of HIV-positive women or those with HIV-positive partners is an essential step in the delivery of services and prevention efforts to reduce the transmission of HIV. Family planning and HIV prevention programs should integrate counseling on dual method use, combining condoms for HIV/STI prevention with a long-acting contraceptive for added protection against unplanned pregnancy.", "To determine which of three different approaches increased women's understanding of risk of pregnancy associated with different contraceptive methods.\n We randomly assigned 461 reproductive-age women to one of three tables presenting pregnancy risk (Food and Drug Administration table with numbers, World Health Organization table with numbers and categories, or table with categories). We evaluated participant knowledge before and after being shown the assigned table.\n The most important reason for choosing a contraceptive was how well it works (53%), followed by ease of use (13%), and protection against sexually transmitted disease or human immunodeficiency virus (11%). Before looking at the tables, about half the participants knew that hormone shots are more effective than pills (48%) and that pills are more effective than condoms (57%). For these two key comparisons, the category table compared to the Food and Drug Administration table with numbers improved knowledge significantly more (37% versus 20% and 27% versus 14%; both P <.05). Compared with those assigned to the Food and Drug Administration table with numbers, significantly fewer participants assigned to the category table said the table was difficult to read (6% versus 19%; P <.01). Most participants in all three groups said their assigned table provided enough information to choose a contraceptive method.\n The table with categories communicated relative contraceptive effectiveness better than the tables with numbers. However, without being presented with numbers, participants grossly overestimated the absolute risk of pregnancy using contraceptives. A combination of categories and a general range of risk for each category may provide the most accurate understanding of both relative and absolute pregnancy risk.", "The objective of the study was to compare 3 different approaches for increasing clients' understanding of contraceptive effectiveness.\n We randomized 900 reproductive-age women in India and Jamaica to 1 of 3 charts presenting pregnancy risk.\n The most important reason for choosing a contraceptive was how well it prevents pregnancy (54%) followed by few side effects (17%). At baseline, knowledge about contraceptive effectiveness was poor. About half knew oral contraceptive pills are more effective than condoms (46%) and intrauterine devices are more effective than injectables (50%). All 3 charts improved knowledge significantly (P < .01) for these 2 questions. No chart improved knowledge better than any other (P > .05). The chart ranking contraceptive methods on a continuum was judged slightly easier to understand than the other 2 charts.\n Only with accurate understanding of pregnancy risk can clients make informed choices. Our results have already informed a global handbook for family planning providers to use the chart ranking contraceptive methods on a continuum." ]

[ "17963434", "15766629", "17683452", "10934569" ]

[ "Early intensive behavioral intervention: outcomes for children with autism and their parents after two years.", "A comparison of intensive behavior analytic and eclectic treatments for young children with autism.", "A two-year prospective follow-up study of community-based early intensive behavioural intervention and specialist nursery provision for children with autism spectrum disorders.", "Randomized trial of intensive early intervention for children with pervasive developmental disorder." ]

[ "An intervention group (n=23) of preschool children with autism was identified on the basis of parent preference for early intensive behavioral intervention and a comparison group (n=21) identified as receiving treatment as usual. Prospective assessment was undertaken before treatment, after 1 year of treatment, and again after 2 years. Groups did not differ on assessments at baseline but after 2 years, robust differences favoring intensive behavioral intervention were observed on measures of intelligence, language, daily living skills, positive social behavior, and a statistical measure of best outcome for individual children. Measures of parental well-being, obtained at the same three time points, produced no evidence that behavioral intervention created increased problems for either mothers or fathers of children receiving it.", "We compared the effects of three treatment approaches on preschool-age children with autism spectrum disorders. Twenty-nine children received intensive behavior analytic intervention (IBT; 1:1 adult:child ratio, 25-40 h per week). A comparison group (n=16) received intensive \"eclectic\" intervention (a combination of methods, 1:1 or 1:2 ratio, 30 h per week) in public special education classrooms (designated the AP group). A second comparison group (GP) comprised 16 children in non-intensive public early intervention programs (a combination of methods, small groups, 15 h per week). Independent examiners administered standardized tests of cognitive, language, and adaptive skills to children in all three groups at intake and about 14 months after treatment began. The groups were similar on key variables at intake. At follow-up, the IBT group had higher mean standard scores in all skill domains than the AP and GP groups. The differences were statistically significant for all domains except motor skills. There were no statistically significant differences between the mean scores of the AP and GP groups. Learning rates at follow-up were also substantially higher for children in the IBT group than for either of the other two groups. These findings are consistent with other research showing that IBT is considerably more efficacious than \"eclectic\" intervention.", "This prospective study compared outcome for pre-school children with autism spectrum disorders (ASD) receiving autism-specific nursery provision or home-based Early Intensive Behavioural Interventions (EIBI) in a community setting.\n Forty-four 23- to 53-month-old children with ASD participated (28 in EIBI home-based programmes; 16 in autism-specific nurseries). Cognitive, language, play, adaptive behaviour skills and severity of autism were assessed at intake and 2 years later.\n Both groups showed improvements in age equivalent scores but standard scores changed little over time. At follow-up, there were no significant group differences in cognitive ability, language, play or severity of autism. The only difference approaching significance (p = .06), in favour of the EIBI group, was for Vineland Daily Living Skills standard scores. However, there were large individual differences in progress, with intake IQ and language level best predicting overall progress.\n Home-based EIBI, as implemented in the community, and autism-specific nursery provision produced comparable outcomes after two years of intervention.", "Young children with pervasive developmental disorder were randomly assigned to intensive treatment or parent training. The intensive treatment group (7 with autism, 8 with pervasive developmental disorder not otherwise specified--NOS) averaged 24.52 hours per week of individual treatment for one year, gradually reducing hours over the next 1 to 2 years. The parent training group (7 with autism, 6 with pervasive developmental disorder NOS) received 3 to 9 months of parent training. The groups appeared similar at intake on all measures; however, at follow-up the intensive treatment group outperformed the parent training group on measures of intelligence, visual-spatial skills, language, and academics, though not adaptive functioning or behavior problems. Children with pervasive developmental disorder NOS may have gained more than those with autism." ]

[ "17608870", "19678461", "18333732", "14718327", "16238507" ]

[ "Increased satisfaction with care and lower costs: results of a randomized trial of in-home palliative care.", "Might massage or guided meditation provide \"means to a better end\"? Primary outcomes from an efficacy trial with patients at the end of life.", "Impact of an inpatient palliative care team: a randomized control trial.", "The comprehensive care team: a controlled trial of outpatient palliative medicine consultation.", "A randomized controlled trial of meditation and massage effects on quality of life in people with late-stage disease: a pilot study." ]

[ "To determine whether an in-home palliative care intervention for terminally ill patients can improve patient satisfaction, reduce medical care costs, and increase the proportion of patients dying at home.\n A randomized, controlled trial.\n Two health maintenance organizations in two states.\n Homebound, terminally ill patients (N=298) with a prognosis of approximately 1 year or less to live plus one or more hospital or emergency department visits in the previous 12 months.\n Usual versus in-home palliative care plus usual care delivered by an interdisciplinary team providing pain and symptom relief, patient and family education and training, and an array of medical and social support services.\n Measured outcomes were satisfaction with care, use of medical services, site of death, and costs of care.\n Patients randomized to in-home palliative care reported greater improvement in satisfaction with care at 30 and 90 days after enrollment (P<.05) and were more likely to die at home than those receiving usual care (P<.001). In addition, in-home palliative care subjects were less likely to visit the emergency department (P=.01) or be admitted to the hospital than those receiving usual care (P<.001), resulting in significantly lower costs of care for intervention patients (P=.03).\n In-home palliative care significantly increased patient satisfaction while reducing use of medical services and costs of medical care at the end of life. This study, although modest in scope, presents strong evidence for reforming end-of-life care.", "This article reports findings from a randomized controlled trial of massage and guided meditation with patients at the end of life. Using data from 167 randomized patients, the authors considered patient outcomes through 10 weeks post-enrollment, as well as next-of-kin ratings of the quality of the final week of life for 106 patients who died during study participation. Multiple regression models demonstrated no significant treatment effects of either massage or guided meditation, delivered up to twice a week, when compared with outcomes of an active control group that received visits from hospice-trained volunteers on a schedule similar to that of the active treatment arms. The authors discuss the implications of their findings for integration of these complementary and alternative medicine therapies into standard hospice care.", "Palliative care improves care and reduces costs for hospitalized patients with life-limiting illnesses. There have been no multicenter randomized trials examining impact on patient satisfaction, clinical outcomes, and subsequent health care costs.\n Measure the impact of an interdisciplinary palliative care service (IPCS) on patient satisfaction, clinical outcomes, and cost of care for 6 months posthospital discharge.\n Multicenter, randomized, controlled trial. IPCS provided consultative, interdisciplinary, palliative care to intervention patients. Controls received usual hospital care (UC).\n Five hundred seventeen patients with life-limiting illnesses from a hospital in Denver, Portland, and San Francisco enrolled June 2002 to December 2003.\n Modified City of Hope Patient Questionnaire, total health care costs, hospice utilization, and survival.\n IPCS reported higher scores for the Care Experience scale (IPCS: 6.9 versus UC: 6.6, p = 0.04) and for the Doctors, Nurses/Other Care Providers Communication scale (IPCS: 8.3 versus UC: 7.5, p = 0.0004). IPCS patients had fewer intensive care admissions (ICU) on hospital readmission (12 versus 21, p = 0.04), and lower 6-month net cost savings of $4,855 per patient (p = 0.001). IPCS had longer median hospice stays (24 days versus 12 days, p = 0.04). There were no differences in survival or symptom control.\n IPCS patients reported greater satisfaction with their care experience and providers' communication, had fewer ICU admissions on readmission, and lower total health care costs following hospital discharge.", "Little is known about the use of palliative care for outpatients who continue to pursue treatment of their underlying disease or whether outpatient palliative medicine consultation teams improve clinical outcomes.\n We conducted a year-long controlled trial involving 50 intervention patients and 40 control patients in a general medicine outpatient clinic. Primary care physicians referred patients with advanced congestive heart failure, chronic obstructive pulmonary disease, or cancer who had a prognosis ranging from 1 to 5 years. In the intervention group, the primary care physicians received multiple palliative care team consultations, and patients received advance care planning, psychosocial support, and family caregiver training. Clinical and health care utilization outcomes were assessed at 6 and 12 months.\n Groups were similar at baseline. Similar numbers of patients died during the study year (P =.63). After the intervention, intervention group patients had less dyspnea (P =.01) and anxiety (P =.05) and improved sleep quality (P =.05) and spiritual well-being (P =.007), but no change in pain (P =.41), depression (P =.28), quality of life (P =.43), or satisfaction with care (P =.26). Few patients received recommended analgesic or antidepressant medications. Intervention patients had decreased primary care (P =.03) and urgent care visits (P =.04) without an increase in emergency department visits, specialty clinic visits, hospitalizations, or number of days in the hospital. There were no differences in charges (P =.80).\n Consultation by a palliative medicine team led to improved patient outcomes in dyspnea, anxiety, and spiritual well-being, but failed to improve pain or depression. Palliative care for seriously ill outpatients can be effective, but barriers to implementation must be explored.", "Certain meditation practices may effectively address spiritual needs near end-of-life, an often overlooked aspect of quality of life (QOL). Among people subject to physical isolation, meditation benefits may be blunted unless physical contact is also addressed.\n To evaluate independent and interactive effects of Metta meditation and massage on QOL in people with acquired immunodeficiency syndrome (AIDS).\n Randomized controlled blinded factorial pilot trial conducted from November 2001 to September 2003.\n An AIDS-dedicated skilled nursing facility in New Haven, Connecticut.\n Fifty-eight residents (43% women) with late stage disease (AIDS or comorbidity).\n Residents were randomized to 1 month of meditation, massage, combined meditation and massage, or standard care. The meditation group received instruction, then self-administered a meditation audiocassette daily. A certified massage therapist provided the massage intervention 30 minutes per day 5 days per week.\n Changes on Missoula-Vitas QOL Index overall and transcendent (spiritual) scores at 8 weeks. Results: The combined group showed improvement in overall (p = 0.005) and transcendent (p = 0.01) scores from baseline to 8 weeks, a change significantly greater (p < 0.05) than the meditation, massage, and control groups.\n The combination of meditation and massage has a significantly favorable influence on overall and spiritual QOL in late-stage disease relative to standard care, or either intervention component alone." ]

[ "17505996", "11940128", "17206693", "17852871", "2021379", "17206698", "12889564", "9930393", "19382342", "3534041", "18831071", "8928537", "4095245", "15479685", "15861266" ]

[ "Effects of a comprehensive lifestyle modification program on quality-of-life in patients with ulcerative colitis: a twelve-month follow-up.", "Impact of a nurse-led counselling service on quality of life in patients with inflammatory bowel disease.", "Quality-of-life measurement in patients with inflammatory bowel disease receiving social support.", "A multiprofessional education programme for patients with inflammatory bowel disease: a randomized controlled trial.", "Evaluation of a psychological treatment for inflammatory bowel disease.", "Group-based intervention program in inflammatory bowel disease patients: effects on quality of life.", "A group-based patient education programme for high-anxiety patients with Crohn disease or ulcerative colitis.", "Effect of psychotherapy on the course of Crohn's disease. Results of the German prospective multicenter psychotherapy treatment study on Crohn's disease. German Study Group on Psychosocial Intervention in Crohn's Disease.", "Evaluation of a psychoeducational intervention for adolescents with inflammatory bowel disease.", "A stress management programme for inflammatory bowel disease patients.", "Profile of depression in adolescents with inflammatory bowel disease: implications for treatment.", "[Ambulatory education of patient with Crohn disease/ulcerative colitis].", "Psychotherapeutic interventions in alexithymic patients. With special regard to ulcerative colitis and Crohn patients.", "A randomised controlled trial to assess the effectiveness and cost of a patient orientated self management approach to chronic inflammatory bowel disease.", "Effects of formal education for patients with inflammatory bowel disease: a randomized controlled trial." ]

[ "To analyze the effects of a comprehensive lifestyle modification program on health-related quality-of-life, psychological distress, and clinical parameters in patients with ulcerative colitis (UC) 3- and 12 months after completion of the program.\n Sixty patients with UC in clinical remission or with low disease activity were randomly assigned to an intervention group or a usual-care control group. Comprehensive lifestyle modification consisted of a structured 60-h training program over a period of 10 weeks which included stress management training, psychoeducational elements, and self-care strategies. Quality-of-life, psychological distress, and clinical disease activity were assessed with standardized questionnaires (Inflammatory Bowel Disease Questionnaire (IBDQ); the MOS Short-Form 36 (SF-36); the Brief Symptom Inventory (BSI), and the Colitis Activity Index (CAI)) at baseline, and 3 months and 12 months after comprehensive lifestyle modification.\n Three months after comprehensive lifestyle modification, patients in the intervention group showed significantly greater improvement in the SF-36 scale physical function (p=0.0175), and a significantly greater reduction in anxiety scores, measured with the BSI (p=0.0294). Use of relaxation techniques was a significant predictor of improvement in the psychological sum score after 3 months of therapy (p=0.034). Though 80% of patients with an initial IBDQ score <170 in the intervention group showed an improvement of >16 points after 3 months, no significant effects of the intervention were found on the IBDQ scales, or on clinical disease parameters, including CAI scores, self-assessed disease activity, hospitalizations, or medical consultations.\n These results are consistent with possible short-term benefits of a comprehensive lifestyle modification program on some aspects of quality-of-life and emotional well-being, but no effects were discernable 12 months after completion of therapy. Comprehensive lifestyle modification had no effect on clinical disease variables. The generalizability of these data is limited because of the inclusion of patients with a relatively low disease activity who were interested in integrative medicine.", "Health related quality of life is impaired in patients suffering from inflammatory bowel disease. Although counselling directed towards physical and psychological morbidity is assumed to improve health related quality of life, this has never been demonstrated.\n Physical and psychological well-being were assessed using questionnaires administered to 100 out-patients in the United Kingdom suffering from inflammatory bowel disease, 50 subjects not suffering from inflammatory bowel disease and a disease control group comprising 28 patients with psoriatic arthritis. A specific nurse led counselling package was given to half the inflammatory bowel disease group and health related quality of life was assessed at baseline, 6 and 12 months.\n Inflammatory bowel disease and psoriatic arthritic patients had a range of physical disease activity, although none were severely ill during the course of the study. Medical therapy was similar in both groups throughout the duration of the trial. The mean Short Form 36 (SF-36) scores for mental health were low in inflammatory bowel disease patients; 62.9 +/- 9.1 (SD) in ulcerative colitis, 60 +/- 9.8 (SD) in Crohn's disease, compared with 72.4 +/- 7.2 (SD) in healthy controls (P < 0.05). Mean SF-36 scores for social function were also reduced in Crohn's disease patients; 68.4 +/- 10.1 (SD) in Crohn's disease, compared with 87 +/- 10.1 (SD) in healthy controls (P < 0.05). As expected, the mean SF-36 scores in psoriatic arthritic patients were significantly low 61.9 +/- 1.5 (SD) compared with 82.4 +/- 14 (SD) in healthy controls (P < 0.05). Crohn's disease patients were significantly more anxious than the other groups, mean HAD score was 10 +/- 3.7 (SD) in Crohn's disease patients and 6.86 +/- 3.5 (SD) in healthy volunteers (P < 0.05), although mean HAD scores for depression were similar in all groups. Maladaptive coping mechanisms were present in a significant proportion of Crohn's disease patients. At follow-up all aspects of psychological morbidity returned to the normal range in the Crohn's disease patients without significant change in the mean physical disease index.\n Health related quality of life can be improved over 6 months by provision of a nurse led counselling service but the effects are not sustained for 12 months.", "Crohn's disease and ulcerative colitis, referred to as inflammatory bowel diseases, affect mainly young adults and have an elevated morbidity and a negative effect on quality of life. This study aimed to compare the health-related quality of life between 2 randomized groups of patients with inflammatory bowel disease: (1) the supported group (SG), patients receiving social support for an 18-month period, and (2) the control group (CG), patients receiving no social support.\n Health-related quality of life was assessed at 4 moments with the Portuguese versions of the Medical Outcomes Study Short Form 36 and the Inflammatory Bowel Disease Questionnaire (IBDQ), both validated in Brazil.\n In the SG, using analysis of variance for repeated measures complemented by the Bonferroni test positive variations were observed (1) in the Social Aspects domain, between the first and third evaluations (P = 0.044), and (2) in the Emotional Aspects domain, between the first and second and the third and fourth evaluations (P = 0.029).\n In the sample studied, social support, measured by use of the Inflammatory Bowel Disease Questionnaire, had a positive impact on the social and emotional aspects of quality of life.", "Health-related quality of life is impaired in patients with inflammatory bowel disease and improved disease-related information can improve this situation. The aims of this study were to create an education programme that could be readily applicable at the clinic and would be suitable for newly diagnosed patients with inflammatory bowel disease, and to investigate whether the programme could improve their health-related quality of life.\n Ninety-three patients with inflammatory bowel disease in remission were included and randomized to an intervention group or a control group. The intervention group attended a multiprofessional education programme while the control group received regular information. Four questionnaires were used for measuring health-related quality of life. Both groups completed the questionnaires at baseline and after 6 months. The intervention group also completed the questionnaires after 1 month.\n No significant differences were found when comparing the two groups at 6 months. However, the multi-professional education programme was highly appreciated by the patients.\n In the present study no improvement could be seen in health-related quality of life in patients with inflammatory bowel disease after participating in an education programme in comparison with the control group. This might be due to the fact that the questionnaires were not sensitive enough or that some patients were not in clinical remission. The patients' enthusiasm for the multiprofessional education programme has led to its being part of the regular care at the clinic.", "Inflammatory bowel disease (IBD) encompasses two related gastrointestinal-tract diseases, ulcerative colitis (UC) and Crohn's Disease (CD). This study, a randomized controlled trial, compared the effectiveness of a multi-component behavioral treatment package (n = 11), which included IBD education, progressive muscle relaxation, thermal biofeedback, and training in use of cognitive coping strategies, to the effectiveness of symptom-monitoring (n = 10) as a control condition; 8 controls subsequently completed treatment. At posttreatment, the treatment group showed mean reductions on 5 symptoms, while the symptom monitoring controls showed mean reductions on all 8 symptoms. On a measure of Total Symptomatic change, the controls showed more improvement than the treated group; the treated controls at posttreatment, showed increases on all 8 symptoms. However, treated subjects perceived themselves as coping better with IBD, as feeling less IBD-related stress, and as experiencing less depression and anxiety. It is hypothesized that inherent differences may have existed between CD and UC subjects which could have led to the differences seen in treatment responses.", "Inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD) have great impact on patients' health-related quality of life (HRQOL). The aim of this study was to develop an integrated medical and psychological/ psychosocial group-based intervention program for IBD patients and to evaluate if such a program could influence the patients' HRQOL and coping abilities.\n IBD patients in remission or with low disease activity were randomized to intervention or control groups. The intervention comprised nine weekly sessions, alternating lectures, and group therapy sessions. The Inflammatory Bowel Disease Questionnaire (IBDQ) and the Sense of Coherence scale (SOC) were used to measure HRQOL and coping ability at 0, 6, and 12 months. The intervention was evaluated by a visual analog scale (VAS) and written comments by a content analysis.\n In all, 24 patients were included in the intervention group and 20 in the control group. The mean IBDQ score showed no statistically significant differences before (173.9) or after the intervention at month 6 (175.7) or at month 12 (171.8), or when comparing intervention and controls at month 12. Similarly, there were no statistically significant differences in mean SOC before or after intervention or when comparing groups. The VAS and the content analysis showed that the intervention was well appreciated by the patients.\n The group-based intervention program was feasible and highly appreciated. There were no statistically significant differences in average IBDQ or SOC over time or in comparison with controls, although a significant increase was seen in patients with short disease duration.", "The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn disease (CD) affect a person's health-related quality of life (HRQOL). IBD patients report high levels of anxiety, which correlates with the degree of perceived dissatisfaction with the information on disease-related themes provided in routine health care. The aim of this study was to evaluate changes in anxiety after participation in a group-based educational intervention for IBD patients screened for high anxiety.\n The programme consisted of 8 sessions, and 49 patients participated. Anxiety was assessed using the Hospital Anxiety and Depression (HAD) Scale at baseline and 6 months after intervention. HRQOL was assessed with the Inflammatory Bowel Disease Questionnaire (IBDQ) and the SF-36 health survey. Participant satisfaction with education was measured using a study-specific questionnaire.\n No significant change on the HAD anxiety score was found at the 6-month follow-up for those who participated in the education programme despite the fact that the participants reported they had gained better knowledge of disease-related items. Furthermore, there were no significant changes over time regarding bowel symptoms, systemic symptoms, emotional functioning and social functioning of the IBDQ or generic HRQOL (SF-36).\n IBD patients with a high anxiety level reported improved satisfaction with information about disease-related items, but did not indicate any benefits in terms of reduced anxiety or improved HRQOL after participating in the education programme, not at least in the short-term perspective. In this selected group of patients, psychosocial problems other than disease-related concerns were found that warrant other approaches.", "Our aim was to study the influence of psychotherapy in addition to a standardized corticosteroid treatment on the somatic and psychosocial course of Crohn's disease.\n In a prospective, randomized multicenter study 108 of 488 patients received either drug treatment or, in the intervention group, additionally psychotherapy in the first half of the 2-year follow-up period.\n Eighty-four patients (77.8%) completed the somatic and 81 (75%) the psychosocial follow-up. Twenty-three per cent of the control group and 30% of the psychotherapy group showed episode-free courses; 29% and 17%, respectively, underwent surgery due to failure of drug treatment. The main analysis, which was based on subranking by number, duration, and severity of relapses, failed to show significant differences between the two groups (P = 0.125). The same result was obtained for the psychosocial status after 1 year in the main target criteria depression, anxiety, psychosocio-communicative status, and quality of life.\n The confirmatory analysis did not prove significantly better courses after additional psychotherapy. There was a tendency towards fewer operations.", "Inflammatory bowel disease (IBD), comprising Crohn's disease, ulcerative colitis, and indeterminate colitis, often has its onset in adolescence. The aim of this study was to evaluate whether a psychoeducational group intervention (aiming to enhance information seeking and giving about the disease, relaxation, social competence, and positive thinking) can strengthen the coping efforts of adolescents with IBD and have a positive effect on their Health-Related Quality of Life (HRQoL).\n Adolescent IBD patients from the Emma Children's Hospital AMC and adolescent members of the Crohn and Ulcerative Colitis Association in The Netherlands, were invited to participate in The intervention study. Using reliable and valid self-report instruments the adolescent's coping styles, feelings of competence, and HRQoL were assessed before and 6-8 months after the intervention. The parents were asked to fill in the Child Behavior Check List. Linear regression analyses were performed to test whether group participation was predictive of the outcome measures while correcting for the first measurement occasion and sex.\n Forty patients responded positively to invitation to the intervention. Eighteen adolescents, however, lived too far away to attend and served as a control group. Twenty-two children were enrolled and attended in groups of four to six children in six group sessions, supervised by two psychologists. The intervention seemed to have a positive effect on: coping (predictive control, P<0.01), feelings of competence (global self-worth, P<0.05 and physical appearance, P<0.01), and HRQoL (body image, P<0.05). These results give good reason to continue this intervention study with a larger population.", "This randomized controlled trial was designed to determine whether practising stress management techniques would decrease activity and promote psychosocial functioning in inflammatory bowel disease patients. Eighty ambulatory adults received a pre-intervention interview, at which time baseline data about disease activity and psychosocial functioning were collected. They were then randomly assigned to either the intervention or control group. The intervention group received six classes on stress management which included autogenics, personal planning skills and communication techniques. All 80 subjects were followed up at 4-month intervals for 1 year by interviewers who were blind to group designation. The data collection instruments, which were used at all assessment points, comprised three questionnaires: the Crohn's Disease Activity Index (CDAI) and the Inflammatory Bowel Disease (IBD) Stress Index. These instruments produced scores which decreased with improvement in physical and psychosocial well-being. At all assessment points, both the CDAI and IBD Stress Index scores dropped significantly (P less than 0.05) from baseline in the treatment group. However, there was no significant change in the scores of the control group throughout the study year. There were no significant changes in medications at any assessment point in either group that could account for changes in the scores. The results of this study indicate that stress management techniques may have therapeutic benefits for IBD patients.", "The purpose was to determine the utility of including neurovegetative symptoms in assessments of depression in youth with inflammatory bowel disease (IBD).\n Forty-one youth with IBD and concurrent depressive symptomatology were enrolled in an intervention trial and received either 9 modules of cognitive-behavioral therapy (PASCET-PI) or treatment as usual (TAU). Youth and their primary caregivers completed the Children's Depression Inventory (CDI) at pre- (T1) and posttreatment (T2). Disease severity measures and current steroid dosage were obtained at each timepoint. Change in the individual items of the CDI was compared across groups and examined in association with change in physical illness course.\n Paired sample t-tests revealed significant changes in CDI item scores from T1 to T2 for a majority of the depressive symptoms assessed in the PASCET-PI group, but not for the TAU group. These changes did not appear to be linked to changes in disease severity and/or steroid dosage across these same timepoints.\n The inclusion of somatic items in the assessment of depression in physically ill youth is important, as these symptoms seem to respond to psychotherapeutic intervention. The present results would suggest that improvements in depressive symptomatology are not solely related to improvements in the course of IBD and that these items do reflect an important part of the profile of depressive symptoms in youth with IBD. Future research is warranted to replicate present findings and explore the generalizability of these results to other pediatric illness populations.", "Patient education has been accepted widely over the past years as a valid component of disease management in patients with chronic diseases. The aim of our study was to evaluate the effects of patient education in patients with inflammatory bowel disease. Participation in a patient education program should increase the patient's disease-related knowledge and positively influence the patient's quality of life, depression, beliefs of internal control and social activity.\n We studied 36 patients with Crohn's disease and ulcerative colitis: 18 were educated in four sessions, 18 were not educated (control-group). The following topics were presented: diagnosis, causes and course of disease; medication and surgery; nutrition and social benefits and stress management and coping with the disease.\n The effects of the program were evaluated before, immediately and three months after the intervention using questionnaires. Participants in the program showed a significant increase in knowledge after three months compared with the non-participants. There were positive, although not significant effects on psychosocial variables.\n Patient education is a valuable means to increase knowledge of disease and treatment in patient's with Crohn's disease and ulcerative colitis. Effects on psychosocial variables need to be examined on a long term basis in larger patient groups.", "Starting from the psychosomatic patients in clinico-medical wards and the inherent two primary alexithymic features \"highly limited introspective capacity' and \"very low motivation concerning dynamic psychotherapy', which we proved empirically, we describe the therapist's attitude and the three steps of supportive psychotherapy which initially represent the most indicated procedure in this patient group. In Hannover, this supportive psychotherapeutic procedure is applied by student auxiliary therapists. On the basis of our empirical findings, the effectivity of supportive psychotherapy, accomplished by students, in the alexithymic psychosomatic clinico-medical inpatients could be clearly demonstrated. Furthermore, we comment on some previous psychotherapeutic findings with regard to Crohn patients. Starting from our pretreatment and our follow-up measurements, we were able to prove that patients who were treated by both supportive psychotherapy and psychoanalytically orientated inpatient ward psychotherapy, showed remarkable improvements at all levels of the measurement techniques. Finally, we outline some clinico-psychosomatic aspects with regard to secondary alexithymia.", "We developed a patient centred approach to chronic disease self management by providing information designed to promote patient choice. We then conducted a randomised controlled trial of the approach in inflammatory bowel disease (IBD) to assess whether it could alter clinical outcome and affect health service use.\n A multicentre cluster randomised controlled trial.\n The trial was conducted in the outpatient departments of 19 hospitals with randomisation by treatment centre, 10 control sites, and nine intervention sites. For patients at intervention sites, an individual self management plan was negotiated and written information provided.\n A total of 700 patients with established inflammatory bowel disease were recruited.\n Main outcome measures recorded at one year were: quality of life, health service resource use, and patient satisfaction. Secondary outcomes included measures of enablement-confidence to cope with the condition.\n One year following the intervention, self managing patients had made fewer hospital visits (difference -1.04 (95% confidence interval (CI) -1.43 to -0.65); p<0.001) without increase in the number of primary care visits, and quality of life was maintained without evidence of anxiety about the programme. The two groups were similar with respect to satisfaction with consultations. Immediately after the initial consultation, those who had undergone self management training reported greater confidence in being able to cope with their condition (difference 0.90 (95% CI 0.12-1.68); p<0.03).\n Adoption of this approach for the management of chronic disease such as IBD in the NHS and other managed health care organisations would considerably reduce health provision costs and benefit disease control.", "Patients with inflammatory bowel disease (IBD) suffer physical dysfunction and impaired quality of life (QOL), and need frequent health care. They often lack knowledge about their disease and desire more education. Educational interventions for other chronic diseases have demonstrated reduced health care use and increased knowledge, medication adherence and QOL.\n Sixty-nine participants were randomly assigned to formal IBD education and standard of care (pamphlets and ad hoc physician education) or standard of care alone. Assessment of IBD knowledge and QOL occurred at baseline, immediately posteducation and eight weeks posteducation. Participants documented medication adherence and health care use in diaries. Patient satisfaction was assessed at the end of the study.\n The education group had higher knowledge scores (P=0.000), perceived knowledge ratings (P=0.01) and patient satisfaction (P=0.001). There was a lower rate of medication nonadherence and health care use for the education group, but the differences were not significant. QOL indices did not change. Significant correlations were found for increased health care use in patients with poorer medication adherence (P=0.01) and lower perceived health (P=0.05).\n Formal IBD patient education improves knowledge, perceived knowledge and patient satisfaction. Further study of long-term effects may better demonstrate potential benefits for QOL, medication adherence and health care use." ]

[ "402186", "4333187", "361143", "466964", "361144", "111890", "69191", "4960773", "10606475", "4571282", "10665784", "3531113" ]

[ "Hyperbaric oxygen as a radiotherapeutic adjuvant in advanced cancer of the uterine cervix: preliminary results of a randomized trial.", "Hyperbaric radiation therapy. Preliminary results of a randomized study of cancer of the urinary bladder and review of the \"oxygen experience\".", "Hyperbaric oxygen and radiotherapy: a Medical Research Council trial in carcinoma of the bladder.", "The Leeds results for radiotherapy in HBO for carcinoma of the head and neck.", "Hyperbaric oxygen and radiotherapy: a Medical Research Council trial in carcinoma of the cervix.", "Carcinoma of the cervix: results of a hyperbaric oxygen trial associated with the use of the cathetron.", "Radiotherapy and hyperbaric oxygen in head and neck cancer. Final report of first controlled clinical trial.", "Megavoltage radiotherapy in hyperbaric oxygen. A controlled trial.", "Radiation therapy with hyperbaric oxygen at 4 atmospheres pressure in the management of squamous cell carcinoma of the head and neck: results of a randomized clinical trial.", "Radiotherapy of advanced carcinoma of the oropharyngeal region under hyperbaric oxygenation. An interim report.", "Carcinoma of the cervix and the use of hyperbaric oxygen with radiotherapy: a report of a randomised controlled trial.", "Irradiation with misonidazole and hyperbaric oxygen: final report on a randomized trial in advanced head and neck cancer." ]

[ "From September 1968 to March 1974, a randomized clinical trial was carried out, using conventional fractionation, i.e., five treatments per week, in 233 patients with advanced cancers of the uterine cervix--Stages IIB, IIA, IIIB and IVA. The age limit was 70 years and all patients had medical clearance. Lymphangiography and, in some patients, an exploratory laparotomy with selective lymphadenectomy, were done prior to treatment to determine the extent of nodal disease. The staging has not been changed either by lymphangiogram or lymphadenectomy findings. A few patients with bulky Stage I and IIA lesions were entered into the trial because of extensive nodal disease demonstrated either by lymphangiogram and/or lymphadenectomy. First, the patients were grouped according to the clinical stage. The secondary stratification was according to the lymphangiogram and/or selective lymphadenectomy findings. The patients were then randomized to air or hyperbaric oxygen within each group. The patients were pressurized in a Vickers chamber at 3 atmosphere absolute, using a 20-minute soak time prior to the irradition. The size of the external beam portal was determined by the status of the nodes. The difference in absolute NED (no evidence of disease) survival rates for both groups as a whole and by stages is not statistically significant. There is no difference in the incidence of failures in the irradiated area between the HPO and air patients. There is no increase in distant metastases in the HP group. It does not seem that the HPO has had an effect on the major complications. However, there was an increase in the incidence of complications with extended fields. The addition of lymphadenectomy had increased the incidence of fatal complications, even with routine pelvic portals. The negative results of this trial with conventional fractioantion should not lead to the conclusion that HPO could not be useful with schemes using a few high dose fractions.", "nan", "In a randomized controlled clinical trial of hyperbaric oxygen in the radiotherapy of carcinoma of the bladder a total of 241 cases were contributed by four radiotherapy centres in the United Kingdom. In this trial where in each centre identical radiotherapy was employed for both oxygen and air cases, no benefit was shown with the use of hyperbaric oxygen.", "Follow-up data at five years are reported for 24 patients with squamous cell carcinoma of the head and neck, included in a randomised prospective MRC study of radiotherapy in hyperbaric oxygen (10 fractions) or air (15 or 20 fractions). Although few, the data show a significant gain in local control (P less than 0.001) and survival (P less than 0.05) with the use of hyperbaric oxygen but no increased tissue reactions or morbidity.", "In a randomized controlled clinical trial of hyperbaric oxygen in the radiotherapy of advanced carcinoma of the uterine cervix a total of 320 cases were contributed by four radiotherapy centres in the United Kingdom. The use of hyperbaric oxygen resulted in improved local control and survival. The benefit was greatest in patients under the age of 55 who presented with stage III disease. There was a slight increase in radiation morbidity but it seemed that the benefit of hyperbaric oxygen outweighed this increase in morbidity and that there was a true improvement in the therapeutic ratio.", "Since 1971, 82 patients with advanced carcinoma of the cervix have been included in a randomised clinical trial in association with the Working Party on Radiotherapy and Hyperbaric Oxygen of the Medical Research Council. External irradiation was given in 10 fractions by an unconventional schedule, either in air or HBO, and combined with three large fractions of intracavitary irradiation using the Cathetron. The results are acceptable overall, with 69% local control, 15% with tumour developing outside the treated volume and 40% survival at five years, but no improvement has been shown with HBO. Symptoms suggestive of some degree of late damage to the small bowel were present in 13% of patients, with a higher but not statistically significant, incidence in the HBO group. It is postulated that the schedule of radiotherapy used has allowed reoxygenation during treatment and that no further gain due to the use of HBO may be achieved. After a review of the results from other centres and taking into account the difficulties of treatment in HBO it is concluded that for advanced carcinoma of the cervix the addition of HBO to radiotherapy is not clinically worthwhile.", "We report the results of a prospective controlled trial of the effect of hyperbaric oxygen as an adjuvant in radiotherapy of head and neck cancer. Patients were allocated randomly to treatment in oxygen or air. The radiotherapy in both groups was identical in planning, dose, and fractionation--i.e., 3500 rads in 10 fractions in 3 weeks. There was no difference in the survival rate between the two groups. However, significantly better local tumour control was seen in the hyperbaric-oxygen group, particularly in smaller lesions; there was significantly greater need for salvage surgery in the air group. Radiation effects on normal tissue appeared somewhat greater in the oxygen series, especially on laryngeal cartilage.", "nan", "The purpose of this study was to present the results of a randomized trial evaluating HBO-4 in combination with hypofractionated radiation therapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).\n Between April 1974 and December 1975, 48 patients with locally advanced unresected SCCHN, referred for primary radiation therapy, were randomized to radiation delivered in air in two fractions of 12.65 Gy over 21 days to a total of 25.30 Gy (air, n = 25); or radiation under HBO-4 in two fractions of 11.50 Gy over 21 days to at total of 23.00 Gy (HBO-4, n = 23). The HBO-4 was administered under general anesthesia to minimize patient discomfort and potential problems with seizures associated with rapid compression to 4 atmospheres. Patients were monitored regularly by the radiation oncologists for toxicity, response, local control, and survival. The original hospital records, radiation records, and hyperbaric treatment logs were recently reviewed, and all data were entered onto a computerized database for the current analysis. The results of this trial have not previously been published.\n The air and HBO-4 arms were evenly matched with respect to age, sex, performance status, hemoglobin level, primary site, and stage of disease. Acute toxicities were acceptable with no significant differences between the two treatment arms. A trend toward excess severe late complications were noted in the hyperbaric arm (12 vs 7). There was a highly significant difference in complete clinical responses between the two arms, with 21/25 in complete dinical responses in the HBO-4 arm compared with 13/25 in complete clinical responses in the air arm, and a statistically insignificant trend toward improved 5-year local control in the HBO-4 arm (29% vs 16%). There were no significant differences between the two arms with respect to 5-year survival, distant metastasis, or second primary tumors.\n Long-term outcome from this historical randomized trial demonstrate substantial improvements in response rate with the use of HBO-4. The hypofractionation scheme used in the trial resulted in relatively low local control and high complication rates in this group of patients with very advanced SCCHN. However, these results support the theory that radioresistant hypoxic cells limit the radiocurability of SCCHN. Further investigations addressing the hypoxic cell problem with hypoxic cytotoxins or hypoxic cell sensitizers in combination with radiation therapy using more conventional fractionation schemes are warranted.", "nan", "A randomised controlled trial of hyperbaric oxygen in the radiotherapy of Stage IIb and III carcinoma of cervix was performed between 1971 and 1980. Apart from an abstract giving an interim report in 1977, results have not been published.\n In a four arm study, 335 patients were randomised to treatment in 10 or 28 fractions, in hyperbaric oxygen or in air. Data is available concerning 327 cases and this has been analysed.\n There was no advantage in tumour control shown with the use of hyperbaric oxygen. There was evidence for an increase in late radiation morbidity when treatment was given in hyperbaric oxygen rather than in air and when, using 10 fractions, a total dose of 45 rather than 40 Gy was achieved. For late intestinal morbidity, the fractionation sensitivity (alpha/beta ratio) was calculated to be 4.3 Gy and the steepness of the dose response curve (gamma50) to be 2.6.\n Hyperbaric oxygen gave no benefit in the treatment of patients with stage IIb and III carcinoma of the cervix treated with radiotherapy using two fractionation regimes. Important data regarding late radiation morbidity has been revealed.", "One hundred and thirty patients with locally advanced squamous carcinoma of the head and neck were treated in a prospective randomized trial to compare conventional irradiation (63.00 Gy in 30 fractions) with a combination sensitizer regimen of misonidazole and hyperbaric oxygen. The drug (2.0 gm/m2) was given with each of six fractions of 6.0 Gy in hyperbaric oxygen at 3 ATA. The results support a previous study and favor the combination at 1 year at better than the 10% level. This regimen could be useful for bulky primary or nodal disease." ]

[ "2060439", "1936479", "8720537", "7623902", "7821128", "12682825", "11300445", "11257323", "8908377", "10333912", "12679450", "12852706", "10421233", "12453903", "2534084", "1936478", "11375358", "11678974", "11092289", "9428831", "7843470", "9516221", "9727896", "9526970" ]

[ "Double-blind evaluation of efficacy and tolerability of metformin in NIDDM.", "Prospective randomized two-years clinical study comparing additional metformin treatment with reducing diet in type 2 diabetes.", "The effects of high- and medium-dose metformin therapy on cardiovascular risk factors in patients with type II diabetes.", "Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group.", "Therapeutic comparison of metformin and sulfonylurea, alone and in various combinations. A double-blind controlled study.", "Six-month efficacy of benfluorex vs. placebo or metformin in diet-failed type 2 diabetic patients.", "Improved endothelial function with metformin in type 2 diabetes mellitus.", "The short-term effect of a switch from glibenclamide to metformin on blood pressure and microalbuminuria in patients with type 2 diabetes mellitus.", "Metformin's effects on glucose and lipid metabolism in patients with secondary failure to sulfonylureas.", "Effect of repaglinide addition to metformin monotherapy on glycemic control in patients with type 2 diabetes.", "Effect of pioglitazone compared with metformin on glycemic control and indicators of insulin sensitivity in recently diagnosed patients with type 2 diabetes.", "Multicenter, randomized, double-masked, parallel-group assessment of simultaneous glipizide/metformin as second-line pharmacologic treatment for patients with type 2 diabetes mellitus that is inadequately controlled by a sulfonylurea.", "Effects of gliclazide versus metformin on the clinical profile and lipid peroxidation markers in type 2 diabetes.", "Rosiglitazone but not metformin enhances insulin- and exercise-stimulated skeletal muscle glucose uptake in patients with newly diagnosed type 2 diabetes.", "Effect of glycaemic control, metformin and gliclazide on platelet density and aggregability in recently diagnosed type 2 (non-insulin-dependent) diabetic patients.", "Comparative three-month study of the efficacies of metformin and gliclazide in the treatment of NIDD.", "The synergistic effect of miglitol plus metformin combination therapy in the treatment of type 2 diabetes.", "Improved glycaemic control by addition of glimepiride to metformin monotherapy in type 2 diabetic patients.", "Nateglinide alone and in combination with metformin improves glycemic control by reducing mealtime glucose levels in type 2 diabetes.", "Efficacy of 24-week monotherapy with acarbose, metformin, or placebo in dietary-treated NIDDM patients: the Essen-II Study.", "One year comparative trial of metformin and glipizide in type 2 diabetes mellitus.", "Efficacy and metabolic effects of metformin and troglitazone in type II diabetes mellitus.", "Irreversibility of the defect in glycogen synthase activity in skeletal muscle from obese patients with NIDDM treated with diet and metformin.", "Metformin decreases food consumption and induces weight loss in subjects with obesity with type II non-insulin-dependent diabetes." ]

[ "To test the efficacy and tolerability of metformin.\n An 8-mo double-blind placebo-controlled parallel-group trial was performed at University hospital diabetic clinics on 60 patients with non-insulin-dependent diabetes mellitus (NIDDM) treated by diet alone. Metformin was administered and built up to a maximum dosage of 1 g three times daily.\n Mean HbA1 fell from 11.7 +/- 0.4 to 10.3 +/- 0.4% (means +/- SE) on metformin but rose from 11.8 +/- 0.4 to 13.3 +/- 0.4% on placebo (P less than 0.001). Final mean fasting blood glucose was 5.1 mM lower with metformin than placebo (P less than 0.001). No other biochemical variable differed significantly, and weight did not change. A favorable glycemic response was not restricted to the obese. The mean final dosage of metformin was 1.7 +/- 0.1 g and was well tolerated.\n Metformin achieved a 23% lower mean HbA1 than placebo without weight gain or significant unwanted effects.", "After a 2 weeks hospital treatment with a strong dietary regime 100 patients not sufficiently controlled (blood glucose fasting 120-180, pp 180-250 mg/100 ml), were randomly allocated to a purely dietary therapy or to a diet-metformin-combination for a duration of 2 years. After 1 and 2 years the patients were rehospitalized for an accurate evaluation. Additionally, HbA1 was controlled every 3 months, in case of problems after shorter periods. If HbA1 exceeded 10% for more than 4 weeks the patients were hospitalized for 5 days in order to decide whether the deterioration of metabolic control was due to the patients' non-compliance to treatment or to treatment failure. During 2 years of observation 30 patients were withdrawn from the treatment for external reasons. 13 patients (6 diet, 7 metformin + diet) were non-compliant with diet, 3 further patients were not metformin-compliant. Therapeutic failures were confirmed in 4 diet patients, none of the metformin + diet patients failed to respond to treatment. After excluding all these patients there was a group of 29 diet and 25 metformin + diet patients with a similar development of criteria of metabolic control during 2 years. Lipid levels deteriorated in the dietary group more noticeably than during additional metformin treatment although without reaching a statistically significant level, though. The stimulated C-peptide was significantly reduced by metformin in comparison to diet only, which supports former findings of an insulin-lowering effect of the drug.", "To study the dose response to metformin in type II diabetic patients.\n Type II diabetic patients with a BMI > 25 were treated with 3,000 mg/day (n = 27), 1,500 mg/day (n = 25), or placebo (n = 23) for 6 months. Venous blood samples were taken at each visit for plasma glucose and insulin, HbA1c, triglyceride and cholesterol, plasminogen activator inhibitor-1 (PAI-1) antigen and activity, tissue plasminogen activator (tPA), and euglobulin clot lysis time (ECLT). Blood pressure was recorded at each visit.\n There were no changes in BMI or blood pressure. Blood glucose fell (mean) by 3.6 mmol/l in the high-dose and 0.5 mmol/l in the low-dose group over the 6-month study (P < 0.001 and NS compared with placebo). HbA1c and plasma insulin fell in both treatment groups (HbA1c, P < 0.001; insulin, P < 0.003 and 0.03). There was a fall in triglyceride (P < 0.05) and cholesterol (P < 0.008) with high-dose metformin. PAI-1 antigen and activity fell by approximately 20% of baseline in both treatment groups (PAI-1 antigen high dose, P < 0.01; PAI-1 antigen low dose, P < 0.002: PAI-1 activity high and low dose, P < 0.003). There were significant falls in total tPA in both groups (P < 0.004), but the overall effect was a fall in ECLT (P < 0.03).\n The results indicate that metformin has favorable effects on cardiovascular risk factors associated with type II diabetes. The effects on glycemic control and lipids are dose-dependent, while the enhanced fibrinolytic response is independent of the doses used.", "Sulfonylurea drugs have been the only oral therapy available for patients with non-insulin-dependent diabetes mellitus (NIDDM) in the United States. Recently, however, metformin has been approved for the treatment of NIDDM.\n We performed two large, randomized, parallel-group, double-blind, controlled studies in which metformin or another treatment was given for 29 weeks to moderately obese patients with NIDDM whose diabetes was inadequately controlled by diet (protocol 1: metformin vs. placebo; 289 patients), or diet plus glyburide (protocol 2: metformin and glyburide vs. metformin vs. glyburide; 632 patients). To determine efficacy we measured plasma glucose (while the patients were fasting and after the oral administration of glucose), lactate, lipids, insulin, and glycosylated hemoglobin before, during, and at the end of the study.\n In protocol 1, at the end of the study the 143 patients in the metformin group, as compared with the 146 patients in the placebo group, had lower mean (+/- SE) fasting plasma glucose concentrations (189 +/- 5 vs. 244 +/- 6 mg per deciliter [10.6 +/- 0.3 vs. 13.7 +/- 0.3 mmol per liter], P < 0.001) and glycosylated hemoglobin values (7.1 +/- 0.1 percent vs. 8.6 +/- 0.2 percent, P < 0.001). In protocol 2, the 213 patients given metformin and glyburide, as compared with the 210 patients treated with glyburide alone, had lower mean fasting plasma glucose concentrations (187 +/- 4 vs. 261 +/- 4 mg per deciliter [10.5 +/- 0.2 vs. 14.6 +/- 0.2 mmol per liter], P < 0.001) and glycosylated hemoglobin values (7.1 +/- 0.1 percent vs. 8.7 +/- 0.1 percent, P < 0.001). The effect of metformin alone was similar to that of glyburide alone. Eighteen percent of the patients given metformin and glyburide had symptoms compatible with hypoglycemia, as compared with 3 percent in the glyburide group and 2 percent in the metformin group. In both protocols the patients given metformin had statistically significant decreases in plasma total and low-density lipoprotein cholesterol and triglyceride concentrations, whereas the values in the respective control groups did not change. There were no significant changes in fasting plasma lactate concentrations in any of the groups.\n Metformin monotherapy and combination therapy with metformin and sulfonylurea are well tolerated and improve glycemic control and lipid concentrations in patients with NIDDM whose diabetes is poorly controlled with diet or sulfonylurea therapy alone.", "To assess and compare the therapeutic efficacy and safety of metformin (M) and sulfonylurea (glyburide, G), alone and in various combinations, in patients with non-insulin-dependent diabetes mellitus (NIDDM).\n Of 165 patients (fasting blood glucose [FBG] > or = 6.7 mmol/l) initially treated with diet alone, 144 (FBG still > or = 6.7 mmol/l) were randomized to double-blind, double-dummy controlled treatment with M, G, or primary combination therapy (MG). The dose was titrated, with FBG < 6.7 mmol/l as target, using, at most, six dose levels. The first three dose levels comprised increasing single-drug therapy (M or G) or primary combination at increasing but low dosage (MGL), and the second three levels were composed of various high-dose combinations, i.e., add-on therapy (M/G or G/M) and primary combination escalated to high dosage (MGH). Medication was maintained for 6 months after completed dose titration.\n The FBG target was achieved in 9% of patients after diet alone. Single-drug therapy was insufficient in 36% and MGL in 25% (NS) of the randomized patients. There was further improvement in glucose control by the high-dose combinations. Mean FBG +/- SE was reduced (P = 0.001) from 9.1 +/- 0.4 to 7.0 +/- 0.2 mmol/l in those maintained on single-drug treatment or low-dose primary combination. Those treated with different high-dose combinations had a large mean FBG reduction, from 13.3 +/- 0.8 to 7.8 +/- 0.6 mmol/l. HbA1c levels showed corresponding reductions, and glycemic levels rose after drug discontinuation. Fasting C-peptide rose during treatment with G and MGL but not with M, while fasting insulin was not significantly changed. Meal-stimulated C-peptide and insulin levels were unchanged by M but increased by G and, to a lesser extent, by MGL. There were no significant insulin or C-peptide differences between the different high-dose combinations (M/G, G/M, and MGH). Body weight did not change following treatment with M or combination but increased by 2.8 +/- 0.7 kg following G alone. Blood pressure was unchanged. Overall effects on plasma lipids were small, with no significant differences between groups. Drug safety was satisfactory, even if the reporting of (usually modest) adverse events was high; the profile, but not the frequency, differed between groups.\n Dose-effect titrated treatment with either metformin or glyburide promotes equal degrees of glycemic control. The former, but not the latter, is able to achieve this control without increasing body weight or hyperinsulinemia. Near-normal glycemia can be obtained by a combination of metformin and sulfonylurea, even in advanced NIDDM.", "Six-month efficacy of benfluorex (Mediator) (150-450 mg/day) was assessed in a double-blind multicenter study vs. placebo or metformin hydrochloride (850-2550 mg/day). After a 2-month run-in period of strict dieting, 722 type 2 diabetic patients were randomized (1:2:2) to receive placebo (n=144), benfluorex (n=294) or metformin (n=284). After a 5-week dose-finding phase, the efficacy of benfluorex was compared with that of placebo (test for difference, main analysis) and metformin (non-inferiority test, secondary analysis) during a 6-month fixed-dose treatment. At entry after strict dieting, there was no difference between groups for HbA(1C) (placebo, 7.4%+/-1.5%; benfluorex, 7.7%+/-1.6%; metformin, 7.8%+/-1.6%) and fasting plasma glucose (FPG; placebo, 9.7+/-2.3 mmol/l; benfluorex, 10.0+/-2.0 mmol/l; metformin, 10.2+/-2.5 mmol/l). At the end of the dose-finding phase, mean doses were 2.71 tablets/day for placebo group, 2.65 tablets/day for benfluorex (397.5 mg/day) and 2.50 tablets/day for metformin (2125 mg/day). At the end of treatment, HbA(1C) level decreased by 0.60% ( p<0.001) in benfluorex patients while it increased by 0.50% ( p<0.001) with placebo (intent-to-treat analysis). The mean endpoint difference was -0.86% (SE, 0.17%; p<0.001). Mean endpoint difference in HbA(1C) between benfluorex and metformin was 0.28% (SE, 0.12%) [90% CI, 0.07 to 0.48] (non-inferiority test, p=0.037). Treatment with benfluorex was well tolerated; 39% of these patients reported one or more emergent adverse events (compared to 38% on placebo and 43% on metformin) and only two patients suffered a treatment-related, serious adverse event. This study demonstrates that benfluorex: (1) significantly reduces HbA1C and fasting plasma glucose when compared to placebo; (2) has a good safety profile; and (3) has relatively lower potency compared to metformin, although the non-inferiority test (equivalence limit for HbA(1C) of 0.5%) was significant.", "This study was designed to assess the effect of metformin on impaired endothelial function in type 2 diabetes mellitus.\n Abnormalities in vascular endothelial function are well recognized among patients with type 2 (insulin-resistant) diabetes mellitus. Insulin resistance itself may be central to the pathogenesis of endothelial dysfunction. The effects of metformin, an antidiabetic agent that improves insulin sensitivity, on endothelial function have not been reported.\n Subjects with diet-treated type 2 diabetes but without the confounding collection of cardiovascular risk factors seen in the metabolic syndrome were treated with metformin 500 mg twice daily (n = 29) or placebo (n = 15) for 12 weeks. Before and after treatment, blood flow responses to intraarterial administration of endothelium-dependent (acetylcholine), endothelium-independent (sodium nitroprusside) and nitrate-independent (verapamil) vasodilators were measured using forearm plethysmography. Whole-body insulin resistance was assessed on both occasions using the homeostasis model (HOMA-IR).\n Subjects who received metformin demonstrated statistically significant improvement in acetylcholine-stimulated flows compared with those treated with placebo (p = 0.0027 by 2-way analysis of variance), whereas no significant effect was seen on nitroprusside-stimulated (p = 0.27) or verapamil-stimulated (p = 0.40) flows. There was a significant improvement in insulin resistance with metformin (32.5% reduction in HOMA-IR, p = 0.01), and by stepwise multivariate analysis insulin resistance was the sole predictor of endothelium-dependent blood flow following treatment (r = -0.659, p = 0.0012).\n Metformin treatment improved both insulin resistance and endothelial function, with a strong statistical link between these variables. This supports the concept of the central role of insulin resistance in the pathogenesis of endothelial dysfunction in type 2 diabetes mellitus. This has important implications for the investigation and treatment of vascular disease in patients with type 2 diabetes mellitus.", "Renal hyperfiltration and albuminuria have a deleterious effect on kidney function. Therefore, we studied the effect of metformin on blood pressure, renal hemodynamics, and microalbuminuria in type 2 diabetic patients.\n A clinical trial was designed in type 2 diabetic patients with incipient nephropathy. All patients were below the age of 65, normotensive, and without evidence of malignant, hepatic, or cardiovascular disorders. They were randomly allocated to receive glibenclamide or metformin. At baseline and 12 weeks thereafter we measured body mass index (BMI), serum insulin, blood glucose, lipid profile, glycosylated hemoglobin, blood pressure, glomerular filtration rate, renal plasma flow, and urine albumin.\n We studied 23 patients in the glibenclamide group and 28 in the metformin group. There was no difference in baseline variables between the groups. Metabolic control was obtained in both groups. In the metformin group, all the following variables decreased: microalbuminuria was reduced by a mean of 24.2 mg/day (p = 0.008); systolic and diastolic blood pressure by a mean of 5.3 mmHg (p = 0.002) and 3.93 mmHg (p = 0.009), respectively; insulin levels by an average of 11.8 microIU/mL (p = 0.001), and total cholesterol levels and triglycerides by an average of 0.45 and 0.18 mmol/L, respectively. Insulin resistance measured by the homeostasis model decreased more in the metformin group than in the glibenclamide group. Patients treated with glibenclamide had an increase in HDL cholesterol of 0.082 mmol/L (p = 0.01).\n Metformin significantly decreased the urine albumin excretion rate with none of the expected changes in renal hemodynamics, probably due to its favorable effects on blood pressure, lipid profile, metabolic control, and insulin resistance.", "To compare results obtained with metformin versus those obtained with DNA-recombinant insulin in obese patients with NIDDM suffering from secondary failure to sulfonylureas.\n We conducted an open, prospective, randomized, and comparative study comprising a total of 60 patients selected and placed in two parallel groups. We had previously confirmed that the subjects had secondary failure to high doses of sulfonylureas. The initial metformin dosage was a single 850 mg tablet, and the dosage was increased to two or three tablets depending on the patient's metabolic changes. The initial dosage of DNA-recombinant insulin was 24 U, subcutaneously administered and divided into two portions: two-thirds at around 8:00 A.M., before breakfast, and the remaining third at 8:00 P.M., before dinner. The dosage was adjusted based on the patient's clinical and metabolic response.\n The initial average glucose value for the metformin group was 269.1 +/- 32.2 mg/dl, decreasing by the end of the study to 159.7 +/- 30.5 mg/dl. For the insulin group, these figures went from 270.7 +/- 24.0 mg/dl at the beginning of the study to 134.8 +/- 26.7 mg/dl. This decrease correlates with the reduction in glycosylated hemoglobin from 12.8 to 8.9% for the first group and from 12.3 to 8.2% for the second, as well as with the reduction in triglyceride values from 230.3 to 183.1 mg/dl and from 218.4 to 186.3 mg/dl, respectively. The BMI (27.5-26.4), blood pressure (systolic from 145.7-132.1 mmHg, diastolic from 90.3-84.8 mmHg), and total cholesterol levels (235-202 mg/dl) decreased in only the metformin group.\n Metformin is an effective, safe, and well-tolerated treatment that improves metabolic control and favorably modifies secondary clinical alterations due to insulin resistance, such as arterial hypertension, overweight, and hyperlipidemia, in obese patients with NIDDM suffering from secondary failure to sulfonylureas.", "To compare the effect of repaglinide in combination with metformin with monotherapy of each drug on glycemic control in patients with type 2 diabetes.\n A total of 83 patients with type 2 diabetes who had inadequate glycemic control (HbA1c > 7.1%) when receiving the antidiabetic agent metformin were enrolled in this multicenter, double-blind trial. Subjects were randomized to continue with their prestudy dose of metformin (n = 27), to continue with their prestudy dose of metformin with the addition of repaglinide (n = 27), or to receive repaglinide alone (n = 29). For patients receiving repaglinide, the optimal dose was determined during a 4- to 8-week titration and continued for a 3-month maintenance period.\n In subjects receiving combined therapy, HbA1c was reduced by 1.4 +/- 0.2%, from 8.3 to 6.9% (P = 0.0016) and fasting plasma glucose by 2.2 mmol/l (P = 0.0003). No significant changes were observed in subjects treated with either repaglinide or metformin monotherapy in HbA1c (0.4 and 0.3% decrease, respectively) or fasting plasma glucose (0.5 mmol/l increase and 0.3 mmol/l decrease respectively). Subjects receiving repaglinide either alone or in combination with metformin, had an increase in fasting levels of insulin between baseline and the end of the trial of 4.04 +/- 1.56 and 4.23 +/- 1.50 mU/l, respectively (P < 0.02). Gastrointestinal adverse events were common in the metformin group. An increase in body weight occurred in the repaglinide and combined therapy groups (2.4 +/- 0.5 and 3.0 +/- 0.5 kg, respectively; P < 0.05).\n Combined metformin and repaglinide therapy resulted in superior glycemic control compared with repaglinide or metformin monotherapy in patients with type 2 diabetes whose glycemia had not been well controlled on metformin alone. Repaglinide monotherapy was as effective as metformin monotherapy.", "Pioglitazone, a thiazolidinedione, improves glycemic control primarily by increasing peripheral insulin sensitivity in patients with type 2 diabetes, whereas metformin, a biguanide, exerts its effect primarily by decreasing hepatic glucose output. In the first head-to-head, double-blind clinical trial comparing these two oral antihyperglycemic medications (OAMs), we studied the effect of 32-wk monotherapy on glycemic control and insulin sensitivity in 205 patients with recently diagnosed type 2 diabetes who were naive to OAM therapy. Subjects were randomized to either 30 mg pioglitazone or 850 mg metformin daily with titrations upward to 45 mg (77% of pioglitazone patients) and 2550 mg (73% of metformin patients), as indicated, to achieve fasting plasma glucose levels of less than 7.0 mmol/liter (126 mg/dl). Pioglitazone was comparable to metformin in improving glycemic control as measured by hemoglobin A1C and fasting plasma glucose. At endpoint, pioglitazone was significantly more effective than metformin in improving indicators of insulin sensitivity, as determined by reduction of fasting serum insulin (P = 0.003) and by analysis of homeostasis model assessment for insulin sensitivity (HOMA-S; P = 0.002). Both OAM therapies were well tolerated. Therefore, pioglitazone and metformin are equally efficacious in regard to glycemic control, but they exert significantly different effects on insulin sensitivity due to differing mechanisms of action. The more pronounced improvement in indicators of insulin sensitivity by pioglitazone, as compared with metformin monotherapy in patients recently diagnosed with type 2 diabetes who are OAM-naive, may be of interest for further clinical evaluation.", "Many patients with type 2 diabetes mellitus (DM) with inadequate long-term blood glucose control with sulfonylurea or metformin monotherapy require additional treatment. The synergistic effects of combining glipizide with metformin on glucose control may be realized by treating the primary effects of type 2 DM, impaired insulin secretion, and insulin resistance.\n This study assessed therapy with glipizide/metformin combination tablets in patients with type 2 DM that is uncontrolled by at least half the maximum labeled daily dose of a sulfonylurea.\n In this multicenter, double-masked, parallel-group, active-controlled study, patients were randomized to receive glipizide 30-mg, metformin 500-mg, or glipizide/metformin 5/500 mg tablets for 18 weeks (metformin and glipizide/metformin doses were titrated to achieve blood glucose control). Maximum total daily doses were glipizide 30 mg, metformin 2000 mg, and glipizide/ metformin 20/2000 mg.\n A total of 247 patients were included in the study. The mean (SD) age was 56.2 (10.1) years; 61.5% of patients were male; 70.0% were white, 15.8% were Hispanic/Latino, 13.0% were black, and 1.2% were Asian/Pacific Islanders. Patients were, on average, obese (mean [SD] body mass index, 31.3 [4.7] kg/m2), had moderate to severe hyperglycemia (mean [SD] glycated hemoglobin [HbA1c], 8.7% [1.1]), and had a mean (SD) DM duration of 6.5 (4.9) years. Glipizide/ metformin tablets controlled the HbA1c level more effectively than did either glipizide or metformin monotherapies (mean treatment differences, in favor of glipizide/ metformin, of -1.06% and -0.98%, respectively, P < 0.001). At study end, an HbA1c level < 7.0% was achieved in approximately 4-fold more patients who were treated with glipizide/metformin (36.3%) compared with glipizide (8.9%) or metformin (9.9%) monotherapies. Glipizide/metformin tablets also reduced the fasting plasma glucose (FPG) level and the 3-hour postprandial glucose area under the concentration-time curve more effectively than did either monotherapy, without increasing the fasting insulin level. The greater blood glucose control with glipizide/ metformin tablets was achieved at a mean daily dose of glipizide/metformin 17.5/1747 mg, compared with mean doses of glipizide 30.0 mg or metformin 1927 mg. Treatments were well tolerated, with a low incidence of symptoms of hypoglycemia evidenced by a fingerstick blood glucose measurement < or = 50 mg/dL in the combination group (12.6%); 1 patient discontinued the study treatment for this reason. No patient required medical assistance for hypoglycemia.\n Glipizide/metformin tablets were more effective than either glipizide or metformin monotherapy in controlling HbA1c and in reducing FPG compared with baseline in patients with blood glucose that was uncontrolled with previous sulfonylurea treatment. In addition, patients receiving glipizide/ metformin were more likely to achieve an HbA1c level < 7.0%. These results were consistent with the synergistic effects on insulin resistance and beta cell dysfunction. Glipizide/metformin was well tolerated, with a low incidence of hypoglycemia.", "The sulfonylurea gliclazide and the biguanide metformin have different mechanisms to reduce glycemia. We performed a randomized study to compare these two agents with respect to glycemic control and effects on lipid peroxidation markers in 36 adult patients with type 2 diabetes. Both agents significantly decreased glycosylated hemoglobin ([HbA1c] P < .05), fructosamine (P < .05), and the glucose-excursion curve during the oral glucose tolerance test ([OGTT] P < .01). With regard to the insulin curve during this test, no significant change was observed with metformin and a significant increase was measured with gliclazide (P < .05). Considering the small number of events, no significant difference was detected in the number of hypoglycemic episodes between the two agents. More upper-gastrointestinal (GI) symptoms were observed with metformin compared with gliclazide (P < .05). Even with no change in the standard lipid profile, both agents increased serum vitamin E (P < .01 for gliclazide and P < .05 for metformin) and decreased the level of lipid peroxidation markers in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles (P < .05). Despite different mechanisms of action, gliclazide and metformin demonstrated comparable levels of efficacy and complementary effects on lipid peroxidation markers.", "Rosiglitazone, a thiazolidinedione, enhances peripheral insulin sensitivity in patients with type 2 diabetes. Because the synergic action of insulin and exercise has been shown to be decreased in insulin resistance, the aim of this study was to compare the effects of rosiglitazone and metformin on muscle insulin responsiveness at rest and during exercise in patients with type 2 diabetes. Therefore, 45 patients with newly diagnosed or diet-treated type 2 diabetes were randomized for treatment with rosiglitazone (4 mg b.i.d.), metformin (1 g b.i.d.), or placebo in a 26-week double-blind trial. Skeletal muscle glucose uptake was measured using fluorine-18-labeled fluoro-deoxy-glucose and positron emission tomography (PET) during euglycemic-hyperinsulinemic clamp and one-legged exercise before and after the treatment period. Rosiglitazone (P < 0.05) and metformin (P < 0.0001) treatment lowered the mean glycosylated hemoglobin. The skeletal muscle glucose uptake was increased by 38% (P < 0.01) and whole-body glucose uptake by 44% in the rosiglitazone group. Furthermore, the exercise-induced increment during insulin stimulation was enhanced by 99% (P < 0.0001). No changes were observed in skeletal muscle or whole-body insulin sensitivity in the metformin group. In conclusion, rosiglitazone but not metformin 1) improves insulin responsiveness in resting skeletal muscle and 2) doubles the insulin-stimulated glucose uptake rate during physical exercise in patients with type 2 diabetes. Our results suggest that rosiglitazone improves synergic action of insulin and exercise.", "Platelet density profiles, intraplatelet nucleotides, intraplatelet beta thromboglobulin (beta TG), plasma beta TG levels, intraplatelet cyclic AMP (cAMP) levels, platelet release reaction, platelet thromboxane (TX)B2 production and plasma fibrinogen levels were investigated in 24 newly diagnosed, non-insulin-dependent diabetic patients and 12 comparable controls. These variables were measured at diagnosis, after a 3-6 week dietary run-in period, and again after 6 months on treatment with either metformin or gliclazide therapy. With dietary restriction of refined carbohydrate and oral hypoglycaemic therapy, there was a reduction in platelet density (p less than 0.05), intraplatelet nucleotides (p less than 0.001), intraplatelet beta TG (p less than 0.001), plasma beta TG (p less than 0.001) and there was an increase in intraplatelet cAMP levels (p less than 0.05). Although these platelet variables returned towards normal, only the platelet density mean returned to within the normal range. There was no significant change in the platelet TXB2 production and plasma fibrinogen levels with treatment. Metformin and gliclazide were equally effective in the glycaemic control of non-insulin-dependent diabetes, and there was no difference between the platelet variables measured in the two groups. We would therefore suggest that improvement of glycaemic control, rather than any specific effect of the oral hypoglycaemic agent employed, is the most important factor in returning these parameters towards normality.", "In order to compare the effects of metformin and gliclazide on fasting serum insulin, 60 non-insulin dependent diabetics were included in a multi-centre study. Patients on a diabetic diet alone or a diabetic diet together with a sulphonylurea hypoglycaemic agent, with a fasting glucose greater than 1.4 g/l, on two measurements were included in the study. They were randomly allocated to two parallel groups and received either gliclazide or metformin. They were treated for three months and attended for consultation at one month and three months. The fasting serum insulin level decreased significantly in the group receiving metformin (26.2 +/- 3.2 mlU/L at entry versus 19.8 +/- 2.3 mlU/L after three months: less than 0.01), and increased in a non-significant way in the group receiving gliclazide (21.6 +/- 3 mlU/L versus 26.5 +/- 5 mlU/L after three months: NS). The difference between the two groups was significant (p less than 0.01). There was a comparable significant improvement in blood sugar levels during the three months in both patients receiving gliclazide and metformin. However, significant weight loss (p less than 0.05) occurred only in patients receiving metformin. There was an identical improvement in blood sugar control in both patients receiving gliclazide and metformin over the three months. On the other hand, fasting serum insulin levels decreased significantly in patients receiving metformin compared to gliclazide. The effect of metformin on serum insulin levels is probably due to its action on insulin resistance and its lack of effect on insulin secretion, in contrast to sulphonylurea hypoglycaemic agents like gliclazide.", "To investigate the efficacy and safety of miglitol in combination with metformin in improving glycemic control in outpatients in whom type 2 diabetes is insufficiently controlled by diet alone.\n In this multicenter, double-blind, placebo-controlled study, 324 patients with type 2 diabetes were randomized, after an 8-week placebo run-in period, to treatment with either placebo, miglitol alone, metformin alone, or miglitol plus metformin for 36 weeks. The miglitol was titrated to 100 mg three times a day and metformin was administered at 500 mg three times a day. The primary efficacy criterion was change in HbA(1c) from baseline to the end of treatment. Secondary parameters included changes in fasting and postprandial plasma glucose and insulin levels, serum triglyceride levels, and responder rate.\n A total of 318 patients were valid for intent-to-treat analysis. A reduction in mean placebo-subtracted HbA(1c) of -1.78% was observed with miglitol plus metformin combination therapy, which was significantly different from treatment with metformin alone (-1.25; P = 0.002). Miglitol plus metformin also resulted in better metabolic control than metformin alone for fasting plasma glucose (-44.8 vs. -20.4 mg/dl; P = 0.0025), 2-h postprandial glucose area under the curve (-59.0 vs. -18.0 mg/dl; P = 0.0001), and responder rate (70.6 vs. 45.52%; P = 0.0014). All therapies were well tolerated.\n In type 2 diabetic patients, miglitol in combination with metformin gives greater glycemic improvement than metformin monotherapy.", "To compare the effect of glimepiride in combination with metformin with monotherapy of each drug on glycaemic control in Type 2 diabetic patients.\n Randomized, double-blind, double-dummy, parallel-group multicentre study conducted in France. Type 2 diabetic patients aged 35-70 years inadequately controlled by metformin monotherapy 2550 mg daily for at least 4 weeks were randomized to either metformin, glimepiride or metformin and glimepiride.\n Three hundred and seventy-two patients aged 56 +/- 8 years were treated for 5 months. Combination treatment was significantly more efficient in controlling HbA1c (% change + 0.07 +/- 1.20 for metformin, + 0.27 +/- 1.10 for glimepiride, -0.74 +/- 0.96 for combination treatment, P < 0.001), fasting blood glucose (FBG) (mmol/l change + 0.8 +/- 0.4 for metformin, + 0.7 +/- 3.1 for glimepiride and -1.8 +/- 2.2 for combination treatment, P < 0.001) and post-prandial blood glucose (PPBG) (mmol/l change + 1.1 +/- 5.9 for metformin, + 0.1 +/- 5.1 for glimepiride and -2.6 +/- 3.9 for combination treatment, P < 0.001) than either glimepiride or metformin alone. There was no significant difference between metformin or glimepiride monotherapy with respect to the change in HbA1c or FBG; however, glimepiride was significantly more effective than metformin in reducing PPBG. The incidence of symptomatic hypoglycaemia was higher in the combination group than in either monotherapy group (P = 0.039).\n Addition of glimepiride to metformin in Type 2 diabetic patients inadequately controlled by metformin alone resulted in superior glycaemic control compared with glimepiride or metformin monotherapy.", "To evaluate the efficacy and tolerability of nateglinide and metformin alone and in combination in type 2 diabetic patients inadequately controlled by diet, focusing on changes in HbA1c, fasting plasma glucose (FPG), and mealtime glucose excursions.\n In this randomized double-blind study, patients with an HbA1c level between 6.8 and 11.0% during a 4-week placebo run-in received 24 weeks' treatment with 120 mg nateglinide before meals (n = 179), 500 mg metformin three times a day (n = 178), combination therapy (n = 172), or placebo (n = 172). HbA1c and FPG were evaluated regularly, and plasma glucose levels were determined after Sustacal challenge at weeks 0, 12, and 24. Hypoglycemia and other adverse events were recorded.\n At study end point, HbA1c was reduced from baseline with nateglinide and metformin but was increased with placebo (-0.5, -0.8, and +0.5%, respectively; P < or = 0.0001). Changes in FPG followed the same pattern (-0.7, -1.6, and +0.4 mmol/l; P < or = 0.0001). Combination therapy was additive (HbA1c -1.4% and FPG -2.4 mmol/l; P < or = 0.01 vs. monotherapy). After Sustacal challenge, there was a greater reduction in mealtime glucose with nateglinide monotherapy compared with metformin monotherapy or placebo (adjusted area under the curve [AUC]0-130 min -2.1, -1.1, and -0.6 mmol x h(-1) x l(-1); p < or = 0.0001). An even greater effect was observed with combination therapy (AUC0-130 min -2.5 mmol x h(-1) x l(-1); P < or = 0.0001 vs. metformin and placebo). All regimens were well tolerated.\n Nateglinide and metformin monotherapy each improved overall glycemic control but by different mechanisms. Nateglinide decreased mealtime glucose excursions, whereas metformin primarily affected FPG. In combination, nateglinide and metformin had complementary effects, improving HbA1c, FPG, and postprandial hyperglycemia.", "To compare the therapeutic potential of acarbose, metformin, or placebo as first line treatment in patients with non-insulin-dependent diabetes mellitus (NIDDM).\n Ninety-six patients with NIDDM (35-70 years of age, body mass index (BMI) < or = 35 kg/m2, insufficiently treated with diet alone, glycated hemoglobin (HbA1c; 7% to 11%) were randomized into 3 groups and treated for 24 weeks with acarbose, 3 x 100 mg/day, or metformin, 2 x 850 mg/day, or placebo. Efficacy, based on HbA1c (primary efficacy criterion), fasting blood glucose (BG) and insulin, 1 hour postprandial BG and insulin (after standard meal test), postprandial insulin increase, plasma lipid profile, and tolerability, based on subjective symptoms and laboratory values were determined every 6 weeks. Analysis of covariance was performed for endvalues with adjustment on baseline values. Ninety-four patients were valid for efficacy evaluation.\n Both active drugs showed the same improvement of efficacy criteria compared with placebo. Baseline adjusted means at endpoint were as follows: BG, fasting and 1 hour postprandial, 9.2 mM and 10.9 mM with placebo, 7.6 mM and 8.7 mM with acarbose, and 7.8 mM and 9.0 mM with metformin; HbA1c was 9.8% with placebo, 8.5% with acarbose, and 8.7% with metformin. Comparisons: acarbose versus placebo and metformin versus placebo were statistically significant, but not acarbose versus metformin. No effect on fasting insulin could be observed. Relative postprandial insulin increase was 1.90 with placebo, 1.09 with acarbose, and 1.03 with metformin. Comparisons: acarbose versus placebo and metformin versus placebo were statistically significant, but not acarbose versus metformin. With respect to lipid profile, acarbose was superior to metformin. Low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol ratio increased by 14.4% with placebo, was unchanged with metformin, but decreased by 26.7% with acarbose. Comparisons: acarbose versus placebo and acarbose versus metformin were statistically significant, but not metformin versus placebo. Slight body weight changes were observed with acarbose (-0.8 kg) and metformin (-0.5 kg), but not with placebo. Acarbose led to mild or moderate intestinal symptoms in 50% of the patients within the first 4 weeks, but in only 13.8% of the patients within the last 4 weeks.\n Acarbose and metformin are effective drugs for the first line monotherapy of patients with NIDDM. With respect to plasma lipid profile, especially HDL cholesterol, LDL cholesterol and LDL/HDL cholesterol ratio acarbose may be superior to metformin.", "Forty-eight diabetic subjects with diet-failed Type 2 mellitus, aged 40-69 years, were randomised to metformin (24 patients) or glipizide (24 patients) therapy, and followed prospectively for 12 months. Most subjects were obese. Metformin gave better fasting plasma glucose control compared to glipizide at 24 (p < 0.01), 36 (p < 0.05) and 52 weeks (p < 0.05) with a lower HbA1 concentration at 52 weeks (p < 0.05). Metformin treated patients lost weight whereas glipizide treated subjects gained weight. The weight change between the treatment groups reached significance at 4 weeks (p < 0.05) and was highly significant (p < 0.001) at 8, 12, 24, 36 and 52 weeks. There were no significant changes in either fasting plasma lipid or blood lactate levels in either the metformin or glipizide treated groups. Both drugs caused a similar reduction in albumin excretion rates. In conclusion, metformin gave better glycaemic control than glipizide, with weight loss rather than weight gain in obese Type 2 patients.", "Combination therapy is logical for patients with non-insulin-dependent (type 2) diabetes mellitus, because they often have poor responses to single-drug therapy. We studied the efficacy and physiologic effects of metformin and troglitazone alone and in combination in patients with type 2 diabetes.\n We randomly assigned 29 patients to receive either metformin or troglitazone for three months, after which they were given both drugs for another three months. Plasma glucose concentrations during fasting and postprandially and glycosylated hemoglobin values were measured periodically during both treatments. Endogenous glucose production and peripheral glucose disposal were measured at base line and after three and six months.\n During metformin therapy, fasting and postprandial plasma glucose concentrations decreased by 20 percent (58 mg per deciliter [3.2 mmol per liter], P<0.001) and 25 percent (87 mg per deciliter [4.8 mmol per liter], P<0.001), respectively. The corresponding decreases during troglitazone therapy were 20 percent (54 mg per deciliter [2.9 mmol per liter], P=0.01) and 25 percent (83 mg per deciliter [4.6 mmol per liter], P<0.001). Endogenous glucose production decreased during metformin therapy by a mean of 19 percent (P=0.001), whereas it was unchanged by troglitazone therapy (P=0.04 for the comparison between groups). The mean rate of glucose disposal increased by 54 percent during troglitazone therapy (P=0.006) and 13 percent during metformin therapy (P= 0.03 for the comparison within the group and between groups). In combination, metformin and troglitazone further lowered fasting and postprandial plasma glucose concentrations by 18 percent (41 mg per deciliter [2.3 mmol per liter], P=0.001) and 21 percent (54 mg per deciliter [3.0 mmol per liter], P<0.001), respectively, and the mean glycosylated hemoglobin value decreased 1.2 percentage points.\n Metformin and troglitazone have equal and additive beneficial effects on glycemic control in patients with type 2 diabetes. Metformin acts primarily by decreasing endogenous glucose production, and troglitazone by increasing the rate of peripheral glucose disposal.", "To assess the reversibility of the defect in glycogen synthase (GS) activity in skeletal muscle from obese patients with NIDDM treated with a hypocaloric diet and metformin.\n Eighteen obese patients newly diagnosed with NIDDM were included in a randomized placebo-controlled double-blind parallel group trial and followed for 3 months. Euglycemic-hyperinsulinemic clamp including indirect calorimetry and biopsy of m. vastus lateralis was performed before and after treatment with a hypocaloric diet plus metformin or placebo. The patients were studied at basal, low, and high insulin concentrations.\n The impaired GS activity in muscle biopsies was not reversed either by acute normalization of glycemia (for 8 h) or by chronic reduction of hyperglycemia by diet plus metformin. In both treatment groups, comparable effects on glycemic control and weight loss were found together with marked insulin suppression of nonesterified fatty acids and increased glucose oxidation. Total glucose disposal at euglycemic-hyperinsulinemic clamp increased significantly in the metformin group by 25% at high insulin level (259 +/- 31 vs. 207 +/- 21 mg x m(-2) x min(-1), P < 0.05). An insignificant increase by 13% was found in the placebo group. There were no significant changes in nonoxidative glucose metabolism. GS activity and glucose utilization showed no significant differences between the two treatment groups when regression coefficients, expressed as incremental changes by increments of insulin, were compared.\n Defective GS activity in obese NIDDM patients is not secondary to hyperglycemia. Metformin and diet had no significant influence on GS activity. The added effect of metformin to that of a hypocaloric diet in improving insulin-stimulated glucose utilization is marginal when blood glucose reduction is obtained by weight loss.", "Metformin often promotes weight loss in patients with obesity with non-insulin-dependent diabetes mellitus (NIDDM). The mechanism may be attributed to decreased food intake. This study has tested the effect of metformin on satiety and its efficacy in inducing weight loss. Twelve diet-treated NIDDM women with obesity were randomly given two dose levels (850 mg or 1700 mg) of metformin or placebo at 0800 for three consecutive days followed by a meal test on the third day on three occasions using a 3x3 Latin square design. The number of sandwich canapes eaten in three consecutive 10-minute periods beginning at 1400 hours was used to quantitate food intake, and the level of subjective hunger was rated just before the sandwich meal with a linear analogue hunger rating scale at 1400 after a 6-hour fast. The prior administration of metformin produced a reduction in calorie intake after each of the two doses of metformin treatment. The 1700-mg metformin dose had the most marked appetite suppressant action. Similarly, hunger ratings were significantly lowered after metformin, and the effect was most pronounced after the administration of 1700 mg of metformin. To assess the efficacy of metformin in reducing bodyweight, 48 diet-treated NIDDM women with obesity who had failed to lose weight by diet therapy were first placed on a 1200-kcal ADA (American Diabetes Association) diet before being randomized to receive either metformin (850 mg) or placebo twice daily in a double-blind fashion for 24 weeks. A 4-week single-blind placebo lead-in period preceded and a 6-week single-blind placebo period followed the 24-week double-blind treatment period. Subjects treated with metformin continued to lose weight throughout 24 weeks of treatment; their mean maximum weight loss was 8 kg greater than that of the placebo group, with corresponding lower HbA1C and fasting blood glucose levels at the end of the active treatment period. These results indicate that metformin decreases calorie intake in a dose-dependent manner and leads to a reduction in bodyweight in NIDDM patients with obesity." ]

[ "7485681", "12749482", "3055456", "8649245", "3328343", "1524143", "9315044", "8665377", "7563259", "2200287", "10084136", "10450426", "7861874", "10717733", "8882175", "16282294", "9452282", "8036656", "8665378" ]

[ "Insecticide-impregnated bed nets for malaria control: varying experiences from Ecuador, Colombia, and Peru concerning acceptability and effectiveness.", "Efficacy of permethrin-treated bed nets in the prevention of mortality in young children in an area of high perennial malaria transmission in western Kenya.", "A trial of bed nets (mosquito nets) as a malaria control strategy in a rural area of The Gambia, West Africa.", "[Study of the impact of deltamethrin impregnated curtains on malaria morbidity in Ankazobe of the Madagascar highlands].", "A trial of permethrin-treated bed nets in the prevention of malaria in Gambian children.", "The effectiveness of permethrin-impregnated bed nets against malaria for migrant workers in eastern Thailand.", "Do insecticide-treated curtains reduce all-cause child mortality in Burkina Faso?", "Insecticide-treated bednets reduce mortality and severe morbidity from malaria among children on the Kenyan coast.", "Deltamethrin impregnated bednets for the control of urban malaria in Kumba Town, South-West Province of Cameroon.", "Permethrin-impregnated curtains and bed-nets prevent malaria in western Kenya.", "Cyfluthrin (EW 050)-impregnated bednets in a malaria control program in Ghassreghand (Baluchistan, Iran).", "Effect of insecticide-treated bed nets on haemoglobin values, prevalence and multiplicity of infection with Plasmodium falciparum in a randomized controlled trial in Tanzania.", "Mortality and morbidity from malaria in Gambian children after introduction of an impregnated bednet programme.", "Insecticide-treated materials for malaria control in Latin America: to use or not to use?", "Pyrethroid-impregnated bed nets for personal protection against malaria for Afghan refugees.", "Protective efficacy of lambda-cyhalothrin treated nets in Anopheles gambiae pyrethroid resistance areas of Côte d'Ivoire.", "A controlled trial of lambda-cyhalothrin-impregnated bed nets and/or dapsone/pyrimethamine for malaria control in Sierra Leone.", "Permethrin-impregnated bed nets for the prevention of malaria in schoolchildren on the Thai-Burmese border.", "Impact of permethrin impregnated bednets on child mortality in Kassena-Nankana district, Ghana: a randomized controlled trial." ]

[ "Between 1991 and 1994, an intervention program with permethrin- and lambdacyhalothrin-impregnated bed nets was carried out over a period of nine months in each of five endemic, malarious areas of Ecuador, Peru, and Colombia. This program was evaluated through household surveys, blood sampling, in-depth longitudinal studies, and entomologic analysis. Eighty-four communities (including approximately 35,000 individuals) were paired according to malaria incidence, size, and coverage with bed nets and then randomly allocated to intervention and control groups. The results showed that peoples' acceptance of the measure was related to their perception of an immediate protective effect against insects. The effectiveness of the bed nets, measured as a reduction of malaria incidence in intervention communities as against control communities, showed large variations between and within the study areas. The protective efficacy varied between 0% and 70% when looking only at the postintervention differences between intervention and control groups. The average protection was 40.8% when considering a four-month incidence of clinical malaria attacks and 28.3% when considering a two-week malaria incidence. Important factors for the success of the bed net program were insect susceptibility to pyrethroids, high coverage with impregnated bed nets, high malaria incidence, good community participation, high mosquito densities when people go to bed, and a high proportion of Plasmodium falciparum. In one area, where DDT spraying in the control communities was executed, the effectiveness of bed net impregnation was slightly better than that of spraying.", "A group-randomized controlled trial of insecticide (permethrin)-treated bed nets (ITNs) was conducted in an area of high perennial malaria transmission in western Kenya to test the effect of ITNs on all-cause mortality in children 1-59 months of age. Child deaths were monitored over a two-year period by biannual household census in Asembo (1997-1998) and in Gem (1998-1999). Overall, 1,722 deaths occurred in children 1-59 months followed for 35,932 child-years. Crude mortality rates/1,000 child-years were 51.9 versus 43.9 in control and ITN villages in children 1-59 months old. The protective efficacy (PE) (95% confidence interval) adjusted for age, study year, study site, and season was 16% (6-25%). Corresponding figures in 1-11- and 12-59-month-old children in control and ITN villages were 133.3 versus 102.3, PE = 23% (11-34%) and 31.1 versus 28.7, PE = 7% (-6-19%). The numbers of lives saved/1,000 child-years were 8, 31, and 2 for the groups 1-59, 1-11, and 12-59 months old, respectively. Stratified analysis by time to insecticide re-treatment showed that the PE of ITNs re-treated per study protocol (every six months) was 20% (10-29%), overall and 26% (12-37%) and 14% (-1-26%) in 1-11- and 12-59-month-old children, respectively. ITNs prevent approximately one in four infant deaths in areas of intense perennial malaria transmission, but their efficacy is compromised if re-treatment is delayed beyond six months.", "An intervention trial was undertaken in a rural area of The Gambia to assess the impact on malaria morbidity of the use of bed nets. Bed nets were allocated at random among a group of 16 Fula hamlets, where they were previously rarely used. The incidence of febrile episodes with associated malaria parasitaemias throughout the rainy season and the prevalence of splenomegaly and parasitaemia at the end of the rainy season were determined in 233 children aged 1-9 years who slept under bed nets and in 163 children who did not. Bed nets were used correctly by the children in the study cohort, but direct observations showed that a significant number of children left their nets for a period during the night. There was no significant difference in the incidence of clinical attacks of malaria or in any other malariometric measurement between the 2 groups. Thus, bed nets were not effective in reducing malaria morbidity in this group of children. The apparent protection from bed nets demonstrated in previous retrospective surveys may have been due to an increased number of infective bites being received by exposed individuals sleeping close to users of bed nets.", "nan", "A trial was undertaken in a rural area of The Gambia to investigate the impact of permethrin-treated bed nets on malaria. Two groups of children, matched for age, sex, and malaria exposure, were followed through the rainy season of 1985 for illness and febrile episodes. One group of 205 children slept under permethrin-treated bed nets (0.5 g/m2); 184 children who slept under placebo-treated nets formed the control group. At the end of the rains the children were examined for splenomegaly and blood samples were taken for determination of packed cell volume (PCV) and parasitaemia. Permethrin treatment of bed nets was well accepted and was without side-effects. Children who slept under treated nets had significantly fewer episodes of clinical malaria than control children. However, at the end of the rains there was no significant difference in the prevalence of splenomegaly or parasitaemia or in the mean PCV between the groups. It is suggested that permethrin treatment of nets may have a greater effect on the duration of probing by mosquitoes for a blood meal than on the number of bites received.", "A randomized, double-blind, field trial was carried out to compare the effectiveness of permethrin-treated bed nets with that of untreated nets as a method of malaria control for migrant workers in eastern Thailand. The study was conducted using 261 subjects in eastern rural areas that are known to be highly endemic for multidrug-resistant Plasmodium falciparum infection. One hundred twenty-six subjects used treated nets, while 135 used untreated nets. During the 35 weeks of observation, 23 subjects using treated nets and 33 workers using untreated nets developed 28 and 51 episodes of malaria, respectively (P = 0.029). The reduction in risk per subject due to treated nets was 0.06. The residual effects of permethrin were tested using a World Health Organization standard bioassay. Anti-mosquito activity was found to be present in the nets for more than 16 months. We conclude that because of the failure of the development of safe, effective, long-lasting prophylactic agents, integrating the use of impregnated nets with large-scale primary health care programs may be a partially effective method for controlling malaria in eastern Thailand.", "To evaluate whether insecticide-treated netting (ITN) reduces child mortality in different epidemiological settings, 4 large, randomized, controlled trials were conducted in Africa. Here we report the findings from the trial in Burkina Faso, in an area of hyperendemic and markedly seasonal malaria transmission. The trial involved 158 villages, with a total population of some 90,000, grouped into 16 geographical clusters. Ascertainment of mortality among children aged 6-59 months began in early 1993. In June/July 1994, 8 of the clusters, randomly selected, received permethrin-treated curtains. Follow-up of children and ascertainment of mortality continued until May 1996. A 15% reduction in all-cause mortality among children aged 6-59 months was observed over the 2-year period following the installation of the curtains (95% c.i. -4% to 30%). In the first year, post-intervention mortality was substantially lower in the clusters receiving curtains compared with the control clusters (rate ratio = 0.74; 95% c.i. 0.57, 0.95) but in the second year, there was no difference between mortality in the two groups (rate ratio = 0.99). The overall two-year impact of the intervention is consistent with the impacts observed in other trials which have demonstrated reductions in child mortality of from 17% to 33%. However, the year-by-year analysis raises some concerns about the long-term effect of ITN. Further follow-up of this population is warranted.", "New tools to prevent malaria morbidity and mortality are needed to improve child survival in sub-Saharan Africa. Insecticide treated bednets (ITBN) have been shown, in one setting (The Gambia, West Africa), to reduce childhood mortality. To assess the impact of ITBN on child survival under different epidemiological and cultural conditions we conducted a community randomized, controlled trial of permethrin treated bednets (0.5 g/m2) among a rural population on the Kenyan Coast. Between 1991 and 1993 continuous community-based demographic surveillance linked to hospital-based in-patient surveillance identified all mortality and severe malaria morbidity events during a 2-year period among a population of over 11000 children under 5 years of age. In July 1993, 28 randomly selected communities were issued ITBN, instructed in their use and the nets re-impregnated every 6 months. The remaining 28 communities served as contemporaneous controls for the following 2 years, during which continuous demographic and hospital surveillance was maintained until the end of July 1995. The introduction of ITBN led to significant reductions in childhood mortality (PE 33%, CI 7-51%) and severe, life-threatening malaria among children aged 1-59 months (PE 44%, CI 19-62). These findings confirm the value of ITBN in improving child survival and provide the first evidence of their specific role in reducing severe morbidity from malaria.", "This study was conducted from January to December 1992 in Kumba, a town situated in the rain forest region of the South-West Province of Cameroon, and consisted of a longitudinal survey including parasitological and clinical studies. Forty households were chosen for the study and randomly divided into two groups, each with approximately 240 inhabitants aged < or = 15 years. One group received deltamethrin impregnated bednets and the other group had no nets (control). For the months of April, June and August (rainy season), deltamethrin impregnated bednets did not reduce malaria prevalence significantly, but the overall malaria prevalence for all months of the study was significantly reduced (chi 2 MH = 9.17, P = 0.002). Enlarged spleen rates (chi 2 MH = 6.73, P = 0.009) and spleen sizes (P = 0.0002) were also significantly reduced by the nets. However, the reduction in the geometric mean parasite density (GMPD) was not significant. Even though some of these reductions were statistically significant, they were relatively low in a global context compared with previous work done mainly in rural areas. In an urban environment, parents and children usually stay up late, and probably receive many mosquito bites before going to sleep.", "The effectiveness of permethrin-impregnated (0.5 g/m2) bed-nets and curtains as malaria control measures was evaluated in Uriri, Kenya in 1988. One hundred five families were randomly assigned to 1 of 3 study groups (control, bed-net, or curtain). All participants were cured of parasitemia with pyrimethamine/sulfadoxine. Selective epidemiologic and entomologic parameters were measured weekly, while knowledge, attitude, and practices surveys were conducted at the beginning and end of the 15 week study. Plasmodium falciparum infections per person week at risk were significantly higher in the control group than in either the curtain group (5.42 vs. 2.35 cases/100 person weeks risk) or the bed-net group (5.42 vs. 3.77 cases/100 person weeks risk). The curtain group had fewer infections per person week at risk than the bed-net group (2.35 vs. 3.77 cases/100 person weeks risk). A difference was found in clinical malaria among the groups: 45% of persons in the bed-net and curtain groups vs. 30% of those in the control group reported no episodes of fever and chills (chi 2, P less than 0.05). Indoor resting Anopheles gambiae or An. funestus were found on 94 occasions in the control houses, but only twice in the treated houses during weekly visits to each house over the study period (chi 2 P less than 0.001). The pyrethrum knockdown method produced similar results with a total of 195, 23, and 3 An. gambiae and An. funestus collected in the control, bed-net, and curtain houses during the same period, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)", "In a study carried out in the Ghassreghand Division (Baluchistan, Iran) from March through November 1995, efficacy of cyfluthrin-impregnated bednets was compared to that of untreated nets, in relation to malaria control. Ten villages with a total population of 4,572 and 3 villages with a total population of 1,935 were used as treatment and control, respectively. The collection, impregnation (target dosage of 40 mg active ingredient [AI]/m2), and redistribution of the nets (9% nylon, 52% light cotton, 30% medium cotton, and 9% heavy cotton), carried out in mid-April, were done by local health workers, supervised by the senior research staff. Anopheles culicifacies was considered to be the main vector of malaria in the named area. This species is mainly zoophilic, endophilic, and exophagic. The initial uptake of the insecticide was lower than the target dosage, with high variation (nylon, 12.5 +/- 5.4 mg AI/m2; light cotton, 33.3 +/- 26.1 mg AI/m2; medium cotton, 25.9 +/- 20 mg AI/m2; heavy cotton, 17.6 +/- 12.5 mg AI/m2). The use of impregnated mosquito nets (used primarily outside) had no significant effect on the incidence of malaria. No difference was detected in the parasite density of patients with positive slides. No significant effect was observed in the parous rate, human blood index, and sporozoite rate of anopheline vectors. Only the indoor resting densities of An. culicifacies and other malaria vectors were drastically reduced after the introduction of the cyfluthrin-impregnated nets into the treatment villages. The residual activity of cyfluthrin was lower than expected. The mortality of anophelines brought in contact with the treated nets for 3 min in bioassays dropped to less than 55% in 3 months. The loss of chemical activity was greatest for the light cotton nets, followed by the medium cotton nets. Cyfluthrin-treated nets were mildly irritating to host-seeking female anophelines in the laboratory. The protective rate of impregnation (all fabric kinds included) in preventing female mosquitoes from biting through the impregnated nets was initially 5-6 times that of the nonimpregnated nets. The study did not detect any significant difference between the use of untreated versus impregnated bednets in the Ghassreghand area. In planning future medium-scale trials, comparison of new compounds and formulations to the more widely used pyrethroids such as permethrin and deltamethrin is highly recommended.", "A randomized controlled trial of insecticide-treated bed nets (ITNs) was conducted in an area of high malaria transmission in Tanzania in order to assess the effects of ITNs on infection and anaemia. One hundred and twenty-two children, aged 5 to 24 months, were randomly allocated to 2 groups, one of which received ITNs. Outcome measures were assessed in 6 consecutive months with monthly cross-sectional surveys. These measures were haemoglobin values, Plasmodium falciparum prevalence and density, and multiplicity of infection determined by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) of the msp2 locus. There was a significant increase in mean heamoglobin values and a significant decrease of 16.4% in microscopically determined P. falciparum prevalence in children in the ITN group six months after the start of the trial. Both effects were more pronounced in younger children. However, no significant difference was observed in parasite density or multiplicity of infection among infected children. Comparison with PCR results indicated that microscopically subpatent parasitaemia was more frequently found in children in the ITN group. This, together with the observed similar multiplicity in the 2 groups, suggests that infections are maintained despite ITN use, owing to the chronicity of infections. This study shows that ITNs reduce the risk of anaemia in highly exposed young children. The virtually unchanged multiplicity of infection indicates that the potentially protective concomitant immunity is not compromised.", "After the success of a controlled trial of insecticide-treated bednets in lowering child mortality, The Gambia initiated a National Insecticide Impregnated Bednet Programme (NIBP) in 1992 with the objective of introducing this form of malaria control into all large villages in The Gambia. Five areas (population 115,895) were chosen as sentinel sites for evaluation of the NIBP. During the first year of intervention a 25% reduction was achieved in all-cause mortality in children 1-9 years old living in treated villages (rate ratio 0.75 [95% CI 0.57-0.98], p = 0.04). If one area where the programme was ineffective was excluded, the reduction was 38% (0.62 [0.46-0.83), p = 0.001). A decrease in rates of parasitaemia and high-density parasitaemia, an increase in mean packed-cell volume (rate ratio 0.75 [95% CI 0.59-0.98], p = 0.04) and an improvement in the nutritional status of children living in treated villages were also detected. In a country such as The Gambia, where nets were widely used and which has a good primary health care system, it is possible to achieve insecticide-treatment of bednets at a national level with a significant reduction in child mortality; but at a cost which the country cannot afford.", "Studies on the protective efficacy of insecticide-treated materials (ITMs) in Plasmodium vivax endemic areas of Latin America have not yielded sufficient evidence for recommendation of their extensive use in the region. Therefore 2 randomized community trials have been conducted on the Pacific Coast of Nicaragua which analysed the minimum coverage of ITMs needed to be effective against malaria. For the characterization of the study area, epidemiological and entomological baseline surveys and household interview surveys were undertaken. Thereafter the communities were paired (6 pairs in the 1st year and 13 pairs in the 2nd year) according to 4-monthly reported malaria incidence rates, population size and bednet coverage, and then randomly allocated to intervention and control groups. In the intervention groups, bednets were impregnated with lambdacyhalothrin; in the control groups, people received general health education. Anopheles albimanus was found to be the main vector with marked indoor biting behaviour late in the evening. P. vivax (99%) clearly outweighed P. falciparum (1%) with low parasite prevalence rates in the asymptomatic general population (8%) and low parasite densities. The protective efficacy of ITMs varied according to the coverage achieved: protective efficacy was 68% in communities with an average ITM coverage of 50% (10 pairs); 31% in communities with an ITM coverage of 16-30% (4 pairs); and no protective efficacy in communities with ITM coverage below 16% (5 pairs). The comparison with other P. vivax endemic areas in Latin America showed that the vector's late biting behaviour and the indoor preference (where ITMs have a repellent effect) probably led to the favourable results in the study. In malaria endemic areas of Latin America, where P. vivax is predominant, studies on vector behaviour should be conducted in order to predict the impact of ITMs on malaria transmission.", "A field trial of permethrin-impregnated bed nets (PIBs) was conducted in 2 Afghan refugee villages in Pakistan. Nets were issued to only 10% of families (= 1398 people); this simulated a situation in which bed nets are gradually adopted by villagers in Afghanistan. A further 10% lacking bed nets were selected as controls from the same villages. An initial survey showed that 86% of household heads were aware that malaria was transmitted by mosquito bites, but only 2% had used bed nets before. Trial families were encouraged to attend the village health centres if they fell ill. Microscopy records showed that, between July and December 1991, 22.4% of the control group became infected with Plasmodium vivax and 13.0% contracted P. falciparum while in the intervention group only 9.9% contracted P. vivax (relative risk 0.58, confidence interval [CI] 95% 0.49-0.68) and only 3.8% contracted P. falciparum (relative risk 0.39, 95% CI 0.29-0.53). A single treatment of the nets with permethrin at 0.5g/m2 remained protective throughout the 6 months' transmission season. 73% of families claimed to use their nets every night; members of families who claimed to use nets less regularly showed an incidence similar to that of the control group. There was no sex or age difference in net use or protective efficacy. Headlouse infestation rates were reduced in PIB users. Few nets were washed, given away or sold. The prospect for PIBs as personal protection appears good, despite people's lack of previous experience.", "The efficacy of nets treated with lambda-cyhalothrin, a pyrethroid insecticide, on malaria infection and disease was assessed for the first time at the community level in Anopheles gambiae pyrethroid resistance areas. The study was carried out in northern Côte d'Ivoire, which is an area of kdr resistance. Four pairs of villages were selected and matched according to demographic, sociological, and ecological criteria. Among each pair, a village was randomly allocated to receive mosquito nets. More than 80% of beds were covered with nets treated with lambda-cyhalothrin and retreated after 6 months. In each village, 54 children aged 0-59 months were randomly selected and clinically monitored for 8 periods of 7 days throughout the year. Results showed that the efficacy of treated nets was maintained with a reduction of the prevalence of asymptomatic malaria infection by 12% and an estimated protective efficacy against malaria disease of 56%.", "A randomized controlled trial investigated the impact of community-wide use of mosquito nets impregnated with lambda-cyhalothrin alone or with dapsone/pyrimethamine (d/p) prophylaxis on clinical malaria due to perennially transmitted Plasmodium falciparum in children in the Bo district of Sierra Leone. The 17 study communities were pair-matched and randomly allocated to receive treated mosquito nets or no nets and the children (age range = 3 months-6 years) in each community were randomly allocated to receive d/p or placebo individually every two weeks. This resulted in each of the approximately 2,000 children recruited being in one of four study groups (impregnated mosquito nets and d/p prophylaxis, impregnated mosquito nets, d/p prophylaxis, and controls). The intervention phase of the study lasted 12 months. A total of 1,800 children attended more than 25% of the 48 total weekly morbidity surveillance surveys and were included in the analysis. The effects of the exclusive use of either treated mosquito nets or d/p prophylaxis on protection against clinical malaria due to P. falciparum was significantly similar (49% and 42%, respectively), while in combination this protective efficacy was significantly increased to 72% (95% confidence interval = 67-76%). Children in the control group had an average of 1.3 clinical malaria episodes per child annually compared with 0.65 episodes or 0.78 episodes for those using treated mosquito nets and d/p, respectively. Children using both treated mosquito nets and d/p prophylaxis had an average of 0.37 episodes per child. The interventions significantly reduced spleen rates and increased hematocrit values, and reduced the duration of episodes of clinical malaria.", "A double-blind controlled trial was undertaken from August 1990 to February 1991 among Karen children on the Thai-Burmese border to evaluate the effects on malaria incidence and prevalence of permethrin-treated bed nets. Three hundred and fifty schoolchildren, aged 4 to 15 years, were allocated at random to receive either a permethrin-impregnated net or a non-treated net. The incidence of malaria infections, confirmed by a blood film, was assessed during 6 months. Three surveys were conducted, on admission and 3 and 6 months later, to measure the prevalence of infections and spleen rates. Compliance was assessed by monthly home visiting. The use of permethrin-treated bed nets reduced the number of parasitaemic Plasmodium falciparum infections by 38% and the number of symptomatic episodes by 42%. The number of P. vivax malaria attacks was similar in each group. The prevalence of positive blood films in the 2 groups did not change significantly during the study. A reduction in spleen rate by 50% in both groups at the end of the study period could not be related to the overall use of nets. Compliance was high and no side-effect was reported. The long-term effects on morbidity and mortality need to be assessed after distribution of permethrin treated bed nets at the village level.", "A community-based randomized, controlled trial of permethrin impregnated bednets was carried out in a rural area of northern Ghana, between July 1993 and June 1995, to assess the impact on the mortality of young children in an area of intense transmission of malaria and no tradition of bednet use. The district around Navrongo was divided into 96 geographical areas and in 48 randomly selected areas households were provided with permethrin impregnated bednets which were re-impregnated every 6 months. A longitudinal demographic surveillance system was used to record births, deaths and migrations, to evaluate compliance and to measure child mortality. The use of permethrin impregnated bednets was associated with 17% reduction in all-cause mortality in children aged 6 months to 4 years (RR = 0.83; 95% CI 0.69-1.00; P = 0.05). The reduction in mortality was confined to children aged 2 years of younger, and was greater in July-December, during the wet season and immediately after (RR = 0.79; 95% CI 0.63-1.00), a period when malaria mortality is likely to be increased, than in the dry season (RR = 0.92, 95% CI 0.73-1.14). The ready acceptance of bednets, the high level of compliance in their use and the subsequent impact on all-cause mortality in this study has important implications for programmes to control malaria in sub-Saharan Africa." ]

[ "10714729", "16389204", "14563543", "17628351", "7261900", "8498759", "18243585", "1787024", "4890477" ]

[ "Methadone maintenance vs 180-day psychosocially enriched detoxification for treatment of opioid dependence: a randomized controlled trial.", "A randomized controlled trial of interim methadone maintenance.", "A randomised controlled trial of methadone maintenance treatment versus wait list control in an Australian prison system.", "A randomized clinical trial of methadone maintenance for prisoners: results at 1-month post-release.", "The Swedish methadone maintenance program: a controlled study.", "Dose-response effects of methadone in the treatment of opioid dependence.", "A randomized trial of 6-month methadone maintenance with standard or minimal counseling versus 21-day methadone detoxification.", "A controlled trial of methadone maintenance in a population of intravenous drug users in Bangkok: implications for prevention of HIV.", "Methadone treatment of randomly selected criminal addicts." ]

[ "Despite evidence that methadone maintenance treatment (MMT) is effective for opioid dependence, it remains a controversial therapy because of its indefinite provision of a dependence-producing medication.\n To compare outcomes of patients with opioid dependence treated with MMT vs an alternative treatment, psychosocially enriched 180-day methadone-assisted detoxification.\n Randomized controlled trial conducted from May 1995 to April 1999.\n Research clinic in an established drug treatment service.\n Of 858 volunteers screened, 179 adults with diagnosed opioid dependence were randomized into the study; 154 completed 12 weeks of follow-up.\n Patients were randomized to MMT (n = 91), which required 2 hours of psychosocial therapy per week during the first 6 months; or detoxification (n = 88), which required 3 hours of psychosocial therapy per week, 14 education sessions, and 1 hour of cocaine group therapy, if appropriate, for 6 months, and 6 months of (nonmethadone) aftercare services.\n Treatment retention, heroin and cocaine abstinence (by self-report and monthly urinalysis), human immunodeficiency virus (HIV) risk behaviors (Risk of AIDS Behavior scale score), and function in 5 problem areas: employment, family, psychiatric, legal, and alcohol use (Addiction Severity Index), compared by intervention group.\n Methadone maintenance therapy resulted in greater treatment retention (median, 438.5 vs 174.0 days) and lower heroin use rates than did detoxification. Cocaine use was more closely related to study dropout in detoxification than in MMT. Methadone maintenance therapy resulted in a lower rate of drug-related (mean [SD] at 12 months, 2.17 [3.88] vs 3.73 [6.86]) but not sex-related HIV risk behaviors and in a lower severity score for legal status (mean [SD] at 12 months, 0.05 [0.13] vs 0.13 [0.19]). There were no differences between groups in employment or family functioning or alcohol use. In both groups, monthly heroin use rates were 50% or greater, but days of use per month dropped markedly from baseline.\n Our results confirm the usefulness of MMT in reducing heroin use and HIV risk behaviors. Illicit opioid use continued in both groups, but frequency was reduced. Results do not provide support for diverting resources from MMT into long-term detoxification.", "Effective alternatives to long waiting lists for entry into methadone hydrochloride maintenance treatment are needed to reduce the complications of continuing heroin dependence and to increase methadone treatment entry.\n To compare the effectiveness of interim methadone maintenance with that of the usual waiting list condition in facilitating methadone treatment entry and reducing heroin and cocaine use and criminal behavior.\n Randomized, controlled, clinical trial using 2 conditions, with treatment assignment on a 3:2 basis to interim maintenance-waiting list control.\n A methadone treatment program in Baltimore.\n A total of 319 individuals meeting the criteria for current heroin dependence and methadone maintenance treatment.\n Participants were randomly assigned to either interim methadone maintenance, consisting of an individually determined methadone dose and emergency counseling only for up to 120 days, or referral to community-based methadone treatment programs.\n Entry into comprehensive methadone maintenance therapy at 4 months from baseline; self-reported days of heroin use, cocaine use, and criminal behavior; and number of urine drug test results positive for heroin and cocaine at the follow-up interview conducted at time of entry into comprehensive methadone treatment (or at 4 months from baseline for participants who did not enter regular treatment).\n Significantly more participants assigned to the interim methadone maintenance condition entered comprehensive methadone maintenance treatment by the 120th day from baseline (75.9%) than those assigned to the waiting list control condition (20.8%) (P<.001). Overall, in the past 30 days at follow-up, interim participants reported significantly fewer days of heroin use (P<.001), had a significant reduction in heroin-positive drug test results (P<.001), reported spending less money on drugs (P<.001), and received less illegal income (P<.02) than the waiting list participants.\n Interim methadone maintenance results in a substantial increase in the likelihood of entry into comprehensive treatment, and is an effective means of reducing heroin use and criminal behavior among opioid-dependent individuals awaiting entry into a comprehensive methadone treatment program.", "The aim was to determine whether methadone maintenance treatment reduced heroin use, syringe sharing and HIV or hepatitis C incidence among prisoners.\n All eligible prisoners seeking drug treatment were randomised to methadone or a waitlist control group from 1997 to 1998 and followed up after 4 months. Heroin use was measured by hair analysis and self report; drugs used and injected and syringe sharing were measured by self report. Hepatitis C and HIV incidence was measured by serology.\n Of 593 eligible prisoners, 382 (64%) were randomised to MMT (n=191) or control (n=191). 129 treated and 124 control subjects were followed up at 5 months. Heroin use was significantly lower among treated than control subjects at follow up. Treated subjects reported lower levels of drug injection and syringe sharing at follow up. There was no difference in HIV or hepatitis C incidence.\n Consideration should be given to the introduction of prison methadone programs particular where community based programs exist.", "Despite its effectiveness, methadone maintenance is rarely provided in American correctional facilities. This study is the first randomized clinical trial in the US to examine the effectiveness of methadone maintenance treatment provided to prisoners with pre-incarceration heroin addiction.\n A three-group randomized controlled trial was conducted between September 2003 and June 2005. Two hundred eleven Baltimore pre-release inmates who were heroin dependent during the year prior to incarceration were enrolled in this study. Participants were randomly assigned to the following: counseling only: counseling in prison, with passive referral to treatment upon release (n=70); counseling+transfer: counseling in prison with transfer to methadone maintenance treatment upon release (n=70); and counseling+methadone: methadone maintenance and counseling in prison, continued in a community-based methadone maintenance program upon release (n=71).\n Two hundred participants were located for follow-up interviews and included in the current analysis. The percentages of participants in each condition that entered community-based treatment were, respectively, counseling only 7.8%, counseling+transfer 50.0%, and counseling+methadone 68.6%, p<.05. All pairwise comparisons were statistically significant (all ps<.05). The percentage of participants in each condition that tested positive for opioids at 1-month post-release were, respectively, counseling only 62.9%, counseling+transfer 41.0%, and counseling+methadone 27.6%, p<.05, with the counseling only group significantly more likely to test positive than the counseling+methadone group.\n Methadone maintenance initiated prior to or immediately after release from prison appears to have beneficial short-term impact on community treatment entry and heroin use. This intervention may be able to fill an urgent treatment need for prisoners with heroin addiction histories.", "Thirty-four drug addicts, aged 20 - 24 years, with a history of 4 - 8 years of intravenous heroin abuse, were randomly assigned either to a methadone maintenance treatment (MMT) (17) or to an untreated group (17). The untreated controls could not apply for entrance to the program until two years later. It was found that after two years 12 MMT patients had abandoned their drug habits and begun work, whereas 5 had recurrent drug abuse problems. Of the controls, one was drug-free and gainfully employed, 12 were continuously abusing heroin (3 of these had incurred potentially fatal diseases in consequence), 2 were in prison and 2 had diet. Two to seven years after their first visit to the Psychiatric Research Center 8 of the original control group have been accepted into the program. At present 19 (out of 25 admitted) are gainfully employed and no longer abusing drugs. Among the remaining controls 4 are dead, 3 are in prison, one in spite of a serious heart condition abuses heroin and one is drug-free. The rehabilitation rate was thus 76 per cent in the program as compared to 6 per cent among the control group. In addition, MMT obviously reduced the high morbidity and mortality rates found in a selection of heroin addicts who fulfilled the admittance criteria of the Swedish program.", "To compare the dose effectiveness of low to moderate doses of methadone in a sample of a contemporary population of opioid abusers, because the optimal dosing of methadone in the treatment of opioid dependence remains an issue.\n A randomized, double-blind, placebo-controlled study.\n A methadone treatment research clinic.\n Participants (n = 247) were opioid-dependent patients with a high rate of cocaine use.\n All participants were initially treated with active methadone for a minimum of 5 weeks and then received 15 weeks of stable dosing at 50, 20, or 0 mg per day. Individual counseling and group therapy were included.\n Treatment retention and illicit drug use as determined by intensive urine monitoring.\n Retention was better for patients who remained on active medication. By treatment week 20, retention was 52.4% for the 50-mg, 41.5% for the 20-mg, and 21.0% for the 0-mg group (50 versus 0 and 20 versus 0, P < 0.05; 50 versus 20, P > 0.05). Only the 50-mg treatment group had a reduced rate of opioid-positive urine samples (56.4% versus 67.6% and 73.6% for the 20-mg and 0-mg groups, respectively; P < 0.05) and cocaine-positive urine samples (52.6% versus 62.4% and 67.1% for the 20- and 0-mg groups, respectively; P < 0.05).\n There is a dose-response effect for methadone treatment. Doses as low as 20 mg may improve retention but are inadequate for suppressing illicit drug use.", "Important questions remain regarding the necessary duration and intensity for methadone treatment to be effective.\n As part of a clinical trial of tuberculosis chemoprophylaxis [Batki, S.L., Gruber, V.A., Bradley, J.M., Bradley, M., Delucchi, K., 2002. A controlled trial of methadone treatment combined with directly observed isoniazid for tuberculosis prevention in injection drug users. Drug Alcohol Depend. 66 283-293. doi:10.1016/S0376-8716(01)00208-3], patients with opioid dependence were recruited from an outpatient 21-day methadone detoxification program and were randomly assigned to one of three treatment conditions: (1) continuation in 21-day methadone detoxification; (2) transfer to 6-month methadone maintenance with only minimal counseling; or (3) transfer to 6-month methadone maintenance with standard twice monthly counseling and as-needed social work and psychiatric services. Both the 6-month maintenance treatments were followed by 1.5 months of detoxification. Urine drug tests and self-report measures were collected at baseline, months 1-6, and month 8.5.\n Compared to 21-day methadone detoxification, 6-month methadone maintenance with either minimal or standard counseling resulted in fewer opiate positive urine tests and days of self-reported heroin and alcohol use. There was no change in cocaine use or other outcome measures. The increased counseling available in the standard counseling condition did not appear to reduce heroin use further than the minimal counseling condition, in contrast to the effect found for more structured counseling in long-term methadone maintenance (McLellan et al., 1993).\n Six months of methadone maintenance, even with minimal counseling, reduces heroin and alcohol use more than 21-day methadone detoxification.", "This study represents the first controlled trial of methadone maintenance and 45-day methadone detoxification in Thailand. We randomly assigned 240 male heroin addicts with at least six prior detoxification treatment episodes to 45-day detoxification or to methadone maintenance treatment conditions. We found that methadone maintenance clients were more likely to complete 45 days of treatment (p less than .00001), were less likely to have used heroin during treatment (p less than .0002), and were less likely to have used heroin on the 45th day of treatment (p less than .000007). These findings are consistent with the results of other studies in the United States, and we conclude that methadone maintenance could be a significant adjunct to AIDS prevention efforts for intravenous drug users in Thailand.", "nan" ]

[ "11111780", "1638191", "12839376", "11993510", "10659481", "4441827" ]

[ "6-mercaptopurine or methotrexate added to prednisone induces and maintains remission in steroid-dependent inflammatory bowel disease.", "Randomised controlled trial of azathioprine withdrawal in ulcerative colitis.", "Azathioprine versus sulfasalazine in maintenance of remission in severe ulcerative colitis.", "The beneficial effect of azathioprine on maintenance of remission in severe ulcerative colitis.", "Role of azathioprine in severe ulcerative colitis: one-year, placebo-controlled, randomized trial.", "Azathioprine in ulcerative colitis: final report on controlled therapeutic trial." ]

[ "As treatment of steroid-dependent patients with inflammatory bowel disease (IBD) is controversial, we analysed the efficacy and tolerance of 6-mercaptopurine (6-MP) and methotrexate (MTX) added to prednisone in increasing and maintaining the disease remission rate.\n Seventy-two steroid-dependent IBD patients, 34 with ulcerative colitis (UC) and 38 with Crohn's disease (CD), receiving treatment with prednisone were randomly assigned in a 2:2:1 ratio to additionally receive, orally, over a period of 30 weeks 1.5 mg/kg/day of 6-MP (group A) or 15 mg/week of MTX (group B), or 3 g/day of 5-aminosalicylic acid (5-ASA) (group C). All patients who achieved remission were included in a maintaining remission study for 76 weeks. Remission was defined after stopping prednisone as a CD activity index of <150 and normal serum orosomucoid concentration for CD patients and a Mayo Clinic score <7 for UC patients.\n With regard to achieved remission, a significantly higher (P< 0.05) rate existed for UC patients in group A (78.6%) than in group C (25%), with no statistical differences in group B (58.3%) versus C. For CD patients, the rates were significantly higher (P< 0.001 and 0.01, respectively) in groups A (93.7%) and B (80%) versus C (14%). With regard to maintaining remission, UC patients in group A (63.6%) presented significantly higher rates (P < 0.0015 and P < 0.001, respectively) versus 14.3% in group B and none in group C. For CD patients, statistical differences (P < 0.001) existed when comparing rates in groups A (53.3%) and B (66.6%) versus none in group C. Noticeable side effects appeared in 13.3% of patients from group A and 11.5% from group B.\n These results suggest that 6-MP or MTX added to prednisone could be effective in steroid sparing, as well as in achieving and maintaining remission in steroid-dependent IBD patients. MTX was less effective in maintaining remission in UC patients.", "To determine whether azathioprine can prevent relapse in ulcerative colitis.\n One year placebo controlled double blind trial of withdrawal or continuation of azathioprine.\n Outpatient clinics of five hospitals.\n 79 patients with ulcerative colitis who had been taking azathioprine for six months or more. Patients in full remission for two months or more (67), and patients with chronic low grade or corticosteroid dependent disease (12) were randomised separately. 33 patients in remission received azathioprine and 34 placebo; five patients with chronic stable disease received azathioprine and seven placebo.\n Rate of relapse. Relapse was defined as worsening of symptoms or sigmoidoscopic appearance.\n For the remission group the one year rate of relapse was 36% (12/33) for patients continuing azathioprine and 59% (20/34) for those taking placebo (hazard rate ratio 0.5, 95% confidence interval 0.25 to 1.0). For the subgroup of 54 patients in long term remission (greater than six months before entry to trial) benefit was still evident, with a 31% (8/26) rate of relapse with azathioprine and 61% (17/28) with placebo (p less than 0.01). For the small group of patients with chronic stable colitis (six were corticosteroid dependent and six had low grade symptoms) no benefit was found from continued azathioprine therapy. Adverse events were minimal.\n Azathioprine maintenance treatment in ulcerative colitis is beneficial for at least two years if patients have achieved remission while taking the drug. Demonstration of the relapse preventing properties of azathioprine has implications for a large number of patients with troublesome ulcerative colitis, who may benefit from treatment with azathioprine.", "Azathioprine is useful as a steroid-sparing drug in patients with ulcerative colitis. Its role as monotherapy in the maintenance of disease remission has not been evaluated.\n In this prospective, randomized, open-label study, 25 patients with severe ulcerative colitis received either azathioprine (2.5 mg/Kg/day; Group A, n = 12) or sulfasalazine (6 g/day; Group B, n = 13). All patients received oral corticosteroids in a tapering dosage schedule initially. Treatment failure was defined as either disease relapse or drug withdrawal because of adverse effects.\n Five of 12 patients in Group A and 8 of 13 patients in Group B had sustained remission during the stipulated study period of 18 months (p = ns). Two patients in Group A had to stop azathioprine because of adverse effects (bone marrow suppression and acute pancreatitis). In Group A, all patients who had treatment failure developed it in the first half of the study while in Group B treatment failure occurred in both halves.\n The relapse rate of ulcerative colitis on maintenance therapy with azathioprine or sulfasalazine is comparable; there was a trend towards earlier treatment failure with azathioprine.", "The search is on to find more effective drug regimens for patients with severe ulcerative colitis, as conventional drugs such as sulfasalazine and its congeners fail to prevent relapse in a significant number of patients. Azathioprine has also been reported to be useful as a steroid-sparing drug in patients who suffer from frequent relapses. As these drugs when used individually fail to sustain remission in a significant number of patients, we evaluated the combination of these two drugs.\n Thirty-five newly diagnosed patients with severe ulcerative colitis were randomized into two groups; group A (combination therapy) received sulfasalazine and azathioprine, while group B (sulfasalazine monotherapy) received sulfasalazine and placebo. In addition, all the patients received steroids initially to achieve clinical remission. The patients were followed-up for a period of 1 year. The therapeutic outcome was measured by the number of patients who suffered relapse in each group.\n All the patients completed the 1-year study period. While 4 patients (23.5%) in group A suffered relapse of disease, 10 (55.6%) in group B suffered relapse, the difference being statistically significant. The relapse-free period was also significantly longer in group A.\n Combination therapy (sulfasalazine and azathioprine) is more effective than sulfasalazine and placebo in the maintenance of remission in patients with severe ulcerative colitis.", "To investigate the efficacy of azathioprine in treating patients with severe ulcerative colitis.\n One-year, randomized, placebo-controlled trial.\n 83 patients with severe ulcerative colitis were enrolled. Fifty patients who relapsed within two months on corticosteroid withdrawal were randomized into two groups. The azathioprine group received oral sulfasalazine (6-8 g/day), oral prednisolone (1 mg/Kg/day) and oral azathioprine (2 mg/Kg/day). The placebo group received oral sulfasalazine (6-8 g/day), oral prednisolone (1 mg/Kg/day) and placebo. Corticosteroids were tapered over 12-16 weeks.\n Five patients (2 in azathioprine group, 3 in placebo group) dropped out of the study. Three patients in the azathioprine group had side effects. The number of patients going into complete remission and partial remission was not significantly different in the two groups. The proportion of relapses in the azathioprine group was lower than in the placebo group (p < 0.05).\n In patients with ulcerative colitis, azathioprine had no effect in achieving remission, when given in combination with prednisolone; however, it lowers the proportion of relapses. Side effects like pancreatitis and hepatitis are mild and respond promptly to drug withdrawal.", "Eighty patients, all of whom were suffering from a frank clinical attack of ulcerative colitis, were admitted to the trial. The attack was treated with a standard course of corticosteroids and the patients were immediately placed on treatment with either azathioprine in a dose of 2.5 mg/kg body weight or dummy tablets. The trial tablets were continued for one year while the patients were maintained under regular clinical, sigmoidoscopic, histological, haematological, and biochemical surveillance. If a patient relapsed during such maintenance treatment he or she was treated with a further course of corticosteroids without interrupting maintenance treatment.In the treatment of an actual attack of ulcerative colitis the results in the attacks which brought the 80 patients into the trial show that no benefit came from the addition of azathioprine to a standard course of corticosteroid therapy.Patients admitted in their first attack of ulcerative colitis showed no benefit from the one-year maintenance treatment with azathioprine, the benefits of which were confined to patients admitted in a relapse of established disease. Even in these the difference between the treated group and the control group failed to reach statistical significance, but the difference was big enough to suggest that there is a prima facie case for regarding azathioprine as of some benefit in this group of patients." ]

[ "12565982", "8181594", "12598347" ]

[ "Treatment of operable breast cancer in the elderly: a randomised clinical trial EORTC 10851 comparing tamoxifen alone with modified radical mastectomy.", "Prospective randomized trial of tamoxifen vs surgery in elderly patients with breast cancer.", "Tamoxifen alone versus adjuvant tamoxifen for operable breast cancer of the elderly: long-term results of the phase III randomized controlled multicenter GRETA trial." ]

[ "For treatment of early breast cancer in older women, little evidence is available from randomised trials. We conducted a randomised trial comparing modified radical mastectomy (MRM) with tamoxifen (TAM) as the sole initial therapy in 164 patients aged >/=70 years with operable breast cancer. 82 were treated by MRM and 82 with TAM. Survival curves were estimated using the Kaplan-Meier method: multivariate analyses were performed using the Cox's proportional hazards model. Endpoints included survival, time to first relapse or progression, loco-regional progression, time to distant progression and progression-free survival. After a median follow-up of approximately 10 years, there was a significantly decreased time to progression in the TAM only group (logrank P<0.0001) and significantly shorter time to local progression within the TAM group (logrank P<0.0001). Overall survival of the two groups was similar. The results indicate that tamoxifen alone leads to an unacceptably high rate of local progression or relapse.", "Between 1982 and 1989, 200 patients aged 70 or over seen in one Breast Unit, who were considered to have a surgically resectable cancer of the breast were prospectively randomized to primary surgery or tamoxifen 20 mg per day. At a median follow-up of 6 years (range 3-11 years) and at the censoring date there were 61 first events in the tamoxifen group. Fifty three patients developed local relapse or progression of the cancer; three patients had simultaneous local progression or relapse and distant metastases. In addition a further five patients developed distant recurrence only. In the surgical arm there were 50 events. Thirty-six patients developed local recurrence only; eight had simultaneous local and distant recurrence. A further six patients developed distant metastases of which two subsequently developed local recurrence. There were 33 deaths in the tamoxifen group and 28 deaths in the surgical group of which 17 and 15, respectively were directly attributable to breast cancer. The disease-free interval did not differ between the two groups. Following treatment with tamoxifen, at the censoring date which was the date of last clinical examination or arbitrarily, the date of death, 39 patients had no evidence of relapse whereas in the surgical arm there were 50 patients who had no evidence of recurrence. Fifty-three patients in the tamoxifen arm had local relapse only and were available for crossover to surgery, 39 accepted surgery. Eight developed further local recurrence, 10 developed distant metastases and 21 remained free of disease. Thirty-six patients in the surgical group developed local relapse only and were available for crossover to tamoxifen. Thirty one accepted treatment with tamoxifen, 14 had progression of their local recurrence, seven developed distant metastases and 10 had no further recurrence. Thus in the tamoxifen group, 39 had no progression of their disease and a further 21 benefited from subsequent surgery: 60% in all. In the surgical group 50 had no recurrence of their disease and a further 10 benefited from subsequent tamoxifen therapy: 60% in all.", "To evaluate the efficacy of tamoxifen as primary treatment in women aged over 70 years with operable breast cancer versus surgery followed by adjuvant tamoxifen.\n Patients randomly received tamoxifen alone (160 mg day 1, then 20 mg/day) for 5 years or surgery followed by tamoxifen (20 mg/day) for 5 years. Overall survival was the main study end point; secondary objectives included breast cancer survival and local control of the disease.\n Between 1987 and 1992, 239 patients were assigned to surgery plus tamoxifen and 235 to tamoxifen alone. Treatment arms were comparable for tumor size, clinical nodal status and performance status. At a median follow-up of 80 months 274 patients had died. No difference between groups had emerged in overall and breast cancer survival. There were 27 local progressions in the surgery plus tamoxifen group and 106 in the tamoxifen-alone group (P = 0.0001). In the surgery plus tamoxifen group, no difference in overall survival had emerged according to the extension of operation.\n The long-term results of the study confirm the 3-year interim analysis already reported. Surgery (radical or minimal) followed by adjuvant tamoxifen does not modify overall and breast cancer survival as compared with tamoxifen alone in early breast cancer of older women. Because of the high rate of local progressions with tamoxifen alone, minimal surgery followed by tamoxifen appears to be the appropriate treatment in such patients. More extensive surgery is not useful. Tamoxifen alone is an adequate alternative treatment in very old or frail patients." ]

[ "2102144", "6644648", "6375800", "11359886", "15913526", "2102672", "11031403", "16550669", "2333596", "2341458", "1991748", "18155581", "6393510", "3349312", "12828699" ]

[ "Ingrowing toenails: studies of segmental chemical ablation.", "Surgical wedge excision versus phenol wedge cauterisation for ingrowing toenail. A controlled study.", "Segmental phenolization of ingrowing toenails: a randomized controlled study.", "Wound healing and infection in nail matrix phenolization wounds. Does topical medication make a difference?", "A prospective randomized comparison of the Zadik procedure and chemical ablation in the treatment of ingrown toenails.", "Randomized, prospective study of nail bed ablation for recurrent ingrowing toenails.", "Are antibiotics necessary in the treatment of locally infected ingrown toenails?", "Honey dressing versus paraffin tulle gras following toenail surgery.", "Ingrowing toenails: improving treatment.", "The treatment of ingrowing toenails. A randomised comparison of wedge excision and phenol cauterisation.", "The surgical treatment of ingrowing toenails.", "Partial matrix excision or orthonyxia for ingrowing toenails.", "[Orthonyxia compared with the conservative treatment in ingrown nails of the great toe. A controlled study].", "Approach to ingrowing toenails: the wedge resection/segmental phenolization combination treatment.", "Nail-splinting technique for ingrown nails: the therapeutic effects and the proper removal time of the splint." ]

[ "Recent studies have suggested that segmental ablation is the treatment of choice for patients with ingrowing toenails and that the success rate is 96%. This procedure has been common practice among chiropodists for 20 years, usually using phenol in the United Kingdom, and sodium hydroxide in the United States. However, there has been little critical evaluation of the relative merits of the two chemicals, of the period of chemical application, or of the duration of post-operative pain and healing time. We therefore embarked upon a number of controlled prospective studies to examine these questions. A prospective study of 422 procedures for patients with ingrowing toenails (onychocryptosis) shows that good results are achieved by segmental chemical ablation performed by chiropodists in 91% of cases. The average period of post-operative pain is 3.6 days. Similar results are obtained using either 80% phenol or 10% sodium hydroxide. We believe that segmental chemical ablation by a chiropodist is the treatment of choice for the typical patient with an ingrowing toe nail.", "nan", "One hundred and three patients, on whom 107 procedures for ingrowing toenails were performed, were randomly allocated into one of two treatment groups: segmental or angular phenolization and wedge excision. There were 53 wedge excisions and 54 segmental phenolizations. Post-treatment discomfort was assessed on a linear analogue scale of 10 cm. There was no difference between the two groups one week after treatment. Over a mean follow-up period of 14 months a total of 20 nail spikes occurred, 4 in the phenolized group and 16 in the wedge excision group, this being a significant difference at the one per cent level.", "After nail matrix ablation using phenolization, a medicated wound dressing (10% povidone iodine), an amorphous hydrogel dressing (Intrasite Gel), and a control dressing (paraffin gauze) were evaluated. Forty-two participants, randomly divided into three dressing groups, were evaluated. Healing time did not differ between the 10% povidone iodine (33 days), amorphous hydrogel (33 days), and the control dressing (34 days). For all groups, the clinical infection rate was lower than in previous studies, and there was no clinical difference between groups (one infection in the povidone iodine and control groups; none in the amorphous hydrogel group). However, in the amorphous hydrogel group, other complications, such as hypergranulation, were more likely. This investigation indicated that medicated or hydrogel dressings did not enhance the rate of healing or decrease infection rates.", "We present the results of a prospective randomized trial of the Zadik procedure versus chemical ablation by sodium hydroxide for the treatment of ingrowing toenails.\n Thirty-eight patients had the Zadik procedure, and 45 patients had chemical ablation by sodium hydroxide. Mean followup was 12.45 months for the Zadik group and 11.69 months for the chemical ablation group.\n In the Zadik group, the average return to normal shoe-wear was 2.13 weeks and in the chemical ablation group 3.73 weeks. Average return to normal activity was 2.18 weeks for the Zadik group and 3.89 weeks for the chemical ablation group. The median number of dressings were 3 and 8 for the Zadik and chemical ablation groups, respectively. The pain score, using the visual analogue scale were not statistically significant between the two groups. The recurrence rates were 23 recurrences in the Zadik group (60.5%) and seven recurrences in the chemical ablation group (15.6%).\n The use of chemical ablation by sodium hydroxide in the treatment of ingrowing toenails shows statistically significant (p < 0.05) reduction in recurrence rates of ingrowing toenails compared to the Zadik procedure.", "A consecutive series of 31 recurrent ingrowing toenails, which had previously undergone at least two surgical procedures, were recruited to this study over a 1-year period. Patients were randomly allocated to one of two treatment groups. Group A underwent nail bed excision whilst group B had nail bed phenolization in addition to excision. Patients were reviewed 2 weeks and 1 year after operation. Seven toes (41%) in group A developed postoperative infection compared with only one (7%) in group B (P less than 0.01). Recurrent nail spicules occurred in ten patients (59%) in group A and six patients (43%) in group B 1 year after operation. High failure rates for ablation of recurrent ingrowing toenails should encourage greater efforts towards adequate treatment at the first presentation.", "A wide variety of generalists and specialists treat locally infected ingrown toenails, with perhaps the most common treatment regimen including resection of the nail border coupled with oral antibiotics.\n To determine whether oral antibiotic therapy is beneficial as an adjunct to the phenol chemical matrixectomy in the treatment of infected ingrown toenails.\n We prospectively enrolled healthy patients with infected ingrown toenails. Each patient was randomly assigned to 1 of 3 groups that received either 1 week of antibiotics and a chemical matrixectomy simultaneously (group 1), antibiotics for 1 week and then a matrixectomy (group 2), or a matrixectomy alone (group 3).\n Institutional ambulatory outpatient clinic.\n Fifty-four healthy patients with infected ingrown toenails were studied. Patients with immunocompromised states, peripheral vascular disease, or cellulitis proximal to the hallux interphalangeal joint were excluded. Groups were age matched for comparison.\n Mean healing times for groups 1, 2, and 3 were 1.9, 2.3, and 2.0 weeks, respectively. Subjects receiving antibiotics and a simultaneous chemical matrixectomy (group 1) healed significantly sooner than those receiving a 1-week course of antibiotics followed by a matrixectomy (group 2). There was not a significant difference in healing time between those that received a chemical matrixectomy alone (group 3) and those that received a matrixectomy coupled with a course of oral antibiotics (group 1).\n The use of oral antibiotics as an adjunctive therapy in treating ingrown toenails does not play a role in decreasing the healing time or postprocedure morbidity.", "Anecdotal reports suggest that certain honey dressings have a positive effect on wound healing. However, there is limited empirical evidence supporting its use. This double-blind randomised controlled trial investigated the effect of a honey dressing on wound healing following toenail surgery with matrix phenolisation.\n Participants (n=100) were randomly assigned to receive either an active manuka honey dressing (n=52) or paraffin-impregnated tulle gras (n=48). The primary outcome was time (days) taken for complete re-epithelialisation of the nail bed.\n Mean healing times were 40.30 days (SD 18.21) for the honey group and 39.98 days (SD 25.42) for the paraffin tulle gras group. Partial avulsion wounds healed statistically significantly faster (p=0.01) with paraffin tulle gras (19.62 days, SD 9.31) than with the honey dressing (31.76 days, SD 18.8), but no significant difference (p=0.21) was found following total avulsion when comparing honey (45.28 days, SD 18.03.) with paraffin tulle gras dressings (52.03 days, SD 21.3).\n The results suggest that patients may benefit more from paraffin tulle gras dressings than honey dressings following partial toenail avulsion. No statistically significant difference was found for healing times after total toenail avulsion, although the marginal benefit of the honey dressing on these healing times warrants further investigation.", "Sixty-six patients with ingrowing toenails were randomly assigned to one of two treatment groups and followed up for 16 to 30 months after surgery. In group A 39 nail edges in 32 patients were treated by excision of the nail edge and chemical ablation of germinal matrix edge with 70% aqueous phenol. There were 34 patients in group B, in whom 46 nail edges and germinal matrix edges were surgically excised. In group A recurring symptoms developed in four (10%) nail edges, necessitating further surgery, and asymptomatic spicules developed in seven (18%) nail edges. Two (4%) nails in group B required reoperation and spicules developed in 10 (22%). Both procedures were performed as outpatient surgery, relieved pain and infection, and were acceptable to patients. At an average 2-year follow-up, both procedures yielded comparable results that were superior to those of simple avulsion.", "We treated 249 patients for ingrowing toenails in a prospective randomised study which compared wedge excision with segmental phenol cauterisation. Follow-up of 97% was at a minimum of 14 months. The analgesic requirement was significantly lower after phenol cauterisation (p less than 0.001), and significantly fewer patients needed to miss school or work (p = 0.001). Recurrence of ingrowth was seen in 16% after wedge excision and 9.6% after phenol cauterisation (not significant), but re-operation was significantly less frequent after phenol (p less than 0.01). Phenol cauterisation gives better short-term and long-term results than wedge resection.", "Two prospective studies of ingrowing toenail management were conducted. In the first, 163 patients (204 ingrowing nail edges) who had not had previous surgery were randomised and treated by total nail avulsion, nail edge excision, or nail edge excision with phenolisation of the germinal matrix; recurrence rates one year postoperatively were 73%, 73% and 9% respectively. In the second study, 63 ingrowing nail edges which had recurred after previous operations underwent nail edge excision and phenolisation. There was a 5% recurrence rate and 5% incidence of dystrophy of the nail one year after operation.", "We wanted to evaluate whether partial matrix excision and orthonyxia are equally effective in the treatment of ingrown toenails of the hallux.\n We conducted a prospective randomized clinical trial with 12-month observer-blinded followup, in the surgical outpatient department of a teaching hospital. We randomized 105 consecutive patients with a total of 109 ingrown toenails to either partial matrix excision (n=58) or an orthonyxia procedure (n=51). The main outcomes measurements were rate of recurrence after 12 months, postoperative morbidity, and time to complete recovery.\n The 12-month followup was completed in 55 of 58 patients undergoing partial matrix excision and 47 of 51 patients having orthonyxia. There were four ingrown toenails, four recurrences in the partial matrix excision group, and eight in the orthonyxia group (NS, p=0.14). Postoperative morbidity parameters (redness, pus, postoperative bleeding); time to complete recovery, wearing shoes (p < 0.01), and performing activities of daily living and hobbies; postoperative symptoms; and patient satisfaction all favored orthonyxia.\n Partial matrix excision and orthonyxia are equally effective treatments for ingrown toenails. But the orthonyxia procedure showed better results, with less postoperative morbidity, shorter time to complete recovery, fewer postoperative symptoms, and greater patient satisfaction.", "nan", "One hundred and seventy procedures were performed on one hundred and forty patients with ingrowing toenails. Each patient was randomly allocated to one of three treatment groups. There were 55 wedge resections (WR), 53 segmental phenolizations (SP) and 62 wedge resection/segmental phenolization combination treatments (WR/SP). All patients were followed up for 6 months. The duration and intensity of postoperative pain was assessed and the recurrence rate monitored. Postoperative pain was less in the WR/SP group (9.4 +/- 13.5 h) than in the WR group (30.0 +/- 37.6 h, P less than 0.001). There were seven recurrences in the WR group, four in the SP group, and none in the WR/SP group. The results in the WR/SP group were statistically significant when compared with the WR group (P less than 0.01) and with the SP group (P less than 0.05). We conclude that the WR/SP combination procedure is a superior form of treatment for ingrowing toenails.", "An ingrown nail is a common disorder that occurs most frequently in the great toe and causes much discomfort in patients. Although many therapeutic methods have been described, most of them can lead to severe damage to the nail or to frequent relapses. The nail-splinting technique is known to be a noninvasive therapeutic method for treating an ingrown nail.\n Our purpose was to access the recurrence rate of the nail-splinting technique and to determine the proper removal time of the splint from the ingrown nail.\n Fifty-seven patients with ingrown nail were treated with the nail-splinting technique. Subjects were randomized into two groups. For group 1 (28 patients), the splint was removed splint 3 days after treatment, whereas for group 2 (29 patients), the splint was removed splint 2 weeks after treatment. All patients underwent a follow-up examination at 1, 2, and 4 weeks after treatment and were evaluated for tissue status and level of pain. After 1 year, we evaluated the rate of recurrence by means of a telephone interview with each patient.\n A low recurrence rate (8.7%) for the nail-splinting technique was observed in both groups (7.1% in group 1 vs. 10.3% in group 2). The tissue status and level of pain were found to improve with time, with no statistical significance between the two groups (P> 0.05).\n This study indicates that the nail-splinting technique constitutes a very simple and effective, noninvasive therapeutic method for treating ingrown nail. We suggest that the 3-day nail-splinting technique is the most useful when the nail is intact or has only a slight defect." ]

[ "19439137", "7204438", "8291628", "18645042", "17885221", "1508765", "17761317", "11503980", "18066530", "19411457", "11521926" ]

[ "Open versus minimal invasive repair with Achillon device.", "Surgical and non-surgical treatment of Achilles Tendon rupture. A prospective randomized study.", "Operative versus nonoperative treatment of Achilles tendon rupture. A prospective randomized study and review of the literature.", "Acute Achilles tendon rupture: minimally invasive surgery versus nonoperative treatment with immediate full weightbearing--a randomized controlled trial.", "Early motion for Achilles tendon ruptures: is surgery important? A randomized, prospective study.", "Separation of tendon ends after Achilles tendon repair: a prospective, randomized, multicenter study.", "End-to-end versus augmented repair in the treatment of acute Achilles tendon ruptures.", "Percutaneous vs. open repair of the ruptured Achilles tendon--a prospective randomized controlled study.", "Open versus percutaneous repair in the treatment of acute Achilles tendon rupture: a randomized prospective study.", "Augmented compared with nonaugmented surgical repair of a fresh total Achilles tendon rupture. A prospective randomized study.", "Acute rupture of tendon Achillis. A prospective randomised study of comparison between surgical and non-surgical treatment." ]

[ "We prospectively analyzed and compared the functional and clinical results of patients with standard open and minimally invasive repair with the Achillon suture system at mid-term followup.\n From February 2004 to May 2007, 40 consecutive patients were operated for the treatment of acute Achilles tendon rupture with two different methods. None of the cases required adjunctive procedures like plantaris, flexor hallucis longus or gastrocnemius augmentation (Lindholm, Bosworth) to allow for acceptable end to end apposition. The patients were divided equally into two groups. In Group 1, only Krakow end-to-end suturing technique and in Group 2, Minimal invasive repair with Achillon suture system (Integra Life Sciences Corporation, Plainsboro, NJ) was used respectively. The average age of the patients was 40 years. Patients in study groups were followed up at mean of 22.4 (range, 10 to 48) months after surgery. At the end of the followup time, functional outcome scores and complications were evaluated.\n The AOFAS hindfoot clinical outcome scores were 98.7 in Group 1, 96.8 in Group 2. Although there was a numerical increase in AOFAS Scores in Group 1, there was no significant difference. The surgical outcome concerning local tenderness, skin adhesions, scar and tendon thickness was better in Group 2 than in Group 1 with statistical significance.\n Although functional outcomes of both treatment groups were the same, minimally invasive repair with the Achillon suture system provided safe, reliable and practical treatment with low risk of complications in the treatment of acute Achilles tendon ruptures.", "One hundred and five consecutive patients with a closed acute rupture of the tendo achillis were assigned randomly for surgical or non-surgical treatment. After treatment, the patients were evaluated clinically and with static and dynamic measurements of plantar flexion strength. Only minor differences were noted between the final results in the two groups. Non-surgical treatment had the advantages of shorter morbidity and no hospital stay. The frequency of major complications was about the same in both groups of patients: two re-ruptures and two deep infections in patients who had operations as compared with five re-ruptures in the conservatively treated patients. I concluded that non-surgical treatment offers advantages over surgical treatment.", "One hundred eleven patients with acute rupture of the Achilles tendon were included in a prospective trial and randomly assigned to groups for operative (56 patients) or nonoperative (55 patients) treatment. All of the patients were followed with clinic evaluations at 4 months and 1 year after the rupture. The major complications in the operative treatment group were three reruptures and two deep infections as compared with seven reruptures, one second rerupture, and one extreme residual lengthening of the tendon in the nonoperative group. There were fewer minor complications in the nonoperative group than in the operative group. The operatively treated patients had a significantly higher rate of resuming sports activities at the same level, a lesser degree of calf atrophy, better ankle movement, and fewer complaints 1 year after the accident. The conclusion we reached through this randomized prospective study is that operative treatment of ruptured Achilles tendons is preferable, but nonoperative treatment is an acceptable alternative.", "Surgical repair of acute Achilles tendon ruptures is considered superior to nonoperative treatment, but complications other than rerupture range up to 34%. Nonoperative treatment by functional bracing seems a promising alternative.\n Nonoperative treatment of acute Achilles tendon rupture with functional bracing reduces the number of complications compared with surgical treatment with a minimally invasive technique.\n Randomized controlled clinical trial; Level of evidence, 2.\n Using concealed random allocation, 83 patients with acute Achilles tendon rupture were assigned to nonoperative treatment by functional bracing or minimally invasive surgical treatment followed by tape bandage. Patients were allowed full weightbearing, and follow-up was 1 year.\n Complications risk other than rerupture by intention-to-treat basis was 9 in 42 patients (21%) for surgical treatment and 15 in 41 patients (36%) for nonoperative treatment (risk ratio, 0.59; 95% confidence interval, 0.29-1.19). Reruptures risk was 5 in 41 patients after nonoperative treatment and 3 in 42 patients for surgical treatment (risk ratio, 0.59; 95% confidence interval, 0.15-2.29). The mean time to work was 59 days (SD, 82) after surgical treatment and 108 days (SD, 115) after nonoperative treatment (difference, 49 days; 95% confidence interval, 4-94; P < .05). The difference between treatments for return to sports (risk ratio, 0.55; 95% confidence interval, 0.23-1.29), pain, and treatment satisfaction did not reach statistical significance.\n There appears to be a clinically important difference in the risk of complications between minimally invasive surgical treatment and nonoperative treatment for acute Achilles tendon ruptures, but this was not statistically significant.", "Comparisons of surgically and nonsurgically treated Achilles tendon ruptures have demonstrated that those treated with surgery allow earlier motion and tend to show superior results. However, early motion enhances tendon healing with or without surgery and may be the important factor in optimizing outcomes in patients with Achilles tendon rupture.\n There is no difference in the outcome of acute Achilles tendon rupture treated nonoperatively or operatively if controlled early motion is allowed as part of the rehabilitation program.\n Randomized, controlled clinical trial; Level of evidence, 1.\n Patients with acute rupture of the Achilles tendon were randomized to surgery or no surgery, with both groups receiving early motion controlled in a removable orthosis, progressing to full weightbearing at 8 weeks from treatment. Both groups were followed prospectively for 12 months with measurements of range of motion, calf circumference, and the Musculoskeletal Functional Assessment Instrument (MFAI) outcome score; any reruptures and any complications were noted.\n Both groups were comparable for age and sex. There were no significant differences between the 2 groups in plantar flexion, dorsiflexion, calf circumference, or the MFAI scores measured at 2, 8, 12, 26, or 52 weeks. One patient in each group was noncompliant and required surgical rerepair of the tendon. There were no differences in complications and a similar low number of reruptures in both groups.\n This study supports early motion as an acceptable form of rehabilitation in both surgically and nonsurgically treated patients with comparable functional results and a low rerupture rate. There appears to be no difference between the 2 groups, suggesting that controlled early motion is the important part of treatment of ruptured Achilles tendon.", "Fifty-seven patients treated for an acute rupture of the Achilles tendon were studied. The patients were randomized into a Mason suture technique or a reinforced continuous six-strand suture technique, and markers were attached to each tendon end perioperatively. The postoperative separation of the markers was studied by repeat radiographic examination. Despite immobilization, separation developed after a biphasic course, and after 7 weeks the mean separation was 10.5 mm. No difference was found between the two techniques. We attempt to correlate the separation to the clinical outcome, examined at 1 year follow up.", "We prospectively analyzed the functional and clinical results of patients who underwent a single end-to-end suture and an augmented tendon repair with plantaris tendon at middle-term follow-up. From January 2003 to May 2005, 30 consecutive patients were operated on for the treatment of acute Achilles' tendon rupture by means of 2 different methods. No cases required adjunctive procedures to allow for acceptable end-to-end apposition. All ruptures were acute and repairable. The patients were divided into 2 groups. In group 1, augmentation with plantaris tendon was performed in addition to the Krakow end-to-end suturing technique in 16 patients, and in group 2, only the Krakow end-to-end suturing technique was used in 14 patients. The average age of the patients was 40.6 years. Patients in the study groups were followed up at a mean of 17.8 months after surgery. At the end of the follow-up, functional and subjective outcome scores were evaluated. The American Orthopaedic Foot and Ankle Society hindfoot clinical outcome scores were 96.7 in group 1 and 98.8 in group 2. Although there was a numerical increase in group 2, no significant difference was determined between the 2 study groups statistically. The surgical outcome concerning local tenderness, skin adhesion scar, and tendon thickness was better in group 2 than in group 1 without a statistical significance. Although functional outcomes of both treatment groups were the same, the end-to-end suturing technique provided a safer and more reliable treatment with a low risk of complications in the treatment of acute Achilles' tendon ruptures compared with the plantaris tendon augmentation technique.", "A prospective randomized controlled trial comparing open and percutaneous repair of closed ruptured Achilles tendons was performed over a period of 30 months. Sixty-six patients from seven district general hospitals were entered into the study with 33 patients randomized into each group. A modification of the technique described by Ma and Griffith was used in the percutaneous group and a Kessler suture supplemented with interrupted sutures was used in the open group. Patients were followed up for a minimum of six months. The mean age was 38.5 years (26 to 53 years). Forty patients were male and 26 female. After the rupturing event but prior to surgery, it was noted that seven patients had paresthesia in the territory of the sural nerve. The mean duration of immobilization was 12.4 weeks (10 to 14). The complications in the open group included seven wound infections (21%), two adhesions (6%) and two cases of re-rupture (6%). In the percutaneous group there were three cases of wound puckering (9%), one re-rupture (3%) and one case with persistent paresthesia in the sural nerve territory (3%). The difference in infective wound complications between the two groups was statistically significant (Fisher's exact test P = 0.01). Percutaneous repair is advocated on the basis of the low rate of complications and improved cosmetic appearance.", "There is no agreement on the ideal type of surgical management for Achilles tendon rupture. The present randomized prospective study was performed to compare outcome data of open and percutaneous repair in the treatment of Achilles tendon rupture. Forty consecutive patients with acute rupture of Achilles tendon were recruited. Patients were randomized to receive open (group A) or percutaneous repair with Tenolig (group B). All patients followed the same rehabilitation protocol except for slight differences in the duration of immobilization. Follow-up included objective evaluation (at 4 and 12 months), subjective evaluation using the SF-12 questionnaire (at 24 months), and bilateral ultrasound scanning and isokinetic testing (at 12 months). The differences in the parameters evaluated clinically were not significant except for ankle circumference, which was significantly greater in group B. There were two minor complications in the open repair group and one case of failed repair in the percutaneous group. SF-12 questionnaire, ultrasound and isokinetic test data did not show significant differences between the groups. The present study demonstrates that the open and the percutaneous technique are both safe and effective in repairing the ruptured Achilles tendon and that both afford the same degree of restoration of clinical, ultrasound and isokinetic patterns. Medium-term results were substantially comparable. Percutaneous repair is performed on a day-surgery basis, it reduces cutaneous complications and operation times, and enables faster recovery, enhancing overall patient compliance. To us, these characteristics make it preferable to open repair in managing subcutaneous ruptures of Achilles tendon in non-professional sports practicing adults.", "Augmented and nonaugmented techniques have been used for the operative repair of a fresh complete Achilles tendon rupture. Augmented techniques have been favored for their stronger pullout strengths but have been avoided because of the risk of wound complications. If proven to be equally good, the nonaugmented technique would be the method of choice. In the present study, we hypothesized that augmentation with a down-turned gastrocnemius fascia flap would not provide better results than would end-to-end suture repair with use of the Krackow locking loop surgical technique.\n Sixty patients with an acute Achilles tendon rupture were randomized preoperatively to receive end-to-end suture repair with use of the Krackow locking loop technique either without augmentation (simple repair group) or with a down-turned gastrocnemius fascia flap as described by Silfverskiöld (augmented repair group). A brace allowed free active plantar flexion of the ankle postoperatively, whereas dorsiflexion was restricted to neutral for the first three weeks. Weight-bearing was limited for six weeks. The follow-up period was one year, and the patients were evaluated in terms of clinical measurements, an outcome score, isokinetic calf muscle performance tests, and tendon elongation measurements.\n The mean operative time was twenty-five minutes longer and the incision was 7 cm longer in the augmented repair group as compared with the simple repair group (p < 0.001 for both). In the simple repair group, the overall ankle score was excellent for nineteen patients (63%) and good for eight patients (27%) and three patients (10%) had an early failure (all because of rerupture). In the augmented repair group, the ankle score was excellent for fourteen patients (56%) and good for six patients (24%) and five patients (20%) had a failure because of rerupture (three) or deep infection (two). The difference between the groups with regard to the overall result was not significant (p = 0.68). In the simple repair group the isokinetic calf muscle strength score was excellent for eleven patients (37%), good for fourteen patients (47%), and fair for two patients (7%), with three patients (10%) having a failure, whereas in the augmented repair group the score was excellent for nine patients (36%), good for seven patients (28%), fair for three patients (12%), and poor for one patient (4%), with five patients (20%) having an early failure. Achilles tendon elongation occurred in both groups, and elongation correlated significantly with isokinetic peak torque deficits (rho = 0.64, p = 0.001) and isometric strength deficits (rho = 0.48, p = 0.026) in the simple repair group. No significant differences were seen between the two groups at the three-month and twelve-month checkups with regard to pain, stiffness, subjective calf muscle weakness, footwear restrictions, range of ankle motion, overall outcome, isokinetic calf muscle strength, mean peak work-displacement relationships, or tendon elongation.\n Augmented repair of a fresh total Achilles tendon rupture does not have any advantage over simple end-to-end repair.", "In a prospective, randomised, multicentre study, 112 patients (99 men and 13 women, aged between 21 and 63 years) with acute, complete rupture of tendo Achillis were allocated either to surgical treatment followed by early functional rehabilitation, using a brace, or to non-surgical treatment, with plaster splintage for eight weeks. The period of follow-up was for two years. Evaluation was undertaken by independent observers and comprised interviews, clinical measurements, isokinetic muscle performance tests, heel-raise tests and an overall outcome score. The rate of rerupture was 20.8% after non-surgical and 1.7% after surgical treatment (p < 0.001). Surgical and non-surgical treatment produced equally good functional results if complications were avoided. However, the rate of rerupture after non-surgical treatment was unacceptably high." ]

[ "8805966", "9300508", "21262413", "21324590", "18794505", "20708444", "10209659", "10225245", "20642328", "16627548", "9300509", "2236369", "18188136", "11992983" ]

[ "Breathing retraining: a three-year follow-up study of treatment for hyperventilation syndrome and associated functional cardiac symptoms.", "A controlled trial of cognitive behavioural therapy for non-cardiac chest pain.", "Short-term cognitive behavioral therapy for non-cardiac chest pain and benign palpitations: a randomized controlled trial.", "Effects of coping skills training and sertraline in patients with non-cardiac chest pain: a randomized controlled study.", "Efficacy of functional relaxation and patient education in the treatment of somatoform heart disorders: a randomized, controlled clinical investigation.", "Heart-focused anxiety as a mediating variable in the treatment of noncardiac chest pain by cognitive-behavioral therapy and paroxetine.", "Group psychological treatment for chest pain with normal coronary arteries.", "Cognitive-behavioral therapy for noncardiac chest pain: a randomized trial.", "Group support to improve psychosocial well-being and primary-care demands among women with cardiac syndrome X.", "Treatment of non-cardiac chest pain: a controlled trial of hypnotherapy.", "Non-cardiac chest pain: why was a brief intervention apparently ineffective?", "Psychological treatment for atypical non-cardiac chest pain: a controlled evaluation.", "Cardiac rehabilitation for the treatment of women with chest pain and normal coronary arteries.", "Beneficial therapeutic effects of physical training and relaxation therapy in women with coronary syndrome X." ]

[ "This study was designed to evaluate the long-term effects of paced diaphragmatic breathing on subjects who reported functional cardiac symptoms and who also demonstrated associated signs of hyperventilation syndrome. Subjects were a representative sample composed of 10 out of the original 41 subjects who had participated three years previously in a study designed to evaluate the short-term effects of breathing retraining on functional cardiac symptoms and respiratory parameters (respiratory rate and end-tidal carbon dioxide). The results of this follow-up study indicate that breathing retraining had lasting effects on both respiratory parameters measured. Subjects evidenced significantly higher end-tidal carbon dioxide levels and lower respiratory rates when compared to pretreatment levels measured three years earlier. Subjects also continued to report a decrease in the frequency of functional cardiac symptoms when compared to pretreatment levels. We conclude that breathing retraining has lasting effects on respiratory physiology and is highly correlated with a reduction in reported functional cardiac symptoms.", "The majority of patients presenting to cardiac clinics with chest pain who are reassured they do not have heart disease or other serious physical disorder continue to experience symptoms, worry about heart disease and restrict their activities. This randomized trial investigated the effectiveness of psychological treatment within routine cardiac care.\n Consecutive patients presenting with chest pain and reassured by a cardiologist they do not have heart disease were reassessed 6 weeks later. Those with persistent limiting symptoms were offered the opportunity to participate in a trial of cognitive behavioural therapy.\n Thirty-seven subjects agreed to take part. A number of subjects were unenthusiastic about psychological intervention or, following explanation of the study, regarded further treatment as not being necessary. At 3 months there were significant differences between the treatment group and the control group on key outcome measures of symptoms, mood and activity. At 6 months there were fewer differences but significant advantages of treatment in terms of limitation of activities and worry about physical symptoms.\n We conclude that there is a need for 'stepped' further care following reassurance in the cardiac clinic and that cognitive behavioural treatment is effective with those with persistent disabling symptoms.", "Many patients with noncardiac chest pain or benign palpitations have poor prognosis in terms of symptom persistence, limitations in everyday activities, and reduced health-related quality of life (HRQOL). The aim of the study was to compare a three-session manualized cognitive behavioral therapy (CBT) intervention with normal care for patients with noncardiac chest pain or benign palpitations in a randomized controlled trial.\n Patients with persistent complaints six months after a negative evaluation at a cardiological outpatient clinic were invited to participate. Of the 94 eligible patients, 40 agreed to participate and were randomly assigned to either an intervention or control group. Patients in the intervention group received three manualized sessions with CBT, including one physical activity exposure session. The control group received usual care from their general practitioner.\n There were significantly larger improvements in the treatment group regarding fear of bodily sensations, avoidance of physical activity, depression and some domains of HRQOL at the end of treatment, and at three- and 12-month follow-up. A substantial proportion (about three-quarters) of the intervention effects on depression and avoidance of physical activity could be attributed to (was mediated by) the large reduction in catastrophic interpretations of bodily sensations.\n A three-session program of manualized CBT, including exposure to physical activity, was effective treatment for patients with noncardiac chest pain and benign palpitations up to the 12-month follow-up.\n Copyright © 2011 Elsevier Inc. All rights reserved.", "Non-cardiac chest pain (NCCP) is a common and distressing condition. Prior studies suggest that psychotropic medication or pain coping skills training (CST) may benefit NCCP patients. To our knowledge, no clinical trials have examined the separate and combined effects of CST and psychotropic medication in the management of NCCP. This randomized clinical trial examined the separate and combined effects of CST and antidepressant medication (sertraline) in participants with non-cardiac chest pain. A sample of individuals diagnosed with NCCP was randomly assigned to one of four treatments: (1) CST plus sertraline (CST+sertraline), (2) CST plus placebo (CST+placebo), (3) sertraline alone, or (4) placebo alone. Assessments of pain intensity, pain unpleasantness, anxiety, pain catastrophizing, depression, and physical disability were collected prior to treatment, and at 10- and 34-weeks following randomization. Data analyses revealed that CST and sertraline either alone or in combination significantly reduced pain intensity and pain unpleasantness. The combination of CST plus sertraline may have the greatest promise in that, when compared to placebo alone, it not only significantly reduced pain but also pain catastrophizing and anxiety. Overall, these findings support the importance of further research on the effects of CST and sertraline for non-cardiac chest pain.\n Copyright © 2010. Published by Elsevier B.V.", "Recurrent heart problems and, especially, chest pain in the absence of somatic heart disease is a common finding, although challenging to treat.\n The authors assessed a body-oriented approach to the somatic fixation frequently seen in these patients.\n They conducted a controlled study to assess the effect of functional relaxation in 22 patients with non-specific chest pain. The primary outcome measures were self-reported changes on the subscales Somatization and Anxiety of the Symptom Checklist of Derogatis, as well as the subscale Cardiovascular Complaints of the Giessen Inventory of Complaints.\n Significant improvements of the primary outcome measures were observed in patients treated with functional relaxation, whereas no significant improvements could be seen in the control group.\n Functional relaxation appears to be a safe and effective, non-pharmacological approach in the treatment of non-specific chest pain.", "We compared the efficacy of cognitive behavior therapy (CBT), paroxetine and placebo in the treatment of noncardiac chest pain (NCCP). We also investigated whether pre- to mid-treatment reduction of (heart-focused) anxiety mediated mid- to post-treatment pain reduction.\n Sixty-nine adults with NCCP were randomly assigned to 16 weeks of outpatient treatment with CBT, paroxetine or placebo. The comparison between placebo and paroxetine was carried out in a double-blind fashion. The main outcome measure was a chest pain index (duration*intensity) as derived from daily pain diaries. Putative mediator measures were general anxiety (HADS:A) and heart-focused anxiety (Cardiac Anxiety Questionnaire).\n Eleven patients treated with paroxetine or placebo dropped out prematurely. Intent-to-treat analysis showed that CBT was significantly superior to placebo and to paroxetine in reducing NCCP at posttreatment. Only CBT significantly reduced heart-focused anxiety compared to placebo at mid- and post-treatment. Pre- to mid-treatment reduction of heart-focused anxiety predicted mid- to post-treatment NCCP reduction. The indirect effect of CBT on pain reduction by reducing heart-focused anxiety was significant compared to placebo but not to paroxetine.\n CBT is an effective treatment option for patients with NCCP. Paroxetine is not more effective than placebo on the short term. Reduction of heart-focused anxiety by CBT seems to mediate subsequent reduction of NCCP compared to placebo. The results provide further support for cognitive-behavioral models of NCCP and point to the potential benefits of, in particular, cognitive-behavioral interventions to modify heart-focused anxiety.\n Copyright (c) 2010 Elsevier Inc. All rights reserved.", "We used a psychological treatment package (education, relaxation, breathing training, graded exposure to activity and exercise, and challenging automatic thoughts about heart disease) to treat 60 patients who had continuing chest pain despite cardiological reassurance following haemodynamically normal angiography. The treatment was delivered in six sessions over eight weeks to groups of up to six patients. The patients kept daily records of chest pain episode frequency and nitrate use. Questionnaires were used to assess anxiety, depression and disability. Exercise tolerance was tested by treadmill electrocardiography, with capnographic assessment of hyperventilation. The results were compared with waiting-list controls. Treatment significantly reduced chest pain episodes (p < 0.01) from median 6.5 to 2.5 per week. There were significant improvements in anxiety and depression scores (p < 0.05), disability rating (p < 0.0001) and exercise tolerance (p < 0.05), and these were maintained at six month follow-up. Treatment reduced the prevalence of hyperventilation from 54% to 34% (p < 0.01) but not the prevalence of ECG-positive exercise tests. Patients continuing to attribute their pain to heart disease had poorer outcomes. Group psychological treatment for non-cardiac chest pain is feasible, reduces pain, psychological morbidity and disability, and improves exercise tolerance.", "Patients with nonischemic chest pain frequently experience recurrent symptoms, have persistent functional and occupational disability, and are high utilizers of health-care resources. Our aim was to evaluate the efficacy of a cognitive-behavioral treatment for patients with noncardiac chest pain.\n Subjects were recruited from patients with at least weekly episodes of noncardiac chest pain, as diagnosed by a cardiologist. The main outcome measures were frequency and intensity of chest pain at 6 and 12 months.\n Seventy-two patients were enrolled in the study; 37 were assigned to cognitive-behavior therapy and 35 to usual care. Sixty-five patients completed the study. Intervention patients improved significantly with regard to frequency and intensity of chest pain: 15 (48%) of the 31 patients in the treatment group were pain free at 12-month follow-up compared with 4 (13%) of the 33 patients in the control group (P = 0.002).\n Cognitive-behavioral therapy for noncardiac chest pain patients was effective compared with usual care.", "Women with angina pectoris, a positive exercise electrocardiogram (ECG) for myocardial ischemia and angiographically smooth coronary arteries (cardiac syndrome X), are often characterized by unresolved symptomatology and a poor quality of life. Psychological morbidity and quality of life appear to be related to social support and social isolation. An investigation of group support as an aid to treatment for cardiac syndrome X was therefore undertaken.\n Forty-nine women with cardiac syndrome X (mean ± standard deviation 61.8 ± 8 years) were randomized to 12 monthly support group meetings or usual care control. The Health Anxiety Questionnaire (HAQ), Hospital Anxiety and Depression Scale (HADS), SF-36, York Angina Beliefs scale, ENRICHD Social Support Instrument (ESSI) and a demographic information scale, along with hospital admissions, general practitioner (GP) or cardiologist appointments were measured at baseline, 6 months and 12 months.\n Support group participants maintained higher levels of social support than controls (ESSI score, 17.18 ± 5.35 vs. 14.45 ± 6.98, p = 0.008). Near significant improvements in health beliefs total score (p = 0.068) and threat perception (p = 0.062) were found among the support group compared to the control; 29% of support patients had made one or more GP visits over the duration of the study, compared with 54% of the control group (p = 0.06).\n Support group participation maintains social support and may reduce health-care demands and misconceived health beliefs among patients with cardiac syndrome X.", "Non-cardiac chest pain (NCCP) is an extremely debilitating condition of uncertain origin which is difficult to treat and consequently has a high psychological morbidity. Hypnotherapy has been shown to be effective in related conditions such as irritable bowel syndrome where its beneficial effects are long lasting.\n This study aimed to assess the efficacy of hypnotherapy in a selected group of patients with angina-like chest pain in whom coronary angiography was normal and oesophageal reflux was not contributory.\n Twenty eight patients fulfilling the entry criteria were randomised to receive, after a four week baseline period, either 12 sessions of hypnotherapy or supportive therapy plus placebo medication over a 17 week period. The primary outcome measure was global assessment of chest pain improvement. Secondary variables were a change in scores for quality of life, pain severity, pain frequency, anxiety, and depression, as well as any alteration in the use of medication.\n Twelve of 15 (80%) hypnotherapy patients compared with three of 13 (23%) controls experienced a global improvement in pain (p = 0.008) which was associated with a significantly greater reduction in pain intensity (p = 0.046) although not frequency. Hypnotherapy also resulted in a significantly greater improvement in overall well being in addition to a reduction in medication usage. There were no differences favouring hypnotherapy with respect to anxiety or depression scores.\n Hypnotherapy appears to have use in this highly selected group of NCCP patients and warrants further assessment in the broader context of this disorder.", "Patients who present with chest pain but have normal coronary angiography and who are told by their cardiologist that they do not have heart disease, have a poor symptomatic, psychological and quality of life outcome and remain concerned about a serious cause of their symptoms. They frequently complain they have not had enough information. The study aimed to test the effectiveness and acceptability of a brief psychological intervention based on cognitive behavioural principles.\n Consecutive patients with chest pain and normal angiograms were assessed and invited to take part in a randomized controlled evaluation. The intervention consisted of an individualized information and discussion session by a specially trained cardiac nurse, together with a handout and cassette providing information and advice and telephone follow-up to discuss progress, answer questions and reiterate advice.\n The treatment proved to be unacceptable to some patients and there was no evidence of efficacy.\n Implications for the preparation of patients undergoing angiography and for the timing and delivery of information and advice following a negative result are discussed.", "Thirty-one patients with atypical non-cardiac chest pain which had persisted despite negative medical investigation were treated in a controlled trial of cognitive-behavioural therapy. The average duration of pain was 4.7 years. Patients were randomized to either immediate treatment or as a control to assessment only. Treatment involved teaching patients how to anticipate and control symptoms, and modification of inappropriate health beliefs. The average number of sessions given was 7.2. There were significant reductions in chest pain. limitations and disruption of daily life, autonomic symptoms, distress and psychological morbidity in the treated group as compared with the control group who were unchanged. The assessment-only group were treated subsequently and showed comparable changes. Improvements were fully maintained by both treated groups at four- to six-months follow-up.", "To explore cardiac rehabilitation (CR) as a treatment for psychological and physiological morbidity in women with chest pain and normal coronary arteries (cardiac syndrome X).\n Sixty-four women aged 57.3+/-8.6 years (mean +/- SD) with cardiac syndrome X were randomly assigned to an 8-week phase III CR exercise program or symptom monitoring control. All women completed the Hospital Anxiety and Depression Scale, Health Anxiety Questionnaire, and Short Form-36 before and after intervention and at the 8-week follow-up. CR patients underwent physical assessment before and after CR.\n After CR, patients demonstrated improved symptom severity (2.0+/-0.8 vs 1.26+/-1.1, P=0.009), Hospital Anxiety and Depression Scale depression score (8.0+/-3.4 vs 6.4+/-3.1, P=0.04), total Health Anxiety Questionnaire score (12.0+/-5.5 vs 9.5+/-6.0, P=0.008), health worry (4.5+/-3.1 vs 3.52+/-2.4, P=0.025) and interference (2.4+/-1.8 vs 1.6+/-1.8, P=0.004), SF-36 physical functioning (53.1+/-20.4 vs 62.3+/-23.9, P = 0.006), energy (36.3+/-20.7 vs 49.8+/-19.1, P<0.001), pain (49.9+/-20.7 vs 58.1+/-22.9, P=0.028), and general health (48.8+/-17.9 vs 57.6+/-17.0, P=0.01) not found among the control women. Improvements were maintained at follow-up. CR patients showed significant improvements in Shuttle Walk Test performance (326.8+/-111.0 vs 423.6+/-133.2 m, P<0.001), diastolic blood pressure (84.7+/-9.4 vs 79.7+/-7.3 mm Hg, P=0.007), and body mass index (29.1+/-6.0 vs 28.4+/-6.17 kg/m2, P=0.003).\n An 8-week phase III CR program improves exercise tolerance, quality of life, psychological morbidity, symptom severity, and cardiovascular risk factors in women with cardiac syndrome X.", "New types of illness are being identified continuously. Owing to the demands for evidence-based practice, physiotherapeutic interventions need to be investigated scientifically prior to application in a new patient population. Coronary syndrome X (syndrome X) is a chronic pain disorder with exercise-induced chest pain despite angiographically normal coronary arteries. Patients with syndrome X constitute a therapeutic problem with considerable residual morbidity associated with functional limitation and reduced quality of life. Therefore, the aim of the present study was to investigate the effects of physical training and relaxation therapy on exercise capacity and quality of life in patients with syndrome X.\n A single-blind, randomized controlled trial design was used. Twenty-four female patients aged 41-65 years were randomly assigned to three groups: A, B and C. All groups were similar at baseline for physical fitness level. Group A performed physical training for eight weeks at 50% of baseline VO2max and group B participated in relaxation therapy for eight weeks. Group C acted as control subjects without any intervention. Before and after the eight-week periods, subjects were assessed by means of several measures of exercise capacity and quality of life.\n The measured variables did not change in the control group during the eight weeks. VO2max (< 0.02), work rate (< 0.002) and distance walked during six minutes (< 0.003) increased only after physical training. The tolerated exertion during six minutes of walking (< 0.05) and the health-related quality of life, measured both by the Stress and Crisis Inventory (SCI) and the Sickness Impact Profile (SIP) (< 0.04), improved after both physical training and relaxation therapy. The general coping capacity, measured by the Sense of Coherence (SOC) questionnaire, remained unchanged in all the groups.\n Female patients with syndrome X benefit from physical training in terms of exercise capacity and quality of life and from relaxation therapy in terms of quality of life." ]

[ "19371497", "358208", "4890289", "592834", "10787400", "10093649", "205633", "2868481", "6674819", "2859274", "1363375", "16118830", "8625628", "6722863", "837817", "3816528", "468763", "3289648", "5045759", "4741512", "7978098", "17374039", "822987", "10549990", "17613965", "1100083", "6137426", "6394514", "12634266", "4567595", "4588385", "6872416", "3902038", "6370437", "2664886", "15236821", "12020181", "1524606", "2000517", "11916372", "358756", "3300587", "6072348", "7433", "3887964", "12047731", "2653057", "17557449", "14557857", "8192130", "7009593", "9201799", "5745947", "6353268", "6641099" ]

[ "A randomized, double-blind comparison of lorazepam and chlordiazepoxide in patients with uncomplicated alcohol withdrawal.", "A double blind study of chlordiazepoxide and hydroxyzine HC1 therapy in acute alcohol withdrawal utilizing chronic electromyography for tremor assessment.", "Treatment of the acute alcohol withdrawal state: a comparison of four drugs.", "Comparative efficacy of propranolol and chlordiazepoxide in alcohol withdrawal.", "Is daily single dosage of diazepam as effective as chlordiazepoxide in divided doses in alcohol withdrawal--a pilot study.", "[Gamma-hydroxybutyrate for treatment of alcohol withdrawal syndrome in intensive care patients. A comparison between with two symptom-oriented therapeutic concepts].", "Residual effects of ethanol and chlordiazepoxide treatments for alcohol withdrawal.", "Clinical conditions and central dopamine metabolism in alcoholics during acute withdrawal under treatment with different pharmacological agents.", "Comparison of chlormethiazole (Heminevrin) and chlordiazepoxide (Librium) in the treatment of acute alcohol withdrawal.", "Halazepam in the management of acute alcohol withdrawal syndrome.", "Effects of beta-blocking drugs in alcohol withdrawal: a double-blind comparative study with propranolol and diazepam.", "Double-blind study of cyamemazine and diazepam in the alcohol withdrawal syndrome.", "Therapy of alcohol withdrawal syndrome in intensive care unit patients following trauma: results of a prospective, randomized trial.", "A double-blind comparison of the efficacy and safety of lorazepam and diazepam in the treatment of the acute alcohol withdrawal syndrome.", "Thioridazine HC1 Vs. chlordiazepoxide HC1 in controlling symptoms attributable to alcohol withdrawal.", "Comparison of two benzodiazepines in the treatment of alcohol withdrawal: effects on symptoms and cognitive recovery.", "MMPI and drug treatment in alcohol withdrawal.", "Alprazolam versus chlormethiazole in acute alcohol withdrawal.", "Delirium tremens: a comparison of intravenous treatment with diazepam and chlordiazepoxide.", "Drug treatment of anxiety and depression in detoxified alcoholic patients.", "Double-blind study of alprazolam, diazepam, clonidine, and placebo in the alcohol withdrawal syndrome: preliminary findings.", "Antiglutamatergic strategies for ethanol detoxification: comparison with placebo and diazepam.", "Control of acute alcoholic withdrawal symptoms: a comparative study of haloperidol and chlordiazepoxide.", "Gamma-hydroxybutyric acid (GHB) in the treatment of alcohol withdrawal syndrome: a randomized comparative study versus benzodiazepine.", "Gamma-hydroxybutyrate reduces both withdrawal syndrome and hypercortisolism in severe abstinent alcoholics: an open study vs. diazepam.", "A controlled trial of chlormethiazole and chlordiazepoxide in the treatment of the acute withdrawal phase of alcoholism.", "A comparison of the efficacy and tolerability of clobazam and chlordiazepoxide in the treatment of acute withdrawal from alcohol in patients with primary alcoholism.", "Tiapride and chlordiazepoxide in acute alcohol withdrawal. A controlled clinical trial.", "Alcohol withdrawal treatment in intoxicated vs non-intoxicated patients: a controlled open-label study with tiapride/carbamazepine, clomethiazole and diazepam.", "Treatment of delirium tremens. A comparative evaluation of four drugs.", "Benzoctamine and oxazepam in the management of alcohol withdrawal states. Comparison by double-blind trial.", "Nonpharmacologic intervention in acute alcohol withdrawal.", "Double-blind controlled trial of bromocriptine, chlordiazepoxide and chlormethiazole for alcohol withdrawal symptoms.", "Double-blind comparison of lorazepam and chlordiazepoxide in the treatment of the acute alcohol abstinence syndrome.", "Double blind study on the efficacy and safety of tetrabamate and chlordiazepoxide in the treatment of the acute alcohol withdrawal syndrome.", "Enlarged double-blind randomised trial of benzodiazepines against psychotropic analgesic nitrous oxide for alcohol withdrawal.", "Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial.", "Carbamazepine versus oxazepam in the treatment of alcohol withdrawal: a double-blind study.", "Transdermal clonidine versus chlordiazepoxide in alcohol withdrawal: a randomized, controlled clinical trial.", "Divalproex sodium (Depakote) for alcohol withdrawal and relapse prevention.", "Delirium tremens: a double-blind comparison of diazepam and barbital treatment.", "Clonidine vs chlordiazepoxide in the management of acute alcohol withdrawal syndrome.", "Comparative evaluation of treatments of alcohol withdrawal syndromes.", "Clorazepate dipotassium (Tranxene): a controlled evaluation in alcoholic patients after withdrawal.", "Double-blind trial of alprazolam and chlordiazepoxide in the management of the acute ethanol withdrawal syndrome.", "The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial.", "Double-blind controlled trial comparing carbamazepine to oxazepam treatment of alcohol withdrawal.", "Self-reported sleep, sleepiness, and repeated alcohol withdrawals: a randomized, double blind, controlled comparison of lorazepam vs gabapentin.", "Alcohol withdrawal severity is decreased by symptom-orientated adjusted bolus therapy in the ICU.", "Propranolol versus diazepam in the management of the alcohol withdrawal syndrome: double-blind controlled trial.", "Double-blind comparison of alprazolam and diazepam for subchronic withdrawal from alcohol.", "A double-blind comparison of abecarnil and diazepam in the treatment of uncomplicated alcohol withdrawal.", "[Comparative study of chlordiazepoxide and hypertonic MgSO4 in the alcohol withdrawal syndrome].", "Clinical symptomatology and computer analyzed EEG before, during and after anxiolytic therapy of alcohol withdrawal patients.", "Diazepam loading: simplified treatment of alcohol withdrawal." ]

[ "For important reasons, lorazepam (Ativan) and chlordiazepoxide (Librium) are both popular treatments for alcohol-withdrawal syndrome. Nevertheless, there is little literature directly comparing the two drugs. A formal comparison is desirable because of pharmacokinetic and other differences that could affect safety and efficacy considerations relevant to practice in developing countries.\n One hundred consecutive consenting male inpatients in a state of moderately severe, uncomplicated alcohol withdrawal at screening were randomized to receive either lorazepam (8 mg/day) or chlordiazepoxide (80 mg/day) with dosing down-titrated to zero in a fixed-dose schedule across 8 treatment days. Double-blind assessments of withdrawal-symptom severity and impairing adverse events were obtained during treatment and for 4 days afterward.\n One chlordiazepoxide patient developed withdrawal delirium. Lorazepam and chlordiazepoxide showed similar efficacy in reducing symptoms of alcohol withdrawal as assessed using the revised Clinical Institute Withdrawal Assessment for Alcohol scale. During withdrawal, irritability and dizziness were more common with lorazepam, and palpitations were more common with chlordiazepoxide. No difficulties in drug discontinuation or differences in impairing adverse events were observed with either drug.\n With the treatment schedule used in this study, lorazepam is as effective as the more traditional drug chlordiazepoxide in attenuating uncomplicated alcohol withdrawal. Lorazepam, therefore, could be used with confidence when liver disease or the inability to determine liver function status renders chlordiazepoxide therapy problematic. The absence of clinically significant withdrawal complications with lorazepam in this large study contrasts with findings from previously published studies and suggests that higher doses of lorazepam than those formerly used may be necessary during alcohol withdrawal.", "nan", "nan", "Propranolol alone was more effective than either chlordiazepoxide or a combination of chlordiazepoxide and propranolol in alleviating the symptoms of the alcohol withdrawal syndrome.", "nan", "Seeing as gamma-hydroxybutyrate (GHB) and benzodiazepines interact with the GABA-transmitter system, we investigated whether GHB can replace the conventional therapy, which uses benzodiazepines in the treatment of alcohol withdrawal syndrome in ICU settings.\n 42 chronic alcoholics were included in this prospective and randomized study. Following the development of alcohol withdrawal syndrome, the patients were randomly allocated to the GHB or to the flunitrazepam group. In addition to this, clonidine was administered in order to treat autonomic signs of withdrawal. In cases were hallucinations occurred, haloperidol was administered.\n There was no significant difference in the efficacy of treatment used in the duration of mechanical ventilation and intensive care unit stay between groups. The patients in the GHB-group required significantly higher dosages of haloperidol and significantly lower dosages of clonidine. 14 out of 21 patients from the GHB-group developed hypernatriaemia and 15 out of 21 developed a metabolic alkalosis.\n Symptoms of the autonomic nervous system were more effectively prevented by GHB as evident in the lower dosage requirement of clonidine. However, GHB may not sufficiently block the hyperactivity of the dopaminergic system or may have an hallucinogenic effect itself. This may be evident from the higher dosages of haloperidol which were necessary. Due to the latter fact, the administration of GHB cannot be recommended in all patients suffering from AWS in ICU settings.", "Eighteen male alcoholics were randomly assigned to one of two alcohol detoxification treatments. One group received a low dose ethanol treatment while the other group received a chlordiazepoxide treatment. This study compares recovery of sleep EEG and clinical symptomatology following these two detoxification treatments. Sleep EEG and clinical measures were obtained for the final medication day and during a 6-day postmedication \"recovery\" period. The chlordiazepoxide treatment produced suppression of rapid eye movement (REM) sleep lasting for about 4 days and virtually eliminated delta sleep (stages III and IV) during the recovery period. The low dose ethanol treatment regimen produced less disruption of REM and delta sleep during the recovery period. These findings suggest that under some circumstances an ethanol treatment regimen may prove more beneficial to the healthy alcoholic patient than current regimens which employ other psychoactive medication. In particular, the long lasting suppression of delta sleep during the recovery period in subjects treated with chlordiazepoxide suggests a vulnerability of the slow wave sleep mechanisms during early alcohol abstinence and raises the possibility that this regimen prolongs functional tolerance to alcohol effects. Continued clinical evaluation of low dose ethanol detoxification treatment is suggested.", "A group of 45 male alcoholics were studied during acute withdrawal. Patients were kept in hospital and treated with amobarbital (15 patients), oxazepam (15 patients), and melperone (15 patients) respectively in a double-blind design. Clinical symptoms were rated with a modified version of the Comprehensive Psychopathological Rating Scale after 1, 4 and 7 days. Blood pressure, body temperature and pulse rate were also recorded. Lumbar cerebrospinal fluid was collected after 1 and 7 days. A group of healthy males served as controls. The three treatment groups showed only small differences with regard to the investigated clinical items, except for a higher incidence of epileptic fits being evidenced in the melperone group. Levels of HVA in the cerebrospinal fluid did not differ between the treatment groups and the controls and did not change during treatment. Statistically significant correlations were noted between levels of HVA and auditory and visual hallucinations as well as concentration difficulties. Assuming that HVA levels reflect the activity of the central nervous dopamine system, the findings indicate a connection between central dopamine metabolism, psychotic symptoms and possibly other symptoms during acute alcohol withdrawal in man.", "This study was carried out to compare the efficacy of chlormethiazole and chlordiazepoxide in the treatment of acute alcohol withdrawal syndrome in 40 patients. Repeated biochemical, clinical, and psychophysiological measurements were obtained in a randomized, double-blind design in which one group of patients received chlormethiazole and a second group received chlordiazepoxide over a period of 7 days. Analysis indicated both drugs to be of equivalent potency and were equally well tolerated by patients. The more severe aspects of withdrawal were brought under control within the first 4 days of treatment. However, even at 7 days, there still persisted some symptoms attributable to the withdrawal from alcohol.", "Eighty patients admitted to a specialized alcohol detoxification unit, who had blood alcohol levels of .15% or less and were not currently intoxicated, participated in a double-blind trial involving treatment with either halazepam or chlordiazepoxide. A flexible dosage schedule was followed for 5 days with the objective of using the largest dose on the first day, followed by daily reductions as clinically feasible. Efficacy evaluations indicated that halazepam was as effective as chlordiazepoxide in the control of symptoms in patients hospitalized for the medical management of acute alcohol withdrawal. No significant side effects were noted.", "Alcohol withdrawal is associated with a decrease in gamma-aminobutyric acid neurotransmission. This explains the efficacy of benzodiazepines. However, an increase in adrenergic activity may also play a part in alcohol withdrawal symptoms, suggesting a potential efficacy of beta-blocking drugs. A double-blind comparative study of propranolol and diazepam was carried out in 28 patients suffering from moderate uncomplicated alcohol withdrawal. Patients were treated for 15 days with either 75 mg of propranolol or 30 mg of diazepam. The results show that both drugs at the dosages used are equipotent in reducing physical withdrawal symptoms and anxiety symptoms. This suggests that most likely the central as well as the peripheral effects determine the clinical usefulness of propranolol in the management of alcohol withdrawal. However, propranolol is ineffective in preventing major motor seizures, suggesting that different neurobiological mechanisms underlie the alcohol withdrawal symptoms.", "Cyamemazine is an original phenothiazine derivative which showed similar efficacy and tolerability to lorazepam during ethanol withdrawal in mice. This study investigated cyamemazine for its efficacy and tolerability in alcohol-dependent patients electing an alcohol withdrawal procedure, in comparison with diazepam.\n A multicenter, randomized, double-blind study in 89 alcohol-dependent patients (CIWA-Ar score between 10 and 30), electing an alcohol withdrawal procedure, was used to find effective doses of cyamemazine and to compare it with diazepam for efficacy and tolerability. On day 1 (D(1)), cyamemazine or diazepam (50 mg and 10 mg capsule, respectively) were administered at hourly intervals to reduce CIWA-Ar = 5, up to a maximum of eight administrations. Starting from D(2), the compounds were given twice a day in progressively decreasing doses during a maximum period of 13 days (D(end)).\n At h(8) (8 h after the first treatment of D(1)), therapeutic success (CIWA-Ar score </= 5) was achieved in 32 out of 43 ITT patients treated with cyamemazine (74.4%), a value very similar to that of diazepam (32/44; 72.7%). Most such patients (29/32) were controlled with 2-6 capsules of cyamemazine (100-300 mg). In the PP population, cyamemazine (n = 28) was significantly non-inferior to diazepam (n = 33), with a threshold of 10% for non-inferiority bound and 2.5% for one-sided type I error rate. Such therapeutic similarity was confirmed by the analysis of other efficacy criteria. Safety analysis did not show substantial differences between the two treatments.\n Cyamemazine showed similar efficacy and tolerability to diazepam for the treatment of alcohol withdrawal symptoms at therapeutic doses in the range 100-300 mg.\n Copyright (c) 2005 John Wiley & Sons, Ltd.", "To assess the effect of three different alcohol withdrawal therapy regimens in traumatized chronic alcoholic patients with respect to the duration of mechanical ventilation and the frequency of pneumonia and cardiac disorders during their intensive care unit (ICU) stay.\n A prospective, randomized, blinded, controlled clinical trial.\n A university hospital ICU.\n Multiple-injured alcohol-dependent patients (n=180) transferred to the ICU after admission to the emergency room and operative management. A total of 180 patients were included in the study; however, 21 patients were excluded from the study after assignment.\n Patients who developed actual alcohol withdrawal syndrome were randomized to one of the following treatment regimens: flunitrazepam/clonidine (n=54); chlormethiazole/haloperidol (n=50); or flunitrazepam/haloperidol (n=55). The need for administration of medication was determined, using a validated measure of the severity of alcohol withdrawal (Revised Clinical Institute Withdrawal Assessment for Alcohol Scale).\n The duration of mechanical ventilation and major intercurrent complications, such as pneumonia, sepsis, cardiac disorders, bleeding disorders, and death, were documented. Patients did not differ significantly between groups regarding age, Revised Trauma and Injury Severity Score and Acute Physiology and Chronic Health Evaluation II score on admission. In all except four patients in the flunitrazepam/clonidine group, who continued to hallucinate, the Revised Clinical Institute Withdrawal Assessment for Alcohol Scale decreased to <20 after initiation of therapy. ICU stay did not significantly differ between groups (p=.1669). However, mechanical ventilation was significantly prolonged in the chlormethiazole/haloperidol group (p=.0315) due to an increased frequency of pneumonia (p=.0414). Cardiac complications were significantly (p=.0047) increased in the flunitrazepam/clonidine group.\n There was some advantage in the flunitrazepam/clonidine regimen with respect to pneumonia and the necessity for mechanical ventilation. However, four (7%) patients had to be excluded from the study due to ongoing hallucinations during therapy. Also, cardiac complications were increased in this group. Thus, flunitrazepam/haloperidol should be preferred in patients with cardiac or pulmonary risk. Further studies are required to determine which therapy should be considered.", "The safety and efficacy of lorazepam and diazepam were compared in the treatment of the acute alcohol withdrawal syndrome during a five-day double-blind trial in alcoholic patients. The daily doses of lorazepam and diazepam were tapered from 6 or 8 mg to 2 mg and from 30 or 40 mg to 10 mg, respectively, during the first four days; no medication was given on day 5. Drug efficacy was measured by Total Severity Assessment Scores (TSAS), the three TSAS factor scores, and by the physician's global evaluation. Of the 55 inpatients enrolled, 47 completed the study. There were no statistically significant differences between the treatment groups in any of the efficacy assessment measures. The physical conditions of the majority of the patients treated with lorazepam (57%) and diazepam (59%) improved during therapy. There were no clinically significant differences between the treatment groups in vital signs or laboratory values. The results of this study indicate that lorazepam is as effective as diazepam in reducing the symptoms of acute alcohol withdrawal. When lorazepam and diazepam are compared in terms of their pharmacokinetics, lorazepam may have therapeutic advantages for the management of the acute alcohol withdrawal syndrome.", "nan", "Forty newly admitted alcohol-dependent patients were randomly allocated to equivalent 6-day regimes of either lorazepam or diazepam, to compare involvement in physical, emotional and cognitive state during the first 8 days in hospital. Diazepam provided a more comfortable withdrawal period and was associated with slightly better cognitive functioning on the eighth day.", "Thirty-four inpatients in a mild phase of alcohol withdrawal, exhibiting anxious and depressive symptoms, were administered an MMPI before and immediately after a 4-week drug treatment period. A double-blind design was used; 17 patients were treated with chlordiazepoxide and 17, with thioridazine. The pretreatment MMPI profile was typical of alcoholic patients; namely, peaks on scales 4 and 2. After the fourth week, the MMPI indicated that thioridazine was significantly more effective than chlordizaepoxide. Decreases in 7 of the 10 clinical scales averaged 7.29 T-score points, whereas only scale 6 was significantly decreased for the patients treated with chlordiazepoxide.", "nan", "nan", "nan", "Both a reduction in the inhibitory effects of GABA (disinhibition) and activation of the sympathetic nervous system are manifested during the alcohol withdrawal syndrome. This study was designed to explore the relative efficacy of medications that differentially affects these two biological systems: the benzodiazepines, which attenuate GABAergic disinhibition, and the alpha 2-adrenergic receptor agonists, which decrease sympathetic activation. The benzodiazepine diazepam (n = 6), the alpha 2-receptor agonist clonidine (n = 7), the benzodiazepine alprazolam (this is also purported to have alpha 2-receptor agonist properties) (n = 6), and placebo (n = 6) were evaluated in their effectiveness in decreasing signs and symptoms of alcohol withdrawal. Drug-free, alcohol-dependent patients were administered 1 of the 4 medications in a double-blind design until symptoms of withdrawal, as measured by the Clinical Instrument Withdrawal Assessment for Alcohol-Revised, were successfully treated. Alprazolam was significantly more efficacious than both clonidine and placebo in decreasing withdrawal symptoms. Diazepam was more effective than clonidine and placebo on some measures of withdrawal. Clonidine decreased systolic blood pressure significantly more than the other two active drugs and placebo, but was no more effective than placebo in decreasing other symptoms of withdrawal. Alprazolam did not significantly decrease blood pressure compared with diazepam or placebo. Despite the small sample size, these preliminary findings suggest that the efficacy of alprazolam in the treatment of alcohol withdrawal is related to its effect at the benzodiazepine receptor and not its alpha 2-receptor agonist properties.", "Benzodiazepines are the standard pharmacotherapies for ethanol detoxification, but concerns about their abuse potential and negative effects upon the transition to alcohol abstinence drive the search for new treatments. Glutamatergic activation and glutamate receptor up-regulation contribute to ethanol dependence and withdrawal. This study compared 3 antiglutamatergic strategies for ethanol detoxification with placebo and to the benzodiazepine, diazepam: the glutamate release inhibitor, lamotrigine; the N-methyl-D-aspartate glutamate receptor antagonist, memantine; and the AMPA/kainite receptor inhibitor, topiramate.\n This placebo-controlled randomized single-blinded psychopharmacology trial studied male alcohol-dependent inpatients (n=127) with clinically significant alcohol withdrawal symptoms. Subjects were assigned to 1 of 5 treatments for 7 days: placebo, diazepam 10 mg TID, lamotrigine 25 mg QID, memantine 10 mg TID, or topiramate 25 mg QID. Additional diazepam was administered when the assigned medication failed to suppress withdrawal symptoms adequately.\n All active medications significantly reduced observer-rated and self-rated withdrawal severity, dysphoric mood, and supplementary diazepam administration compared with placebo. The active medications did not differ from diazepam.\n This study provides the first systematic clinical evidence supporting the efficacy of a number of antiglutamatergic approaches for treating alcohol withdrawal symptoms. These data support the hypothesis that glutamatergic activation contributes to human alcohol withdrawal. Definitive studies of each of these medications are now needed to further evaluate their effectiveness in treating alcohol withdrawal.", "nan", "Benzodiazepine has been shown to be one of the most effective class of drugs in the management of alcohol withdrawal syndrome (AWS). Gamma-hydroxybutyric acid (GHB) has recently been introduced in the treatment of alcohol problems, including AWS. At present there are no comparative studies between benzodiazepines and GHB in AWS treatment. The aim of the present randomized, controlled, single-blind study was to evaluate the efficacy and safety of GHB compared with diazepam in the treatment of AWS.\n Sixty alcoholics affected by AWS were enrolled in the study. Diazepam (0.5-0.75 mg/kg body weight for 6 days, tapering the dose 25% daily until day 10) was administered orally to 30 patients (25 males, 5 females; mean age 44.3 +/- 10.9 years); GHB (50 mg/kg body weight for 10 days) was administered orally to 30 patients (26 males,4 females; mean age 41.7 +/- 10.4 years). The Clinical Institute Withdrawal Assessment for Alcohol-revised scale (CIWA-Ar) was used to evaluate the AWS physical symptoms. The State Anxiety Inventory test for current anxiety assessment and the Zung self-rating Depression Scale for current depression assessment were performed.\n Eight patients (26.6%) in the diazepam group and 4 patients (13.3%) in the GHB group dropped out. Both treatments were effective in reducing AWS. No significant difference was found between the groups in CIWA-Ar total score at baseline and at the different times of observation. Considering the CIWA-Ar subscore and Zung scale, a significant reduction of anxiety on day 4 (p < 0.02), agitation on day 5 (p < 0.02) and time of recovery of depression on day 5 (p < 0.02) was observed in the GHB group with respect to the diazepam group. Drowsiness and vertigo developed after initial drug administration in the GHB (19.2%) and diazepam (36.4%) groups and quickly resolved in both groups.\n GHB is as effective in the management of AWS as benzodiazepine and it seems to be quicker in reducing anxiety, agitation, and depression. Both drugs are safe and well-tolerated in AWS management.", "In 42 alcoholic inpatients we performed an open randomized study to compare the effects of diazepam and gamma-hydroxybutyrate (GHB) on the suppression of severe alcohol withdrawal syndrome and hypercortisolism. Both diazepam (.5 mg/kg bodyweight, q.i.d.) and GHB (50 mg/kg bodyweight, q.i.d.) were orally administered for three weeks. During all study period, GHB was more able than diazepam in reducing both withdrawal syndrome and hypercortisolism. These effects were evident during the first week of treatment and persisted throughout the study period. The results confirm a strict correlation between high levels of plasma cortisol and alcohol withdrawal symptoms and they show a slight superiority of GHB over diazepam in the suppression of both ethanol withdrawal and hypercortisolism. Taken together, our data suggest that GHB may act as potent anti-withdrawal agent in severe abstinent alcoholics.", "nan", "Forty patients with primary chronic alcoholism took part in a randomized, double-blind, comparative group study of clobazam and chlordiazepoxide in the treatment of acute alcohol withdrawal. Assessments were carried out during an initial in-patient week followed by a week of out-patient assessments. Both benzodiazepines were shown to be highly effective when compared with baseline measurements. However, the Hamilton Anxiety Rating Scale showed clobazam to be more effective than chlordiazepoxide at both 7 days (p = 0.03) and 14 days (p less than 0.05). The clobazam group showed significant improvements compared with baseline for all four factors of the Leeds Sleep Evaluation Questionnaire, whereas the chlordiazepoxide group showed a significant improvement in only one factor. At the end of the in-patient week, clobazam showed a significant improvement (p less than 0.01) compared to chlordiazepoxide for the Linear Analogue Rating Scale of anxiety/tension. The 1,5 benzodiazepine clobazam has been shown to be a valuable addition to currently available regimens when used alone in the treatment of acute alcohol withdrawal, especially during the initial period where anxiety and insomnia related symptoms are at their peak.", "The efficacy of chlordiazepoxide and tiapride in the management of acute alcohol withdrawal syndrome was compared in a randomized, parallel-group, double-blind trial. The mean daily dose for both preparations on the first two days was four capsules, i.e., 200 mg for chlordiazepoxide and 400 mg for tiapride. Thereafter the patients were treated according to the relief of symptoms obtained. The treatment periods lasted 3-5 days. Both drugs effectively alleviated alcohol withdrawal symptoms, especially anxiety, fear, hallucinations, insomnia, sweating, tremor, abdominal pain and vertigo. Seventy percent of the patients in the chlordiazepoxide and 42% in the tiapride group considered the drug effective. The difference was statistically significant in favour of chlordiazepoxide (p less than 0.05). Tiapride is an alternative drug in the treatment of this condition, if benzodiazepines are to be avoided.", "Alcohol withdrawal treatment efficacy of tiapride/carbamazepine (A) vs clomethiazole (B) vs diazepam (C) in non-intoxicated patients and vs tiapride/carbamazepine in intoxicated patients (D; breath alcohol concentration > or = 1 g/l) was tested (n = 127) in a controlled randomized open-label study.\n Efficacy and safety were not different between groups (total group: delirium, 3.9%; seizure, 0.8%), except for a lack of efficacy in 18% of intoxicated tiapride/carbamazepine patients. A change of medication in this group was necessary only when primarily intoxicated patients had reached the non-intoxicated range.\n Treatment with tiapride/carbamazepine in alcohol-intoxicated patients proved to be safe.", "nan", "nan", "The importance of nonpharmacologic and pharmacologic interventions in the treatment of alcohol withdrawal is not known. A randomized, double-blind, placebo-controlled trial was conducted with 41 patients in alcohol withdrawal in an emergency department. The patients received either supportive care (10 min of standardized assessments, reassurance, reality orientation, and nursing care an hour) with three doses of sublingual lorazepam 2 mg every 2 hr (21 patients, drug group) or supportive care with three doses of sublingual placebo every 2 hr (20 patients, no-drug group). Immediately before each drug dose, the clinical course of alcohol withdrawal was assessed hourly by the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-A). Interraters reliability in using CIWA-A was high. After each assessment, supportive care was given for 10 min before each dose. After completion of a 7-hr initial phase, patients were discharged and reassessed daily for 5 days. Thirty-seven patients (90.2%) improved in the initial phase. Treatment failures (CIWA-A greater than 10) were more common in the patients treated without drug (3/20, 15%) than in those treated with drug (1/21, 4.8%). Overall variations in intergroup CIWA-A scores during the initial phase were not significant. The rate of improvement of CIWA-A scores over the first 2 hr after drug was slightly faster in patients receiving lorazepam than in the control group. CIWA-A scores were the same during follow-up. These results indicate that most outpatients in mild to moderate alcohol withdrawal without medical complications improve without drug therapy in the emergency department setting.", "Seventy-one patients undergoing withdrawal from alcohol were randomly assigned to treatment with oral bromocriptine, chlormethiazole or chlordiazepoxide. Forty-one percent had alcoholic hepatitis and/or cirrhosis. Patients were stratified into two groups: major and minor withdrawal symptoms. The latter group included a placebo tratment. Bromocriptine was ineffective in treating withdrawal symptoms, whilst chlormethiazole and chlordiazepoxide were equally effective. These findings do not support the evidence from animal and clinical studies suggesting that the disturbances in the dopaminergic system found in alcohol dependence and withdrawal can be reversed by dopamine agonists.", "The anxiolytic efficacy and safety of lorazepam and chlordiazepoxide were evaluated and compared during a five-day double-blind trial in 50 male inpatients who were experiencing acute alcohol withdrawal symptoms. The total daily doses of lorazepam and chlordiazepoxide were tapered from 6 to 2 mg and from 150 to 50 mg, respectively, during the first four days; no medication was given on day 5. Drug effectiveness was measured by improvements in the total severity assessment score (TSAS), in the three composite TSAS factors, and by the physician's global rating. No drug-related adverse effects occurred during treatment. Vital signs remained stable, and laboratory test results remained within normal limits. The results indicate that lorazepam was as effective as chlordiazepoxide in reducing the symptoms of acute alcohol withdrawal. Because of its simpler and more predictable metabolic pathway and its insignificant accumulation in plasma during multiple-dose therapy, lorazepam may be the drug of choice if benzodiazepine therapy is required for chronic alcoholics with acute withdrawal symptoms.", "1. Efficacy and safety of tetrabamate and chlordiazepoxide in the treatment of the acute or Primary Alcohol Withdrawal Syndrome (PAWS) were assessed during a randomized double blind clinical trial, carried out on sixty male alcoholic in-patients. 2. The two drugs were administered four times a day in double dummy conditions, according to a fixed-flexible decreasing dosage schedule (six days basic regimen). 3. Drug efficacy was measured daily throughout the study period using a battery of standard instruments for collecting quantitative clinical, behavioral, psychopathological and laboratory data. Side effects were daily recorded. 4. Tetrabamate was found to be as efficient as chlordiazepoxide in reducing the intensity of the PAWS, improving sleep and vital signs rapidly and alleviating anxiety progressively. 5. Tetrabamate was found particularly beneficial for severe tremor. Psychomotor and mood scores consistently favored tetrabamate, suggesting psychoanaleptic properties of this compound (increased diurnal vigilance). 6. Side effects were minimal with tetrabamate and generally of weak intensity with chlordiazepoxide. 7. The results of this study indicate that tetrabamate may represent a new alternative drug of choice for the therapy of the acute alcohol withdrawal syndrome.", "We report a randomised double-blind controlled study with an enlarged cohort of participants (N = 51) using psychotropic analgesic nitrous oxide (PAN) versus benzodiazepines (BZs) for treating acute alcoholic withdrawal states. An additional 28 participants having received a BZ the night previous to the study were pooled with the previously analysed 23 (with no additional BZ). These pooled results showed that PAN is superior to a BZ regimen at P = .05 level, despite additional BZs. Our work provides further support for previous findings that show that PAN is a safe, rapid, and effective therapy for acute mild to moderately severe withdrawal states.", "In alcohol withdrawal, fixed doses of benzodiazepine are generally recommended as a first-line pharmacologic approach. This study determines the benefits of an individualized treatment regimen on the quantity of benzodiazepine administered and the duration of its use during alcohol withdrawal treatment.\n We conducted a prospective, randomized, double-blind, controlled trial including 117 consecutive patients with alcohol dependence, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, entering an alcohol treatment program at both the Lausanne and Geneva university hospitals, Switzerland. Patients were randomized into 2 groups: (1) 56 were treated with oxazepam in response to the development of signs of alcohol withdrawal (symptom-triggered); and (2) 61 were treated with oxazepam every 6 hours with additional doses as needed (fixed-schedule). The administration of oxazepam in group 1 and additional oxazepam in group 2 was determined using a standardized measure of alcohol withdrawal. The main outcome measures were the total amount and duration of treatment with oxazepam, the incidence of complications, and the comfort level.\n A total of 22 patients (39%) in the symptom-triggered group were treated with oxazepam vs 100% in the fixed-schedule group (P<.001). The mean oxazepam dose administered in the symptom-triggered group was 37.5 mg compared with 231.4 mg in the fixed-schedule group (P<.001). The mean duration of oxazepam treatment was 20.0 hours in the symptom-triggered group vs 62.7 hours in the fixed-schedule group (P<.001). Withdrawal complications were limited to a single episode of seizures in the symptom-triggered group. There were no differences in the measures of comfort between the 2 groups.\n Symptom-triggered benzodiazepine treatment for alcohol withdrawal is safe, comfortable, and associated with a decrease in the quantity of medication and duration of treatment.", "The use of more than 130 drugs and drug combinations against the alcohol withdrawal syndrome reflects the fact that views on its treatment are far from being unequivocal. Benzodiazepines are the first choice treatment but it should not be disregarded that they have side effects and, above all, a varying risk of dependency themselves. In recent years many trials have focused on carbamazepine in this respect. Its efficacy was proven in various open and double-blind studies, most of them using concomitant sedative drugs, thereby diminishing the reliability of the results. In a double-blind study we compared the efficacy of carbamazepine with that of oxazepam, in 60 in-patients suffering from alcohol withdrawal syndrome. The main rating instrument was the Clinical Institute Withdrawal Scale--Alcohol (CIWA-A). The 7-day trial showed equal efficacy of carbamazepine and oxazepam during the first 5 days and a statistically significant superiority of carbamazepine on days 6 and 7. Four patients in each group had to be dropped from the study due to side effects or after having withdrawn informed consent. There was no decrease in white blood counts under carbamazepine. The experiences with carbamazepine up to now suggest a more widespread use, especially in non-delirious withdrawal states.", "In a prospective, double-blind comparison, we assessed the efficacy of transdermal clonidine with that of chlordiazepoxide in the treatment of moderately severe acute alcohol withdrawal syndrome. While having significant withdrawal symptoms, 50 hospitalized men were randomly assigned to receive either transdermal clonidine or chlordiazepoxide over a 4-day study period. Outcome was evaluated daily, medically and psychiatrically, using both objective and subjective measurements for dependent variables. No patient in either study group had seizures or progression to delirium tremens. The group receiving transdermal clonidine had a more significant response globally for the signs and symptoms of alcohol withdrawal, as measured by the Alcohol Withdrawal Assessment Scale. Also, clonidine more effectively lowered elevated systolic and diastolic blood pressure and heart rate. The core target symptom, anxiety, decreased significantly more in the patients receiving transdermal clonidine when measured by the Hamilton Anxiety Rating Scale and its subscale for somatic anxiety. Cognitive function responded equally in both study populations. Clonidine-treated patients reported less diarrhea, dizziness, headache and fatigue, and the chlordiazepoxide-treated patients reported less nausea and vomiting. We conclude that transdermal clonidine is effective treatment for the acute alcohol withdrawal syndrome.", "This pilot study evaluates the safety and efficacy of divalproex sodium (Depakote) for alcohol withdrawal and relapse prevention. Sixteen patients in moderate alcohol withdrawal were randomized to receive a standard benzodiazepine detoxification, depakote detoxification, or depakote detox plus maintenance. Symptom reduction occurred more rapidly and consistently in the depakote treated patients than in the benzodiazepine control group, and at six-week follow up a greater percentage of patients in the depakote maintenance group were completely abstinent than either detox-only group. There were no significant differences in sociodemographic or drinking data amongst the three cohort samples at baseline. Our findings suggest that the anticonvulsant divalproex sodium (Depakote) may be a safe and efficacious alternative to benzodiazepines for the treatment of alcohol withdrawal. It may be an advantageous alternative for outpatient detoxification, as it has no abuse potential, pharmacologic synergy with alcohol, or substantial cognitive or psychomotor side effects.", "The effect of diazepam and barbital in the treatment of delirium tremens and other acute conditions related to alcohol abuse was evaluated in a double-blind trial. 91 patients participated in the study, 44 in the diazepam group, 47 in the barbital group. The choice of diazepam rather than chlordiazepoxide was motivated by its major anticonvulsive properties. Barbital was given by the oral route, diazepam as intramuscular injections. Different ways of drug administration to patients with delirium tremens are discussed. It is concluded that the two different ways used in the study probably did not have a noteworthy influence on the results. All patients were excluded who had taken psychoactive drugs before admission. Nevertheless a considerable part of the patients had diazepam, but not barbital, in the blood before treatment was initiated. This may give support to the use of barbital as a \"special purpose drug\" in the treatment of these conditions. The patients were divided into three diagnostic categories, according to the severity of the clinical condition. No difference between the two drugs tested was found in the milder conditions, but barbital was found superior to diazepam in the treatment of fully developed delirium tremens.", "To our knowledge, this is the first reported comparison of clonidine with benzodiazepine in the management of acute alcohol withdrawal syndrome. In a double-blind trial, 61 men experiencing acute alcohol withdrawal were randomly assigned to receive clonidine or chlordiazepoxide over a 60-hour treatment period. Clonidine was more effective than chlordiazepoxide at reducing alcohol withdrawal scale scores, systolic blood pressures, and heart rates over the entire study period. Clonidine was as good as chlordiazepoxide at improving Cognitive Capacity Screening Exam, Hamilton Anxiety Rating Scale, and Self-Rating Scale scores. Adverse drug reactions reported by each group were similar, though less nausea and vomiting were observed in the clonidine group. Clonidine may represent a new alternative agent for the management of acute alcohol withdrawal syndrome.", "nan", "nan", "A sequential sample of 101 patients hospitalized for ethanol withdrawal and requiring sedation for evolving withdrawal syndromes was assigned randomly according to a double-blind protocol to treatment with either alprazolam or chlordiazepoxide administered orally. The data from one patient were unevaluable due to acute bleeding, leaving a sample of 100 (50 in each condition). At discharge, three independent ratings of diaphoresis, tremor, hallucinations, nausea/vomiting, and overall severity of withdrawal were obtained, and the occurrence of delirium tremens and grand mal seizures was noted. Patients also completed the Beck Depression Inventory, and their disposition following discharge was recorded. There were no statistically significant differences between the two treatment groups on any of the dependent variables studied. It was concluded that the choice between alprazolam and chlordiazepoxide for managing ethanol withdrawal should be based on criteria other than efficacy of control. Potential antidepressant effects and drug kinetics were suggested as the basis for rational decision-making.", "Benzodiazepines are the mainstay of treatment for mild-to-moderate alcohol withdrawal in outpatient settings, but they can interact with alcohol, cause motor incoordination, or be abused. This study compared the therapeutic responses of the benzodiazepine lorazepam and the anticonvulsant carbamazepine for the outpatient treatment of acute alcohol withdrawal in terms of patients' previous detoxification histories, and compared the effects of these 2 medications on drinking behaviors in the immediate postdetoxification period.\n This was a randomized double-blind trial comparing patient responses to carbamazepine and lorazepam across 2 levels of detoxification histories (0-1 or >or=2 previous medicated detoxifications).\n A university medical center substance abuse clinic in Charleston, SC.\n One hundred thirty-six patients in moderate alcohol withdrawal were randomized. Major exclusions were significant hepatic or hematologic abnormalities and use of medications that could alter withdrawal symptoms.\n Patients received 600-800 mg of carbamazepine or 6-8 mg of lorazepam in divided doses on day 1 tapering to 200 mg of carbamazepine or 2 mg of lorazepam.\n The Clinical Institute Withdrawal Assessment for Alcohol-Revised was used to assess alcohol withdrawal symptoms on days 1 through 5 and postmedication at days 7 and 12. Daily drinking was measured by patient report using a daily drinking log and a breath alcohol level with each visit. Side effects were recorded daily.\n Carbamazepine and lorazepam were equally effective at decreasing the symptoms of alcohol withdrawal. In the post-treatment period, 89 patients drank on at least 1 day; on average, carbamazepine patients drank less than 1 drink per drinking day and lorazepam patients drank almost 3 drinks per drinking day (P =.003). Among those with multiple past detoxifications, the carbamazepine group drank less than 1 drink per day on average and the lorazepam group drank about 5 drinks per day on average (P =.033). Lorazepam-treated patients had a significant rebound of alcohol withdrawal symptoms post-treatment (P =.007) and the risk of having a first drink was 3 times greater (P =.04) than for carbamazepine-treated patients. Twenty percent of lorazepam-treated patients had dizziness, motor incoordination, or ataxia and did not recognize their impairment. Twenty percent of carbamazepine-treated patients reported pruritus but no rash.\n Carbamazepine and lorazepam were both effective in decreasing the symptoms of alcohol withdrawal in relatively healthy, middle-aged outpatients. Carbamazepine, however, was superior to lorazepam in preventing rebound withdrawal symptoms and reducing post-treatment drinking, especially for those with a history of multiple treated withdrawals.", "Of 86 alcoholic men with severe alcohol withdrawal who began a double-blind controlled study comparing carbamazepine, 800 mg/day, to oxazepam, 120 mg/day, 66 (carbamazepine, N = 32; oxazepam, N = 34) completed the 7-day trial. In general, the drugs were found to be equally efficacious in treating the withdrawal syndrome and not significantly different with respect to side effects. The subjects taking oxazepam had an increase in global psychological distress from day 3 to day 7, and those taking carbamazepine exhibited a decline. The study suggests that carbamazepine is as effective and safe as benzodiazepine treatment for alcohol withdrawal.", "Insomnia is a central symptom of alcohol withdrawal and increases relapse potential. The primary objective of this study was to compare the efficacy of gabapentin to lorazepam in alleviating sleep disturbances and daytime sleepiness during an episode of alcohol withdrawal. The secondary objective of this study was to determine if drug treatment efficacy differed by the patient history of previous treatments for alcohol withdrawal.\n Outpatients in treatment for alcohol withdrawal received a 4-day fixed-dose taper of gabapentin or lorazepam in a double-blind, randomized, controlled trial with an 8-day follow-up. Daily across a 5 day outpatient treatment and Days 7 and 12 post-treatment, patients self-reported daytime sleepiness using the Epworth Sleepiness Scale. Self-reports of depression (Beck Depression Inventory) were completed at Days 1, 5, 7 and 12. Staff assessed daily alcohol withdrawal using the Clinical Institute Withdrawal Assessment for Alcohol. From these instruments, self-reported sleep and sleepiness were extracted and assessed in the context of limited (0-1) or multiple (2 or more) previously treated alcohol withdrawal episodes.\n Patients with limited previous withdrawals reported similar treatment effects on self-reports of sleep and sleepiness for gabapentin and lorazepam. In contrast, patients with multiple previous alcohol withdrawals receiving gabapentin reported reduced sleep disturbances and sleepiness in comparison to those receiving lorazepam.\n During treatment for alcohol withdrawal, gabapentin as compared to standard therapy with lorazepam, was superior on multiple sleep measures, in patients who had previous withdrawals. Lorazepam subjects experienced rebound symptoms. Early drinking was related to persisting insomnia with both drugs.", "To examine the effect of bolus vs. continuous infusion adjustment on severity and duration of alcohol withdrawal syndrome (AWS), the medication requirements for AWS treatment, and the effect on ICU stay in surgical intensive care unit (ICU) patients.\n Prospective randomized, double-blind controlled trial in a surgical ICU.\n 44 patients who developed AWS after admission to the ICU.\n Patients were randomized to either (a). a continuous infusion course of intravenous flunitrazepam (agitation), intravenous clonidine (sympathetic hyperactivity), and intravenous haloperidol (productive psychotic symptoms) if needed (infusion-titrated group), or (b). the same medication (flunitrazepam, clonidine, or haloperidol) bolus adjusted in response to the development of the signs and symptoms of AWS (bolus-titrated group).\n The administration of \"as-needed\" medication was determined using a validated measure of the severity of AWS (Clinical Institute of Withdrawal Assessment). Although the severity of AWS did not differ between groups initially, it significantly worsened over time in the infusion-titrated group. This required a higher amount of flunitrazepam, clonidine, and haloperidol. ICU treatment was significantly shorter in the bolus-titrated group (median difference 6 days) due to a lower incidence of pneumonia (26% vs. 43%).\n We conclude that symptom-orientated bolus-titrated therapy decreases the severity and duration of AWS and of medication requirements, with clinically relevant benefits such as fewer days of ventilation, lower incidence of pneumonia, and shorter ICU stay.", "Thirty-seven male alcoholics admitted electively for detoxification were randomized to treatment with either diazepam or propranolol. Subjects were comparable both in age and in duration and quantity of alcohol consumed. Admission laboratory parameters did not distinguish between the groups. Eleven subjects required no medication to control withdrawal signs/symptoms. Both groups showed improvement in blood pressure, pulse, and withdrawal tremor. None of the subjects randomized to diazepam manifested withdrawal seizures or hallucinations. By contrast, one subject in the propranolol group had a single withdrawal seizure. Another subject manifested increasing withdrawal that required parenteral paraldehyde treatment. Thus, this study confirms that a significant number of subjects admitted electively for alcohol withdrawal can be managed without medication. Minor tranquilizers still remain the \"gold standard\" for management of the withdrawal syndrome.", "The efficacy and safety of a new triazolobenzodiazepine, alprazolam, was compared to diazepam in 46 alcoholics in a double-blind study. The drugs were administered for 21 days starting on the fifth day after the last drink. The mean optimal daily oral dose of alprazolam was 2.2 mg and of diazepam 20.2 mg given in a t.i.d. fashion. Alprazolam was as effective as diazepam in the relief of anxiety as measured by the Hamilton Anxiety Rating Scale, Physician's Global Impressions, Patient's Global Impressions, Hopkins Symptom Checklist and Target Symptoms Record. At the end of the trial 95% of patients in both groups experienced moderate to marked therapeutic effect and felt much or very much better as compared to the start of the study. The number of side effects was similar in both groups and they were mostly described by patients as \"mild\".", "Treatment of the alcohol withdrawal syndrome is best accomplished using pharmacologic agents that have minimal interaction with alcohol, have limited adverse effects, and are without abuse potential. The partial benzodiazepine receptor agonist beta-carboline compound, abecarnil, has been shown in animal and human studies to possess a number of these characteristics and to be useful in the reduction of alcohol withdrawal convulsions in mice. In this study, 49 alcohol-dependent inpatients who exhibited at least moderate symptoms of uncomplicated alcohol withdrawal were treated over a 5-day detoxification period with abecarnil or diazepam and rated daily for alcohol withdrawal symptoms and adverse events. Both the abecarnil and diazepam treatment groups exhibited a similar marked reduction in withdrawal symptoms over time. In addition, similar rates of successful treatment and improvement were observed after 1 day of treatment and at termination in alcoholics treated with either medication. Overall, rates of adverse events and changes in liver enzymes were similar in both treatment groups and were generally benign. Because of the unique pharmacologic profile of abecarnil in animal and in non-clinical human studies, including anticonvulsant action, low abuse liability, and a favorable side effect profile, further study of compounds of the partial benzodiazepine receptor agonist type in the treatment of alcohol withdrawal syndromes seems warranted.", "nan", "In a double-blind study the clinical symptomatology and quantitatively analyzed EEG of 42 hospitalized chronic alcoholics (ICD 303) undergoing alcohol withdrawal were investigated before, during and after 3 weeks' treatment with 2 pharmacokinetically different benzodiazepines: the short-acting lopirazepam (a new pyridodiazepine) and the long-acting prazepam. At the end of weeks 1 and 3 the titrated optimal daily doses were 24 and 23 mg lopirazepam and 35 and 32 prazepam, respectively, thus confirming our earlier pharmaco-EEG predictions that on a mg to mg basis the former drug is slightly more CNS potent than the latter. Thereafter, the patient population was divided into 6 subgroups: 2 groups continuing on active medication, 2 groups receiving placebo, and 2 groups with no pharmacotherapy for 1 week. Clinical assessments included the CGI, the Hamilton Anxiety Score, the Zung Self-Rating Scale for Anxiety and Depression, the Zerssen Befindlichkeitsskala and the questionnaire for somatic findings and side effect and were carried out on days 0, 7, 21 and 28 as was a radioreceptor assay for benzodiazepines in plasma. Quantitative EEG investigations were carried out on days 0, 21 and 28 and included recordings before and 2 h after one single dose of 10 mg. Statistical analysis demonstrated a marked and highly significant decrease in psychopathology as well as good drug tolerance at the end of the first week of therapy and thereafter a slight continuation in improvement until the end of the 3rd week. There were, however, no statistically significant differences between the 2 active compounds, nor were there any statistically significant differences between the 6 subgroups in the 4th week. On the other hand, blood level investigations demonstrated that even after a 3-week treatment period, blood levels dropped down to a morning minimum 12 h after the last evening medication of the short-acting lopirazepam, while plasma levels of the long-acting prazepam remained high. This was also reflected in the spectral analyzed EEG, which showed, after one single dosage of both drugs, a typical anxiolytic profile which was more pronounced after lopirazepam than prazepam, while after the chronic administration (12 h after the evening medication) only prazepam showed an anxiolytic profile. The lopirazepam-treated patients exhibited on the one hand a lack of benzodiazepine-specific alterations, but showed on the other hand EEG changes possibly reflecting clinical improvement. The relevance of the findings will be discussed.", "Alcohol withdrawal therapy can be simplified with a loading dose of diazepam, taking advantage of the kinetic tapering afforded by the drug's long t 1/2s and its metabolites, and of the effectiveness of nonpharmacologic maneuvers. In a double-blind trial, 50 inpatients in moderate to severe alcohol withdrawal received 20 mg oral diazepam and supportive care (n = 25) or placebo and supportive care (n = 25) every 2 hr until they were asymptomatic. Fifty-six percent of patients responded to placebo within 5 +/- 2.9 hr (mean +/- SD), whereas 72% responded to initial diazepam within 6.3 +/- 3.9 hr. Patients treated with diazepam had more rapid and greater improvement than those treated with placebo. Patients who did not respond to six doses of diazepam received further (unblinded) diazepam, 20 mg, every 1 to 2 hr. All patients who did not initially respond (n = 18) improved after more diazepam. Thus all patients who received diazepam (n = 36), during the experimental phase or subsequently, were effectively treated. There were no adverse effects. The median number of 20-mg diazepam doses to treat alcohol withdrawal were three, given over a period of 7.6 hr (range = 1 to 12 and 0.33 to 45 hr). Complications occurred only in those who received placebo during the experimental phase, indicating that delay in therapy may be responsible for the appearance of complications in alcohol withdrawal." ]

[ "11428448", "1644539", "9697913", "15946379", "10029389", "9082107", "16954994", "11452819", "10341919", "16493528", "9973793", "11805893", "1300901", "3276296" ]

[ "Selective use of drains in thyroid surgery.", "Drainage after thyroidectomy: a randomized clinical trial.", "Does draining the neck affect morbidity following thyroid surgery?", "Is the routine drainage after surgery for thyroid necessary? A prospective randomized clinical study [ISRCTN63623153].", "Drainage systems in thyroid surgery: a randomised trial of passive and suction drainage.", "[Gravity or suction drainage in thyroid surgery? Control of efficacy with ultrasound determination of residual hematoma].", "Is lack of placement of drains after thyroidectomy with central neck dissection safe? A prospective, randomized study.", "Drainage in thyroid surgery: a prospective randomised clinical study.", "Drainage after thyroid surgery: a prospective randomized study.", "Is the insertion of drains after uncomplicated thyroid surgery always necessary?", "[The role of drainage and antibiotic prophylaxis in thyroid surgery].", "[Assessment of drain insertion in thyroid surgery?].", "[Prophylactic drainage after thyroidectomy: a randomized trial].", "To drain or not to drain in thyroid surgery. A controlled clinical study." ]

[ "To identify whether there are differences in the use of drains and, if used, which would be the best for thyroid surgery.\n Prospective, longitudinal, comparative, randomized study.\n General Hospital Mexico City, Mexico.\n One hundred fifty patients were studied, divided into three groups: group A, without drain; group B, with a Penrose drain; and group C, with a semirigid suction drain. On the basis of the preoperative diagnosis, subtotal or total thyroidectomy or hemithyroidectomy was performed. Analyzed variables were thyroid volume (TV), transoperative bleeding (TOB), flow of postoperative drain (PD), length of hospital stay (HS), and complications, such as seromas, hematomas, and hemorrhages. Statistical Analysis. Multiple variant analysis, using Scheffe's procedure and chi2.\n Group A had an average TOB of 107 mL, HS of 2 days, and TV of 153.24 mL with two complications (seromas). Group B had an average TOB of 149.8 mL, HS of 2.6 days, TV of 175.4 mL, PD of 29.6 mL, and three complications (2 seromas and 1 hematoma). Group C had an average TOB of 161.5 mL, HS of 3.11 days, TV of 173.5 mL, PD of 25.84 mL, and two seromas. No differences existed regardless of the type of drain used between groups B and C.\n Statistical analysis showed that the size of the gland, diagnosis, type of surgery, transoperative bleeding, and complications are not valid arguments to leave an external drain in thyroid surgery. No advantages were found between the Penrose or the semirigid suction drains. Hospital stay was longer in patients with the suction drain. These results support the notion that the use of wound drainage cannot substitute for meticulous dissection and transoperative hemostasis.", "A randomized clinical trial of surgical drainage in thyroid surgery was performed on 97 patients. Morbidity was not significantly different between both groups. The length of hospital stay was shorter in the undrained group. However, this RCT is not an indication of the value of drainage after thyroid surgery because the series is too small. Using a meta-analysis of the RCTs reported it is possible to show that to drain is not useful.", "A prospective randomized study questioning the benefit of neck drainage in thyroid surgery is presented. Two hundred consecutive patients, candidates for elective thyroid surgery, were randomized into Group A (no drain) and Group B (drain). Reoperation for bleeding was necessary for two patients of Group A and for one patient in Group B. Minor hematomas occurred in seven patients from Group A and five patients from Group B; wound infection occurred in two and four patients in Groups A and B, respectively; and lymphatic discharge occurred in two patients from Group B. These differences were not statistically different. The present study failed to demonstrate any protective value from the use of drains. However, the hospital stay was shorter and pain scores were smaller in the non-drain Group A.", "Drains are usually left after thyroid surgery to prevent formation of hematoma and seroma in the thyroid bed. This is done to reduce complications and hospital stay. Objective evaluation of the amount collected in the thyroid bed by ultrasonography (USG) can help in assessing the role of drains.\n A randomized prospective control study was conducted on 94 patients undergoing 102 thyroid surgeries, over a period of fifteen months. Patients included in the study were randomly allocated to drain and non-drain group on the basis of computer generated random number table. The surgeon was informed of the group just before the closure of the wound Postoperatively USG neck was done on first and seventh postoperative day by the same ultrasonologist each time. Any swelling, change in voice, tetany and tingling sensation were also recorded. The data was analyzed using two-sample t-test for calculating unequal variance.\n Both groups were evenly balanced according to age, sex, and size of tumor, type of procedure performed and histopathological diagnosis. There was no significant difference in collection of thyroid bed assessed by USG on D1 & D7 in the two groups (p = 0.313) but the hospital stay was significantly reduced in the non-drain group (p = 0.007). One patient in the drain group required needle aspiration for collection in thyroid bed. No patient in either group required re-operation for bleeding or haematoma.\n Routine drainage of thyroid bed following thyroid surgery may not be necessary. Not draining the wound results in lesser morbidity and decreased hospital stay.", "To investigate the effectiveness of high-vacuum and passive drainage systems after elective thyroid resection.\n Prospective randomised clinical study and multicentre postal survey.\n Military hospital, Germany.\n 80 patients, treated with passive closed drains (n = 40) or high-vacuum systems (n = 40).\n 1. Measuring the amount of blood collected during drainage and the extent of residual haematoma on ultrasonography. 2. Survey in Austria, Germany and Switzerland of annual number of bilateral thyroid resections, type of drainage used, and volume of postoperative drainage.\n 799 of the 1698 hospitals surveyed replied (47.2%). 785 (98.2%) of the 799 surgeons said that they used drainage systems of whom 766 (97.6%) used high-vacuum systems. In the 40 patients in whom passive closed drainage was used, the median volume drained was 34 ml (range 0-175) compared with 115 ml (40-346) in the high vacuum group (p < 0.01). In the passive drainage group the extent of residual haematoma measured by us was 4.4 ml (range 0-21.7) compared with 5.3 ml (0.6-24.9) in the high vacuum group.\n The high-vacuum drainage that is most commonly used in Austria, Germany, and Switzerland results in increased blood loss with no reduction in the extent of residual wound haematoma and offers no additional advantage over passive drainage systems in thyroid surgery.", "In a prospective randomized trial, the common high-vacuum drainage system according to Redon was compared with the nonsuction system according to Robinson in 80 patients undergoing elective thyroid surgery between January 1995 and August 1995. Forty patients were provided with nonsuction, passive drains, and another 40 patients were allocated to a control group with the high-vacuum system. Twenty-four h postoperatively, the wound area was analyzed by sonography after drainage removal. The dimension of the remaining hematoma was determined by scanning the operation field in six to seven layers (thickness per layer T = 1 cm). The area (A) of the hematoma was measured per layer, and thus the volume was determined by the formula: V = T x (A1 + A2.. + A(n)). Simultaneously, the quantity of discharge was determined. Patients receiving nonsuction drainage had significantly lower median drainage volume (34 ml; range: 0-175 ml vs-115 ml; range: 40-346 ml; P < 0.01) and a remaining hematoma, measured sonographically, of similar volume to that of the patients receiving high-vacuum treatment (4.4 ml; range: 0-21.7 ml vs 5.3 ml; range: 0.6-24.9 ml; not significant). No complications were observed. An advantage to using the nonsuction device is seen with respect to similar resting wound hematoma, lower fluid evacuation, and painless drain removal. This study supports prophylacity routine nonsuction wound drainage after elective thyroid surgery.", "Selective use of drains after thyroidectomy has been suggested in the literature. Although the safety of thyroidectomy without drains has been reviewed, there is little specific data available to identify the safety of thyroidectomy combined with central neck dissection (CND) without drains. This study aims to determine the feasibility and safety of thyroidectomy without drains, especially in cases of combined CND.\n Prospective, randomized study.\n One hundred ninety-eight consecutive thyroidectomized patients were enrolled in this study. Drain group (n = 101) consisted of 41 hemithyroidectomies (HT), 28 total thyroidectomies (TT), and 32 total TT with CND. No-drain group (n = 97) consisted of 42 HT, 18 TT, and 37 TT with CND. The following variables were examined: perioperative complications (hemorrhage, hematoma, seroma), intraoperative bleeding, operation time, volume of resected thyroid gland, time of hospital discharge after operation, duration of drain placement, and total amount of drainage (drain group).\n There were no significant differences in age, sex, volume of resected thyroid gland, types of operation, operation time, and histopathlologic diagnosis between two groups. In the drain group, overall perioperative complications occurred in seven (7/101, 6.9%) patients. In the no-drain group, overall perioperative complications occurred in nine (10/97, 10.3%) patients. There was no significant difference in overall perioperative complications between the drain and no-drain groups, even in cases of performing CND. Time of hospital discharge after operation was significantly shorter in the no-drain group than the drain group (P < .05).\n We conclude that thyroidectomy without drains is safe and effective even in combination with CND and appears to confer several advantages over the routine drainage method. In addition, we achieved significant reduction of hospital stay, which led to a reduction in costs for the patients.", "Drainage in thyroid surgery is still an area of controversy. We analysed the results of a prospective randomised trial conducted in our institution in order to assess the utility of drainage after thyroid surgery. Sixty patients were entered into the study, thirty of whom were drained after surgery and thirty who received no drainage. The two groups were well matched with regard to most characteristics. There was no difference between the two groups in terms of early or late postoperative complications. We therefore conclude that, in our experience, drainage after uncomplicated thyroid surgery is of no benefit.", "Between November, 1996 and May, 1997 a series of 100 consecutive unselected patients undergoing all types of thyroid surgery--including even those inducing large dead space e.g. substernal goitre and carcinoma thyroid with recurrent nerve dissection--were randomly allotted to either receive drainage (n = 43) or not (n = 57). Patients with cervical dissection for lymph node metastasis were not included. Severe intra-operative haemorrhage was not a reason for exclusion. No complications such as haematoma or seroma were found in the undrained group whereas only minor complications such as haematoma (n = 4) were noted in the drained group. Whatever the group, none of the patients required re-exploration. The difference in overall hospital stay (1.72 days in the group of undrained patients versus 2.09 days in the drained group) was not statistically significant.", "We conducted a prospective, randomized study to evaluate the necessity of drainage after uncomplicated thyroid surgery.\n The subjects were 135 patients who underwent thyroid surgery between September 2002 and February 2004. The patients were randomized into two groups according to whether drains were inserted at the time of surgery. Group 1 consisted of 68 patients with drains and group 2 consisted of 67 patients without drains. The indications for surgery, procedures performed, local complications (such as infection, seroma, and bleeding or hematoma), necessity for reoperation, and hospital stay were recorded.\n There were 110 (81.5%) women and 25 (18.5%) men, with a median age of 46.9 +/- 12.5 years. The mean hospital stay was 2.6 +/- 1.0 days in group 1 and 1.3 +/- 0.7 days in group 2 (P = 0.001). Local complications developed in five (7.3%) patients from group 1, as wound infections in two (2.9%), seroma in one (1.5%), and hemorrhage in two (2.9%); and in two (3%) patients from group 2, as seroma in one (1.5%) and hematoma in one (1.5%). Both of the group 1 patients with postoperative hemorrhage required reoperation within 8 h after initial surgery. The hematoma in the group 2 patient was treated successfully with needle aspiration.\n These findings suggest that the routine use of drains may be abandoned in uncomplicated thyroid surgery, since serious postoperative bleeding rarely occurs and hematomas can be treated by needle aspiration if drains have not been placed. Furthermore, the use of drains prolongs hospital stay and increases the risk of infection.", "It is our habit to employ an open drainage after thyroid surgery in our department. We have also found a large number of surgical infections in these patients (5.8% vs 2.5). Aim of the study is to evaluate prospectively if contamination happens during surgical procedure or in a later time according to the presence of the open drainage.\n From October 1995 to November 1996, 113 patients who underwent a subtotal thyroidectomy were randomized into two groups: group A with antibiotic prophylaxis (57 patients) and group B without it (56 patients).\n One case (1.7%) of sepsis among 57 patients of group A and 2 cases (3.4%) among 56 patients of group B were observed.\n No statistical difference was found between the two groups despite antibiotic prophylaxis covering surgical procedure. It is personal opinion that sepsis arose after surgical procedure, due to the presence of the open drainage.", "Although generally recommended the benefit of suction drains in thyroid surgery is not proven.\n Therefore, we started a prospective randomized trial including all patients who were referred to our institution for resection of an euthyroid goiter (n = 52 with drains and 48 without). On the third postoperative day as well as four weeks later the patients were questioned and physically examined, including an ultrasound of the neck and, if present, the measurement of a hematoma.\n Two patients had to be reoperated due to a hemorrhage detected by the drains. Further the study revealed that patients without drains left the hospital significantly earlier (3.9 vs 4.6 days, p = 0.006). On the other hand the hematoma size in this group was larger than in the group with drains (1.9 ml vs. 0.9 ml, p = 0.016). The other clinical parameters were comparable in both groups. Four weeks postoperatively no differences were detected.\n So far neither our results nor those in the literature could prove that severe postoperative hemorrhage can be recognized or treated faster with the use of drains. Although drains reduce the size of hematomas significantly, the quantity is too small for any clinical relevance. Based on these results a general insertion of drains after resection of an euthyroid goiter is not recommended.", "A randomized clinical trial of surgical drainage in thyroid surgery was performed with 97 patients. Using equivalence testing it is reported that morbidity was not significantly different between the two groups and the length of hospital stay was shorter in the undrained group. It is possible to perform thyroidectomy without drainage in a selected population.", "Drainage after thyroid surgery is widely used to prevent postoperative complications by evacuation of blood and fluids. However, to our knowledge no study has shown the benefit of drainage. Therefore, we performed a prospective, randomized study on the rate of complications after drainage or no drainage in thyroid surgery. One hundred fifty patients were allocated to drainage or no drainage. No difference was seen between the two groups according to the experience of the surgeon, type of operation, diagnosis, weight of thyroid specimens, operation time, and hospital stay. All complications were recorded and resulted in two patients receiving reoperation because of bleeding, two permanent laryngeal nerve palsies, one case of permanent hypocalcemia, ten minor hematomas, one wound infection, and one lymphatic leakage. No difference was seen between the groups. This study does not support prophylactic routine drainage after uncomplicated thyroid surgery." ]

[ "9764337", "12424933", "8447522", "9546419", "1406879", "1730079" ]

[ "Effect of iron chelation therapy on mortality in Zambian children with cerebral malaria.", "Deferiprone (L1) as an adjuvant therapy for Plasmodium falciparum malaria.", "Iron chelation as a chemotherapeutic strategy for falciparum malaria.", "Assessment of the effect of the oral iron chelator deferiprone on asymptomatic Plasmodium falciparum parasitemia in humans.", "Effect of iron chelation therapy on recovery from deep coma in children with cerebral malaria.", "Iron chelation with desferrioxamine B in adults with asymptomatic Plasmodium falciparum parasitemia." ]

[ "To examine the effect of iron chelation on mortality in cerebral malaria, we enrolled 352 children in a trial of deferoxamine in addition to standard quinine therapy at 2 centres in Zambia, one rural and one urban. Entrance criteria included age < 6 years, Plasmodium falciparum parasitaemia, normal cerebral spinal fluid, and unrousable coma. Deferoxamine (100 mg/kg/d infused for a total of 72 h) or placebo was added to a 7 d regimen of quinine that included a loading dose. Mortality overall was 18.3% (32/175) in the deferoxamine group and 10.7% (19/177) in the placebo group (adjusted odds ratio 1.8; 95% confidence interval 0.9-3.6; P = 0.074). At the rural study site, mortality was 15.4% (18/117) with deferoxamine compared to 12.7% (15/118) with placebo (P = 0.78, adjusted for covariates). At the urban site, mortality was 24.1% (14/58) with deferoxamine and 6.8% (4/59) with placebo (P = 0.061, adjusted for covariates). Among survivors, there was a non-significant trend to faster recovery from coma in the deferoxamine group (adjusted odds ratio 1.2; 95% confidence interval 0.97-1.6; P = 0.089). Hepatomegaly was significantly associated with higher mortality, while splenomegaly was associated with lower mortality. This study did not provide evidence for a beneficial effect on mortality in children with cerebral malaria when deferoxamine was added to quinine, given in a regimen that included a loading dose.", "Mortality due to Plasmodium falciparum infection remains high in India, hence any modality of treatment which can improve the outcome of this disease is worth exploring. The present study was undertaken to see whether addition of an oral iron chelator, deferiprone (L1) to the conventional treatment regime for P. falciparum infection improves the clinical course and final outcome.\n In this prospective, randomised double blind trial, 45 consecutive patients with P. falciparum infection were randomised into two groups. Patients in Group I (control group, 21 patients) received standard quinine and doxycycline therapy along with supportive therapy and placebo capsules for 10 days. Patients in Group II (24 patients) received the same treatment as Group I but in place of placebo capsule received deferiprone capsules 75 mg/kg/day in 12 hourly divided doses. The parameters evaluated included the time taken in resolution of parasitaemia, fever and coma, differences in final outcome i.e., death or other severe complications, and side effects and deferiprone tolerance.\n Four patients in Group I and two in Group II died (P > 0.05). The resolution of fever and coma was significantly faster in Group II (P < 0.05) and parasitaemia cleared 24 h earlier in this Group. The drug was well tolerated and had no side effects.\n Deferiprone (L1) seems to be a promising agent as an adjuvant in the treatment for severe P. falciparum malaria infection.", "To examine the effect of iron chelation against human malaria, 37 Zambians with asymptomatic Plasmodium falciparum infections were randomly assigned to 72-hr infusions of desferrioxamine B or placebo. Mean concentrations of ring forms decreased significantly with desferrioxamine B (P < 0.001) but not with a placebo. Over seven days of observation, mean parasite concentrations remained at the initial levels in six individuals originally given placebo, but decreased promptly with administration of desferrioxamine B (P = 0.001). Mean parasitemia was significantly lower for up to four weeks in 16 subjects treated with desferrioxamine B when compared with the eight who had received placebo only (P = 0.027). We conclude that iron chelation has antiplasmodial activity and may offer a new therapeutic strategy for falciparum malaria.", "While the parenteral iron-chelating agent desferrioxamine B has anti-malarial activity in humans, the usefulness of an orally active chelator for this indication has not been investigated previously in vivo. We conducted a prospective, double-blind, placebo-controlled, cross-over trial of deferiprone (L1; CP20; 1,2-dimethyl-3-hydroxypyridin-4-one) in 25 adult Zambians with asymptomatic Plasmodium falciparum parasitemia. Deferiprone was administered daily for three or four days in divided doses of 75 or 100 mg/kg of body weight, dosages that are effective for treating iron overload. No reduction in asexual intra-erythrocytic parasites was observed during or after deferiprone treatment. The mean peak plasma concentration of deferiprone (108.9 +/- 24.9 micromol/L) achieved was within the range demonstrated to inhibit the growth of P. falciparum in vitro, but the systemic exposure as determined by the 24-hr plasma concentration-time curve would not be predicted inhibit growth in vivo. No evidence of deferiprone-associated hematological toxicity was noted in this short-term study of these subjects, all of whom had clinical evidence of normal body iron stores. Because of the risk of neutropenia and other adverse effects with higher doses or prolonged use of the chelator, additional trials of deferiprone as a sole anti-malarial agent would not seem to be justified. In contrast, further efforts are needed to develop other orally active iron-chelating agents specifically for their anti-malarial action.", "Cerebral malaria is a severe complication of Plasmodium falciparum infection in children, with a mortality rate of 15 to 50 percent despite antimalarial therapy.\n To determine whether combining iron chelation with quinine therapy speeds the recovery of consciousness, we conducted a randomized, double-blind, placebo-controlled trial of the iron chelator deferoxamine in 83 Zambian children with cerebral malaria. To be enrolled, patients had to be less than six years old, have P. falciparum parasitemia, have normal cerebrospinal fluid without evidence of bacterial infection, and be in a coma from which they could not be aroused. Deferoxamine (100 mg per kilogram of body weight per day, infused intravenously for 72 hours) or placebo was added to standard therapy with quinine and sulfadoxine-pyrimethamine. The time to the recovery of full consciousness, time to parasite clearance, and mortality were examined with Cox proportional-hazards regression analysis.\n The rate of recovery of full consciousness among the 42 patients given deferoxamine was 1.3 times that among the 41 given placebo (95 percent confidence interval, 0.7 to 2.3); the median time to recovery was 20.2 hours in the deferoxamine group and 43.1 hours in the placebo group (P = 0.38). Among 50 patients with deep coma, the rate of recovery of full consciousness was increased 2.2-fold with deferoxamine (95 percent confidence interval, 1.1 to 4.7), decreasing the median recovery time from 68.2 to 24.1 hours (P = 0.03). Among 69 patients for whom data on parasite clearance were available, the rate of clearance with deferoxamine was 2.0 times that with placebo (95 percent confidence interval, 1.2 to 3.6). Among all 83 patients, mortality was 17 percent in the deferoxamine group and 22 percent in the placebo group (P = 0.52).\n Iron chelation therapy may hasten the clearance of parasitemia and enhance recovery from deep coma in cerebral malaria.", "To determine if iron chelation therapy has activity against human malaria, we administered desferrioxamine B in amounts of 100 mg/kg per day by continuous 72-hour subcutaneous infusions to 28 volunteers with asymptomatic Plasmodium falciparum infection in a randomized, double-blind, placebo-controlled crossover trial. Peripheral blood concentrations of P falciparum ring forms were determined at 12-hour intervals in all subjects and serum concentrations of desferrioxamine B + ferrioxamine (the iron complex of desferrioxamine B) were measured in 26 subjects. Geometric mean concentrations of asexual intraerythrocytic parasites decreased with both chelator and placebo treatment, but the decrement with desferrioxamine B was significantly greater than that with placebo (P less than .006) during both the initial and crossover periods. Compared with placebo, desferrioxamine B treatment was associated with an almost 10-fold enhancement of the rate of parasite clearance during both phases of the trial (P less than .007). Mean +/- SEM steady state concentrations of desferrioxamine B + ferrioxamine were 6.90 +/- 0.60 mumol/L at 36 hours and 7.72 +/- 0.68 mumol/L at 72 hours; in vitro, the ID50 has been reported to be approximately 4 to 20 mumol/L. No drug toxicity was detected. Parasitemia recurred in 19 of 24 participants followed-up over 1 to 6 months. We conclude that desferrioxamine B enhances the clearance of P falciparum parasitemia and that iron chelation may provide a new strategy to be developed for the treatment of malaria." ]

[ "1683333" ]

[ "[Double-blind comparison of 3 x 75 mg zotepine und 3 x 4 mg haloperidol in acute schizophrenic patients]." ]

[ "To assess the efficiency/risk ratio, fixed doses of zotepine and haloperidol were compared by means of a double-blind study in acute schizophrenics over a 4-week period. The assessment tools were BPRS, CGI, and the Simpson-Angus scale for the extrapyramidal disturbances, and a free report on side effects. No differences between the groups were found in respect of efficacy. According to the Simpson-Angus scale, the patients who had been treated with zotepine achieved better values, this being a general trend. There were significant differences according to the free report on side effects. Especially at onset of treatment, the patients treated with zotepine complained of tiredness. Partly marked extrapyramidal disturbances were seen in the patients who had been treated with haloperidol." ]

[ "10279492", "9744187", "9424040", "9686713", "1907834", "14702491", "15153053", "16461871", "9232713", "16530147", "3301990", "8341774", "7361966", "12236273", "7109747", "8050255", "8075732", "9002097", "3973336", "1985140", "7871143", "7921293", "1401675", "1544078", "1913409", "3565663", "3282026", "15629993", "9521970", "2066823", "8322736", "14993085", "9559706", "1403212", "7847110", "9481466", "2597431", "1437427", "9076288", "12972790", "1940817", "21263970", "9917436", "3454893", "1517726" ]

[ "The flu shot study: using multiattribute utility theory to design a vaccination intervention.", "Postcard reminders from GPs for influenza vaccine: are they more effective than an ad hoc approach?", "Increasing immunization rates among inner-city, African American children. A randomized trial of case management.", "Influenza immunization in a managed care organization.", "Evaluation of a follow-up system in a county health department's immunization clinic.", "Identification and recall of children with chronic medical conditions for influenza vaccination.", "Quality improvement in immunization delivery following an unsuccessful immunization recall.", "Effect of telephone reminder/recall on adolescent immunization and preventive visits: results from a randomized clinical trial.", "Impact of postal invitations and user fee on influenza vaccination rates among the elderly. A randomized controlled trial in general practice.", "Challenges and successes of immunization registry reminders at inner-city practices.", "Influenza vaccination in community elderly. A controlled trial of postcard reminders.", "Evaluation of telephoned computer-generated reminders to improve immunization coverage at inner-city clinics.", "Effectiveness of a mailed reminder on the immunization levels of infants at high risk of failure to complete immunizations.", "Boosting uptake of influenza immunisation: a randomised controlled trial of telephone appointing in general practice.", "Do postcard reminders improve influenza compliance? A prospective trial of different postcard \"cues\".", "Patient-specific reminder letters and pediatric well-child-care show rates.", "A randomized trial of the effectiveness of computer-generated telephone messages in increasing immunization visits among preschool children.", "Computer-generated recall letters for underimmunized children: how cost-effective?", "Increasing the pneumococcal vaccination rate of elderly patients in a general internal medicine clinic.", "Computer-generated physician and patient reminders. Tools to improve population adherence to selected preventive services.", "School health nurse interventions to increase immunisation uptake in school entrants.", "Computer-based vs manual health maintenance tracking. A controlled trial.", "Exporting a successful influenza vaccination program from a teaching hospital to a community outpatient setting.", "Use of reminders to increase compliance with tetanus booster vaccination.", "Use of reminders for preventive procedures in family medicine.", "Increasing influenza vaccination among high-risk elderly: a randomized controlled trial of a mail cue in an HMO setting.", "Vaccination of high-risk patients for influenza. A comparison of telephone and mail reminder methods.", "Implementation of universal influenza immunization recommendations for healthy young children: results of a randomized, controlled trial with registry-based recall.", "Effectiveness and cost-effectiveness of letters, automated telephone messages, or both for underimmunized children in a health maintenance organization.", "A target-based model for increasing influenza immunizations in private practice. Genesee Hospital Medical Staff.", "Do computer-generated reminder letters improve the rate of influenza immunization in an urban pediatric clinic?", "The impact of reminder-recall interventions on low vaccination coverage in an inner-city population.", "The impact of interventions by a community-based organization on inner-city vaccination coverage: Fulton County, Georgia, 1992-1993.", "Computer-generated mailed reminders for influenza immunization: a clinical trial.", "Improving the immunization coverage of children less than 7 years old in a family practice residency.", "Randomized controlled study of customized preventive medicine reminder letters in a community practice.", "Improving preventive care at a medical clinic: how can the patient help?", "Improving influenza vaccination rates in children with asthma: a test of a computerized reminder system and an analysis of factors predicting vaccination compliance.", "A randomised intervention study to examine the effect on immunisation coverage of making influenza vaccine available at no cost.", "Hepatitis A and B vaccination in a sexually transmitted disease clinic for men who have sex with men.", "Influenza immunization: the impact of notifying patients of high-risk status.", "The telephone: an overlooked technology for prevention in family medicine.", "A randomized study of tracking with outreach and provider prompting to improve immunization coverage and primary care.", "Early results from the Northland immunisation register.", "The effect of patient education on pediatric immunization rates." ]

[ "Differences between the multiattribute utility (MAU) profiles of participants who had previously gotten flu shots and those who had not done so were used to design an informational brochure urging influenza vaccination. The effectiveness of the MAU brochure was evaluated in a VA ambulatory care clinic with a long-standing influenza vaccination program. The target population for the intervention was high-risk clinic patients who had not gotten a shot the previous year. Participants received either a letter urging them to get a flu shot, or a letter plus the informational brochure. A significantly larger proportion of the patients who received the brochure got shots; 36% versus 23% for the letter only. While a 13 percentage point increase is modest, influenza and related complications (preventable through vaccination) are the fourth-leading killers of older persons. Adding a MAU-based brochure to an ongoing vaccination program is inexpensive and may save additional lives.", "All persons 65 years and older are recommended to be immunised against influenza each autumn. As immunisation rates remain low, we conducted a randomised control trial in a three-partner urban general practice to evaluate the differential effectiveness of a single postcard reminder in a general practice setting compared to usual care. All non-residential patients aged 65 years and over were identified from the age/sex/disease register. After exclusions, 325 patients were stratified by sex (125 men and 200 women) and randomised to receive either a postcard reminder in large print mailed in April or usual care. General practitioners (GPs) were blind to the randomisation. A blinded record audit performed in July demonstrated that the postcard was effective in increasing immunisation for men (chi(2)1df = 3.85; p = 0.05) but not for women (chi(2)1df = 0.45; p = 0.50). After adjusting for 1995 immunisation status, the effect of the postcard on immunisation rates was even stronger in men (Wald chi(2)1df = 6.20; p = 0.01) but remained non-significant in women (Wald chi(2)1df = 1.38; p = 0.24). With this adjustment, the odds of having the 1996 flu vaccine for men sent the postcard reminder were three times that of men in the control group (OR = 3.0; 95% CI 1.3-6.9). In a general practice setting, a single postcard reminder appears to be a promising way to boost influenza immunisation rates among ageing men. Replication of the study is recommended.", "Immunization rates in the inner city remain lower than in the general US population, but efforts to raise immunization levels in inner-city areas have been largely untested.\n To assess the effectiveness of case management in raising immunization levels among infants of inner-city, African American families.\n Randomized controlled trial with follow-up through 1 year of life.\n Low-income areas of inner-city Los Angeles, Calif.\n A representative sample of 419 African American infants and their families.\n In-depth assessment by case managers before infants were 6 weeks of age, with home visits 2 weeks prior to when immunizations were scheduled and additional follow-up visits as needed.\n Percentage of children with up-to-date immunizations at age 1 year, characteristics associated with improved immunization rates, and cost-effectiveness of case management intervention.\n A total of 365 newborns were followed up to age 1 year. Overall, the immunization completion for the case management group was 13.2 percentage points higher than the control group (63.8% vs 50.6%; P=.01). In a logistic model, the case management effect was limited to the 25% of the sample who reported 3 or fewer well-child visits (odds ratio, 3.43; 95% confidence interval, 1.26-9.35); for them, immunization levels increased by 28 percentage points. Although for the case management group intervention was not cost-effective ($12022 per additional child immunized), it was better ($4546) for the 25% of the sample identified retrospectively to have inadequate utilization of preventive health visits.\n A case management intervention in the first year of life was effective but not cost-effective at raising immunization levels in inner-city, African American infants. The intervention was demonstrated to be particularly effective for subpopulations that do not access well-child care; however, currently there are no means to identify these groups prospectively. For case management to be a useful tool to raise immunizations levels among high-risk populations, better methods of tracking and targeting, such as immunization registries, need to be developed.", "To compare the effects of different types of computer-generated, mailed reminders on the rate of influenza immunization and to analyze the relative cost-effectiveness of the reminders.\n Randomized controlled trial.\n Multispecialty group practice.\n We studied 24,743 high-risk adult patients aligned with a primary care physician.\n Patients were randomized to one of four interventions: (1) no reminder, which served as control; (2) a generic postcard; (3) a personalized postcard from their physician; and (4) a personalized letter from their physician, tailored to their health risk.\n The immunization rate was measured using billing data. A telephone survey was conducted in a subgroup of patients to measure reactions to the mailed reminders. To evaluate the cost-effectiveness, a model was constructed that integrated the observed effect of the interventions with published data on the effect of immunization on future inpatient health care costs.\n All three of the reminders studied increased the influenza vaccination rate when compared with the control group. The vaccination rate was 40.6% in the control group, 43.5% in the generic postcard group, 44.7% in the personalized postcard group, and 45.2% in the tailored letter group. The rates of immunization increased as the intensity of the intervention increased (p < .0001). Seventy-eight percent of patients in the letter group deemed the intervention useful, and 86% reported that they would like to get reminders in the future. The cost-effectiveness analysis estimated that in a nonepidemic year, the net savings per 100 reminders sent would be $659 for the personalized postcard intervention and $735 for the tailored letter intervention. When these net cost-savings rates were each applied to the entire high-risk cohort of 24,743 patients, the estimated total net savings was $162,940 for the postcard and $181,858 for the tailored letter.\n Although the absolute increase in immunization rates with the use of reminders appeared small, the increases translated into substantial cost savings when applied to a large high-risk population. Personalized reminders were somewhat more effective in increasing immunization, and personalized letters tailored to the patients' condition were deemed useful and important by the individuals who received them and had a beneficial indirect effect on patient satisfaction.", "We designed a pilot follow-up system using two mailed reminders and evaluated it for use in the immunization clinic of a relatively large county health department in Washington State. Compliance with the recommended interval for DTP immunizations increased by 33.9% in the group of children receiving two postcard reminders compared to the control group. Over half of the respondents (52%) in the control group and 28% in the intervention group reported that transportation barriers and clinic problems prevented their return.", "Despite long-standing recommendations to provide annual influenza vaccination to children with chronic medical conditions, immunization rates are <10% in most primary care settings. Many obstacles impede implementation of these recommendations, including the challenge of identifying targeted children and the need to immunize yearly in a short time interval. The objective of this study was to assess the accuracy of billing data for identifying children who have high-risk conditions (HRCs) and need influenza vaccination and 2) to evaluate the efficacy of reminder/recall for children with HRCs.\n The study was conducted in 4 private pediatric practices in metropolitan Denver, Colorado, that share a computerized billing system and also participate in an immunization registry. For all children aged 6 to 72 months, registry records were linked with the billing database. Patients with >or=1 encounters for an HRC in the previous 24 months were selected, with HRCs identified from International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes. Using medical records as the \"gold standard,\" we reviewed 327 randomly selected records to determine the sensitivity, specificity, and accuracy of billing data for identifying HRCs. For children with an HRC, we then conducted a randomized, controlled trial of reminder/recall for influenza vaccination. The primary outcome of the recall trial was receipt of influenza vaccine.\n Billing data had a sensitivity of 72% (95% confidence interval [CI]: 48%-95%), specificity of 95% (95% CI: 90%-100%), and overall accuracy of 90% (95% CI: 84%-96%) in determining which children had an HRC. Of the 17,273 patients aged 6 to 72 months, 2007 had >or=1 HRCs (12% overall; range: 9%-14% per practice). Asthma/reactive airways disease accounted for 87% of all HRCs. Reminder/recall significantly increased influenza immunization in children with HRCs, with a vaccination rate of 42% in those recalled, compared with 25% in control subjects. Recalled subjects were more likely to have an office visit (68% vs 60%) and less likely to have a missed opportunity to immunize (28% vs 37%) compared with control subjects.\n Diagnosis-based billing data accurately identified children who had HRCs and needed annual influenza vaccination, and registry-driven reminder/recall significantly increased influenza immunization in targeted children.", "Within a clinic serving disadvantaged children, 1) to evaluate a multifaceted quality improvement (QI) project to improve immunization (IZ) up-to-date (UTD) rates and 2) to assess the efficacy of IZ reminder/recall performed following QI.\n A year-long QI project followed by a trial of reminder/recall. QI interventions were targeted at previously identified barriers to IZ and were designed specifically to improve the efficacy of reminder/recall. QI interventions were designed to 1) increase the use of medical record releases to document IZs received elsewhere; 2) improve the accuracy of parental contact information; and 3) reduce missed opportunities by utilizing chart prompts, provider education, and provider reminders. Following QI, we conducted a randomized trial of reminder/recall.\n UTD rates for 7-11 month olds increased from 21% before the QI project to 52% after (P <.0001); rates for 12-18 month olds increased from 16% before QI to 44% after (P <.0001); 19-25 month olds 18% before to 33% after (P <.001). After QI, an average of 61 records per month were updated with IZs received elsewhere. However, the accuracy of parental contact information worsened (29% unreachable before QI vs 44% after, P <.001) and missed opportunities did not improve (8% before vs 6% after, P = not significant [NS]). A subsequent trial of reminder/recall did not increase UTD rates, with 17% of recalled children brought UTD vs 16% of controls (P = NS).\n Clinic-based QI increased documented UTD rates in a disadvantaged patient population. However, IZ reminder/recall did not further increase UTD rates above the rates achieved by the QI process.", "To measure the effect of telephone-based reminder/recall on immunization and well-child care (WCC) visit rates among adolescents in urban practices.\n Randomized clinical trial of telephone-based reminder/recall over 18 months.\n Four urban primary care practices.\n Adolescents aged 11 to 14 years.Intervention Adolescents within practices were randomized to study (n = 1496) or control groups (n = 1510). The study group was sent audiotaped telephone reminders about a scheduled or needed immunization or WCC visit. Households were called weekly if there was no response; telephone numbers were updated weekly. Controls received standard care.\n Baseline demographics and immunization and WCC visit rates were similar for study and control groups. The intervention was largely ineffective in improving immunization or WCC visit rates. Although at the end of the study, the study group had slightly higher hepatitis B coverage (3 vaccinations) (62% vs 57.8%; P = .02), WCC visits were the same (53% and 54%), and impact on other vaccinations was minimal. The effect of reminder/recall was equivalent across demographic subgroups (e.g., age, race/ethnicity, insurance). The major factor limiting intervention effectiveness was inaccurate telephone numbers. Seventy-one percent of study subjects with single telephone numbers throughout the study had a WCC visit vs 25% of study subjects with multiple/changed telephone numbers and 54% of controls (P<.001).\n An intensive telephone reminder and recall system was only minimally successful in improving immunization and WCC visit rates among urban adolescents. Lack of success was largely owing to changed or inaccurate telephone numbers.", "To examine the impact of postal invitations and user fee on influenza vaccination rates.\n A controlled randomized trial in 13 general practices. One third of the participating patients received postal invitations to influenza vaccination free of charge. Another third received postal invitations to influenza vaccination on paying the usual fee (US$ 40-60). The last third served as a control group, being vaccinated at their own request and paying the usual fee.\n General practice in the Counties of Funen and Vejle, Denmark.\n Five hundred and eighty-five patients aged 65 years or older, recognized by their general practitioner (GP) as being in the risk group for whom influenza vaccination is recommended.\n Influenza vaccination rates.\n In the control group 25% (19-31%, 95% confidence interval) of the patients were vaccinated, compared with 49% (42-56%) in the group who received a postal reminder and paid the usual fee, and 72% (65-78%) in the group invited to be vaccinated free of charge.\n It is suggested that GPs send postal invitations to their elderly patients in the risk groups urgently recommending influenza vaccination. Attention should also be given to offering free influenza vaccination to elderly patients who have recognized indications for vaccination.", "To assess the effectiveness of two serial registry reminder protocols and the interactive effects of reminders with child characteristics on immunization rates.\n At an inner city practice network in New York City we randomized 1662 children aged 6 weeks-15 months due or late for a diphtheria-tetanus-pertussis (DTaP) to 3 groups: continuous reminders (as needed), limited reminders (up to 3) and controls, for 6 months. Reminders were triggered by the hospital registry and immunizations were tracked with both the hospital and city registries. Analyses were based on intention to treat.\n At randomization, the study groups were comparable (9.2 months of age, 77% Latino, 86% Medicaid, 49.3% up-to date). A quarter of the children were sent false reminders, 15% had incorrect contact information, and 15% had missed opportunities for vaccination. In the univariate analysis, reminders improved coverage rates, but only for the children sent continuous reminders (51.2% vs. 44.9% controls, p < .01). Multivariate analysis showed reminders had no independent effect on immunization outcomes. Age, up-to-date and Medicaid status at randomization were strong predictors of a child receiving any subsequent immunization. However, reminders interacted synergistically with Medicaid to increase the likelihood of receiving an immunization.\n At an inner city practice network, registry reminders were not effective at improving immunization outcomes due to major system barriers. Immunization registries are powerful vehicles for identifying children in need of immunizations and generating reminders but system challenges must be addressed if this promise is to be achieved in inner city practices.", "Available strategies to increase influenza vaccination rates in the elderly have not been tested in the private sector where most elderly receive care. We performed a randomized controlled trial of a postcard reminder in the three private general internal medicine practices. The observed vaccination rates of 55% in experimental patients (N = 262) and 54% in control patients (N = 278) were similar, though much higher than estimated national rates of 20%. The data indicated that the baseline (control group) vaccination rate was high probably because study participants were exposed to many community vaccination cues, separate from the study cue. That vaccination rates were not higher after additional exposure to the study cue suggests that a \"ceiling effect\" occurred. Including 70 patients not randomized into the trial because they received flu shots prior to randomization, the vaccination rate in patients who had a clinic visit during autumn months was 75% compared to a rate of 52% in patients not visiting the clinic (P less than .001). Our results suggest that vaccination rates can be considerably higher in the private sector than those reported in the past, and that both vaccination cues and direct patient contact appear important to promote vaccination. This and other studies suggest that traditional cues may have a ceiling effect, yielding vaccination rates no higher than 55 to 65%; further increases in rates will require other approaches.", "The authors evaluated the effectiveness of computer-generated telephoned reminders used to raise the rates of on-time immunization among preschool-age children in two public clinics in Atlanta, GA. The overall effect of the intervention on immunization levels appeared to be minimal (crude relative risk = 1.07, 95 percent confidence interval = 0.78, 1.46), in part because only about 80 percent of children in both the randomly selected intervention group and in the control group were members of a household with a telephone number listed in clinic records. However, logistic regression analysis indicated that 36 of 68 children (52.9 percent) in the intervention group whose households were reached were vaccinated within 30 days of their due dates, compared to 31 of 75 children (41.3 percent) in the control group whose household telephone numbers were recorded but not called (adjusted odds ratio = 2.12, 95 percent confidence interval = 1.01, 4.46). This analysis indicates that telephoned reminders demonstrated a level of effectiveness in improving immunization levels at inner-city clinics that recommends further trial and study.", "The Ohio Department of Health initiated a program of mailing an immunization reminder to the mothers of six-month-old children predicted to be at high risk of failure to receive vaccinations based on birth certificate information. The evaluation results indicated a 50% gain in immunizations amongst children whose parents received the letter when compared with those not receiving the letter.", "Immunisation against influenza is an effective intervention that reduces serologically confirmed cases by between 60% and 70%. Almost all influenza immunisation in the UK is done within general practice. Current evidence on the effectiveness of patient reminders for all types of immunisation programmes is largely based on North American studies.\n To determine whether telephone appointments offered bygeneral practice receptionists increase the uptake of irfluenza immunisation among the registered population aged over 65 years in east London practices.\n Randomised controlled trial.\n Three research general practices within the East London and Essex network of researchers (ELENoR).\n Participants were 1,820 low-risk patients aged 65 to 74 years who had not previously been in a recall system for influenza immunisation at their general practice. The intervention, during October 2000, was a telephone call from the practice receptionist to intervention group households, offering an appointment for influenza immunisation at a nurse-run. clinic Main outcome measures were the numbers of individuals in each group receiving immunisation, and practice costs of a telephone-appointing programme.\n intention to treat analysis showed an immunisation rate in the control group of 44%, compared with 50% in the intervention group (odds ratio = 1.29, 95% confidence interval = 1.03 to 1.63). Of the patients making a telephone appointment, 88% recieved immunisation, while 22% of those not wanting an appointment went on to be immunised. In the controlgroup, income generated was 11.35 pounds per immunisation, for each additional immunisation in the intervention group the income was 5.20 pounds. The 'number needed to telephone' was 17.\n Uptake of influenza immunisation among the low-risk older population in inner-city areas can be boosted by around 6% using a simple intervention by receptionists. Immunisation rates in this low-risk group fell well short of the 60% government target. Improving immunisation rates will require a sustained public health campaign. Retaining the item-of-service payments to practices should support costs of practice-based interventions.", "A randomized trial of various postcard reminder \"cues\" was performed to improve understanding of health-related behavior and to find better strategies for improving influenza vaccination compliance. Data were gathered on 283 high-risk patients (92 per cent response rate) who received: 1) a \"neutral\" cue simply announcing the availability of vaccine; 2) a \"Health-Belief-Model\" card written to take advantage of the association between certain health beliefs and vaccination behavior; 3) a \"personal\" card signed by the patient's physician; or 4) no postcard. The highest rate of vaccination occurred among recipients of the Health-Belief-Model postcard (51.5 per cent vs. 20.2 per cent for control, p less than 0.001). Linear logistic regression analysis found that age, prior vaccination history and experimental group had a significant effect on likelihood of being vaccinated. After adjusting for age and prior vaccination experience, the vaccination rate was found to be significantly higher for persons receiving the Health-Belief-Model postcard compared with persons receiving no postcard or a neutral postcard. We conclude that reminder postcards emphasizing elements of the health belief model may help increase vaccination rates.", "The objective of this study was to determine whether patient-specific letters, which describe the content of an upcoming well-child appointment, improve the show rate of well-child appointments better than postcard reminders. In this prospective clinical trial conducted at a pediatric continuity clinic in a teaching hospital, 288 newborns were randomized to a letter, postcard, or control group. For every well-child appointment, families were sent either a letter pertaining to the particular well-child appointment or a postcard; the control group received no reminders. There were no differences in demographics among the groups. The show rates between the letter and postcard groups were not different, but were significantly higher than the show rate for the control group (75.0%, 73.7%, and 67.5%, respectively; P < .05). A cost comparison between the use of postcards versus not using postcards revealed a benefit in the former. We concluded postcard reminders are effective in improving show rates for well-child-care visits, and that patient-specific letters have no additional benefit above that of postcard reminders.", "To assess the effectiveness of computer-generated telephone reminder and recall messages in increasing preschool immunization visits.\n Randomized, controlled trial.\n Fourteen counties in urban and rural Georgia.\n Children (N = 8002) who were younger than 2 years; had telephone numbers listed in preexisting computerized immunization databases; and were due or late for immunization(s) during the 4-month enrollment period.\n Households of children were randomized to receive or not receive a general or vaccine-specific computer-generated telephone reminder or recall message the day before the child was due, or immediately after randomization if the child was late.\n The rates of immunization visits during the 30-day follow-up period.\n Of the 4636 children whose households were randomized to receive a message, 1684 (36.3%) visited the health department within 30 days compared with 955 (28.4%) of the 3366 children whose households were not contacted (risk ratio [RR] = 1.28; 95% confidence interval [CI] = 1.20 to 1.37; P < .01). Immunization visits were more frequent (41.1%) among the 3257 children whose households actually received the message (RR = 1.45; 95% CI = 1.36 to 1.56; P < .01). Improvement in immunization visits was similar for general and specific messages, greater for recall than reminder messages, and greatest for children who were late for the third dose of the diphtheria-tetanus-pertussis vaccine and the measles-mumps-rubella vaccine.\n These data suggest a simple and effective way to increase preschool immunization visits, particularly for vaccines associated with the lowest immunization rates.", "To evaluate the effectiveness and cost effectiveness of computer-generated recall letters to parents of children overdue for immunizations.\n This randomized controlled trial included children of two facilities in a regional health maintenance organization. Parents of 20-month-olds who had not yet received a measles-mumps-rubella (MMR) immunization were identified via a computerized immunization tracking system. One half were mailed personalized letters that included the recommended immunization schedule and a request to call for an appointment; the other half served as a control group. Receipt of the MMR between 20 and 24 months of age was evaluated with the computerized tracking system. A telephone survey was conducted with parents whose children had not received the MMR by 24 months. Decision analysis was used to project the theoretical outcomes and costs of a recall letter policy for other populations.\n Among 20-month-old children 10% had not received the MMR; 289 families were included in the analysis. Of families who were mailed letters, 54% (82 of 153) received the MMR by 24 months of age, compared with 35% (47 of 136) of those in the control group (P = 0.001). The telephone survey was completed with 110 parents of children who still did not appear on the health plan computer as having received the MMR by 24 months. Fifteen percent said the child had received an immunization at an outside provider, and of the rest 62% said they had not been aware that an immunization was due. In the cost effectiveness analysis it was projected that recall letters would increase the immunization rate for the regional population of approximately 30000 children from 86% to 90% at a total cost of $5031 annually. The cost per additional child appropriately immunized was $4.04. In sensitivity analyses this cost effectiveness ratio varied depending on the baseline population coverage rate as well as the estimated effectiveness of recall letters.\n Computer-generated letters to recall children overdue for immunizations resulted in a higher proportion of children appropriately immunized in this setting. However, the strategy was not as cost-effective as intuition might suggest. Further studies in health maintenance organization (HMO) settings should compare the cost effectiveness of letters with other low cost strategies including automated telephone reminders.", "To improve the pneumococcal vaccination status of an elderly patients group, those older than 64 years of age were identified from a computer file of all continuing care patients in a general internal medicine clinic. In a randomly chosen study group (N = 163), 91 elderly patients (56 per cent) had received the pneumococcal vaccine. Factors associated with a higher rate of pneumococcal vaccination included receiving the previous year's influenza vaccine, a medical problem list attached to the patient's chart, active clinic status (i.e., seen in the year before the study began), and more than two problems listed in the computer record. Letters encouraging pneumococcal vaccination were then sent to patients who had not been vaccinated. Twenty of 72 patients (28 per cent) who received the letter were vaccinated during the next year; 8 per cent of control patients (three of 39) who did not receive the letter were vaccinated. The 95 per cent confidence limit for the relative difference between the study and control group is 6 to 53 per cent. The relative difference was also significant for influenza vaccination between the intervention group and the portion of the control group that had not been vaccinated at the first chart review. Factors associated with pneumococcal vaccination rate following the mailing of the reminder letter were active clinic status and being up to date for either influenza or tetanus vaccination.(ABSTRACT TRUNCATED AT 250 WORDS)", "Despite an emerging consensus on appropriate preventive services, a minority of patients receive them. A study was undertaken to assess the impact of computer-generated reminders to adult patients, their physicians, or both patients and physicians on adherence to five recommended preventive services: cholesterol measurements, fecal occult blood testing, mammography, Papanicolaou smears, and tetanus immunization. During the academic year 1988-1989, all 7397 adult patients and their 49 physicians in a university family medicine clinical practice were randomized by practice group into one of four study groups: control, physician reminders, patient reminders, and both physician and patient reminders. Adherence was defined in community-oriented terms: the percentage of patients within each group who had received the preventive service in the recommended interval. During the study period, adherence to four of the five preventive services increased significantly, with the largest increases in the physician and patient reminder group: cholesterol measurements increased from 19.5% to 38.1%, fecal occult blood testing 9.3% to 27.0%, mammography 11.4% to 27.1%, and tetanus immunization 23.4% to 35.4% (for each increase, P less than .0001, McNemar's chi-square test). In general, increases were greater in blacks and in patients with any form of insurance coverage. Computer-based physician and patient reminder systems have great promise of improving adherence to preventive services in primary care settings.", "In New South Wales, health screening of school entrants provides the only mechanism for routine monitoring of immunisation uptake in children. School health nurses are in the best position to improve the compliance with immunisation at this age. We compared two interventions to be used by the nurses to increase immunisation uptake in school entrants who reported missing either the measles-mumps vaccine and/or the pre-school diphtheria-tetanus toxoid and oral polio vaccine boosters. Parents in the passive intervention group were sent a letter and leaflet encouraging immunisation; the active intervention group received a telephone reminder from the nurse in addition to the written materials. Both groups were followed up at a later date to assess final immunisation outcome. Of 817 children screened, 88.2% had been immunised against measles and 73.6% had received the booster; 239 children were randomised to the two interventions. Excluding children lost to follow up and those fully immunised at the start of the study, 20 (37%) of 54 were immunised following the passive intervention, and 35 (71%) out of 49 following the active intervention (P = 0.001). Receipt of the letter and leaflet was associated with an increased uptake of booster vaccination (P = 0.036). The active intervention required 14.7 telephone calls and 1.6 uses of the interpreter service per completed immunisation. The passive intervention resulted in worthwhile increases in immunisation rate with minimum cost. A greater improvement in immunisation outcome was achieved by the active intervention, but its use was labour intensive and may only be warranted if high immunisation rates in this age-group are given priority.", "To compare computer-based with manual health maintenance tracking systems to determine whether (1) a computer-based system will result in better provider compliance with the practice health maintenance protocol, (2) the incremental cost of operating a computer-based vs a manual health maintenance tracking system differs, and (3) inactive patients will respond to health maintenance reminders.\n Two-year prospective, randomized, controlled trial.\n Rural, multiple-office, nonprofit, fee-for-service family practice.\n Adult members of families in which at least one member had been seen by the practice within the past 2 years.\n A computer-based health maintenance tracking system that generated annual provider and patient reminders for all patients regardless of appointment status compared with a manual flowchart-based tracking system in which patient reminders were triggered by provider request.\n Provider compliance with the health maintenance protocol determined by preintervention and postintervention chart audits, costs of computer-based tracking, and response of inactive patients to health maintenance reminders.\n Overall provider compliance with the health maintenance protocol increased 15 percentage points in the computer-based tracking group and four percentage points in the manual group. The computer-based tracking group had significantly higher provider compliance than the manual group for eight of 11 procedures. The computer-based tracking system cost 78 cents per patient per year to operate. It was not associated with increased office visits or patient billings.\n Computer-based health maintenance tracking improved provider health maintenance compliance compared with a manual system. The finding that health maintenance compliance improved without a significant increase in patient visits or billings requires confirmation in other settings but suggests that considerable health maintenance can be incorporated into ongoing patient care.", "To assess whether we could export a successful multifaceted influenza vaccination program from an academic medical center to a community setting.\n Pre/post study using concurrent control groups.\n Clinics in a staff model Health Maintenance Organization (HMO). One urban and one suburban clinic were chosen as intervention clinics, while two similar clinics were selected as control clinics.\n All patients aged 65 and over enrolled in the four clinics.\n An informational mailing to patients, a standing-order policy allowing nurses to administer vaccine, a vaccination reminder on daily appointment lists, and availability of walk-in visits for vaccination. Patients in the control clinics received usual care.\n Vaccination rates were determined using a validated postcard survey of 150 randomly selected patients at each clinic both at baseline (1988-89) and after the intervention (1989-90).\n The baseline vaccination rates ranged from 51.4% to 74.6%, with nearly all vaccinations taking place at the HMO. In one intervention clinic, the vaccination rate improved from 56.4% to 72.3%, P = 0.01. In the other, the baseline rate was 74.6% and did not change significantly after the intervention. There was no change in the vaccination rate in the control clinics after the intervention period.\n An influenza vaccination program that combines several organizational interventions may be successfully exported from an academic to a community setting and may serve as a useful model for others.", "To assess the effect of three computerized reminder systems on compliance with tetanus vaccination.\n Prospective randomized controlled trial.\n Ottawa Civic Hospital Family Medicine Centre.\n Of 8069 patients 20 years of age or more who were not in a hospital or institution 5589 were randomly assigned, by family, to a control group, a physician reminder group, a telephone reminder group or a letter reminder group. The remaining 2480 patients were not included in the randomized portion of the study but were monitored. Results are presented for the 5242 randomized patients and the 2369 nonrandomized patients for whom there was no up-to-date record of tetanus vaccination at the start of the trial.\n For the patients in the physician reminder group the physician was reminded at an office visit to assess the patient's tetanus vaccination status and to recommend vaccination; those in the other two reminder groups received a telephone call or letter enquiring about their tetanus vaccination status and recommending a booster dose.\n Proportion of patients who received tetanus toxoid during the study year or who had a claim of vaccination in the previous 10 years.\n The rate of recorded tetanus vaccination in the randomized control group was 3.2%. The difference between that rate and those for the three reminder groups was 19.6% in the physician reminder group (95% confidence interval [CI] 17.1% to 22.2%, p less than 0.00001), 20.8% in the telephone reminder group (95% CI 18.3% to 23.5%, p less than 0.00001) and 27.4% in the letter reminder group (95% CI 24.8% to 30.2%, p less than 0.00001)). The letter reminders were more effective than either the telephone reminders (p = 0.00013) or the physician reminders (p less than 0.00001) in improving compliance. The cost to the practice per additional vaccination recorded was 43 for the physician reminders, $5.43 for the telephone reminders and $6.05 for the letter reminders.\n Although all three reminder systems increased the rate of recorded tetanus vaccination they fell far short of achieving complete population coverage. More intensive interventions would be required to approach that goal. However, such interventions do not appear to be justified given the rarity of tetanus.", "To compare the effectiveness of three computerized reminder systems in the delivery of five preventive procedures in family practice.\n Prospective, randomized, controlled study.\n Ottawa Civic Hospital Family Medicine Centre.\n Of 8502 patients 15 years of age or more who were not in a hospital or institution 5883 were randomly assigned, by family, to a control group, a physician reminder group (passive) or a telephone or letter reminder group (active). The remaining 2619 patients were not included in the randomized portion of the study but were monitored.\n During 1 year the patients in the active reminder groups received a telephone call or letter reminding them of any overdue preventive procedures; for those in the passive reminder group the physician was reminded at an office visit to provide any overdue service.\n Rates of completion of the preventive procedures required.\n All three reminder systems significantly improved the delivery of preventive services (p less than 0.001). The procedure completion rates were 42.0% in the letter reminder group, 42.0% in the telephone reminder group, 33.7% in the physician reminder group and 14.1% in the randomized control group. The use of a letter was more cost-effective than the telephone system, but the physician reminder system was the most cost-effective.\n Computerized reminder systems do improve the delivery of preventive services in family practice.", "A randomized controlled trial demonstrated that a single mailed influenza vaccination cue increased the vaccination rate among elderly HMO members with high-risk chronic conditions (n = 2217) from 30 per cent to 39 per cent during the fall and winter of 1984/85.", "During the 1984-1985 influenza season two study groups were used to compare telephone and letter reminder methods with a control group that received no reminder to determine which was the most effective strategy to increase influenza vaccination rates among the high-risk patient population of a university-based family practice. Seven hundred eighty-seven high-risk patients were randomly assigned to one of the three study groups: a mailed-reminder group, a telephone-reminder group, and a control group. Vaccination rates for both reminder methods were significantly higher than for the control group (P less than .02), and if successfully contacted, the telephone-reminder group had a significantly better vaccination rate than the mailed-reminder group (P less than .05). If successful telephone contact can be made, this reminder method is more effective than a letter reminder to increase influenza vaccination rates among high-risk patients.", "An Advisory Committee on Immunization Practices policy of encouraging influenza vaccination for healthy 6- to 23-month-old children was in effect during the 2003-2004 influenza season, which was unusually severe in Colorado. We collaborated with 5 pediatric practices to attempt universal influenza immunization in this age group.\n The objectives were (1) to assess the maximal influenza immunization rates that could be achieved for healthy young children in private practice settings, (2) to evaluate the efficacy of registry-based reminder/recall for influenza vaccination, and (3) to describe methods used by private practices to implement the recommendations.\n The study was conducted in 5 private pediatric practices in Denver, Colorado, with a common billing system and immunization registry. Although recommendations by the Advisory Committee on Immunization Practices included children who were 6 to 23 months of age at any point during the influenza season, our practices chose not to recall children 22 to 23 months of age, because they would have become >24 months of age during the study period. Therefore, our study population consisted of all healthy children 6 to 21 months of age from the 5 practices (N = 5193), who were randomized to intervention groups (n = 2595) that received up to 3 reminder/recall letters or to control groups (n = 2598) that received usual care. The primary outcome was receipt of >or=1 influenza immunization, as noted either in the immunization registry or in billing data.\n Immunization rates for >or=1 dose of influenza vaccine for the intervention groups in the 5 practices were 75.9%, 75.4%, 68.1%, 55.6%, and 44.3% at the end of the season. Overall, 62.4% of children in the intervention groups and 58.0% of children in the control groups were immunized (4.4% absolute difference), with absolute differences, compared with control values, ranging from 1.0% to 9.1% according to practice. However, before intensive media coverage of the influenza outbreak began (November 15, 2003), absolute differences, compared with control values, ranged from 5.1% to 15.3% and were 9.6% overall. Before November 15, significant effects of recall were seen for children in the intervention groups, in both the 12- to 21-month age category (10.4% increase over control) and the 6- to 11-month category (8.1% increase over control); at the end of the season, however, significant effects of recall were seen only for the older age group (6.2% increase over control). The rates of receipt of 2 vaccine doses >or=1 month apart for eligible children ranged from 21% to 48% among the practices. Four of the 5 practices held influenza immunization clinics during office hours, evenings, or weekends, and these clinics achieved higher coverage rates.\n These results demonstrated that, in an epidemic influenza year, private practices were able to immunize the majority of 6- to 21-month-old children in a timely manner. Although media coverage regarding the epidemic blunted the effect of registry-based recall, recall was effective in increasing rates early in the epidemic, especially for children between 1 and 2 years of age. The practices that achieved the highest immunization rates were proactive in planning influenza clinics to handle the extra volume of immunizations required.", "Immunization rates have improved in the United States, but are still far from the national 90% goal for the year 2000. There is scant evidence about the effectiveness and costs of automated telephone messages to improve immunization rates among privately insured children.\n To evaluate the effectiveness and cost-effectiveness of sending letters, automated telephone messages, or both to families of underimmunized 20-month-olds in a health maintenance organization (HMO).\n In this randomized trial, underimmunized 20-month-olds identified by the HMO's computerized immunization tracking system were assigned to one of four interventions: 1) an automated telephone message alone; 2) a letter alone; 3) an automated telephone message followed by a letter 1 week later; and 4) a letter followed by an automated telephone message 1 week later. The primary outcome was receipt of any needed immunization by 24 months of age. Decision analysis was used to evaluate the projected cost-effectiveness of the alternative strategies.\n A total of 648 children were randomized. A letter followed by a telephone message (58% immunized) was significantly better than either a letter alone (44% immunized) or a telephone message alone (44% immunized). A telephone message followed by a letter (53% immunized) also was more effective than either alone, although the differences were not statistically significant. Among a similar comparison group that received no systematic intervention, 36% were immunized. The estimated cost per child immunized was $7.00 using letters followed by automated telephone messages, $9.80 using automated telephone messages alone, and $10.50 using letters alone. Under alternative cost assumptions for automated telephone messages and mailed messages, the cost per child immunized ranged from $2.20 to $6.50.\n For underimmunized 20-month-olds in this HMO setting, letters followed by automated telephone messages were more effective and cost-effective than either message alone. The cost-effectiveness of automated telephone messages and letters may vary widely depending on the setting, and choices among strategies should be tailored to the populations being served.", "To measure the impact of a population-based tracking system on influenza immunization rates.\n Thirteen practices with 45 physicians were randomized to a control and two intervention groups.\n Private practices.\n All patients aged 65 years and over who were seen in participating physicians' practices within the preceding two years.\n In both intervention groups influenza immunization rates for physicians were recorded weekly as cumulative percentages of their target populations, using a specially prepared poster. In addition, postcard reminders were sent to all the patients in one of the intervention groups.\n Immunization rates in the two intervention groups were 30% higher than in the control group; the control group immunized 50% (2,405/4,772) of its target population, while the poster and poster/postcard groups immunized 66% (1,420/2,149) and 67% (2,427/3,604), respectively.\n A population-based strategy that monitors performance can significantly improve rates of influenza immunization in private practices.", "nan", "Reminder-recall interventions have improved immunization rates in numerous studies.\n To evaluate the impact of large-scale, registry-based reminder-recall interventions on low immunization rates in an inner-city population.\n Randomized, controlled, effectiveness trial.\n Fulton County, Georgia.\n A total of 3050 children (76% black, 14% Hispanic, 7% white, and 3% other or unknown; median age, 9 months; range, 1-14 months) identified in an immunization registry as receiving health care in the public sector.\n Each child was randomly assigned to 1 of 4 groups: control (usual care), autodialer (automated telephone or mail reminder recall), outreach (in-person telephone, mail, or home visit recall), and combination (autodialer with outreach backup). Interventions continued until the child reached 24 months of age.\n Completion by the age of 24 months of the 4-3-1-3 vaccination series based on intention-to-treat analysis.\n A total of 260 (34%) of the 763 patients in the control group, 306 (40%) of the 763 in the autodialer group, 284 (37%) of the 760 in the outreach group, and 293 (38%) of 764 in the combination group completed the vaccination series.\n Large-scale, registry-based reminder-recall interventions produced only small improvements in low immunization rates of an inner-city population.", "To evaluate the impact of interventions by a community-based organization on immunization rates.\n Controlled community intervention trial.\n Children aged 3 to 59 months in Fulton County, Georgia, who were patients of 1 of 4 public clinics (clinic based), or residents of 1 of 9 inner-city communities (residence based).\n (1) Clinic-based intervention included monthly review of clinic vaccination records to identify undervaccinated children followed by contact with family (reminder-recall strategy); (2) residence-based intervention included door-to-door assessment and education campaigns followed by mobile van vaccinations, temporary on-site vaccination stations, free child care and transportation to providers, incentives of food and baby products, focus groups, and coalitions with local organizations (community saturation with vaccination messages and opportunities).\n Change in vaccination rates after 1 year based on clinic record reviews and population surveys.\n For clinic-based intervention, series completion rates improved from 43% (87/204) to 58% (99/170) in intervention clinics (P=.003), while rates in control clinics did not change from the baseline of 52% (81/157 to 78/150), for a net difference between intervention and control arms of +15 percentage points (P=.046). For residence-based intervention, age-appropriate vaccination rates improved from 44% (154/347) to 61% (260/429) in intervention communities (+17 percentage points; P<.001) compared with improvement of 44% (78/178) to 58% (129/221) for control communities (+14 percentage points; P=.004), but the difference between arms was not significant (+3 percentage points, P=.78).\n Reminder-recall activities by the community-based organization improved vaccination rates in intervention clinics compared with control clinics. A statistically significant impact on vaccination rates could not be detected for residence-based interventions by the community-based organization.", "A randomized, single-blind, controlled trial was performed at a community health center to measure the impact of computer-generated reminders mailed to patients on the rate of influenza immunization. High-risk patients were randomized to one of three groups: 1) usual care, 2) one reminder letter, offering free influenza immunization without an appointment, or 3) two sequential reminder letters, offering the same. The reminders did not significantly affect rates of influenza immunization. Analysis of the combined groups indicates that an appointment with a primary care provider remains the most reliable method of immunizing high-risk patients at this health center.", "This prospective cohort study was designed to evaluate the effectiveness of mail and telephone contact with parents as a means to improve the immunization coverage of children less than 7 years old in a family practice residency clinic.\n Immunization records for 519 children enrolled in an outpatient clinic were reviewed and updated. Children whose immunizations were current (55) were excluded, which left 464 children whose immunizations were more than 1 month behind for their age groups. A random sample of one-half of these children (231) were mailed a postcard listing the immunizations that they required to be up to date. The mailing was followed up with telephone contact, when necessary, to prompt compliance. The other one-half of the children were not contacted and served as the control group. Immunizations provided to the two groups were compared 6 months after the initial mailing.\n Before the initiation of the study, only 10.6 percent of the infants and children in the practice had their immunizations completed or were up to date. There were 124 immunizations given to 49 children in the intervention group compared with 84 immunizations to 33 children in the control (P < 0.047). Thirty-four children were brought up to date in the control group compared with 17 in the intervention cohort (P < 0.011).\n Direct mail reminders and telephone contact with parents of children who were behind in their immunizations were effective methods to encourage compliance. The increased number of immunizations received by the children in the intervention group was overshadowed by the poor coverage of the entire practice, a highly mobile and predominantly indigent group. Additional interventions are urgently needed to improve immunization levels in infants and children.", "To test the effectiveness of customized, family-oriented reminder letters in activating patients to seek appropriate preventive services.\n Randomized clinical trial. One group received computer-generated, customized letters explaining recommended preventive procedures for each family member. A second group received a form letter listing recommendations for all preventive procedures for all age and sex groups. A third group (control group) received no letters.\n A private medical centre, without university affiliation, in rural Quebec.\n From 8770 patients who met study criteria, 719 families were randomly selected. Data were available for 1971 of 1998 patients in these families.\n The Family Received Index is the proportion of all procedures for which a family was overdue that they received. The Family End-of-study Up-to-date Index is the proportion of procedures for which the family was eligible and for which they were up-to-date at the end of the study.\n The Family Received Index for families mailed customized letters was more than double the index for patients not mailed letters (Kruskal-Wallis P = .0139). Comparison of the Family End-of-study Up-to-date indices also demonstrated that families of patients sent customized letters were more likely to be up-to-date than families not sent letters (Kruskal-Wallis P = .0054). No statistically significant difference appeared between the number of preventive measures received by the control group and the form-letter group.\n This study demonstrates a clinically small but statistically significant value to customizing reminder letters.", "We developed a comprehensive individualized preventive care reminder system and then tested the hypothesis that directly involving patients in the reminder process would lead to greater use of preventive services than involving physicians only. There were three experimental groups of 350 patients each: in group 1 physicians and patients received the reminder; in group 2 physicians only received the reminder; in group 3 neither physicians nor patients received the reminder. Nine preventive care services were studied: blood pressure measurement; dental exam; ocular pressure measurement; stool exam for occult blood; influenza, pneumococcal, and tetanus vaccinations; mammography; and Papanicolaou smears. Need for these services was determined by telephone interview and chart review. To determine whether services were obtained, charts were reviewed after four to eight months of follow-up. For overall compliance with preventive recommendations and for several individual services (stool exam for occult blood, tetanus vaccination, mammography), group 1 patients received significantly more preventive care than group 2. Likewise, group 2 patients received more preventive care than group 3. These data show that involving patients in reminder efforts is an effective means of raising the level of preventive services.", "Fewer than 10% of children with moderate or severe asthma receive an annual influenza vaccination despite their heightened susceptibility to severe infections and recommendations by the American Academy of Pediatrics and the Immunization Practices Advisory Committee that all such children be vaccinated annually. Patient, provider, and system factors leading to this poor vaccination rate are not well understood. This study tested the effectiveness of a computerized reminder system in improving influenza vaccination rates in children with asthma and examined patient barriers to vaccination at one pediatric clinic in an urban teaching hospital. A computer database identified 124 children with moderate or severe asthma. Patients were randomly assigned either to study group (n = 63), who were sent a personalized letter reminder about the need for an influenza vaccination, or to a control group (n = 61), who received no reminder. Study group mothers were interviewed 2 months after the letter was sent to assess factors associated with receipt of vaccination, including demographic features, parental worry about asthma and vaccine side effects, the four dimensions of the Health Belief Model, and health locus of control beliefs. Nineteen study group patients (30%) received an influenza vaccination, compared with only 4 control patients (7%) (P < .01). Forty-three mothers of children in the study group were interviewed; 14 (33%) of these children had received the vaccination. Of the characteristics investigated, two significantly correlated with vaccination compliance: high levels of parental worry about asthma (positively correlated: odds ratio = 23.3, P < .01) and high levels of parental worry about vaccine side effects (negatively correlated: odds ratio = 0.087, P = .025).(ABSTRACT TRUNCATED AT 250 WORDS)", "This study aims to assess the effects of two interventions on influenza vaccination coverage: a simple organisational strategy, and making the vaccine available free.\n Sixteen general practitioners in the Auckland region were randomly selected to participate. Patients over 65 years of these general practitioners were randomly allocated to control, letter of invitation for a flu vaccine, or offer of a free flu vaccine. Administration of a flu vaccine for each person in the study was documented in each general practitioner surgery. Vaccine coverage for each of the three groups was measured.\n Results were available for 15 of the 16 participating general practitioners, a total of 2791 subjects. Immunisation coverage rates for control, letter of invitation and vaccine at no cost, were 17%, 27% and 45% respectively. Statistical analysis, allowing for the cluster method used to obtain subjects, showed risk ratios of 1.55 and 2.65 for the two interventions, with p values of < 0.00001.\n A potential source of bias in this study is underreporting of administration of vaccine to people in group 1. Notwithstanding this potential bias, both interventions were highly effective at increasing the uptake of influenza vaccine in the elderly population. General practitioners should be recommended to routinely invite patients over 65 years to have a flu vaccine. Given the commitment of the Ministry of Health to the vaccination against influenza of people over 65, this study would suggest that serious consideration should be given to making the vaccine available at no cost to this age group.", "Sexually transmitted disease clinics can deliver hepatitis vaccines to men who have sex with men, but have been reluctant to do so because of perceived low vaccination completion rates.\n The goal was to evaluate hepatitis A and B vaccination eligibility, acceptance, and completion and the effectiveness of reminder/recall in a sexually transmitted disease clinic serving men who have sex with men.\n Clients self-reported their eligibility for free vaccine. Consenting clients who accepted a first dose of vaccine were systematically assigned to receive telephone reminder/recall or standard follow-up.\n Of 1203 clients, 71.8% were eligible for both vaccines; 62.6% of those eligible accepted both. Reminder/recall was associated with increased receipt of the second dose of hepatitis B vaccine (86.7% versus 80.4% among intervention and control groups, respectively), but not with completion of both vaccine series (55.9% versus 58.8%).\n The majority of clients were eligible for both hepatitis vaccines, and most eligible clients accepted a first dose of both vaccines. Reminder/recall, as delivered at this clinic, failed to increase the proportion of clients who received all vaccine doses. New delivery mechanisms should be explored.", "The influenza immunization rate in the high-risk military and retired military population has not been reported. To determine this rate, and to test whether the rate could be improved by notifying patients of their high-risk status, a clinical trial was conducted using a postcard reminder as an intervention.\n All 1068 high-risk patients enrolled in a large, residency-affiliated, military family practice department were identified. Of these, 519 patients were randomly selected to receive a reminder postcard; the remainder (549) were not sent a card. The immunization rates of each group were compared.\n A significantly higher percentage of those to whom postcards were sent received an influenza immunization (25.2% vs 9.1%, P less than .001). This difference was significant in all demographic groups except in those less than 21 years of age and those 21 to 40 years of age, in which very few patients presented for immunization. In those in the study group aged 65 years and over, 46.7% were immunized vs 20% of controls (P less than .001). Those aged 65 years and older and those in the higher income group had higher immunization rates, while those aged 40 years and under had very low immunization rates.\n The influenza immunization rate among military beneficiaries in high-risk groups is low, but can be significantly improved with a reminder postcard. This intervention may be more effective in the older and higher-income segments of the high-risk population. The low immunization rates of the lower-income group and the younger age groups have significant public health implications and should be studied further.", "Annual influenza vaccination has long been recommended for the elderly population. Despite this recommendation, immunization rates have remained very low. This study measured the effects of two approaches to the provision of influenza immunization to the 65-years-and-over age group in a single family practice. The \"drop-in\" group (N=123) was informed of the availability of the vaccine at visits made during the vaccination period. The \"phone\" group (N=120) was notified of the availability of the vaccine by telephone and was invited to come in for the shot. An immunization rate of 50.8% for the \"phone\" group and 26.8% for the \"drop-in\" group was obtained (P=.0002). These results contrast strongly with the overall immunization rates of 5.9% and 9.5% obtained during the previous two years, when no active immunization policy was in place. The telephone approach was found to benefit the type of patient at greatest risk from influenza: the chronically ill and the aged. It is clear that having a defined immunization policy substantially improves the provision of influenza vaccination. The authors discuss the effectiveness and practicality of these approaches to the delivery of influenza vaccine and their applicability to other forms of prevention in family medicine.", "To compare and measure the effects and cost-effectiveness of two interventions designed to raise immunization rates.\n Nine primary care sites serving impoverished and middle-class children.\n Complete birth cohorts (ages 0 to 12 months; n = 3015) from these sites.\n Two 18-month duration interventions: 1) tracking with outreach [tracking/outreach] to bring underimmunized children to their primary care provider office, and 2) a primary care provider office policy change to identify and reduce missed immunization opportunities (prompting).\n Randomized, controlled trial, randomizing within sites using a two-by-two factorial design. Subjects were allocated to one of four study groups: control, prompting only, tracking/outreach only, and combined prompting with tracking/outreach. Outcomes were obtained by blinded chart abstraction.\n Immunization status for age; number of days of delay in immunization; primary care utilization; and rates of screening for occult disease.\n Out of 3015 subjects, 274 subjects (9%) transferred out of the participating sites or had incomplete charts and were excluded. The 2741 (91%) remaining subjects were assessed. At baseline, study groups did not differ in age, gender, insurance type, or immunization status. Of the remaining subjects, 63% received Medicaid. Final series-complete immunization coverage levels were: control, 74%; prompting-only, 76%; tracking/outreach-only 95%; and combined tracking/outreach with prompting, 95%. Analysis of variance showed that: 1) tracking/outreach increased immunization rates 20 percentage points; 2) tracking/outreach decreased mean immunization delay 63 days; 3) tracking/outreach increased mean health supervision visits 0.44 visits per child; 4) tracking/outreach increased mean anemia screening 0.17 screenings per child and mean lead screenings 0.12 screenings per child; 5) impact of tracking/outreach was greatest for uninsured and impoverished patients; and 6) the prompting intervention had no impact on the studied outcomes, and its failure was caused by inconsistent use of prompts and failure to vaccinate ill children when prompted. Using tracking/outreach, the cost per additional child fully immunized was $474. Each $1000 spent on the tracking/outreach intervention resulted in: 2.1 additional fully vaccinated children and 668 fewer child-days of delayed immunization; 4.6 additional health supervision visits and 5.9 additional other visits to the primary care provider; and 1.8 additional anemia screenings and 1.3 additional lead screenings.\n Outreach directed toward children not up-to-date on immunizations improves not only immunization status, but also health supervision visit attendance and screening rates. The cost per additional child immunized was high, but should be interpreted in view of the spillover benefits that accompanied improved immunization. Effective means to improve coverage by reducing missed immunization opportunities still need to be identified.", "A controlled trial to determine the effects of introducing a centralised, computerised immunisation register commenced in Northland in May 1985. All infants born since 1 January 1985 have been registered on the Health Department's mainframe computer and assigned to either control or test groups. This birth information has been used to study two interventions aimed at increasing immunisation levels in the experimental group. The first involves sending to general practitioners lists of infants due for immunisation, and the second sending immunisation reminder cards to parents. Results show significant differences in immunisation levels between test group infants and comparable controls: an 18.2% increase for the six week immunisation, a 16.7% increase for the three month immunisation, and a 4.7% increase for the five month immunisation. A user survey has shown a high degree of acceptance by GPs and practice nurses. The pilot scheme will continue through 1986, and will be used over this period to improve acceptability to users and assist in planning a possible national computerised immunisation information system.", "Over the last decade, the immunization rate among preschool children has decreased, especially in the lower socioeconomic population. During this period, reports of outbreaks of immunizable diseases, especially pertussis and measles, have correspondingly increased. This study was designed to evaluate the effect of a brief patient education encounter with new mothers on pediatric immunization rates.\n Two hundred thirty-eight mothers and infants were assigned to an intervention or control group. On the first day postpartum, the mothers in the intervention group participated in a 10- to 15-minute discussion on the importance of immunizations and were given a patient education handout. A reminder letter was mailed to the intervention group at 2 months postpartum. The control group received no special intervention. Infants were followed for their 2- and 4-month immunizations for diphtheria, pertussis, and tetanus and oral polio vaccine (DPT/OPV). At 1 year of age, the infants' immunization records were assessed for the completion of their first three DPT/OPV immunizations.\n There was no statistically significant difference, by chi-square analysis, in the immunization rates of the control and intervention groups at 2, 4, or 12 months of age. At 1 year of age, 29 of 122 (24%) of the control group had received all three DPT/OPV immunizations, compared with 33 (28%) of 116 infants in the intervention group.\n Concordant with similar studies, the immunization rate among infants of parents of lower socioeconomic status (26%) is low. An educational intervention presented to mothers in the postpartum period did not improve the rate of immunization by the age of 12 months. There are undoubtedly several reasons for this failure. Other means to improve immunization rates of infants should be developed and tested." ]

[ "19204394", "17852714", "16979870", "18569647", "15070225" ]

[ "Self-evaluation of voice as a treatment outcome measure.", "The relative effectiveness of vocal hygiene training and vocal function exercises in preventing voice disorders in primary school teachers.", "Vocal problems among teachers: evaluation of a preventive voice program.", "Effects of voice training and voice hygiene education on acoustic and perceptual speech parameters and self-reported vocal well-being in female teachers.", "The impact of preventive voice care programs for training teachers: a longitudinal study." ]

[ "This study addressed two self-evaluation questionnaires in investigating the effects of voice hygiene lecture (VHL, 3 h) and additional voice training (VT) or Voice Massage (VM; both 5 h) in 90 female teachers. The subjects assessed their voice quality, ease of phonation and tiredness of throat before and after a working day at the beginning and end of the school term using a visual analogue scale (VAS) (Questionnaire 1). At the end of the term, the degree of positive influence of the interventions was reported on VAS, and the type of influence was indicated by choosing one or more of three alternatives (voice quality, audibility and endurance) or by writing a free comment (Questionnaire 2). Questionnaire 1 was pretested and found to be reliable and valid for self-evaluation of voice. At the end of term, the VM and VT groups reported more positive influence of the interventions than did the VHL group. The reported influence did not correlate with working-day-related changes in sensations. Increased difficulty of phonation and tiredness of throat was found in the VHL group at the end of the term. However, the groups did not differ significantly from each other. The challenges of self-evaluations as outcome measures are discussed.\n Copyright 2009 S. Karger AG, Basel.", "Voice disorders in teachers have a significant impact on their occupational functioning and well being. Teachers are believed to have a high prevalence of voice problems because of the unfavourable acoustic environments in which they work and the high vocal demands and stress levels associated with teaching. Although the types of voice problems teachers experience should be preventable because they are caused by factors that teachers can change, there is limited information available regarding the effectiveness of different preventative strategies. Therefore, the aim of this study was to investigate the effectiveness of vocal hygiene training (VH) and vocal function exercises (VFE) in reducing vocal symptoms and vocal misuse, and increasing knowledge of voice care, maximum phonation time, and maximum phonational frequency range in school teachers. Thirty-seven teachers from four schools in Melbourne, Australia, participated in the study. Schools were randomly allocated to one of three groups: VH, VFE, and no-treatment control. The VH and VFE participants reported improved vocal characteristics and voice knowledge after training while the control group showed deterioration on most variables. The VH participants showed greater improvements than the VFE participants. These fundings indicate that preventative voice training for teachers is likely to be effective.", "Vocal education programs for teachers may prevent the emergence of vocal disorders; however, only a few studies have tried to evaluate the effectiveness of these preventive programs, particularly in the long term. Two hundred and sixty-four subjects, mostly kindergarten and primary school female teachers, participated in a course on voice care, including a theoretical seminar (120 minutes) and a short voice group therapy (180 minutes, small groups of 20 subjects). For 3 months, they had to either attend the vocal ergonomics norms and, as psychological reinforcement, they had to make out a daily report of vocal abuse, or to follow the given exercises for a more efficient vocal technique, reporting on whether the time scheduled was respected or not. The effectiveness of the course was assessed in a group of 21 female teachers through a randomized controlled study. Evaluation comprehended stroboscopy, perceptual and electro-acoustical voice analysis, Voice Handicap Index, and a course benefit questionnaire. A group of 20 teachers matched for age, working years, hoarseness grade, and vocal demand served as a control group. At 3 months evaluation, participants demonstrated amelioration in the global dysphonia rates (P=0.0003), jitter (P=0.0001), shimmer (P=0.0001), MPT (P=0.0001), and VHI (P=0.0001). Twelve months after the course, the positive effects remained, although they were slightly reduced. In conclusion, a course inclusive of two lectures, a short group voice therapy, home-controlled voice exercises, and hygiene, represents a feasible and cost-effective primary prevention of voice disorders in a homogeneous and well-motivated population of teachers.", "Voice education programs may help in optimizing teachers' voice use. This study compared effects of voice training (VT) and voice hygiene lecture (VHL) in 60 randomly assigned female teachers. All 60 attended the lecture, and 30 completed a short training course in addition. Text reading was recorded in working environments and analyzed for fundamental frequency (F0), equivalent sound level (Leq), alpha ratio, jitter, shimmer, and perceptual quality. Self-reports of vocal well-being were registered. In the VHL group, increased F0 and difficulty of phonation and in the VT group decreased perturbation, increased alpha ratio, easier phonation, and improved perceptual and self-reported voice quality were found. Both groups equally self-reported increase of voice care knowledge. Results seem to indicate improved vocal well-being after training.", "The teaching profession puts vocal health at a higher risk than other professions, causing what is referred to as \"occupational dysphonia.\" There is a need for primary prevention of \"occupational dysphonia\" among the teaching profession, where good vocal health is promoted before a problem occurs. To investigate the primary prevention of occupational dysphonia among teachers, this study uses a sample population of 55 training teachers, in the postgraduate certificate of education (PGCE) course at the University of Ulster, Northern Ireland, who were randomly assigned to three training groups: control, indirect, and direct. The vocal performance of the three groups was measured at two points over the year of the PGCE course: first before any teaching or training began, and again after the first teaching practice. The training for the indirect and direct groups was provided before the teaching practices. Acoustic and self-perceptual measurements were used to assess the multidimensional outcomes. The results demonstrate interesting trends, that although not found to be significant, are approaching significance. Their voices will be reevaluated at a third point of measurement. The acoustic measurement reflects deterioration from time 1 to time 2 for the control group, improvement for the direct group, and no change for the indirect group, indicating that the training has proved beneficial. The self-rating scores vary in agreement with the acoustic results, presenting interesting findings. The findings of this study will be of benefit to teachers, their educators, voice therapists, health promoters, and human resource personnel." ]

[ "16826475", "18008241" ]

[ "Randomized trial of 2-dose versus monthly sulfadoxine-pyrimethamine intermittent preventive treatment for malaria in HIV-positive and HIV-negative pregnant women in Malawi.", "Two-dose versus monthly intermittent preventive treatment of malaria with sulfadoxine-pyrimethamine in HIV-seropositive pregnant Zambian women." ]

[ "Intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) decreases placental malaria parasitemia and associated maternal anemia, premature delivery, and low birth weight. However, the optimal regimen in the setting of a high prevalence of human immunodeficiency virus (HIV) infection remains unclear.\n In Malawi, where the efficacy of SP for the treatment of malaria in children is decreasing, we conducted a randomized, nonblinded study to compare the efficacy of monthly SP IPTp with a 2-dose regimen for the prevention of placental parasitemia in HIV-positive and -negative primigravid and secundigravid women.\n Of HIV-positive women, 7.8% who received monthly SP had placental malaria, compared with 21.5% of those who received 2-dose SP (relative risk [RR], 0.36 [95% confidence interval {CI}, 0.17-0.79]). Of HIV-negative women, 2.3% who received monthly SP and 6.3% who received 2-dose SP had placental malaria (RR, 0.37 [95% CI, 0.11-1.19]). Less than 1% of women reported adverse drug reactions, with no increase in HIV-positive women or those who received monthly SP.\n In HIV-positive pregnant women, monthly SP IPTp is more efficacious than a 2-dose regimen in preventing placental malaria. The study also demonstrates the continued efficacy of SP for the prevention of placental malaria, even in the face of its decreasing efficacy for the treatment of malaria in children. In areas with intense transmission of falciparum malaria and a high prevalence of HIV infection, monthly SP IPTp should be adopted.", "Intermittent preventive treatment of malaria during pregnancy (IPTp) reduces placental infection, maternal anemia, and low birth weight (LBW). However, the optimal dosing regimen in settings in which human immunodeficiency virus (HIV) is highly prevalent among pregnant women remains controversial.\n We conducted a randomized, double-blind, placebo-controlled study of IPTp comparing the standard 2-dose sulfadoxine-pyrimethamine (SP) regimen with monthly IPTp among a cohort of HIV-positive pregnant Zambian women. Primary outcomes included placental malaria (by smear and histology) and maternal peripheral parasitemia at delivery.\n There were no differences between monthly IPTp (n=224) and standard IPTp (n=232) in placental malaria by histopathology (26% vs. 29%; relative risk [RR], 0.90 [95% confidence interval {CI}, 0.64-1.26]) or placental parasitemia (2% vs. 4%; RR, 0.55 [95% CI, 0.17-1.79]). There also were no differences in maternal anemia, stillbirths, preterm delivery, LBW, or all-cause mortality of infants at 6 weeks.\n In an area of mesoendemicity in Zambia, monthly SP IPTp was not more efficacious than the standard 2-dose regimen for the prevention of placental malaria or adverse birth outcomes. IPTp policy recommendations need to take into account local malaria transmission patterns and the prevalence of HIV.\n ClinicalTrials.gov identifier: NCT00270530." ]

[ "10830757", "12188409", "15733880", "23506189", "10078577", "14995919", "15778231", "2529841" ]

[ "A prospective randomized study comparing acupuncture with physiotherapy for low-back and pelvic pain in pregnancy.", "Effect of the \"sitting pelvic tilt exercise\" during the third trimester in primigravidas on back pain.", "The effect of exercise on the intensity of low back pain in pregnant women.", "Treatment of Pregnancy-Related Lumbar and Pelvic Girdle Pain by the Yoga Method: A Randomized Controlled Study.", "Water-gymnastics reduced the intensity of back/low back pain in pregnant women.", "Acupuncture relieves pelvic and low-back pain in late pregnancy.", "Effects of acupuncture and stabilising exercises as adjunct to standard treatment in pregnant women with pelvic girdle pain: randomised single blind controlled trial.", "Evaluation of a maternity cushion (Ozzlo pillow) for backache and insomnia in late pregnancy." ]

[ "The aim of this study was to describe the effects of acupuncture in the treatment of low-back and pelvic pain during pregnancy and compare it with physiotherapy.\n Sixty pregnant women were allotted to acupuncture or physiotherapy. The women estimated the severity of their pain using a visual analog scale (VAS) from 0 to 10 and disability in performing twelve common daily activities using a disability-rating index (DRI) from 0 to 10.\n In the acupuncture group all 30 women completed the study (two exclusions), in the physiotherapy group only 18. Before treatment the two study groups were rather similar with respect to pain and disability. After treatment the mean morning VAS had declined from 3.4 to 0.9 (p<0.01) in the acupuncture group and from 3.7 to 2.3 (NS) in the physiotherapy group. The corresponding evening values had declined from 7.4 to 1.7 (p<0.01) and 6.6 to 4.5 (p<0.01), respectively. The mean VAS values were lower after acupuncture than after physiotherapy both in the morning (p=0.02) and in the evening (p<0.01). After treatment also the mean DRI values had decreased significantly in the acupuncture group for 11 of 12 activities and the values were significantly lower for all activities than in the physiotherapy group where no significant changes had taken place. Overall satisfaction was good in both groups. There were no serious adverse events in any of the patients.\n Acupuncture relieved pain and diminished disability in low-back pain during pregnancy better than physiotherapy.", "A single center, prospective, randomized, single blinded, controlled study comparing the effects and safety of \"sitting pelvic tilt exercise\" in relieving back pain during the third trimester in primigravida was carried out. The samples were composed of 67 primigravidas who attended the prenatal clinic at King Chulalongkorn Memorial Hospital. All subjects were selected by the random sampling technique and allocated into two groups for the experimental group and the control group; for 32 and 35 pregnants, respectively. The experimental group received the pelvic tilt exercise program for 8 weeks during the third trimester. Pain intensity was measured by visual analogue scale (VAS) at day 0 and day 56 in both groups. The result of the study revealed 1) The mean VAS of back pain in the experimental group was significantly lower at day 56 than at day 0 and lower than the control group at day 56 (p< 0.05) by unpaired t-test 2) There was no incidence of preterm labor, low birth weight or neonatal complication in the experimental group. In conclusion, the \"sitting pelvic tilt exercise\" during the third trimester in primigravidas could decrease back pain intensity without incidence of preterm labor, low birth weight or neonatal complication.", "To investigate the effect of exercise during pregnancy on the intensity of low back pain and kinematics of spine.\n A prospective randomized study was designed. 107 women participated in an exercise program three times a week during second half of pregnancy for 12 weeks and 105 as control group. All filled a questionnaire between 17-22 weeks of gestation and 12 weeks later for assessment of their back pain intensity. Lordosis and flexibility of spine were measured by Flexible ruler and Side bending test, respectively, at the same times. Weight gain during pregnancy, Pregnancy length and neonatal weight were recorded.\n Low back pain intensity was increased in the control group. The exercise group showed significant reduction in the intensity of low back pain after exercise (p<0.0001). Flexibility of spine decreased more in the exercise group (p<0.0001). Weight gain during pregnancy, pregnancy length and neonatal weight were not different between the two groups.\n Exercise during second half of the pregnancy significantly reduced the intensity of low back pain, had no detectable effect on lordosis and had significant effect on flexibility of spine.", "Abstract Objective: Pregnancy-related lumbopelvic pain is a major problem for the majority of pregnant women. Complementary medicine has been used to alleviate pain, and yoga is one of the most commonly chosen alternative methods. The objective of this study was to assess the effectiveness of Hatha yoga in the reduction of lumbopelvic pain in pregnancy. Methods: A randomized controlled trial with 60 pregnant women (age range, 14-40 years) who reported lumbopelvic pain at 12 to 32 weeks of gestation was conducted from June 2009 to June 2011. Pregnant women who had twin pregnancies, had medical restrictions for exercise, used analgesics, and participated in physical therapy were excluded from the study. Pregnant women were divided into two groups: the yoga group, practicing exercises guided by this method, and the postural orientation group, performing standardized posture orientation according to instructions provided in a pamphlet. Treatment in each group lasted 10 weeks. A visual analog scale (VAS) was used to measure pain intensity. Lumbar pain and posterior pelvic pain provocation tests were used to confirm the presence of pain. Statistical analysis included the Mann-Whitney test, the McNemar test, a paired Wilcoxon test, and analysis of covariance. Results: The median pain score was lower in the yoga group (p<.0058) than the postural orientation group. Lumbar pain provocation tests showed a decreased response in relation to posterior pelvic pain provocation tests and a gradual reduction in pain intensity during 10 yoga sessions (p<.024). Conclusions: The yoga method was more effective at reducing lumbopelvic pain intensity compared with postural orientation.", "To investigate if water-gymnastics during pregnancy may reduce the intensity of back/low back pain and the number of days on sick-leave.\n A prospective, randomized study. One hundred and twenty-nine women were randomized to participate in water-gymnastics once a week during the second half of pregnancy and 129 were randomized to a control group. The women in both groups filled in questionnaires in gestational weeks 18, 34 and within the first postpartum week. Every day from week 18 to labor they assessed the intensity of back/low back pain.\n Back pain intensity increased during pregnancy. No excess risk for the pregnancy associated with water-gymnastics was observed. The women participating in water-gymnastics recorded a lower intensity of back/low back pain. The total number of days on sick-leave because of back/low back pain was 982 in the water-gymnastics group (124 women) compared with 1484 in the control group (120 women). After weeks 32 33, seven women in the water-gymnastics group compared with 17 in the control group were on sickleave because of back/ low back pain (p=0.031).\n Intensity of back/low back pain increased with advancing pregnancy. There was no excess risk for urinary or vaginal infections associated with water-gymnastics. Water-gymnastics during the second half of pregnancy significantly reduced the intensity of back/ low back pain. Water-gymnastics decreased the number of women on sick-leave because of back/low back pain. Water-gymnastics during pregnancy can be recommended as a method to relieve back pain and may reduce the need for sick-leave.", "The study was designed to evaluate the analgesic effect and possible adverse effects of acupuncture for pelvic and low-back pain during the last trimester of pregnancy.\n Following individual informed consent, 72 pregnant women reporting pelvic or low-back pain were randomized during pregnancy weeks 24-37 to an acupuncture group (n = 37) or to a control group (n = 35) at three maternity wards in southern Sweden. Traditional acupuncture points and local tender points (TP) were chosen according to individual pain patterns and stimulated once or twice a week until delivery or complete recovery in acupuncture patients. Control patients were given no sham stimulation. Throughout the study period each patient made weekly visual analog scale (VAS) evaluations of maximal and minimal pain intensity as well as three-point assessments of pain intensity during various activities.\n During the study period, VAS scorings of pain intensity decreased over time in 60% of patients in the acupuncture group and in 14% of those in the control group (p < 0.01). At the end of the study period, 43% of the acupuncture patients were less bothered than initially by pain during activity compared with 9% of control patients (p < 0.01). No serious adverse effects of acupuncture were found in the patients, and there were no adverse effects at all in the infants.\n Acupuncture relieves low-back and pelvic pain without serious adverse effects in late pregnancy.", "To compare the efficacy of standard treatment, standard treatment plus acupuncture, and standard treatment plus stabilising exercises for pelvic girdle pain during pregnancy.\n Randomised single blind controlled trial. Settings East Hospital, Gothenburg, and 27 maternity care centres in Sweden.\n 386 pregnant women with pelvic girdle pain.\n Treatment for six weeks with standard treatment (n = 130), standard treatment plus acupuncture (n = 125), or standard treatment plus stabilising exercises (n = 131).\n Primary outcome measure was pain (visual analogue scale); secondary outcome measure was assessment of severity of pelvic girdle pain by an independent examiner before and after treatment.\n After treatment the stabilising exercise group had less pain than the standard group in the morning (median difference = 9, 95% confidence interval 1.7 to 12.8; P = 0.0312) and in the evening (13, 2.7 to 17.5; P = 0.0245). The acupuncture group, in turn, had less pain in the evening than the stabilising exercise group (-14, -18.1 to -3.3; P = 0.0130). Furthermore, the acupuncture group had less pain than the standard treatment group in the morning (12, 5.9 to 17.3; P < 0.001) and in the evening (27, 13.3 to 29.5; P < 0.001). Attenuation of pelvic girdle pain as assessed by the independent examiner was greatest in the acupuncture group.\n Acupuncture and stabilising exercises constitute efficient complements to standard treatment for the management of pelvic girdle pain during pregnancy. Acupuncture was superior to stabilising exercises in this study.", "The effect of a wedge-shaped pillow (Ozzlo pillow) was compared with a standard hospital pillow, used to support the abdomen of a pregnant woman while lying on her side, in preventing or alleviating backache and backache-related insomnia; 92 women at 36 weeks' gestation completed the study. Backache was found to be very common (87%), the onset of pain occurring before 29 weeks in 59%. Age, parity, previous backache and type of bed used did not correlate with the backache scores during the period of study. Lower scores for backache were recorded by women in the week they used the Ozzlo pillow compared with the week they used the standard pillow. Sleeping was deemed better by the patient with the Ozzlo pillow, though actual sleeping scores did not corroborate this. While significantly more felt the Ozzlo pillow was superior to a standard pillow for backache and sleeping, some found both methods helpful. The simple measure of supporting the abdomen with a pillow when in lateral recumbency is likely to benefit many women in late pregnancy. A wedge-shaped pillow of the Ozzlo type, conforming to the shape of the abdomen and supporting it more closely, may be of greater help than a standard cushion or pillow." ]

[ "14586916", "15543446", "11594641", "11823669", "9626282", "11322472", "16151035", "10985439", "11228945", "8503751", "15473116", "12468788", "10768528" ]

[ "A treadmill and overground walking program improves walking in persons residing in the community after stroke: a placebo-controlled, randomized trial.", "Stepping over obstacles to improve walking in individuals with poststroke hemiplegia.", "Walking training of patients with hemiparesis at an early stage after stroke: a comparison of walking training on a treadmill with body weight support and walking training on the ground.", "Speed-dependent treadmill training in ambulatory hemiparetic stroke patients: a randomized controlled trial.", "A new approach to retrain gait in stroke patients through body weight support and treadmill stimulation.", "The effect of treadmill training on the ambulation of stroke survivors in the early stages of rehabilitation: a randomized study.", "Treadmill exercise rehabilitation improves ambulatory function and cardiovascular fitness in patients with chronic stroke: a randomized, controlled trial.", "Conventional physiotherapy and treadmill re-training for higher-level gait disorders in cerebrovascular disease.", "Comparison of partial body weight-supported treadmill gait training versus aggressive bracing assisted walking post stroke.", "Task-specific physical therapy for optimization of gait recovery in acute stroke patients.", "Aerobic treadmill plus Bobath walking training improves walking in subacute stroke: a randomized controlled trial.", "Treadmill training with partial body weight support and an electromechanical gait trainer for restoration of gait in subacute stroke patients: a randomized crossover study.", "Task-related circuit training improves performance of locomotor tasks in chronic stroke: a randomized, controlled pilot trial." ]

[ "To evaluate the effectiveness of a treadmill and overground walking program in reducing the disability and handicap associated with poor walking performance after stroke.\n Randomized, placebo-controlled clinical trial with a 3-month follow-up.\n General community.\n A volunteer sample of 29 ambulatory individuals (less 2 dropouts) who were living in the community after having suffered a stroke more than 6 months previously.\n The experimental group participated in a 30-minute treadmill and overground walking program, 3 times a week for 4 weeks. The control group received a placebo consisting of a low-intensity, home exercise program and regular telephone contact.\n Walking speed (over 10 m), walking capacity (distance over 6 min), and handicap (stroke-adapted 30-item version of the Sickness Impact Profile) measured by a blinded assessor.\n The 4-week treadmill and overground walking program significantly increased walking speed (P=.02) and walking capacity (P<.001), but did not decrease handicap (P=.85) compared with the placebo program. These gains were largely maintained 3 months after the cessation of training (P</=.05).\n The treadmill and overground walking program was effective in improving walking in persons residing in the community after stroke. This suggests that the routine provision of accessible, long-term, community-based walking programs would be beneficial in reducing disability after stroke.", "For this study, we evaluated two training interventions for improving gait parameters in individuals with poststroke hemiplegia using a training methodology that required them to step over objects. Gait velocity, step length, ability to step over obstacles, and walking endurance were compared before and after 2 weeks of training and 2 weeks after cessation of training. Twenty subjects with poststroke hemiplegia completed six intervention sessions in which they were asked to step over either virtual objects while walking on a motorized treadmill or real foam objects on a 10 m walkway. With the virtual object training, if either foot collided with the virtual object, a tone sounded and a vibrotactile stimulus was applied to the colliding foot. All subjects tolerated the training sessions well, and no incidences of falling or undue cardiovascular responses occurred. The virtual obstacle training generated greater improvements in gait velocity compared with real training (20.5% vs. 12.2% improvement) during the fast walk test (p < 0.01). Improvements in gait velocity for both training methods were similar in the self-selected walk test (33.3% vs. 34.7% improvement). Overall, subjects showed clinically meaningful changes in gait velocity, stride length, walking endurance, and obstacle clearance capacity as a result of either training method. These changes persisted for 2 weeks posttraining. The inclusion of enhanced safety and visual augmentation may be responsible for the effectiveness of the virtual object intervention. These results demonstrate preliminary evidence for clinical effectiveness of obstacle training for improving gait velocity poststroke. In addition, these results provide evidence for enhanced clinical performance with virtual obstacle training.", "To compare the effect of walking training on a treadmill with body weight support (BWS) and walking training on the ground at an early stage of rehabilitation in patients with hemiparesis after stroke.\n Randomized controlled experimental study.\n Multicentre design; three departments of rehabilitation medicine.\n Seventy-three consecutive first stroke patients admitted to a rehabilitation clinic were randomized into a treatment group and a control group.\n The treatment group received walking training on a treadmill with BWS for 30 minutes, 5 days a week. The control group received walking training according to the Motor Relearning Programme (MRP) on the ground for 30 minutes 5 days a week, not including treadmill training. During the time in the rehabilitation department (about two months), all patients in the study also received professional stroke rehabilitation besides the walking training in the two groups.\n Functional Independence Measure (FIM), walking velocity for 10 m, Functional Ambulation Classification (FAC), Fugl-Meyer Stroke Assessment and Berg's Balance Scale. The assessments were performed at admission, at discharge and at 10-month follow-up.\n There were no statistically significant differences between the groups at discharge or at the 10-month follow-up with regard to FIM, walking velocity, FAC, Fugl-Meyer Stroke Assessment, and Berg's Balance Scale. Patients in both groups improved in these variables from admission to the 10-month follow-up.\n Treadmill training with BWS at an early stage of rehabilitation after stroke is a comparable choice to walking training on the ground.", "A new gait training strategy for patients with stroke seeks to increase walking speed through treadmill training. This study compares the effects of structured speed-dependent treadmill training (STT) (with the use of an interval paradigm to increase the treadmill speed stepwise according to principles of sport physiology) with limited progressive treadmill training (LTT) and conventional gait training (CGT) on clinical outcome measures for patients with hemiparesis.\n Sixty ambulatory poststroke patients were each randomly selected to receive 1 of the 3 different gait therapies: 20 subjects were treated with STT, 20 subjects were trained to walk on a treadmill with a 20% increase of belt speed over the treatment period (LTT), and 20 subjects were treated with CGT. Treatment outcomes were assessed on the basis of overground walking speed, cadence, stride length, and Functional Ambulation Category scores.\n After a 4-week training period, the STT group scored significantly higher than the LTT and CGT groups for overground walking speed (STT versus LTT, P<0.001; STT versus CGT, P<0.001), cadence (STT versus LTT, P=0.007; STT versus CGT, P<0.001), stride length (STT versus LTT, P<0.001; STT versus CGT, P<0.001), and Functional Ambulation Category scores (STT versus LTT, P=0.007; STT versus CGT, P<0.001).\n Structured STT in poststroke patients resulted in better walking abilities than LTT or CGT. This gait training strategy provides a dynamic and integrative approach for the treatment of gait dysfunction after stroke.", "A new gait training strategy for patients with stroke proposes to support a percentage of the patient's body weight while retraining gait on a treadmill. This research project intended to compare the effects of gait training with body weight support (BWS) and with no body weight support (no-BWS) on clinical outcome measures for patients with stroke.\n One hundred subjects with stroke were randomized to receive one of two treatments while walking on a treadmill: 50 subjects were trained to walk with up to 40% of their body weight supported by a BWS system with overhead harness (BWS group), and the other 50 subjects were trained to walk bearing full weight on their lower extremities (no-BWS group). Treatment outcomes were assessed on the basis of functional balance, motor recovery, overground walking speed, and overground walking endurance.\n After a 6-week training period, the BWS group scored significantly higher than the no-BWS group for functional balance (P = 0.001), motor recovery (P = 0.001), overground walking speed (P = 0.029), and overground w alking endurance (P = 0.018). The follow-up evaluation, 3 months after training, revealed that the BWS group continues to have significantly higher scores for overground walking speed (P = 0.006) and motor recovery (P = 0.039).\n Retraining gait in patients with stroke while a percentage of their body weight was supported resulted in better walking abilities than gait training while the patients were bearing their full weight. This novel gait training strategy provides a dynamic and integrative approach for the treatment of gait dysfunction after stroke.", "The objective of this study was to compare the effects of conventional over-ground gait training with treadmill training on the restoration of gait in people with hemiparesis following a stroke. Twenty-five individuals in the early stages of rehabilitation were alternately assigned to one of two treatment groups. In addition to conventional physical therapy, the experimental group participated in 15 treadmill-training sessions in which a handrail was used for external support. The control group received the same number of equal length sessions of over-ground ambulation. Treatment effects were established by pre- and posttreatment assessment of: 1) functional walking ability, 2) walking speed, 3) stride length, 4) temporal characteristics of gait, and 5) electromyographic activity of calf muscles. Normal values were obtained from eight healthy individuals of approximately the same age as the stroke survivors. The study demonstrates that individuals following a stroke are well able to tolerate treadmill training in the early stage of their rehabilitation process without the use of a weight support apparatus. Furthermore, the findings suggest that treadmill training may be more effective than conventional gait training for improving some gait parameters such as functional ambulation, stride length, percentage of paretic single stance period, and gastrocnemius muscular activity.", "Physical inactivity propagates disability after stroke through physical deconditioning and learned nonuse. We investigated whether treadmill aerobic training (T-AEX) is more effective than conventional rehabilitation to improve ambulatory function and cardiovascular fitness in patients with chronic stroke.\n Sixty-one adults with chronic hemiparetic gait after ischemic stroke (>6 months) were randomized to 6 months (3x/week) progressive T-AEX or a reference rehabilitation program of stretching plus low-intensity walking (R-CONTROL). Peak exercise capacity (Vo2 peak), o2 consumption during submaximal effort walking (economy of gait), timed walks, Walking Impairment Questionnaire (WIQ), and Rivermead Mobility Index (RMI) were measured before and after 3 and 6 months of training.\n Twenty-five patients completed T-AEX and 20 completed R-CONTROL. Only T-AEX increased cardiovascular fitness (17% versus 3%, delta% T-AEX versus R-CONTROL, P<0.005). Group-by-time analyses revealed T-AEX improved ambulatory performance on 6-minute walks (30% versus 11%, P<0.02) and mobility function indexed by WIQ distance scores (56% versus 12%, P<0.05). In the T-AEX group, increasing training velocity predicted improved Vo2 peak (r=0.43, P<0.05), but not walking function. In contrast, increasing training session duration predicted improved 6-minute walk (r=0.41, P<0.05), but not fitness gains.\n T-AEX improves both functional mobility and cardiovascular fitness in patients with chronic stroke and is more effective than reference rehabilitation common to conventional care. Specific characteristics of training may determine the nature of exercise-mediated adaptations.", "to compare the therapeutic effects of two approaches to gait re-training--a schedule of conventional physiotherapy and treadmill re-training--in patients with higher-level gait disorders associated with cerebral multiinfarct states.\n single-blind crossover study involving a 4-week baseline period, 4 weeks of treadmill re-training and 4 weeks of conventional physiotherapy.\n a large teaching hospital.\n patients with cerebral multi-infarct states who met the criteria for higher-level gait disorders. Computed tomographic brain scans showed at least one large vessel infarct, basal ganglia and white matter lacunes or extensive leukoaraiosis.\n a schedule of treadmill re-training and a specific schedule of physiotherapy containing 31 interventions in three treatment modules: (i) for gait ignition failure and turning; (ii) to improve postural alignment and enhance balance reactions; and (iii) for other components of cerebral multi-infarct state disordered gait.\n spatial and temporal gait measures and activity of daily living assessments.\n we recruited 18 patients, mean (SD) age 79.1 (6.8) years. Patients walked an average of 7.9 (5.5) km on the treadmill and had an average of 6.7 (3.2) h of physiotherapy. There were clinically moderate but highly statistically significant (P < 0.001) improvements in the following indices: time taken to complete the sit-to-stand test; time taken to walk 10 m; number of steps over 10 m; walking velocity; right and left step lengths; and time taken to complete the 'S' test. There were no differences in the results obtained in each limb of the study.\n there is no difference between the effects of conventional physiotherapy and treadmill re-training on the gait of patients with higher-level gait disorders associated with cerebral multi-infarct states. However, the improvements seen during the treatment period suggest that there is scope to improve the gait of this group of frail, elderly patients.", "To test the hypothesis that partial body weight-supported treadmill training (PBWSTT) provides more effective gait training than an equally supportive but less physiologic aggressive bracing assisted walking (ABAW) program.\n Following informed consent, patients participating in an inpatient rehabilitation program with significant leg weakness and need for at least moderate assistance for walking, without orthostatic hypotension, symptomatic dyspnea, or angina pectoris were randomized to receive PBWSTT vs. ABAW. PBWSTT was provided by a commercially available, overhead motorized hoist attached to a parachute-type body harness, which provided partial support of the patient's weight over a treadmill. Therapists assisted with weight shifting, leg advancement, and foot placement as needed. ABAW included aggressive early therapist-assisted ambulation using knee-ankle combination bracing and hemi-bar if needed. Treatment sessions of up to 45 minutes per day, five days per week were given as tolerated for the duration of the inpatient stay or until patients could walk over-ground unassisted. All patients had an additional 45-minute session of functionally oriented physical therapy each day with or without bracing as judged appropriate by the patient's individual therapist.\n Fifty-six patients a mean age of 71 +/- 1 SEM were enrolled 40 +/- 3 days post stroke. Although the outcome of the two groups as a whole did not differ, a subgroup with major hemispheric stroke defined by the presence of hemiparesis, hemianopic visual deficit, and hemihypesthesia who received more than 12 treatment sessions showed significantly better over-ground endurance (90 +/- 34 vs. 44 +/- 10 meters) and speed scores (12 +/- 4 vs. 8 +/- 2 meters/minute) for PBWSTT vs. ABAW, respectively.\n PBWSTT and ABAW are equally effective gait training techniques except for a subset of patients with major hemispheric stroke who are difficult to mobilize using ABAW alone.", "A randomized controlled pilot trial was conducted to estimate the effects of early, intensive, gait-focused physical therapy on ambulatory ability in acute, stroke patients. Twenty-seven patients with middle cerebral artery infarct of thromboembolic origin confirmed by computed axial tomography scan were stratified and randomly assigned to the experimental group, to a control group that received early, intensive and conventional therapy, or to a group receiving routine conventional therapy that started later and was not intense. Assessments at entry, six weeks, and three and six months by independent evaluators permitted comparisons with reference to clinical measures of motor performance, balance, and functional capacity, and laboratory measures of gait movements. Group results at six weeks demonstrated that gait velocity was similar in the two conventional groups thereby eliminating the timing of the interventions as an important factor. At that point, gait velocity was faster in the experimental group. The difference translated into a moderate effect size of 0.58. The time dedicated to gait training but not to total therapy time was correlated (rs = 0.63) to gait velocity. This effect disappeared at three and six months after stroke. These pilot results justify planning a large trial to test the effectiveness of a therapeutic protocol that focuses on early and intense gait therapy in an effort to facilitate early ambulation following stroke.", "To evaluate the immediate and long-term effects of aerobic treadmill plus Bobath walking training in subacute stroke survivors compared with Bobath walking training alone.\n Randomized controlled trial.\n Rehabilitation unit.\n Fifty patients, first-time supratentorial stroke, stroke interval less than six weeks, Barthel Index (0-100) from 50 to 80, able to walk a minimum distance of 12 m with either intermittent help or stand-by while walking, cardiovascular stable, minimum 50 W in the bicycle ergometry, randomly allocated to two groups, A and B.\n Group A 30 min of treadmill training, harness secured and minimally supported according to patients' needs, and 30 min of physiotherapy, every workday for six weeks, speed and inclination of the treadmill were adjusted to achieve a heart rate of HR: (Hrmax-HRrest)*0.6+HRrest; in group B 60 min of daily physiotherapy for six weeks.\n Primary outcome variables were the absolute improvement of walking velocity (m/s) and capacity (m), secondary were gross motor function including walking ability (score out of 13) and walking quality (score out of 41), blindly assessed before and after the intervention, and at follow-up three months later.\n Patients tolerated the aerobic training well with no side-effects, significantly greater improvement of walking velocity and capacity both at study end (p =0.001 versus p =0.002) and at follow-up (p <0.001 versus p <0.001) in the experimental group. Between weeks 0 and 6, the experimental group improved walking speed and capacity by a mean of.31 m/s and 91 m, the control group by a mean of 0.16 m/s and 56 m. Between weeks 0 and 18, the experimental group improved walking speed and capacity by a mean of 0.36 m/s and 111 m, the control group by a mean of 0.15 m/s and 57 m. Gross motor function and walking quality did not differ at any time.\n Aerobic treadmill plus Bobath walking training in moderately affected stroke patients was better than Bobath walking training alone with respect to the improvement of walking velocity and capacity. The treatment approach is recommended in patients meeting the inclusion criteria. A multicentre trial should follow to strengthen the evidence.", "The purpose of this study was to compare treadmill and electromechanical gait trainer therapy in subacute, nonambulatory stroke survivors. The gait trainer was designed to provide nonambulatory subjects the repetitive practice of a gait-like movement without overexerting therapists.\n This was a randomized, controlled study with a crossover design following an A-B-A versus a B-A-B pattern. A consisted of 2 weeks of gait trainer therapy, and B consisted of 2 weeks of treadmill therapy. Thirty nonambulatory hemiparetic patients, 4 to 12 weeks after stroke, were randomly assigned to 1 of the 2 groups receiving locomotor therapy every workday for 15 to 20 minutes for 6 weeks. Weekly gait ability (functional ambulation category [FAC]), gait velocity, and the required physical assistance during both kinds of locomotor therapy were the primary outcome measures, and other motor functions (Rivermead motor assessment score) and ankle spasticity (modified Ashworth score) were the secondary outcome measures. Follow-up occurred 6 months later.\n The groups did not differ at study onset with respect to the clinical characteristics and effector variables. During treatment, the FAC, gait velocity, and Rivermead scores improved in both groups, and ankle spasticity did not change. Median FAC level was 4 (3 to 4) in group A compared with 3 (2 to 3) in group B at the end of treatment (P=0.018), but the difference at 6-month follow up was not significant. The therapeutic effort was less on the gait trainer, with 1 instead of 2 therapists assisting the patient at study onset. All but seven patients preferred the gait trainer.\n The newly developed gait trainer was at least as effective as treadmill therapy with partial body weight support while requiring less input from the therapist. Further studies are warranted.", "To evaluate the immediate and retention effects of a 4-week training program on the performance of locomotor-related tasks in chronic stroke.\n Randomized, controlled pilot study with 2-month follow-up.\n Rehabilitation center.\n A convenience sample consisting of 12 chronic stroke subjects was used. Subjects were randomly assigned to the experimental or the control group. Three subjects withdrew from the study.\n Both experimental and control groups participated in exercise classes three times a week for 4 weeks. The exercise class for the experimental group focused on strengthening the affected lower limb and practicing functional tasks involving the lower limbs, while the control group practiced upper-limb tasks.\n Lower-limb function was evaluated by measuring walking speed and endurance, peak vertical ground reaction force through the affected foot during sit-to-stand, and the step test.\n The experimental group demonstrated significant immediate and retained (2-month follow-up) improvement (p < or = .05) compared with the control group in walking speed and endurance, force production through the affected leg during sit-to-stand, and the number of repetitions of the step test.\n The pilot study provides evidence for the efficacy of a task-related circuit class at improving locomotor function in chronic stroke." ]

[ "11556937", "15911726", "12709089" ]

[ "Primary care for patients infected with human immunodeficiency virus: a randomized controlled trial.", "Physician specialization and the quality of care for human immunodeficiency virus infection.", "Physician specialization and antiretroviral therapy for HIV." ]

[ "To measure the impact of a teaching intervention and to compare process and outcomes of care for HIV-infected patients randomly assigned to a general medicine clinic (GMC) or an infectious disease clinic (IDC) for primary care.\n Prospective, randomized, controlled trial.\n University hospital in Durham, NC.\n Two hundred fourteen consecutive HIV-infected patients presenting for primary care.\n Physicians at the GMC received HIV-related training and evidence-based practice guidelines.\n Utilization of services, health-related quality of life, preventive and screening measures, and antiretroviral use for one year.\n At baseline GMC patients were more likely to be African American (85% vs 71%; P =.03) and had lower baseline CD4+ cell counts than IDC patients (262 +/- 269 vs 329 +/- 275; P =.05). A similar and high proportion of patients in both groups received appropriate preventive care services including Pneumocystis carinii pneumonia (PCP) prophylaxis, pneumococcal vaccination, and antiretroviral therapy. Screening for TB was more frequent in GMC (89% vs 68%; P =.001). In the year following randomization, GMC patients made more visits to the emergency department than IDC patients (1.6 +/- 3.0 vs 0.7 +/- 1.5; P =.05). Hospital use was higher for GMC patients with average length of stay 7.8 +/- 6.3 days compared to 5.7 +/- 3.8 days for IDC patients (P =.01). In analyses, which adjust for potential baseline imbalances, these differences remained.\n Targeted education in GMC achieved similar provision of primary care for GMC patients, yet use of health care services was higher for this group. The delivery of adequate primary care is necessary but not sufficient to produce changes in health care utilization.", "There is debate over the types of physicians who should treat patients with complex chronic medical conditions such as human immunodeficiency virus (HIV) infection. We sought to assess the relationship between specialty training and expertise and the quality of care delivered to patients with HIV infection.\n We selected random samples of HIV-infected patients receiving care at 64 Ryan White CARE (Comprehensive AIDS Resources Emergency) Act-funded clinics throughout the country and their primary HIV physicians for an observational cohort study in which quality-of-care measures were assessed by medical record review.\n We studied 5247 patients linked to 177 physicians who responded to a survey. Fifty-eight percent of the physicians were general medicine physicians (\"generalists\") and 42% were infectious diseases specialists. Sixty-three percent of the generalists (37% overall) considered themselves expert in HIV care. In hierarchical logistic regression models that controlled for patient characteristics, infectious diseases physicians and expert generalists had similar performance. In contrast, nonexpert generalists delivered lower quality care. More than 80% of the appropriate patients being cared for by infectious diseases physicians and expert generalists were receiving highly active antiretroviral therapy, compared with 73% of appropriate patients of nonexpert generalists (P<.001). Physicians with fewer than 20 patients with active HIV had fewer appropriate patients on highly active antiretroviral therapy (73% vs 82% of physicians with >/=20 such patients, P = .04) and saw patients less frequently.\n These findings extend previous work by examining a range of quality-of-care measures and suggest that generalists with appropriate experience and expertise in HIV care can provide high-quality care to patients with this complex chronic illness.", "Since the introduction of the first protease inhibitor in January 1996, there has been a dramatic change in the treatment of persons infected with HIV. The changing nature of HIV care has important implications for the types of physicians that can best care for patients with HIV infection.\n To assess the association of specialty training and experience in the care of HIV disease with the adoption and use of highly active antiretroviral (ARV) therapy (HAART).\n Observational cohort study of patients under care for HIV infection and their physicians.\n This analysis used data collected from a national probability sample of noninstitutionalized persons with HIV infection participating in the HIV Costs and Service Utilization Study and their primary physicians. We analyzed 1,820 patients being cared for by 374 physicians.\n Rates of HAART use at 12 months and 18 months after the approval of the first protease inhibitor.\n Forty percent of the physicians were formally trained in infectious diseases (ID), 38% were general medicine physicians with self-reported expertise in the care of HIV, and 22% were general medicine physicians without self-reported expertise in the care of HIV. The majority of physicians (69%) reported a current HIV caseload of 50 patients or more. In multivariable models controlling for patient characteristics, there were no differences between generalist experts and ID physicians in rates of HAART use in December 1996. When compared to ID physicians, however, patients being treated by non-expert general medicine physicians were less likely to be on HAART (odds ratio [OR], 0.32; 95% confidence interval [95% CI], 0.17 to 0.61). Patients being treated by low-volume physicians were also much less likely to be on HAART therapy than those treated by high-volume physicians (OR, 0.26; 95% CI, 0.14 to 0.48). These findings were attenuated by June 1997, suggesting that over time, the broader physician community successfully adopted HAART therapy. This finding is consistent with prior research on the diffusion of innovations.\n Similar proportions of patients treated by expert generalists and ID specialists were on appropriate HAART therapy by December 1996 and July 1997. Patients treated by non-expert generalists, most of whom were the lowest-volume physicians, were much less likely to be on appropriate ARV therapy in the earlier time period. Our findings demonstrate that expert generalists who develop specialized expertise are able to provide care of quality comparable to that of specialists." ]

[ "10966281", "9661544", "10892945", "11081528" ]

[ "Comparison of hyperventilation and inhaled nitric oxide for pulmonary hypertension after repair of congenital heart disease.", "The effects of inhaled nitric oxide on postoperative pulmonary hypertension in infants and children undergoing surgical repair of congenital heart disease.", "Randomized controlled study of inhaled nitric oxide after operation for congenital heart disease.", "Inhaled nitric oxide and prevention of pulmonary hypertension after congenital heart surgery: a randomised double-blind study." ]

[ "Pulmonary hypertension is associated with congenital heart lesions with increased pulmonary blood flow. Acute increases in pulmonary vascular resistance (PVR) occur in the postoperative period after repair of these defects. These increases in PVR can be ablated by inducing an alkalosis with hyperventilation (HV) or bicarbonate therapy. Studies have shown that these patients also respond to inhaled nitric oxide (iNO), but uncertainty exists over the relative merits and undesirable effects of HV and iNO.\n Alkalosis and iNO are equally effective in reducing PVR and pulmonary artery pressure (PAP) in children with pulmonary hypertension after open heart surgery.\n Critical care unit of a tertiary care pediatric hospital.\n Prospective, randomized, crossover design.\n Twelve children with a mean PAP > 25 mm Hg at normal pH after biventricular repair of congenital heart disease.\n Patients were assigned to receive iNO or HV (pH > 7.5) in random order, and the effect on hemodynamics was measured. Each treatment was administered for 30 mins with a 30-min washout period between treatments. Finally, both treatments were administered together to look for a possible additive effect.\n Cardiac output and derived hemodynamic parameters using the dye dilution technique. Hyperventilation, achieved by an increase in ventilator rate without a change in mean airway pressure, decreased Pa(CO2) from a mean (SD) of 43.7+/-5.3 to 32.3+/-5.4 mm Hg and increased pH from 7.40+/-0.04 to 7.50+/-0.03. This significantly altered both pulmonary and systemic hemodynamics with a reduction in PAP, PVR, central venous pressure, and cardiac output and an increase in systemic vascular resistance. In comparison, iNO selectively reduced PAP and PVR only. The reduction in PVR was comparable between treatments, although addition of iNO to HV resulted in a small additional reduction in PVR. An additional decrease in PAP was seen when HV was added to iNO, attributable to a reduction in cardiac output rather than a further decrease in PVR.\n Inhaled NO and HV are both effective at lowering PAP and PVR in children with pulmonary hypertension after repair of congenital heart disease. The selective action of iNO on the pulmonary circulation offers advantages over HV because a decrease in cardiac output and an increase in SVR are undesirable in the postoperative period.", "The role of inhaled nitric oxide in the immediate post-bypass period after surgical repair of congenital heart disease is uncertain. In a controlled, randomized, double-blind study, we tested the hypothesis that inhaled nitric oxide (NO) would reduce pulmonary hypertension immediately after surgical repair of congenital heart disease in 40 patients with preoperative evidence of pulmonary hypertension (mean pulmonary arterial pressure [MPAP] exceeding 50% of mean systemic arterial pressure [MSAP]). Patients were then followed in the intensive care unit (ICU) to document the incidence of severe pulmonary hypertension. Of the patients, 36% (n = 13) emerged from bypass with MPAP > 50% MSAP. In these patients, inhaled NO reduced MPAP by 19% (P = 0.008) versus an increase of 9% in the placebo group. No effect on MPAP was observed in patients emerging from bypass without pulmonary hypertension (n = 23). Inhaled NO was required five times in the ICU, always in the patients who had emerged from cardiopulmonary bypass with pulmonary hypertension (5 of 13 [38%] versus 0 of 23). We conclude that, in infants and children undergoing congenital heart surgery, inhaled NO selectively reduces MPAP in patients who emerge from cardiopulmonary bypass with pulmonary hypertension and has no effect on those who emerge without it. Implications: In a randomized double-blind study, inhaled nitric oxide selectively reduced pulmonary artery pressures in pediatric patients who developed pulmonary hypertension (high blood pressure in the lungs) immediately after cardiopulmonary bypass and surgical repair.", "Inhaled nitric oxide selectively decreases pulmonary vascular resistance. This study was performed to determine whether inhaled nitric oxide decreases the incidence of pulmonary hypertensive crises after corrective procedures for congenital heart disease.\n Patients with a systolic pulmonary arterial pressure of 50% or more of the systolic systemic arterial pressure during the early postoperative period were randomized to receive 20 parts per million inhaled nitric oxide (n = 20) or conventional therapy alone (n = 20). Acute hemodynamic and blood gas measurements were performed at the onset of therapy. The efficacy of sustained therapy was determined by comparing the number of patients in each group who experienced a pulmonary hypertensive crisis.\n In comparison to controls, there were no significant differences in the baseline and 1-hour measurements of patients who were treated with nitric oxide. Four patients in the control group and 3 patients in the nitric oxide group experienced a pulmonary hypertensive crisis.\n Nitric oxide did not substantially improve pulmonary hemodynamics and gas exchange immediately after operation for congenital heart disease. Nitric oxide also failed to significantly decrease the incidence of pulmonary hypertensive crises.", "Pulmonary hypertensive crises (PHTC) are a major cause of morbidity and mortality after congenital heart surgery. Inhaled nitric oxide is frequently used as rescue therapy. We did a randomised double-blind study to investigate the role of routinely administered inhaled nitric oxide to prevent pulmonary hypertension in infants at high risk.\n We enrolled 124 infants (64 male, 60 female; median age 3 months [IQR 1-5]), 76% with large ventricular or atrioventricular septal defects, who had high pulmonary flow, pressure, or both, and were undergoing corrective surgery for congenital heart disease. They were randomly assigned continuous low-dose inhaled nitric oxide (n=63) or placebo (n=61) from surgery until just before extubation. We measured the numbers of PHTC, time on study gas, and hours spent in intensive care. Analysis was done by intention to treat.\n Compared with placebo, infants receiving inhaled nitric oxide had fewer PHTC (median four [IQR 0-12] vs seven [1-19]; relative risk, unadjusted 0.66, p<0.001, adjusted for dispersion 0.65, p=0.045) and shorter times until criteria for extubation were met (80 [38-121] vs 112 h [63-164], p=0.019). Time taken to wean infants off study gas was 35% longer in the nitric oxide group than in the placebo group (p=0.19), but the total time on the study gas was still 30 h shorter for the nitric oxide group (87 [43-125] vs 117 h [67-168], p=0.023). No important toxic effects arose.\n In infants at high risk of pulmonary hypertension, routine use of inhaled nitric oxide after congenital heart surgery can lessen the risk of pulmonary hypertensive crises and shorten the postoperative course, with no toxic effects." ]

[ "8583618" ]

[ "Ameliorative effect of allopurinol on nonbacterial prostatitis: a parallel double-blind controlled study." ]

[ "Nonbacterial prostatitis is a common problem in young men. It is a disease that is often recurrent and each episode lasts for several months. Different causative mechanisms of the disease have been discussed, including identified and unidentified microorganisms, stone formation and psychological factors. We have demonstrated in a previous study that urinary reflux (as shown by a high creatinine concentration in prostatic fluid) occurs to a varying extent into the prostatic ducts, and this reflux has been related to prostatic pain and urate concentration in expressed prostatic secretion.\n We performed a paralled double-blind controlled study of the objective and subjective effects of allopurinol on patients with nonbacterial prostatitis. Twenty patients received placebo, 18 received 300 mg. allopurinol daily and 16 received 600 mg allopurinol daily for 240 days. All patients began medication at the same time regardless of whether the disease was in an active state. No side effects were noted in the treatment groups.\n Significant effects were noted on the concentrations of serum urate, urine urate, expressed prostatic secretion urate, expressed prostatic secretion xanthine and subjective discomfort.\n Allopurinol has a significant, positive effect on nonbacterial prostatitis. It is safe and worthy of trial for all at least a 3-month period at each episode to relieve the symptoms of nonbacterial prostatitis." ]

[ "12853806", "14972468" ]

[ "Pelvic floor exercises, electrical stimulation and biofeedback after radical prostatectomy: results of a prospective randomized trial.", "Comparative study of effects of extracorporeal magnetic innervation versus electrical stimulation for urinary incontinence after radical prostatectomy." ]

[ "We assessed the effect of pelvic muscle exercises (PMEs), electrical stimulation (ES) and biofeedback (BFB) on urinary incontinence after radical retropubic prostatectomy.\n We randomized 139 patients who underwent radical retropubic prostatectomy into 3 groups. Group 1 received instructions about postoperative PMEs. Group 2 received the same instructions and ES for 15 minutes twice daily. Patients in group 3 were also treated with BFB for 15 minutes twice daily. Treatment was started immediately after catheter removal and performed for 3 months. The outcome was assessed using the 20-minute pad test and a urine symptom inventory. Results at baseline, and 3 and 12 months postoperatively were available for 139, 120 and 128 (questionnaire), and 116, 79 and 124 (pad test) patients, respectively.\n An overall subjective spontaneous continence rate (questionnaire) 1 day after catheter removal of 21.4% increased within the first 3 months up to 59.2%. There was no significant difference among the 3 groups. The continence rate increased from 3 to 12 months postoperatively from 59.2% to 85.9%. An overall objective spontaneous continence rate (pad test) 1 day after catheter removal of 32.9% increased within the first 3 months up to 65% and up to 83% after 12 months without any significant difference in all 3 groups.\n A treatment program of ES and BFB enhanced PMEs did not affect continence after radical prostatectomy after 3 or 12 months. Up to 711 euro can be saved per patient.", "To perform a randomized comparative study to investigate the clinical effects of extracorporeal magnetic innervation (ExMI) and functional electrical stimulation (FES) on urinary incontinence after retropubic radical prostatectomy.\n Thirty-six patients with urinary incontinence after radical prostatectomy were randomly assigned to three groups (12 patients each in the FES, ExMI, and control groups). For FES, an anal electrode was used. Pulses of 20-Hz square waves at a 300-micros pulse duration were used for 15 minutes twice daily for 1 month. For ExMI, the Neocontrol system was used. The treatment sessions were for 20 minutes, twice a week for 2 months. The frequency of the pulse field was 10 Hz for 10 minutes, followed by a second treatment at 50 Hz for 10 minutes. For the control group, only pelvic floor muscle exercises were performed. Objective measures included bladder diaries, 24-hour pad weight testing, and a quality-of-life survey, at 1, 2, and 4 weeks and 2, 3, 4, 5, and 6 months after removing the catheter.\n The leakage weight during the 24 hours after removing the catheter was 684, 698, and 664 g for the FES, ExMI, and control groups, respectively. At 1 month, it was 72, 83, and 175 g (FES versus control, P <0.05) and at 2 months was 54, 18, and 92 g (ExMI versus control, P <0.05) in the FES, ExMI, and control groups, respectively. Finally, 6 months later, the average 24-hour leakage weight was less than 10 g in all groups. Quality-of-life measures decreased after surgery, but gradually improved over time in all groups. No complications were noted in any of the groups.\n ExMI and FES therapies offered earlier continence compared with the control group after radical prostatectomy. We consider ExMI and FES to be recommendable options for patients who want quick improvement of postoperative urinary incontinence." ]

[ "12616178", "1831972", "6216275", "17459741", "2967314", "15911537", "9216352", "17621203", "9346145", "12973134", "9541083", "1534400", "1408299", "2932330", "18242858", "18663487", "18155934", "17143986", "2147702", "6229707", "15661440", "9596385", "2521930", "2949196", "6227304", "7654161" ]

[ "Secondary prevention of work-related disability in nonspecific low back pain: does problem-solving therapy help? A randomized clinical trial.", "Operant-behavioural and cognitive-behavioural treatment for chronic low back pain.", "Comparison of group progressive-relaxation training and cognitive-behavioral group therapy for chronic low back pain.", "A randomised controlled study of reflexology for the management of chronic low back pain.", "Comparison of operant behavioral and cognitive-behavioral group treatment for chronic low back pain.", "Randomised controlled trial to compare surgical stabilisation of the lumbar spine with an intensive rehabilitation programme for patients with chronic low back pain: the MRC spine stabilisation trial.", "Incorporation of cognitive-behavioral treatment into the medical care of chronic low back patients: a controlled randomized study in German pain treatment centers.", "Active exercise, education, and cognitive behavioral therapy for persistent disabling low back pain: a randomized controlled trial.", "Chronic low back pain rehabilitation programs: a study of the optimum duration of treatment and a comparison of group and individual therapy.", "Randomized clinical trial of lumbar instrumented fusion and cognitive intervention and exercises in patients with chronic low back pain and disc degeneration.", "Health economic assessment of behavioural rehabilitation in chronic low back pain: a randomised clinical trial.", "Comparison of cognitive-behavioral group treatment and an alternative non-psychological treatment for chronic low back pain.", "The effectiveness of psychological interventions for the rehabilitation of low back pain: a randomized controlled trial evaluation.", "A controlled evaluation of paraspinal EMG biofeedback in the treatment of chronic low back pain.", "Exposure in vivo versus operant graded activity in chronic low back pain patients: results of a randomized controlled trial.", "Intensive group training protocol versus guideline physiotherapy for patients with chronic low back pain: a randomised controlled trial.", "A randomized controlled trial of exposure in vivo for patients with spinal pain reporting fear of work-related activities.", "Effectiveness and cost-effectiveness of adding a cognitive behavioral treatment to the rehabilitation of chronic low back pain.", "Effectiveness of behavioral therapy for chronic low back pain: a component analysis.", "EMG biofeedback used to reduce standing levels of paraspinal muscle tension in chronic low back pain.", "A trial of an activating intervention for chronic back pain in primary care and physical therapy settings.", "Combined exercise and motivation program: effect on the compliance and level of disability of patients with chronic low back pain: a randomized controlled trial.", "The secondary prevention of low back pain: a controlled study with follow-up.", "EMG biofeedback training, relaxation training, and placebo for the relief of chronic back pain.", "Hypnosis compared to relaxation in the outpatient management of chronic low back pain.", "Cognitive-behavioural therapy versus EMG biofeedback in the treatment of chronic low back pain." ]

[ "Given the individual and economic burden of chronic work disability in low back pain patients, there is a need for effective preventive interventions. The aim of the present study was to investigate whether problem-solving therapy had a supplemental value when added to behavioral graded activity, regarding days of sick leave and work status.\n Randomized controlled trial.\n Employees who were recently on sick leave as a result of nonspecific low back pain were referred to the rehabilitation center by general practitioner, occupational physician, or rehabilitation physician. Forty-five employees had been randomly assigned to the experimental treatment condition that included behavioral graded activity and problem-solving therapy (GAPS), and 39 employees had been randomly assigned to behavioral graded activity and group education (GAGE).\n Days of sick leave and work status. Data were retrieved from occupational health services.\n Data analyses showed that employees in the GAPS group had significantly fewer days of sick leave in the second half-year after the intervention. Moreover, work status was more favorable for employees in this condition, in that more employees had a 100% return-to-work and fewer patients ended up receiving disability pensions one year after the intervention. Sensitivity analyses confirmed these results.\n The addition of problem-solving therapy to behavioral graded activity had supplemental value in employees with nonspecific low back pain.", "Fifty-eight outpatients with chronic low back pain were randomly allocated to one of six experimental conditions. Four conditions were designated as treatment conditions and two as control conditions. The four treatment groups consisted of: cognitive treatment (either with or without relaxation training) and behavioural treatment (either with or without relaxation training). The cognitive and behavioural groups also received physiotherapy. The two control conditions consisted of: attention (physiotherapy plus discussion sessions) and no-attention (physiotherapy-only) conditions. All conditions, including the two controls, received the same physiotherapy back-education and exercise program. For the sample as a whole, improvements were obtained on measures of affective distress, functional impairment, medication use, pain-related dysfunctional cognitions and use of active coping strategies. These improvements were generally maintained at 6- and 12-month follow-ups. The combined psychological/physiotherapy treatment conditions improved significantly more than the physiotherapy-only conditions from pre to posttreatment on measures of pain intensity, self-rated functional impairment and pain-related dysfunctional cognitions. However, these differences were only weakly maintained at 6- and 12-month follow-ups. The behavioural conditions improved significantly more than the cognitive conditions from pre to posttreatment on the self-rated measure of functional impairment, but this difference was not maintained at 6- and 12-month follow-ups. Progressive relaxation training was found to make little contribution to either cognitive or behavioural treatments.", "nan", "The use of complementary and alternative medicine (CAM) for the management of chronic low back pain (CLBP) continues to rise. However, questions regarding the efficacy of many CAM therapies for CLBP remain unresolved. The present study investigated the effectiveness of reflexology for CLBP. A pragmatic randomised controlled trial was conducted. N=243 patients were randomised to one of three groups: reflexology, relaxation, or non-intervention (usual care). All completed a questionnaire booklet before and after the treatment phase, and at six months follow up. This measured their general health status, pain, functioning, coping strategies and mood. After adjusting for pre-treatment scores repeated measures ANCOVA found no significant differences between the groups pre and post treatment on the primary outcome measures of pain and functioning. There was a main effect of pain reduction, irrespective of group. Trends in the data illustrated the pain reduction was greatest in the reflexology group. Thus, the current study does not indicate that adding reflexology to usual GP care for the management of CLBP is any more effective than usual GP care alone.", "nan", "To assess the clinical effectiveness of surgical stabilisation (spinal fusion) compared with intensive rehabilitation for patients with chronic low back pain.\n Multicentre randomised controlled trial.\n 15 secondary care orthopaedic and rehabilitation centres across the United Kingdom.\n 349 participants aged 18-55 with chronic low back pain of at least one year's duration who were considered candidates for spinal fusion.\n Lumbar spine fusion or an intensive rehabilitation programme based on principles of cognitive behaviour therapy.\n The primary outcomes were the Oswestry disability index and the shuttle walking test measured at baseline and two years after randomisation. The SF-36 instrument was used as a secondary outcome measure.\n 176 participants were assigned to surgery and 173 to rehabilitation. 284 (81%) provided follow-up data at 24 months. The mean Oswestry disability index changed favourably from 46.5 (SD 14.6) to 34.0 (SD 21.1) in the surgery group and from 44.8 (SD14.8) to 36.1 (SD 20.6) in the rehabilitation group. The estimated mean difference between the groups was -4.1 (95% confidence interval -8.1 to -0.1, P = 0.045) in favour of surgery. No significant differences between the treatment groups were observed in the shuttle walking test or any of the other outcome measures.\n Both groups reported reductions in disability during two years of follow-up, possibly unrelated to the interventions. The statistical difference between treatment groups in one of the two primary outcome measures was marginal and only just reached the predefined minimal clinical difference, and the potential risk and additional cost of surgery also need to be considered. No clear evidence emerged that primary spinal fusion surgery was any more beneficial than intensive rehabilitation.", "Cognitive behavioral treatment has been incorporated into standard medical treatment procedures in German pain centers. Acceptance of the treatment by patients and outcome in terms of pain, coping, and disability was investigated. Components of the psychological treatment are education, relaxation and imagery, modifying thoughts and feelings, enhancement of pleasant activities, and training of good postural habits. The program was conducted in a group setting in accordance with a treatment manual and consists of 12 weekly 2.5-h sessions. A two-factor experiment with repeated measures on one factor was applied. Ninety-four consecutive patients with low-back pain were randomly assigned to an experimental group having a combined medical and cognitive-behavioral treatment, or to a control group with medical treatment only. Assessments were taken pre-treatment, post-treatment, and--in the treated group only--at a 6-months follow-up. At each assessment, patients kept a pain diary over a period of 4 weeks, and filled in self-report questionnaires. The sample consisted of 36 experimental and 40 control subjects at post-treatment. Experimental subjects reported less pain, better control over pain, more pleasurable activities and feelings, less avoidance and less catastrophizing. In addition, disability was reduced in terms of social roles, physical functions and mental performance. The results were maintained at follow-up. Patients who only received medical treatment showed little improvement. Data indicate that the program meets the needs of the patients and should be continued.", "A randomized controlled trial.\n To determine 1) whether, among patients with persistent disabling low back pain (LBP), a group program of exercise and education using a cognitive behavioral therapy (CBT) approach, reduces pain and disability over a subsequent 12-month period; 2) the cost-effectiveness of the intervention; and 3) whether a priori preference for type of treatment influences outcome.\n There is evidence that both exercise and CBT delivered in specialist settings is effective in improving LBP. There is a lack of evidence on whether such interventions, delivered by trained individuals in primary care, result in improved outcomes.\n The study was conducted in nine family medical practices in East Cheshire, UK. Patients 18 to 65 years of age, consulting with LBP, were recruited; those still reporting LBP 3 months after the initial consultation were randomized between the two trial arms. The intervention arm received a program of eight 2-hour group exercise session over 6 weeks comprising active exercise and education delivered by physiotherapists using a CBT approach. Both arms received an educational booklet and audio-cassette. The primary outcome measures were pain (0-100 Visual Analogue Scale) and disability (Roland and Morris Disability Scale; score 0-24).\n A total of 196 subjects (84%) completed follow-up 12 months after the completion of the intervention program. The intervention showed only a small and nonsignificant effect at reducing pain (-3.6 mm; 95% confidence interval, -8.5, 1.2 mm) and disability (-0.6 score; 95% confidence interval, -1.6, 0.4). The cost of the intervention was low with an incremental cost-effectiveness ratio of pound5000 (U.S. $8650) per quality adjusted life year. In addition, patients allocated to the intervention that had expressed a preference for it had clinically important reductions in pain and disability.\n This intervention program produces only modest effects in reducing LBP and disability over a 1-year period. The observation that patient preference for treatment influences outcome warrants further investigation.", "Eighty-four patients with chronic low back pain were treated using cognitive behavioral principles on a pain management program. Outcome data were collected at four points: 10 weeks before treatment, immediately before and immediately after treatment, and 6 months after treatment. In part 1 of the study, patients were assigned randomly to group or individual treatment contexts. In part 2 of the study, patients were assigned randomly to programs of 15, 30, or 60 hours duration.\n To identify the differences in outcome between programs that treated patients as part of a group and those that treated patients individually and the effects of duration of treatment on outcome.\n Cognitive behavioral programs have been shown to be an effective means of managing chronic low back pain. The literature is concerned with group programs, however, the duration of which vary widely.\n Psychological and functional variables were measured before and after treatment and at the 6-month follow-up visit. Changes in these variables were measured, and comparisons were made between group and individual programs and between 15-, 30-, and 60-hour programs.\n Data analysis showed a significant, beneficial effect of intervention in terms of the majority of variables; however, these changes were generally independent of whether patients were treated as part of a group or individually and whether patients completed a 15-, 30-, or 60-hour program.\n Cognitive behavioral rehabilitation programs have been demonstrated to be an effective means of reducing psychological distress, of changing cognition, and of improving the function of patients with chronic low back pain; however, the length of program and whether patients were treated individually or as part of a group did not affect outcome. This finding has clinical and economic implications.", "Single blind randomized study.\n To compare the effectiveness of lumbar instrumented fusion with cognitive intervention and exercises in patients with chronic low back pain and disc degeneration.\n To the authors' best knowledge, only one randomized study has evaluated the effectiveness of lumbar fusion. The Swedish Lumbar Spine Study reported that lumbar fusion was better than continuing physiotherapy and care by the family physician.\n Sixty-four patients aged 25-60 years with low back pain lasting longer than 1 year and evidence of disc degeneration at L4-L5 and/or L5-S1 at radiographic examination were randomized to either lumbar fusion with posterior transpedicular screws and postoperative physiotherapy, or cognitive intervention and exercises. The cognitive intervention consisted of a lecture to give the patient an understanding that ordinary physical activity would not harm the disc and a recommendation to use the back and bend it. This was reinforced by three daily physical exercise sessions for 3 weeks. The main outcome measure was the Oswestry Disability Index.\n At the 1-year follow-up visit, 97% of the patients, including 6 patients who had either not attended treatment or changed groups, were examined. The Oswestry Disability Index was significantly reduced from 41 to 26 after surgery, compared with 42 to 30 after cognitive intervention and exercises. The mean difference between groups was 2.3 (-6.7 to 11.4) (P = 0.33). Improvements inback pain, use of analgesics, emotional distress, life satisfaction, and return to work were not different. Fear-avoidance beliefs and fingertip-floor distance were reduced more after nonoperative treatment, and lower limb pain was reduced more after surgery. The success rate according to an independent observer was 70% after surgery and 76% after cognitive intervention and exercises. The early complication rate in the surgical group was 18%.\n The main outcome measure showed equal improvement in patients with chronic low back pain and disc degeneration randomized to cognitive intervention and exercises, or lumbar fusion.", "The aim of this cost-effectiveness study was to compare a combined operant programme plus cognitive/relaxation programme with an operant programme plus attention-control and to compare both programmes with a waiting-list control group and with operant rehabilitation provided, as usual, by the same rehabilitation centre. One hundred and forty eight patients with chronic low back pain were randomly assigned to the different conditions. The economic endpoints were the costs of the programme and other health care utilisation, costs for the patient, and indirect costs associated with production losses due to low back pain. The effects were measured in terms of global assessment of change and utilities, using rating scale and standard gamble methods. The 3-year study determined that adding a cognitive component to an operant treatment did not lead to significant differences in costs and improvement in quality of life when compared with the operant treatment alone. Compared with the common individual rehabilitation therapy it can be concluded that the same effects can be reached at the same or lower costs with a shorter, more intense standardised group programme. The operant treatment alone is more effective than providing no treatment in the waiting-list control group.", "This study was designed to investigate the relative efficacy of cognitive-behavioral group treatment, including relaxation training, in comparison with a control condition in a sample of 20 outpatients with chronic low back pain. Subjects in both conditions also received the same physiotherapy back-education and exercise program. The control condition included a control for the attention of the therapist in the cognitive-behavioral treatment. The combined psychological treatment and physiotherapy condition displayed significantly greater improvement than the attention-control and physiotherapy condition at post-treatment on measures of other-rated functional impairment, use of active coping strategies, self-efficacy beliefs, and medication use. These differences were maintained at 6 month follow-up on use of active coping strategies and, to a lesser degree, on self-efficacy beliefs and other-rated functional impairment.", "Forty-five low back pain patients were randomly assigned to either a standard inpatient rehabilitation program or the standard program with additional psychological components. The standard program emphasized education, support, and physical reconditioning through exercise. Patients receiving the psychological program were given additional training in relaxation and other coping skills and received contingent reinforcement for exercise. Both programs included reduction of medication intake and an emphasis on family involvement after discharge. Measures of functional status were taken prior to the program, at discharge from the 3-week inpatient program, and at a 6-month follow-up appointment. These data revealed that patients improved their overall functioning at discharge and maintained these gains at the follow-up assessment. A similar pattern of findings was obtained for self-reported pain and interference. Furthermore, 81% of the patients had returned to work or were engaged in active job retraining by the follow-up. Using a conservative measure of full-time return to the same or an equivalent job, 57% were employed by the follow-up. Patient improvement, however, was not differentially affected by treatment group assignment, suggesting that the psychological treatment failed to add to the effectiveness obtained by the standard rehabilitation program. Results are discussed in the context of improving patient outcomes from rehabilitation for low back pain.", "Sixty-six chronic low back pain sufferers were randomly divided into three groups. Following individual assessments consisting of psychological questionnaires, pain monitoring, and measurement of paraspinal electromyogram (EMG), one group received paraspinal EMG biofeedback and another a placebo treatment. The third group received no intervention. Two further assessments were carried out on all groups immediately after treatment and at a 3-month follow-up. All groups showed significant reduction in pain, anxiety, depression, and paraspinal EMG following treatment and at follow-up, but there were no differences between groups. A regression analysis failed to identify subjects' characteristics that predicted positive outcome in the biofeedback group. However, high scores on the Evaluative scale of the McGill Pain Questionnaire and high hypnotizability were significant predictors of positive outcome for the placebo group. It is concluded that paraspinal EMG biofeedback is not a specific treatment for chronic low back pain in a nonhospitalized population.", "Since pain-related fear may contribute to the development and maintenance of chronic low back pain (CLBP), an exposure in vivo treatment (EXP) was developed for CLBP patients. We examined the effectiveness as well as specific mediating mechanisms of EXP versus operant graded activity (GA) directly and 6 months post-treatment in a multi-centre randomized controlled trial. In total, 85 patients suffering from disabling non-specific CLBP reporting at least moderate pain-related fear were randomly allocated to EXP or GA. It was demonstrated that EXP, despite excelling in diminishing pain catastrophizing and perceived harmfulness of activities, was equally effective as GA in improving functional disability and main complaints, although the group difference almost reached statistical significance favouring EXP. Both treatment conditions did not differ in pain intensity and daily activity levels either. Nor was EXP superior to GA in the subgroup of highly fearful patients. Irrespective of treatment, approximately half the patients reported clinically relevant improvements in main complaints and functional disability, although for the latter outcome the group difference was almost significant favouring EXP. Furthermore, the effect of EXP relative to GA on functional disability and main complaints was mediated by decreases in catastrophizing and perceived harmfulness of activities. In sum, this study demonstrates that up to 6 months after treatment EXP is an effective treatment, but not more effective than GA, in moderately to highly fearful CLBP patients, although its superiority in altering pain catastrophizing and perceived harmfulness of activities is clearly established. Possible explanations for these findings are discussed.", "Intensive group training using principles of graded activity has been proven to be effective in occupational care for workers with chronic low back pain. Objective of the study was to compare the effects of an intensive group training protocol aimed at returning to normal daily activities and guideline physiotherapy for primary care patients with non-specific chronic low back pain. The study was designed as pragmatic randomised controlled trial with a setup of 105 primary care physiotherapists in 49 practices and 114 patients with non-specific low back pain of more than 12 weeks duration participated in the study. In the intensive group training protocol exercise therapy, back school and operant-conditioning behavioural principles are combined. Patients were treated during 10 individual sessions along 20 group sessions. Usual care consisted of physiotherapy according to the Dutch guidelines for Low Back Pain. Main outcome measures were functional disability (Roland Morris disability questionnaire), pain intensity, perceived recovery and sick leave because of low back pain assessed at baseline and after 6, 13, 26 and 52 weeks. Both an intention-to-treat analysis and a per-protocol analysis were performed. Multilevel analysis did not show significant differences between both treatment groups on any outcome measures during the complete follow-up period, with one exception. After 26 weeks the protocol group showed more reduction in pain intensity than the guideline group, but this difference was absent after 52 weeks. We finally conclude that an intensive group training protocol was not more effective than usual physiotherapy for chronic low back pain.", "Pain-related fear is related to disability in persistent pain conditions. Exposure treatment has been reported to be of great benefit in replicated single case experiments.\n To evaluate the effects of exposure in vivo on fear and function in patients with persistent pain and work disability.\n We recruited 46 patients suffering from long-term back pain and reduced function, who also were deemed fearful according to standardized measures. Participants were randomized into either an exposure plus usual treatment or waiting list control plus usual treatment group. After the waiting period the control group crossed over and received the exposure treatment.\n Between group comparisons showed a significantly better result for the exposure group on function, but not for fear or pain and effect sizes were modest (function=.6; fear=.4; pain=.1). When the control group crossed over to treatment significant treatment effects were noted for fear and function. For all patients treated, the pre to post-treatment effect sizes were large (function=.7; fear=1.1; pain=.9). There were 12 dropouts (8 in exposure and 4 in the control) during the first treatment phase and an additional 4 when the control group crossed over to exposure.\n Compared to a group receiving usual treatment and waiting for exposure, the exposure in vivo group demonstrated a significantly larger improvement on function. Overall exposure had moderate effects on function, fear and pain intensity. We conclude that exposure may be important in treatment, but is not recommended as a \"stand alone\" adjunct to usual treatment.", "To investigate return to work and cost-effectiveness of the addition of cognitive-behavioral treatment to standard therapy compared to standard 3-week inpatient rehabilitation for patients with chronic low back pain.\n A prospective economic evaluation alongside a randomized controlled trial was performed. Outcomes included days off work due to spinal complaints, health-related quality of life, and direct and indirect disease-related costs.\n A total of 409 patients with chronic low back pain, who were admitted to a 3-week inpatient rehabilitation, were randomly assigned to usual care or usual care plus cognitive behavioral treatment. Average incremental costs for psychological treatment during rehabilitation were Euros 127 (95% CI 125.6, 130.9; p < 0.001). Six months after rehabilitation, patients in the intervention group were absent from work an average of 5.4 (95% CI -1.4, 12.1; p = 0.12) days less than patients receiving usual treatment. Between groups, there were no significant differences in quality-adjusted life-years gained or in direct medical or nonmedical costs. The cognitive behavioral treatment showed lower indirect costs: Euros 751 (95% CI -145, 1641; p = 0.097).\n Adding a cognitive behavioral component to standard therapy may reduce work days lost and thus decrease indirect costs. From a societal perspective, the cost of the psychological treatment was compensated by lower indirect costs.", "The effects of outpatient group behavioral therapy including aerobic exercise (BE), behavioral therapy only (B), and aerobic exercise only (E) on pain and physical and psychosocial disability were evaluated and compared in a group of mildly disabled chronic low-back-pain patients. Ninety-six Ss were randomly assigned to the 3 treatments and a waiting-list control (WL) condition and assessed on a variety of patient self-report, spouse-rated, and direct observational measures at pretreatment, posttreatment, and 6- and 12-month follow-ups. Patients in the BE condition, but not the B or E conditions, improved significantly more pretreatment to posttreatment than did WL patients on the patient self-report and observer-rated measures. At both follow-ups, all 3 treatment groups remained significantly improved from pretreatment, with no significant differences among treatments.", "Twenty chronic low back pain (LBP) patients with relatively high standing paraspinal EMG levels (greater than 5 microV) were randomly assigned to 2 groups. One group (N = 10) received EMG biofeedback training to reduce standing paraspinal EMG levels, the other group (N = 10) served as a waiting list control group. Changes in perceived pain (duration X intensity) and paraspinal EMG in standing position were measured at a 3 week pretreatment baseline, during the 3 week treatment period, and at a 3 week post-treatment baseline. Compared to patients in the waiting list control group, those who received EMG biofeedback showed a significant decrease in standing paraspinal EMG from pretreatment to post-treatment baseline. However, no significant differences in reported pain were found during these periods. It is concluded that reduction of standing paraspinal EMG does not lead to reduction in pain.", "In primary care and physical therapy settings, we evaluated an intervention for chronic back pain patients which incorporated fear reducing and activating techniques. Primary care patients seen for back pain in primary care were screened to identify persons with significant activity limitations 8-10 weeks after their visit. Eligible and willing patients were randomized (N=240). A brief, individualized program to reduce fear and increase activity levels was delivered by a psychologist and physical therapists. Over a 2 year follow-up period, intervention patients reported greater reductions in pain-related fear (P<0.01), average pain (P<0.01) and activity limitations due to back pain (P<0.01) relative to control patients. The percent with greater than a one-third reduction in Roland Disability Questionnaire scores at 6 months was 42% among Intervention patients and 24% among control patients (P<0.01). Over the 2 year follow-up, fewer intervention patients reported 30 or more days unable to carry out usual activities in the prior 3 months (P<0.01). The adjusted mean difference in activity limitation days was 4.5 days at 6 months, 2.8 days at 12 months, and 6.9 days at 24 months. No differences were observed in the percent unemployed or the percent receiving worker's compensation or disability benefits, but these outcomes were relatively uncommon. We conclude that an intervention integrating fear reducing and activating interventions into care for chronic back pain patients produced sustained reductions in patient fears, common activity limitations related to back pain, and days missed from usual activities due to back pain.", "To assess the effect of a combined exercise and motivation program on the compliance and level of disability of patients with chronic and recurrent low back pain.\n A double-blind prospective randomized controlled trial.\n Physical therapy outpatient department, tertiary care.\n Ninety-three low back pain patients were randomly assigned to either a standard exercise program (n = 49) or a combined exercise and motivation program (n = 44).\n Patients were prescribed 10 physical therapy sessions and were advised to continue exercising after treatment termination. The motivation program consisted of five compliance-enhancing interventions. Follow-up assessments were performed at 3 1/2 weeks, 4 months, and 12 months.\n Disability (low back outcome score), pain intensity, physical impairment (modified Waddell score, fingertip-to-floor distance, abdominal muscle strength), working ability, motivation, and compliance.\n The patients in the motivation group were significantly more likely to attend their exercise therapy appointments (p = .0005). Four and 12 months after study entry there was a significant difference in favor of the motivation group with regard to the disability score (p = .004) and pain intensity (p < or = .026). At 4 months, there was a significant advantage for the motivation group in the fingertip-to-floor distance (p = .01) and in abdominal muscle strength (p = .018). No significant differences were found in motivation scores, self-reported compliance with long-term exercise, and modified Waddell score. In terms of working ability, there was a trend favoring the combined exercise and motivation program.\n The combined exercise and motivation program increased the rate of attendance at scheduled physical therapy sessions, ie, short-term compliance, and reduced disability and pain levels by the 12-month follow-up. However, there was no difference between the motivation and control groups with regard to long-term exercise compliance.", "The current investigation studied the effectiveness of a secondary prevention program for nurses with back pain who were deemed at risk for developing a chronic problem. A 2 X 3 repeated measures design was employed with 2 groups and 3 assessment periods. The treatment group received an intervention designed to reduce current problems, but above all to prevent reinjury and minor pains from becoming chronic medical problems, and it included a physical and behavioral therapy package. The control group was placed on a waiting-list. Results indicated that the treatment group had significantly greater improvements than the control group for pain intensity, anxiety, sleep quality and fatigue ratings, observed pain behavior, activities, mood, and helplessness. These differences were generally maintained at the 6 month follow-up. In addition, the treatment group broke a trend for increasing amounts of pain-related absenteeism, while the control group did not. Taken as a whole, the results suggest that a secondary prevention program aimed at altering life style factors may represent an effective method for dealing with musculoskeletal pain problems.", "24 patients with chronic low back pain were randomly assigned to three treatment conditions: EMG biofeedback, relaxation training, and a placebo condition. Patients were seen for eight sessions and were evaluated before Session 1 and after Session 8. Eight analyses of covariance which were adjusted for age and pretest scores were computed on the final scores to find which variables could detect significant difference between treatments. Age was included as a covariate because the differences in age between conditions were significant. Four variables with significant and nearly significant differences were chosen for analysis. The second set of analyses identified the nature of the differences among the three conditions. These included a priori planned comparisons among conditions, and paired t tests. Relaxation-trained subjects were significantly superior to subjects in the placebo condition, in decreasing pain during the function test, increasing relaxation, and decreasing Upper Trapezius EMG. They were superior to EMG Biofeedback training in increasing reported activity. Both Relaxation and EMG trained subjects were able to reduce Upper Trapezius EMG by Session 8. Relaxation-trained subjects showed significant change on eight of the 14 possible comparisons for each treatment condition. EMG biofeedback training showed significant favorable results in only one condition; the placebo condition showed no significant results. Relaxation training gave better results in reducing EMG and pain, and in increasing relaxation and activity than either EMG biofeedback alone or a placebo condition.", "Chronic low back pain (CLBP) presents a problem of massive dimensions. While inpatient approaches have been evaluated, outpatient treatment programs have received relatively little examination. Hypnosis and relaxation are two powerful techniques amenable to outpatient use. Seventeen outpatient subjects suffering from CLBP were assigned to either Self-Hypnosis (n = 9) or Relaxation (n = 8) treatments. Following pretreatment assessment, all subjects attended a single placebo session in which they received minimal EMG feedback. One week later the subjects began eight individual weekly treatment sessions. Subjects were assessed on a number of dependent variables at pretreatment, following the placebo phase, one week after the completion of treatment, and three months after treatment ended. Subjects in both groups showed significant decrements in such measures as average pain rating, pain as measured by derivations from the McGill Pain Questionnaire, level of depression, and length of pain analog line. Self-Hypnosis subjects reported less time to sleep onset, and physicians rated their use of medication as less problematic after treatment. While both treatments were effective, neither proved superior to the other. The placebo treatment produced nonsignificant improvement.", "Forty-four chronic, but relatively well functioning, low back pain patients were assigned to either Cognitive Behaviour Therapy (CBT). Electromyographic Biofeedback (EMGBF) or Wait List Control (WLC). Both treatments were conducted over eight sessions in groups of four subjects. Results at post-treatment indicated significant improvements in functioning on measures of pain intensity, perceived level of disability, adaptive beliefs about pain and the level of depression in both the CBT and EMGBF conditions. These improvements were not evident for the WLC condition. At 6 months follow-up, treatment gains were maintained in the areas of pain intensity, pain beliefs, and depression, for both treatment groups, with further improvements occurring in anxiety and use of active coping skills. No significant differences were found between CBT and EMGBF on any of the outcome measures at either post-treatment or at 6 months follow-up. Further research is required to determine the degree to which these results reflect the mild level of psychological impairment and disability status of patients in the present study." ]

[ "7139504", "2797920", "7622763", "10807817", "10227336", "6581062", "10609622", "8176575", "9236507", "7038565", "8109809", "8630614", "10919682", "9692126", "9357377", "9498940", "3987769", "8074262", "9669832", "1516608", "9892032", "7759460", "7874928", "10208190", "10077140", "1439226", "2817307", "3046409", "6581064", "2044734", "7719894", "10390425", "3410154", "7995387", "9751068", "2938515", "3553277", "10919681", "10027428", "6954092", "7795451", "8486025", "2647819", "3234516", "399858", "9793619", "9616533", "7878558", "10228142", "8177971", "7008642", "2735519", "8617079", "3890601", "7893268", "9426081", "9282236", "10208191", "589786", "2683835" ]

[ "Salbutamol: comparison of bronchodilating effect of inhaled powder and aerosol in asthmatic subjects.", "Comparison of a new multidose powder inhaler with a pressurized aerosol in children with asthma.", "Clinical equivalence of a novel non-chlorofluorocarbon-containing salbutamol sulfate metered-dose inhaler and a conventional chlorofluorocarbon inhaler in patients with asthma.", "The protective effect of salbutamol inhaled using different devices on methacholine bronchoconstriction.", "Clinical comparability of albuterol delivered by the breath-actuated inhaler (Spiros) and albuterol by MDI in patients with asthma.", "Fenoterol inhalation powder as an alternative to treatment with the metered dose inhaler.", "Proventil HFA prevents exercise-induced bronchoconstriction in children.", "Comparison of inhaled terbutaline administered by either the Turbuhaler dry powder inhaler or a metered-dose inhaler with spacer in preschool children with asthma.", "Proventil HFA provides protection from exercise-induced bronchoconstriction comparable to proventil and ventolin.", "A comparison between aerosol and inhaled powder administration of fenoterol in adult asthmatics.", "A novel multiple dose powder inhaler. Salbutamol powder and aerosol give equal bronchodilatation with equal doses.", "The inhalation device influences lung deposition and bronchodilating effect of terbutaline.", "Equivalence of salbutamol 200 microg four times daily propelled by propellants 11 and 12 or HFA 134a in mild to moderate asthmatics. Eastern European study group.", "The bronchoprotective efficacy of salbutamol inhaled from a new metered-dose powder inhaler compared with a conventional pressurized metered-dose inhaler connected to a spacer.", "Pilot study of bronchodilator response to inhaled albuterol delivered by metered-dose inhaler and a novel dry powder inhaler.", "Proventil HFA provides bronchodilation comparable to ventolin over 12 weeks of regular use in asthmatics.", "Comparison of inhaled salbutamol powder and aerosol in asthmatic patients with low peak expiratory flow level.", "A comparison of terbutaline inhaled by Turbuhaler and by a chlorofluorocarbon (CFC) inhaler in children with exercise-induced asthma.", "Albuterol delivered by metered-dose inhaler (MDI), MDI with spacer, and Rotahaler device--a comparison of efficacy and safety.", "Kinetics of action of salbutamol inhaled from a metered dose inhaler (MDI) and a \"Diskhaler\".", "Cumulative dose response study comparing HFA-134a albuterol sulfate and conventional CFC albuterol in patients with asthma.", "Albuterol aerosol versus albuterol Rotacaps in exercise-induced bronchospasm in children.", "Dry powder inhalers are bioequivalent to metered-dose inhalers. A study using a new urinary albuterol (salbutamol) assay technique.", "Safety of long-term treatment with HFA albuterol.", "Switching patients with asthma from chlorofluorocarbon (CFC) albuterol to hydrofluoroalkane-134a (HFA) albuterol.", "Comparative assessment of a new breath-actuated inhaler in patients with reversible airways obstruction.", "Treatment of asthma in pre-school children with inhalation of terbutaline in Turbuhaler compared with Nebuhaler.", "Turbuhaler: a new device for dry powder terbutaline inhalation.", "Ventilation effects of fenoterol powder and freon-propelled aerosol in patients with asthma.", "Bricanyl Turbuhaler in the treatment of asthma: a six week multi-centre study carried out in Sweden, the United Kingdom, Denmark, Norway and Finland.", "Dose potency relationship of terbutaline inhaled via Turbuhaler or via a pressurized metered dose inhaler.", "Protection against methacholine bronchoconstriction to assess relative potency of inhaled beta2-agonist.", "Evaluation of a breath operated powder inhaler.", "Terbutaline via pressurised metered dose inhaled (P-MDI) and Turbuhaler in highly reactive asthmatic patients.", "Bronchodilator responses to salbutamol using diskhaler versus metered-dose inhaler.", "Ipratropium bromide (Atrovent) as inhalation powder. A double-blind study of comparison with ipratropium as a pressure aerosol in patients with reversible airways obstruction.", "Comparison of inhaled albuterol powder and aerosol in asthma.", "Equivalence of as-required salbutamol propelled by propellants 11 and 12 or HFA 134a in mild to moderate asthmatics. German Study Group.", "Comparative efficacy and safety of albuterol sulfate Spiros inhaler and albuterol metered-dose inhaler in asthma.", "The effect of powder aerosol compared to pressurized aerosol.", "GR106642X: a new, non-ozone depleting propellant for inhalers.", "Bronchodilator delivery from Gentlehaler, a new low-velocity pressurized aerosol inhaler.", "Albuterol treatment for children with asthma: a comparison of inhaled powder and aerosol.", "A new multiple dose powder inhaler, (Turbuhaler), compared with a pressurized inhaler in a study of terbutaline in asthmatics.", "Long-term comparison of salbutamol powder with salbutamol aerosol in asthmatic out-patients.", "Comparison of the bronchodilating efficacies of a novel salbutamol metered dose powder inhaler and a pressurised metered dose aerosol with a spacer.", "Safety and efficacy of a high cumulative dose of salbutamol inhaled via Turbuhaler or via a pressurized metered-dose inhaler in patients with asthma.", "Comparison of terbutaline and placebo from a pressurised metered dose inhaler and a dry powder inhaler in a subgroup of patients with asthma.", "Equivalent bronchodilation with salbutamol given via pMDI or turbuhaler.", "Easyhaler, a novel multiple dose powder inhaler: clinically equivalent to salbutamol metered dose inhaler and easier to use.", "Salbutamol by powder or spray inhalation in childhood asthma.", "A multiple dose powder inhaler (Turbuhaler) compared with a conventional aerosol. An acceptance study in asthmatics.", "Cumulative dose-response study of non-CFC propellant HFA 134a salbutamol sulfate metered-dose inhaler in patients with asthma.", "Fenoterol inhalation powder and aerosol in the treatment of asthma.", "Clinical equivalence of a novel multiple dose powder inhaler versus a conventional metered dose inhaler on bronchodilating effects of salbutamol.", "Differences in bronchodilating potency of salbutamol in Turbuhaler as compared with a pressurized metered-dose inhaler formulation in patients with reversible airway obstruction.", "Influence of inspiratory capacity on bronchodilatation via Turbuhaler or pressurized metered-dose inhaler in asthmatic children: a comparison.", "Clickhaler (a novel dry powder inhaler) provides similar bronchodilation to pressurized metered-dose inhaler, even at low flow rates.", "Comparison of salbutamol Rotahaler with conventional pressurized aerosol.", "A double-blind comparison between a new multidose powder inhaler (Turbuhaler) and metered dose inhaler in children with asthma." ]

[ "In the treatment of asthma salbutamol can be administered as an aerosol with a metered-dose inhaler or as a powder with a breath-actuated device (Rotahaler). The two forms of the drug were compared in a double-blind placebo-controlled study involving 10 asthmatic adults who were known to respond to salbutamol. The bronchodilating effect of the aerosol and the powder at doses of 200 micrograms and of the powder at doses of 200 and 400 micrograms was compared, bronchodilation being measured in terms of forced expiratory volume and vital capacity. The response was far greater to salbutamol than to placebo, but there was no significant difference between the two forms of the drug or between the lower and higher doses of powder. No side effects were observed.", "Thirteen children with asthma were treated with cumulative doses of terbutaline delivered as a pressurized aerosol and from a new multidose powder inhaler (Turbuhaler) in a randomized cross-over dose-response study. The cumulative dose of terbutaline was 2 mg on each study day. All children used a correct aerosol inhalation technique. At no time was there any difference in forced expiratory volume in 1 s (FEV1), forced midexpiratory flow, forced vital capacity, peak expiratory flow rate, or percent increase in these parameters between the two inhalers. The mean total increases in FEV1 after 2 mg terbutaline were 60% (aerosol) and 62% (Turbuhaler); 90% of these increases were measured after a cumulative dose of 0.5 mg terbutaline. One milligram of terbutaline inhaled from a Nebuhaler at the end of each study day did not result in additional increase of pulmonary functions, indicating that maximal bronchodilation had been achieved with both inhalers. After a cumulative dose of 2 mg terbutaline from the aerosol seven children complained of tremor and one of restlessness. No side effects were reported when the Turbuhaler was used (P less than 0.02). 1989; 7:00-00.", "New formulations of non-chlorofluorocarbon-containing propellants for pressurized metered-dose inhaler delivery systems must be developed in response to the forthcoming ban on chlorofluorocarbon (CFC) production.\n This study compared the bronchodilator effects of 100, 200, and 300 micrograms (base equivalent) of salbutamol in a novel CFC-free propellant system (Airomir in the 3M CFC-Free System; 3M Pharmaceuticals, St. Paul, Minn.; 108 micrograms of salbutamol sulfate or 90 micrograms of salbutamol base equivalent per inhalation) with that of 100 and 200 micrograms of salbutamol base in a conventional CFC propellant system (Ventolin, CFC-11/12; Allen and Hanburys, Division of Glaxo Inc., Research Triangle Park, N.C.; 90 micrograms of salbutamol base per inhalation) and placebo.\n Twenty-six patients with chronic, stable asthma, who had a forced expiratory volume in 1 second (FEV1) between 50.0% and 75.0% of predicted normal value, entered this randomized, double-blind, double-dummy, 6-period, crossover study. FEV1 was measured before and at multiple time points (ranging from 10 to 480 minutes) after administration of one, two, and three inhalations of salbutamol/CFC-free (100, 200, and 300 micrograms); one and two inhalations of salbutamol/CFC (100 and 200 micrograms); and placebo. Safety parameters included adverse events, heart rate, blood pressure, physical examinations, electrocardiograms, and clinical laboratory tests. Parametric analysis of variance models appropriate for a 6-period crossover design were used, along with multiple comparisons according to Tukey's method.\n All active treatments produced significantly (p < 0.0001) greater bronchodilation than placebo. The bronchodilator effect, as measured by FEV1 (peak percent change, peak as a percent of predicted value, duration, and area under the curve) after two inhalations of salbutamol/CFC-free was clinically comprable to two inhalations of salbutamol/CFC, with no clinically meaningful differences in safety parameters between the two delivery systems or between different dose levels.\n These results suggest that salbutamol/CFC-free may offer a suitable alternative for salbutamol/CFC when the need arises to change from CFC-containing salbutamol products.", "To determine the protective effect of salbutamol, 100 microg, inhaled by different devices (pressurized metered-dose inhaler [pMDI; Ventolin; GlaxoWellcome; Greenford, UK], pMDI + spacer [Volumatic; GlaxoWellcome], or breath-activated pMDI [Autohaler; 3M Pharmaceuticals; St. Paul, MN]) on bronchoconstriction induced by methacholine.\n Randomized, double-blind, cross-over, placebo-controlled study.\n Eighteen subjects with stable, moderate asthma, asymptomatic, receiving regular treatment with salmeterol, 50 microg bid, and inhaled beclomethasone dipropionate, 250 microg bid, in the last 6 months, with high hyperreactivity to methacholine (baseline provocative dose of methacholine causing a 20% fall in FEV(1) [PD(20)] geometric mean [GM], 0.071 mg). Subjects were classified into two groups: subjects with incorrect (n = 5) pMDI inhalation technique, and subjects with correct (n = 13) inhalation technique.\n After cessation of therapy for 3 days, all subjects underwent four methacholine challenge tests, each test 1 week apart, each time 15 min after inhalation of salbutamol, 100 microg (via pMDI, pMDI + spacer, or Autohaler), or placebo. The protective effect on methacholine challenge test was evaluated as the change in the PD(20), and expressed in terms of doubling doses of methacholine in comparison with placebo treatment.\n The PD(20) was significantly higher after salbutamol inhalation than after placebo inhalation, but no significant difference was observed among the three different inhalation techniques. Only when salbutamol was inhaled via pMDI + spacer, PD(20) was slightly but not significantly higher (pMDI GM, 0.454 mg; pMDI + spacer GM, 0.559 mg; and Autohaler GM, 0.372 mg; not significant [NS]) than other inhalation techniques. Similar results (mean +/-SEM) were obtained with doubling doses of methacholine (pMDI, 2 +/- 0.47; pMDI + spacer, 3 +/- 0.35; and Autohaler, 2.4 +/- 0.40; NS). No significant difference was found among techniques when subjects with correct or incorrect inhalation technique were separately considered.\n Our data show that the protective effect of salbutamol, 100 microg, on methacholine-induced bronchoconstriction is not affected by the different inhalation techniques, although inhalation via pMDI + spacer tends to improve the bronchoprotective ability of salbutamol. These data confirm the clinical efficacy of salbutamol, whatever the device, and the patient's inhalation technique.", "This study compares the efficacy and safety of one and two actuations of albuterol sulfate powder delivered via a breath-actuated, effort-assisted, investigational inhaler (Spiros, Dura Pharmaceuticals, Inc) and albuterol delivered via a conventional propellant-driven metered dose inhaler (Ventolin, Glaxo, Inc).\n Randomized, double-blind, placebo-controlled, 5-way crossover study.\n Sixty patients with mild-to-moderate asthma (FEV1 59% predicted) were enrolled and 44 completed the study.\n FEV1 values over 6 hours were analyzed by ANCOVA and the Finney relative potency model. The relative potency of the inhalers (albuterol MDI: albuterol DPI) was 1.132 (90% CI, 0.680 to 2.252) indicating 1.132 actuations of albuterol MDI provided the same bronchodilation as one actuation of albuterol DPI. ANCOVA analyses further indicated that there were no significant differences between the two delivery systems with respect to FEV1, FVC, FEF25-75%, or PEF. Both inhalers had similar effects on serum potassium levels, QTc interval, blood pressure, and heart rate.\n In patients with mild-to-moderate asthma in this study, the albuterol DPI was determined to be therapeutically comparable to albuterol MDI in the delivery of one and two actuations of albuterol.", "Nine adult asthmatics took part in a cumulative dose response comparison of fenoterol (Berotec) inhalation powder and fenoterol metered dose inhaler. The study was carried out as a double-blind investigation using a double-dummy technique. No significant difference was observed in the lung function, in tremor or pulse rate on comparison of the two modes of administration. It is concluded that fenoterol inhalation powder is an effective and freon-free alternative to the metered dose inhaler.", "Short-acting inhaled beta2-agonists used just prior to exercise are an effective method for preventing exercise-induced bronchoconstriction (EIB) in children. This was a randomized, single-blind, placebo-controlled, four-period crossover study that compared the effectiveness of albuterol formulated in hydrofluoroalkane-134a (HFA) to albuterol formulated in chlorofluorocarbons (CFCs) and to placebo in protecting asthmatic children age 6-11 from EIB. Patients self-administered either HFA albuterol, two different CFC albuterol products, or placebo 30 min prior to exercise challenge. Spirometry was performed predose and 5, 10, 15, 30, 45, 60, 75, and 90 min after the exercise challenge was completed. The smallest percent change from the predose forced expiratory volume in 1 sec (FEV1) after exercise challenge was similar for the three active treatments, and each of the active treatments was significantly better than placebo. Each active treatment had significantly fewer patients unprotected from EIB (unprotected defined as having >20% fall in FEV1 after exercise challenge) than placebo. Changes in heart rate, blood pressure and electrocardiogram (ECG) intervals were similar for the three active treatments following exercise. HFA albuterol is as effective as albuterol products formulated in CFCs and more effective than placebo in protecting asthmatic children from EIB.", "We compared the bronchodilator response of terbutaline delivered either by a dry powder inhaler, the Turbuhaler, or by a metered-dose inhaler attached to a Nebuhaler inhaler in 10 children with stable asthma who were 3 to 6 years of age. The bronchodilator response did not differ between the two inhalational devices. The dry powder inhaler Turbuhaler is a suitable alternative to a metered-dose inhaler in the delivery of terbutaline to preschool children with stable asthma if adequate inhalational technique is used.", "During the 1970s, scientists suggested that the growing use of chlorofluorocarbons (CFCs) was contributing to depletion of the stratospheric ozone layer with potentially harmful results. A committee on the ozone layer organized the preparation of the Montreal Protocol. This protocol mandated the cessation of production and use of CFCs by January 1, 1996. The primary exemption to this ban is for the use of CFCs as propellants in metered dose inhalers (MDIs) for the treatment of asthma. Suitable replacement hydrofluoroalkane (HFA) propellants, such as HFA-134a, for use in MDIs have been identified. Albuterol, a selective beta-adrenergic agonist, currently widely available for inhalation asthma therapy, has been reformulated in HFA-134a (Proventil HFA). OBJECTIVE; To compare the efficacy of Proventil HFA to Ventolin, Proventil, and placebo (HFA-134a) MDI in protecting asthmatic patients from exercise-induced bronchoconstriction.\n This was a randomized, single-blind, placebo-controlled, 4-period crossover study of asthmatic patients with documented exercise-induced broncho-constriction. Twenty patients self administered two puffs of either Proventil HFA, Ventolin, Proventil or placebo, from an MDI, 30 minutes prior to performing a standardized exercise challenge at the study site. Spirometry was performed predose and 5, 10, 15, 30, 45, 60, 75, and 90 minutes after completion of the exercise challenge. Heart rate and blood pressure were measured just prior to spirometry and a 12-lead ECG was performed 15 minutes after completion of the exercise challenge for measurement of the QT corrected interval.\n The primary efficacy variable was the smallest percent change from the predose FEV1 following exercise. The smallest percent change from predose FEV1 for Proventil HFA was 2.0 +/- 9.9 SD, similar to the 2.0 +/- 11.4 SD for Ventolin, and the 3.6 +/- 10.2 SD for Proventil. The smallest percent change from predose FEV1 for each of the active treatments was significantly different from placebo, -23.7 +/- 14.5. Twelve of the patients had a > or = 20% fall in FEV1 post-exercise with placebo pretreatment, but only 1, 1, and 0 had > or = 20% FEV1 falls after treatment with Proventil HFA, Ventolin, and Proventil respectively. Changes in heart rate, blood pressure and QT corrected interval were similar for the three active treatments following exercise.\n Proventil HFA provides protection against exercise-induced bronchoconstriction comparable to Ventolin and Proventil and protection superior to placebo. Proventil HFA has a safety profile similar to Ventolin when used to prevent exercise-induced bronchoconstriction.", "Eleven adult asthmatics were given fenoterol either as a metered aerosol dose or as an inhaled powder with appropriate controls, in a randomised double-blind fashion. The increase in FEV1 was the same after both dosage forms and no side effects occurred indicating that powder inhalation is a safe and effective alternative to aerosol inhalation in the treatment of asthma with sympathomimetics.", "Twenty adult patients with stable asthma were treated with cumulatively increasing doses of salbutamol delivered from a metered dose inhaler (MDI) and from a novel multiple dose powder inhaler (MDPI), Easyhaler, in a randomized 3-period crossover study. Four doses of salbutamol (delivered doses to the patient: 90, 90, 180, 360 micrograms; cumulative dose of 720 micrograms) were administered during each of the three study days and were inhaled every 30 minutes. Drug doses were released from the powder inhaler either before or during inhalation. Spirometry was performed at the beginning of each study day and 20 minutes after each dose. The lung function parameters after cumulative dosing of salbutamol were equal during each study day. The maximal percentage changes in forced expiratory volumes in one second after 720 micrograms of salbutamol were 24% with the MDI and 23% and 24% with the Easyhaler inhaler, respectively. Ten patients reported mild side effects when using the MDI, three when the powder was released before inhalation and five when the MDPI was actuated during inhalation. No significant changes in heart rate or blood pressure were observed during the study. We conclude that the novel multiple dose powder inhaler is clinically equally effective and slightly better tolerated than conventional metered dose inhaler when equal doses of salbutamol are inhaled by asthmatic patients.", "The development of new inhalation devices for asthma drugs raises the issue of the relationship between pulmonary deposition and therapeutic effect of inhaled drugs in patients with obstructive lung diseases. We thus conducted a randomized, double-blind and double-dummy, four-period crossover study in 13 patients with moderate asthma (mean age 36 yr; FEV1 59% of predicted), who inhaled 0.25 and 0.5 mg terbutaline sulphate on separate occasions either via a pressurized metered dose inhaler (pMDI) or Turbuhaler (TBH). Pulmonary deposition was 8.1 +/- 2.7% and 8.3 +/- 2.3%, respectively, of the nominal dose for pMDI and 19.0 +/- 7.3%, and 22.0 +/- 8.1% for TBH. The FEV1 increase after 0.25 mg terbutaline sulphate via TBH was significantly greater than after 0.25 mg via pMDI. No significant differences in FEV1 increase were observed between 0.25 mg via TBH, 0.5 mg via pMDI, or 0.5 mg via TBH. Other lung function variables showed similar dose- and device-related changes. We concluded that: (1) the dose of terbutaline sulphate deposited in the lungs is dependent on which inhalation system is used; (2) TBH delivers about twice the amount of drug to the lungs as the pMDI; and (3) the observed difference in deposition is reflected in the bronchodilating effect.", "The phasing out of chlorofluorocarbons (CFCs) requires the development of an alternative non-ozone depleting propellant for use in pressurized metered dose inhalers (pMDIs). The present study assessed the effects on tolerability and efficacy of a switch from the currently available formulation containing the CFC propellants 11 and 12 to an alternative non-CFC formulation using the propellant hydrofluoroalkane (HFA) 134a in patients with mild to moderate asthma. After a 4-week run-in period during which patients received salbutamol 200 microg four times daily from a CFC pMDI, 547 patients were randomized to 12 weeks of treatment with salbutamol 200 microg four times daily administered from either an HFA 134a pMDI (Ventolin CFC-free; 277 patients) or CFC pMDI (Ventolin, 270 patients). At the end of this period, all patients then received a further 4 weeks of treatment with the same dose of salbutamol via a CFC pMDI (run-out period). On the basis that high doses of beta2-agonists are known to increase heart rate, change in heart rate was selected as the primary outcome variable. Small increases in heart rate were observed during the treatment period and these changes were comparable in both groups; the 90% confidence interval for the treatment differences was within the predefined limits for clinical equivalence (+/- 10 beats min(-1)). The incidence of adverse events was similar in both groups and there were no reports of paradoxical bronchospasm. Furthermore, daily PEF measurements showed comparability in terms of lung function. Symptom scores and use of additional bronchodilator were also similar in both groups. These results demonstrate that salbutamol (800 microg day(-1)), formulated with HFA 134a is equivalent to the current CFC formulation in terms of tolerability and efficacy.", "The aim of this study was to compare the efficacy of 100 micrograms of salbutamol inhaled from a new metered-dose powder inhaler (MDPI, Leiras Taifun, Finland) with that of a same dose of salbutamol inhaled from a conventional pressurized metered-dose inhaler with a large volume spacer (pMDI + S) in protecting against methacholine (Mch) induced bronchoconstriction. This was a 3 day, randomized, cross-over, partly blinded, placebo-controlled multicentre study where the pMDI + S was used as an open control. Twenty-six asthmatic outpatients with a baseline FEV1 > or = 60% of predicted and with bronchial hyperreactivity (PD20 FEV1 < or = 890 micrograms of Mch) were studied. On each study day the patients underwent an Mch provocation 30 min after inhaling placebo from the MDPI or a dose of 100 micrograms of salbutamol from the MDPI and from the pMDI + S. PD20 FEV1 and dose-response slope [DRS; maximal change in FEV1 (%)/dose of Mch (mumol)] were used to evaluate efficacy. The median values of PD20 FEV1 were 250, 622 and 1737 micrograms after placebo MDPI, salbutamol pMDI + S and salbutamol MDPI, respectively. The corresponding DRS values were -11.0%, -4.5% and -2.0% mumol-1. With both parameters, all differences were statistically significant (P < 0.05). In conclusion, 100 micrograms of salbutamol inhaled from Leiras Taifun MDPI offers better protection against Mch-induced bronchoconstriction than 100 micrograms of salbutamol from a pMDI connected to a large volume spacer device.", "The metered-dose inhaler is currently one of the most prescribed methods of delivering drugs to the lungs. In the United States, most currently marketed metered dose inhalers use chlorofluorocarbons as the system propellant and require patient breath coordination. These factors lead to the need for a delivery system that is independent of propellants and patient coordination.\n To compare the magnitude and time course of bronchodilation between albuterol delivered by Ventolin metered dose inhaler and albuterol sulfate powder (Rotacaps) delivered by a novel dry powder inhaler that generates a respirable drug aerosol over a range of inspiratory flow rates.\n A single-center, single-dose, randomized, placebo-controlled, partial-blind, 3-way crossover study was conducted in an outpatient asthma Clinical Research Center. Twelve mild to moderate asthmatic patients 12 to 36 years of age participated in this study that involved three treatments, each separated by three to eight days, consisting of 2 puffs (90 micrograms/puff) albuterol by Ventolin metered-dose inhaler, two inhalations (100 micrograms/puff) albuterol sulfate powder (Rotacaps) by dry powder inhaler, and two inhalations (12.5 mg/inhalation) lactose powder by dry powder inhaler. Spirometry, blood pressure, and heart rate were measured at 30 minutes, 15 minutes, and immediately before treatment and then at 15, 30, 45, 60, 90, 120, 180, 240, and 300 minutes after each treatment. Serum potassium and glucose, and electrocardiograms were measured at 30 minutes before, and 30, 60, 90, and 180 minutes after each treatment. Endpoints were compared with analysis of variance.\n Five patients (one metered-dose inhaler and four dry powder inhaler) did not respond with > 15% FEV1 increase over baseline within 30 minutes. Metered-dose inhaler and dry powder inhaler mean FEV1 results, respectively, for 11 and 8 responders were 15 minutes in onset, 202.9 and 185.4 minutes in duration, 24.8% and 25.1% maximum change, and 18.6 and 18.2 area-under-FEV1-bronchodilation-curve. Statistical analysis of all patients and responders-only revealed both active treatments to be different from placebo (P = .0018), but not different from each other (P = .1291). No safety endpoints were significantly different among all three treatments (P > .10 for all safety endpoints).\n In this study, the dry powder inhaler safely and effectively delivered a commercially available albuterol sulfate powder (Rotacaps) into human lungs with bronchodilation comparable to Ventolin metered-dose inhaler.", "To compare the bronchodilator effectiveness of albuterol reformulated in the chlorofluorocarbon-free propellant hydrofluoroalkane (HFA)134a (Proventil HFA) to that of Ventolin and HFA placebo over 12 weeks of regular dosing.\n Randomized, double-blind, double-dummy, parallel group, placebo-controlled, multi-center trial of asthmatics requiring inhaled beta-adrenergic bronchodilators for symptom control.\n Treatment qid with Proventil HFA, Ventolin, or HFA-134a placebo for 12 weeks.\n At weeks 0, 4, 8, and 12, spirometry was performed predose and serially over 6 h after dosing with study drug. Bronchodilator efficacy variables, based on FEV1 response to study drug, were proportion of responders, time to onset of effect, peak percent change, time to peak effect, duration of effect, and area under the curve (AUC).\n Demographic and baseline characteristics were similar for patients randomized to Proventil HFA (193), Ventolin (186), and HFA-134a placebo (186). No significant differences were found between the Proventil HFA and Ventolin treatment groups for any FEV1 efficacy variable, either predose or during 6 h of serial spirometry, at weeks 0, 4, 8, and 12. For all efficacy variables, except time to onset of effect, the Proventil HFA and Ventolin results were significantly greater than placebo. Time to onset of effect for the HFA-134a placebo group is misleading; only 13 patients (7%) were found to be responders in the intent-to-treat database. These efficacy results were found to be consistent across subgroup analyses of inhaled and nasal corticosteroid use, age (18 to 35 and 36 to 66 years), sex, race, weight (<60, 60 to 100, and >100 kg), and baseline FEV1 (< or =55% and >55% predicted). The peak FEV1 effect, duration of FEV1 effect, and AUC for FEV1 were all significantly smaller at weeks 4, 8, and 12 than week 0 for both the Proventil HFA and Ventolin treatment groups.\n Proventil HFA provided bronchodilation comparable to Ventolin and superior effects to HFA-134a placebo over 12 weeks of regular dosing. There was a diminution in bronchodilator response to both Proventil HFA and Ventolin after 4 weeks of use.", "The short-term bronchodilator effects of dry salbutamol powder and a pressurized salbutamol aerosol were compared in 22 patients with severe asthma, on 3 consecutive mornings, in a double-dummy cross-over study. Only patients with peak expiratory flow (PEF) rate lower than 250 l/min, were recruited. PEF measurement was employed to assess changes in ventilatory function induced by inhalation of the drugs. No significant difference was found between the PEF changes induced by the dry salbutamol powder (400 micrograms) and the pressurized aerosol (200 micrograms). Both forms of the drug produced a significant rise in mean PEF values. The study shows that even in asthmatic patients with poor ventilation, a dry powder inhaler and pressurized aerosol are effective means of drug delivery to the lungs.", "The present study compared the bronchodilating effect of inhalation from the Turbuhaler (0.5 mg terbutaline x 2) with the effect of inhalation from the chlorofluorocarbon (CFC) inhaler (0.25 mg terbutaline x 4) in children aged 9-17 years with reproducible, exercise-induced asthma (EIA). The treatments were given on two occasions, 5 min apart (terbutaline 0.5 mg + 0.5 mg). The study was performed as a double-blind, double-dummy, and placebo-controlled trial in 12 asthmatic children. The study was conducted on three separate days. The bronchoconstriction was induced by steady running on a treadmill. Forced expiratory volume in 1 s (FEV1.0), vital capacity (VC), and volume of trapped gas (VTG) were measured before and after the exercise test and after treatment. The study showed that the same amount of terbutaline inhaled from the Turbuhaler or from a CFC inhaler is equally effective for reversing EIA, and that the Turbuhaler is possibly more effective for treating spasm in small airways.", "A randomized double-blind, triple crossover study was conducted on 20 asthmatic patients (7 males and 13 females; age 40.9 +/- 14.2 Caucasians, 11 blacks, and 1 oriental. Criteria for admission included FEV1 < or = 80% of predicted when inhaled beta-agonists were witheld for at least 6 hrs and oral beta-agonists for 12 hr, in addition to at least 15% increase in FEV1, 15 min after treatment with albuterol with spacer delivery. Each of the study patients were tested on each of 3 separate days (within the same week) at baseline, 15, 30, 60, 120, 180, 240, 300, and 360 min post treatment. On each day albuterol was delivered by one of the 3 delivery devices and the other two methods delivered placebo. Albuterol was administered at the maximum recommended dosages of two puffs for MDI. Two puffs for MDI with spacer, and two capsules for Rotahaler. Spirometry, blood pressure and heart rate were measured at each testing interval. The mean percentage in FEV1 was higher in Rotahaler group compared to MDI with spacer (p < 0.001) and no significant difference in FEV1 was found between Rotahaler and MDI alone (p = 0.31). No significant changes in heart rate or blood pressure were associated with albuterol delivery by any of the three methods. Albuterol inhaled as a microfine powder was more effective than the same drug delivered as an aerosol by either MDI or MDI with spacer.", "In a double-blind cross-over study, 12 patients with reversible airways obstruction were treated with 200 micrograms salbutamol base in aerosol or 400 micrograms of powder following methacholine-induced bronchoconstriction. Salbutamol was inhaled either from a conventional metered dose inhaler (MDI) or from an inhaler (Diskhaler) utilizing the powdered form of the drug. The efficacy of both forms was identical whether assessed in terms of FEV1 or vital capacity. The ratio of the increase in FEV1 or vital capacity after bronchodilatation to the decrease during the prior bronchoconstriction was 1.4, indicating that both FEV1 and vital capacity improved over baseline following bronchodilatation. In six subjects, the onset of action of the powder form was more rapid, and in four the MDI acted more rapidly. In the group as a whole, the mean time constant for the action of salbutamol was identical (3.8 min) for the two forms. It is concluded that salbutamol powder has a similar efficacy and time course of action as the aerosol, probably because both formulations produce similar sized particles of the drug.", "As a result of the pending ban on chlorofluorocarbon production, the non-chlorofluorocarbon propellant 1,1,1,2-tetrafluoroethane (HFA-134a) is being evaluated as a replacement for CFCs in metered-dose inhalers.\n This cumulative dose response study compared the safety and bronchodilator efficacy of 16 cumulative inhalations of albuterol sulfate in an HFA-134a, CFC-free propellant system (108 microg of albuterol sulfate, equivalent to 90 microg of albuterol base) with that of equivalent doses of albuterol in a conventional CFC propellant system.\n Twenty-two patients with at least a 12-month history of stable asthma, who were currently taken an inhaled beta-adrenergic bronchodilator, and who had a FEV1 between 40% and 80% of predicted, were enrolled in this randomized, modified-blind, two-period crossover study. One, 1, 2, 4, and 8 inhalations of study drug were self-administered at 30-minute intervals, resulting in 16 cumulative inhalations. Pulmonary function and safety measures were assessed after each dosing interval.\n A significant dose response was found for HFA-134a albuterol sulfate and CFC albuterol with regard to changes in FEV1, serum potassium, heart rate, and blood pressure after 16 cumulative inhalations. No significant differences were demonstrated between HFA-134a albuterol sulfate and CFC albuterol for any FEV1 or safety parameter at any cumulative dose level. No clinically meaningful laboratory or physical examination abnormalities were found with administration of either HFA-134a albuterol sulfate or CFC albuterol.\n HFA-134a albuterol sulfate provides bronchodilation comparable to CFC albuterol and has a similar safety profile.", "The purpose of this study was to determine the safety and effectiveness of albuterol aerosol 180 micrograms and albuterol powder 200 micrograms in the prevention of exercise-induced bronchospasm in children. Forty-six patients aged 4-11 years with asthma and exercise-induced bronchospasm were enrolled in this randomized, double-blind, single-dose, three-way crossover study comparing albuterol aerosol, albuterol powder, and placebo. Exercise challenge was performed at the screening visit for qualifying and baseline determinations of pulmonary function and then 15 min after drug administration at each of three visits. Prevention of exercise-induced bronchospasm was assessed by comparing across all treatment groups the percentage change in FEV1 from pre- to postexercise, the percentage of patients protected by treatment, postexercise minimum FEV1, and postexercise change in FEV1. Safety was assessed by observation of clinical adverse events, laboratory tests, physical examination, electrocardiogram and rhythm strips, vital signs, and pulmonary auscultation. Forty-four patients completed the study. Mean postexercise FEV1 decreased 6% from preexercise values when patients were treated with either albuterol formulation; FEV1 decreased 23% when patients were treated with placebo. Exercise-induced bronchospasm was prevented in 95% of patients when treated with albuterol powder, in 91% treated with albuterol aerosol, and in 57% treated with placebo. Patients maintained significantly higher mean minimum FEV1 values after treatment with albuterol powder and albuterol aerosol than when treated with placebo. Treatment with either albuterol formulation produced a significantly smaller decrease in mean FEV1 from pre- to postexercise than treatment with placebo. No drug-related adverse events were reported, and safety assessments were within normal limits.(ABSTRACT TRUNCATED AT 250 WORDS)", "Metered-dose inhalers (MDIs) are extensively used to deliver drugs to the lungs but are driven by chlorofluorocarbon (CFC) propellants. The worldwide phasing out of CFCs within the next 5 to 10 years presents difficulties to the pharmaceutical industry. The mean +/- SD relative lung bioavailability of albuterol to the lung following inhalation of 400 micrograms of albuterol from an MDI, the Rotahaler and Diskhaler in 10 well-trained volunteers, was 2.83 (0.78), 1.72 (0.99), and 2.64 (1.23)%, respectively, expressed as a percentage of the nominal dose. The delivery of albuterol to the lungs from the MDI and Diskhaler was similar. In nine asthmatic subjects, the relative lung bioavailability of albuterol following inhalation with the MDI and Diskhaler was 1.19 (0.79) and 2.38 (1.46)%, respectively, expressed as a percentage of the nominal dose. There was no difference in reversibility 30 min after administration of the dose by the two methods. Similar lung deposition from the Diskhaler in volunteers probably is due to efficient MDI technique, which was absent in the asthmatic subjects. The Diskhaler does not rely on coordination during inhalation and therefore is easier to use.", "Chlorofluorocarbons (CFCs) used as propellants in metered-dose inhalers deplete stratospheric ozone, which results in serious public health concerns. Albuterol has been reformulated in the non-ozone-depleting propellant, hydrofluoroalkane-134a (HFA albuterol).\n The primary objective was to compare the safety of HFA albuterol to an albuterol product formulated in chlorofluorocarbon propellants (CFC albuterol) during 1 year of treatment in asthmatics. Bronchodilator efficacy of the two products was assessed as a secondary objective.\n The results from two open-label, parallel-group trials of similar design in asthmatics requiring short-acting beta-agonists for symptom control were combined. Patients took two puffs bid of either HFA albuterol or CFC albuterol for 1 year. Additional puffs of study drug were allowed as needed to control asthma symptoms. Adverse events were recorded at clinic visits. Patients self-administered study drug at quarterly visits and underwent serial spirometry during a 6-h period postdose. Bronchodilator efficacy variables, based on FEV1 response to study drug, were proportion of responders, time to onset of effect, peak percent change, time to peak effect, duration of effect, and area under the curve. Differences between products and changes over time in efficacy variables were assessed using an analysis of variance model. Regression analyses with FEV1 as a covariate were performed post-hoc to analyze changes in bronchodilator efficacy over time.\n Demographic and baseline characteristics were similar for patients receiving HFA albuterol (n = 337) and CFC albuterol (n = 132). Total reported adverse events were similar for the two treatments. Differences in only four individual adverse events were noted: the HFA albuterol group reported more gastroenteritis and dizziness; the CFC albuterol group reported more epistaxis and expectoration. Adverse events attributed to study drug use were infrequent. No serious adverse events were related to study drug use. Predose FEV1 at quarterly visits increased to a small extent in both groups from month 0 to month 12. The bronchodilator efficacy of HFA albuterol was comparable to that of CFC albuterol at the quarterly visits, but decreased from baseline for both products over the 12 months of treatment. Use of inhaled corticosteroids, nasal corticosteroids, or theophylline did not explain the increase in predose FEV1 over time and did not protect patients from developing reduced bronchodilator efficacy by month 12. The change in predose FEV1 did not entirely account for the reduced bronchodilator efficacy over time.\n HFA albuterol has a safety profile similar to that of CFC albuterol during chronic, scheduled use, and both drugs are well tolerated. HFA albuterol and CFC albuterol provided comparable bronchodilator efficacy, but bronchodilator efficacy decreased for both products with 1 year of use.", "Chlorofluorocarbon (CFC) propellants deplete stratospheric ozone. Production and use of CFCs, except for certain critical exemptions, has been prohibited by the Montreal Protocol. Use of CFCs as propellants in metered-dose inhalers (MDIs) is still allowed, but the U.S. Food and Drug Administration is planning the transition to alternative propellants for use in MDIs. Hydrofluoroalkane-134a (HFA), a non-ozone-depleting propellant, has been used to reformulate albuterol (HFA albuterol). This study evaluates whether comparable safety and efficacy continues for 12 weeks after patients with asthma are switched from CFC albuterol to HFA albuterol. Patients with asthma stabilized on CFC albuterol during a 12-week safety and efficacy trial were randomized to either continue receiving CFC albuterol or to be switched to receive HFA albuterol in a yearlong safety and efficacy trial. Safety and efficacy were compared over the first 12 weeks of the yearlong trial between patients who had remained on CFC albuterol and those who had been switched to HFA albuterol. Bronchodilator efficacy was evaluated by serial spirometry for 6 hr after the patients self-administered the study drug in the clinic. Safety was assessed by measuring changes in pulse rate, blood pressure, and electrocardiogram (ECG) intervals after dosing with study drug, monitoring adverse events, and performing prestudy and poststudy laboratory testing and physical examinations. No significant differences in bronchodilator efficacy between the patients continuing to receive CFC albuterol and those switched to HFA albuterol were found in the 12 weeks after the switch. No differences between the two products were found for changes in pulse rate, blood pressure, and ECG intervals. Adverse event profiles were similar for the two products, except the patients remaining on CFC albuterol reported increased asthma symptoms and rhinitis significantly more often than the patients switched to HFA albuterol. No clinically meaningful changes in laboratory tests or physical examinations were found in either treatment group. Patients with asthma switched from CFC albuterol to HFA albuterol receive comparable bronchodilation with a similar safety profile as those continuing to receive CFC albuterol.", "Twenty-five patients with reversible airways obstruction inhaled salbutamol (200 micrograms) from the standard press and breathe-metered dose inhaler or a new breath-actuated metered dose inhaler (Aerolin in the Autohaler inhalation device; 3M Health Care Ltd.) in a single dose, double-blind, double-dummy, 2-period, cross-over study. Forced expiratory volume in 1 s, forced vital capacity and peak expiratory flow rate were measured in the 4-hour period after inhalation. The equivalence of the two inhaler devices was determined by analysis of the peak change and time to peak, with reference to the initial recorded baselines of the measured parameters. The efficacy of the two devices was very similar. The breath-actuated device is likely to benefit inhaler users who suffer from poor co-ordination of actuation and inhalation with a standard inhaler.", "The aim of this study was to evaluate the efficacy, safety and preference of pre-school children with regard to two different devices for treatment of bronchial asthma with terbutaline. Turbuhaler, a powder inhaler preloaded with pure terbutaline for inhalation, was compared with a pressurized metered dose inhaler, attached to a Nebuhaler. The study had an open, cross-over randomized design. Each treatment period consisted of 2 weeks. Diary cards were filled in every morning and evening by the parents regarding PEF, asthma symptoms, extra inhalations of terbutaline, and side effects. Twenty-one children (mean age 3.9 years) were included in the study. A highly significant (P less than 0.001) increase in peak expiratory flow (PEF) was obtained after inhalation with both devices. The PEF values in the mornings after inhalation of terbutaline with Turbuhaler were significantly higher (P = 0.046) than those with Nebuhaler. Further, the PEF baseline values in the evenings before inhalation were also significantly higher (P = 0.03) with Turbuhaler. No difference was found in asthma symptoms and extra medication between the two devices. Side effects were mild and few with both devices. The parents found Turbuhaler easier to handle and 19 of 21 preferred this device for future use.", "The aim of this study was to compare bronchodilator response and adverse effects of terbutaline when administered with the metered dose inhaler (MDI) Bricanyl and with the dry powder inhaler Bricanyl Turbuhaler (BT). Nine adult patients with bronchial asthma participated. The study was of an open crossover design. At 30-min intervals the patients inhaled increasing doses of terbutaline (0.25 mg to 5.0 mg cumulated) from either the conventional MDI or from the BT. After each inhalation FEV1, FVC, heart rate, muscle tremor and adverse effects were recorded. Both treatments, BT and MDI, resulted in a dose-related increase in lung function, without any statistical difference. Taste sensation, muscle tremor and increase in heart rate were observed in both groups. Because of the design of the BT one may assume that inhalation failure can be avoided.", "The efficacy of fenoterol powder (Berotec, Boehringer-Ingelheim) was investigated in ten patients with moderate or severe asthma. Double-blind comparison to placebo powder showed a significant difference (p less than 0.05) between 30 to 180 min after a single dose of 0.2 mg. There was no difference between fenoterol powder and aerosol (0.2 mg). No adverse effects were encountered.", "Two hundred and fifty eight adult patients with bronchial asthma participated in an open, parallel group study of 8 wks duration. During a 2 wk run-in period the beta 2-agonist terbutaline (0.5 mg q.i.d) was delivered via a pressurized freon aerosol, Bricanyl metered dose inhaler (MDI). During the following 6 wks, one third of the patients continued with MDI and two thirds with the same dose of terbutaline in the form of dry powder, Bricanyl Turbuhaler. There were no statistically significant differences in the increases in peak expiratory flow rate (PEFR) after inhalation between the two treatment groups. The asthma symptom scores decreased in the Turbuhaler group during the study but remained the same in the MDI group. No difference in use of extra trial medication during the day was found. During the night, the difference was statistically significant in favour of Turbuhaler (p less than 0.05). Turbuhaler was well accepted and easy to use. As compared with the MDI used during run-in, 50% of the patients in the Turbuhaler group preferred to use Turbuhaler and 26% MDI, whilst 24% had no preference. In conclusion, Turbuhaler was at least as effective as MDI during the whole Turbuhaler life-span (6 wks).", "The relative dose potency of cumulative doses of terbutaline sulfate inhaled via Turbuhaler and via a pressurized metered dose inhaler was estimated with respect to lung efficacy and systemic effect.\n The study was an open, crossover, randomized, multicenter study including 31 adult patients with asthma [forced expiratory volume in one second (FEV1), 65% of predicted]. The patients inhaled terbutaline doses of 0.125, 0.125, 0.25, 0.5, 1.0, and 2.0 mg (a total of 4 mg) at 30-minute intervals. Lung function [FEV1, forced vital capacity (FVC), forced expiratory flow at 75% of FVC (FEF75%), and peak expiratory flow (PEF)], and systemic effect variables (serum potassium, tremor, pulse, blood pressure) were monitored prior to the first inhalation and 15 to 25 minutes after each inhaled dose.\n The mean relative dose potency of terbutaline inhaled via Turbuhaler compared with pressurized metered dose inhaler was 1.5 (95% confidence interval: 1.2 to 1.8) with respect to FEV1 and serum potassium, respectively. The corresponding relative dose potencies for PEF, FVC, and FEF75% were 1.0, 1.2, and 1.6, respectively, with no statistically significant difference between the two devices. No differences between the devices were evident with regard to blood pressure and pulse.\n The results suggest that Turbuhaler is more efficient in the delivery of inhaled terbutaline to the lungs compared with the conventional pressurized metered dose inhaler.", "The purposes of this study were to estimate the relative dose potency (RP) of two formulations of salbutamol pressurized metered-dose inhalers (Proventil-HFA and Ventolin-CFC MDIs) to protect against methacholine bronchoconstriction, to validate this method and provide recommendations. The protective effects of 100-, 200-, and 400-micrograms doses of Proventil-HFA were compared with the same doses of Ventolin-CFC in 18 adult asthmatics (mean FEV1, 92% predicted; mean baseline PC20 methacholine, 1.8 mg/ml), in a dose-level blind, balanced, eight-period, crossover, placebo-controlled study. The log-transformed PC20 values after each dose of the drugs were compared by repeated-measures analysis of variance (ANOVA). A significant dose-effect was present (p < 0.0001). Using the Finney assay, the RP of Proventil-HFA compared with Ventolin-CFC was 1.08 (90% CI, 0.81-1.46) (80% power). This was also estimated using a nonlinear Emax model to validate the Finney method. The most precise estimate of RP was obtained with the comparison between 100- and 200-micrograms doses (RP, 1.00; 90% CI, 0.77-1.31). There were no adverse events resulting from the drugs or methacholine. We conclude that Proventil-HFA salbutamol is bioequivalent to Ventolin-CFC salbutamol. Bronchoprotection to methacholine is a valid method of demonstrating bioequivalence. By this method, 100- and 200-micrograms doses of salbutamol inhalations from an MDI will suffice.", "A randomized, double-blind, double-dummy crossover study on 42 asthmatics was carried out to compare the single dose effects of salbutamol administered from the widely used metered dose inhaler and a breath operated system (Diskhaler). The bronchodilator response (change in forced expiratory volume in the first second) was almost identical for the two systems. The Diskhaler system however, since it is breath operated, obviates the need for hand-breath coordination.", "There is some concern over the environmental consequences of chlorofluorocarbons (CFCs) used in pressurized metered-dose inhalers (p-MDIs). Turbuhaler was designed to deliver a drug as a dry powder without administering additives directly to the airways. The aim of this study was to evaluate the comparative irritant and bronchodilating effects of the same dose of terbutaline delivered by a p-MDI and via Turbuhaler. Ten symptomatic, asthmatic patients, with highly reactive airways (provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20) < 0.2 mg.ml-1), inhaled, on separate days, 0.25 mg terbutaline via p-MDI or Turbuhaler. Changes in airway calibre were followed as specific airways conductance (sGaw). On a third day, patients inhaled from a placebo p-MDI containing all constituents except terbutaline. The study was conducted in a single-blind fashion and in random order. There were no significant differences in baseline sGaw on any of the study days. Inhalation of terbutaline from the p-MDI produced a transient percentage fall in sGaw at 1 min, reaching a mean maximum +/- SD of 17 +/- 8% at 10 s and then returning to baseline value after 20 s, followed by a progressive increase in sGaw to a maximum of 39 +/- 45% above baseline at 45 min. In contrast, inhalation of terbutaline via Turbuhaler caused no significant bronchoconstriction (fall in sGaw, 3 +/- 16%) at 10 s and achieved a greater increase in sGaw, reaching 63 +/- 51% at 45 min, although just failing to reach statistical significance compared to terbutaline p-MDI inhalation.(ABSTRACT TRUNCATED AT 250 WORDS)", "In adults inhaling salbutamol via metered-dose inhalers (MDls) 200 microg doses are recommended, but with diskhalers the manufacturer advocates 400 rather than 200 microg doses. To assess this advice, a partially double-blind, placebo-controlled salbutamol dose response, crossover study (also incorporating MDI doses) was conducted in 12 mild/moderate asthmatics. After active treatment, mean peak expiratory flow rate (PEFR) increments yielded no clinically or statistically significant differences; compared to placebo, respective median differences in PEFR increments (95% Cls) were 10 (-10, 50), 20 (0, 50), and 15 (0, 30) following 400 and 200 microg via diskhalers and 200 microg via MDls. Diskhalers are a suitable alternative for patients with poor MDI technique, but the use of 400 rather than 200 microg salbutamol doses is not supported by evidence.", "The bronchospasmolytic effects of 40 micrograms ipratropium bromide (Atrovent) given either as an aerosol (2 puffs of 20 micrograms) or as a powder inhalation were compared in a double-blind cross-over study. Following a randomisation list the drug was given on 2 successive days to 20 patients with stable bronchospasm in whom it had previously been shown that the bronchial obstruction was reversible after administration of 40 micrograms ipratropium bromide as an aerosol (with an increase over the baseline value of the FEV1 of at least 15% 1 h after drug administration). The effects of the two presentations of ipratropium bromide were followed by respiratory function tests from 15 min to 6 h after administration of the drug. With both formulations excellent bronchospasmolytic effects were noted in each of the parameters measured. The peak of the effects was noted approximately 1 h after the inhalations. Six hours later there was still a significant improvement in comparison with the baseline values. There was no significant difference between the results with the two different formulations. Inhalation powder of ipratropium bromide was well tolerated and there were no complaints of irritation or coughing. It would appear, therefore, to be a valuable alternative to the pressure aerosol.", "In this multicenter, randomized, double-blind study comparing the efficacy and safety of aerosolized albuterol with the dry powder formulation, 231 patients with chronic reversible obstructive airway disease were randomly allocated to receive either placebo albuterol aerosol followed immediately by active albuterol powder (200 micrograms) or active albuterol aerosol (two puffs, 180 micrograms) followed immediately by placebo lactose powder four times a day for a period of 12 weeks. No statistically significant differences were found between the powder and aerosol formulations with respect to pulmonary function, length of time mean FEV1 remained greater than or equal to 15% above baseline, physicians' assessments of patients' clinical response, or patients' subjective symptom scores. There were also no significant differences between treatment groups in cardiovascular effects, laboratory values, or adverse events. Among patients who expressed a preference for one of the delivery systems, half preferred using the powder. Results of this study demonstrate that 200 micrograms of albuterol powder is as safe and effective as 180 micrograms of albuterol aerosol.", "This randomized, double-blind, parallel-group study compared the efficacy and tolerability of as-required salbutamol 100 microg administered from either a chlorofluorocarbon (CFC) pressurized metered dose inhaler (pMDI; Ventolin) or from a non-CFC hydrofluoroalkane (HFA) 134a pMDI (Ventolin CFC-free) in patients with mild to moderate asthma. All patients (n = 423) continued with their standard asthma therapy, and recorded their daily use of study medication, morning and evening peak expiratory flow (PEF) and symptom scores, throughout the 4-week treatment period. Clinic lung function was measured at 2-week intervals. The median daily use of inhaled study medication remained constant at four actuations per day throughout the study in both treatment groups and statistical analysis indicated that the two formulations were equivalent. Small improvements in both treatment groups were reported in mean morning and evening PEF, clinic forced expiratory volume in 1 sec and clinic PEF and there were no significant differences between the two groups. Both formulations were well tolerated. This study indicates that as-required salbutamol 100 microg administered via a HFA 134a pMDI is as effective and safe as the currently available CFC-propelled formulation.", "To compare the long-term efficacy and safety of albuterol administration using a Spiros Inhalation System (Dura Pharmaceuticals; San Diego, CA) dry powder inhaler (DPI) and albuterol (Ventolin; Glaxo Wellcome; Research Triangle Park, NC) administration using a metered-dose inhaler (MDI) in patients with asthma.\n This was a phase III, 12-week, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, multicenter study of 283 adolescent and adult patients with mild to moderate asthma. The patients were randomized into one of three treatment groups: the Spiros group, who were given 108 microg/actuation of albuterol sulfate equivalent to 90 microg of albuterol base; the MDI group, who were given 90 microg/actuation of albuterol; and the placebo group.\n Over the length of the study, the Spiros and MDI groups were comparable in all FEV1 parameters. Both active treatment groups were superior to the placebo group for each FEV1 parameter at all visits. With the exception of differences at treatment week 0 for the maximum percent change in the FEV1, the duration of effect, and the area under the curve at baseline, there were no statistically significant differences between the Spiros and MDI groups for any FEV1 parameters. Using a repeated-measures analysis, the FEV1 parameters at week 0 for the Spiros group were not statistically significantly different from the parameters at weeks 4, 8, and 12. The same analysis effect at week 0 for the MDI group was greater for maximum percent change in the FEV1 from baseline (weeks 4, 8, and 12) and duration of effect. Adverse events and changes in clinical laboratory values, vital signs, ECG results, and physical examinations were reported with similar incidence in each of the three treatment groups.\n Both active treatments were superior to the placebo treatment. The Spiros DPI was well tolerated and was as effective as the albuterol MDI in treating patients with moderate asthma.", "A comparison was performed between inhalation of salbutamol as a powder aerosol or as a pressurized aerosol. Seven intrinsic asthmatics, well-trained in inhalation technique, were studied in an open randomized crossover comparison of the two different modes of administration. Five doses were inhaled of salbutamol from the pressurized aerosol, 0.1-2.4 mg, and five doses as a powder aerosol from a Rotahaler, 0.2-4.8 mg. The FEV1 dose-response curves were almost identical indicating bronchodilating equipotency between the two modes of administration. A preliminary report is given of the effects on morning cortisol of inhalation of beclomethasone dipropionate as a powder aerosol or as a pressurized aerosol in 10 healthy volunteers trained in inhalation technique. Morning cortisol decreased to the same degree after both modes of administration and the decrease was dose-dependent when beclomethasone dipropionate was given in the doses 200 micrograms, 500 micrograms and 1000 micrograms q.i.d. Thus, in patients with a good inhalation technique the powder aerosol does not seem to be better than the pressurized aerosol. We think, however, that it could be offered as an alternative to patients with poor inhalation technique.", "nan", "We have compared radioaerosol deposition pattern and bronchodilator response following inhalation of 100 micrograms of albuterol from a correctly used conventional metered dose inhaler (MDI) to those from Gentlehaler, a new compact low-velocity pressurized aerosol device (Schering Corporation), in a group of ten asthmatic patients (mean baseline FEV1 52 percent; reversibility > 15 percent). Whole lung deposition (mean 18.8 percent of dose by conventional MDI, mean 19.9 percent of dose by Gentlehaler), regional lung deposition, and bronchodilator response were similar for the two devices, but oropharyngeal deposition was halved by Gentlehaler. The spray velocity from Gentlehaler was less than 2 m s-1 compared with a velocity of greater than 30 m s-1 commonly found in the conventional device. Gentlehaler may therefore play a valuable role in inhalation therapy, notably by reducing \"cold Freon\" problems (respiratory inhibition) in pressurized aerosol delivery, and by reducing oropharyngeal losses of inhaled corticosteroids.", "A dose-ranging study and a 12-week treatment study were conducted in children with asthma, aged 4 to 12 years, to assess the efficacy and safety of albuterol inhaled as either an aerosol or as dry powder. Both studies were double-blind and placebo-controlled with randomized assignment to treatment. The dose-ranging study in 30 patients indicated that similar single doses of albuterol aerosol and powder had comparable effects with the intermediate doses (i.e., 180 micrograms of aerosol and 200 micrograms of powder) providing effective bronchodilation with minimal adverse effects. In the subsequent 12-week, parallel-group study, 204 children received albuterol as either aerosol, 180 micrograms, or powder, 200 micrograms four times a day. Both formulations were equally effective with no untoward cardiovascular effects and only one incident of mild tremor. Among those children who expressed a preference for one of the delivery systems, significantly more children preferred the powder (44% versus 26%, p less than 0.01). Albuterol taken four times a day as either aerosol or dry powder is both effective and well tolerated in children with asthma.", "Twelve adult asthmatic patients participated in an open, randomized, cross-over comparison between cumulatively increasing doses of terbutaline sulphate administered via the multiple dose powder inhaler (Turbuhaler) or via a pressurized inhaler. Turbuhaler and the pressurized inhaler showed equipotency both with respect to bronchodilatation and side effects. Both treatments produced a significant increase in pulmonary function measurements, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). No increase in pulse rate was seen with either treatment but there was an increase in tremor at higher doses with both treatments. Inhalation of beta-agonists via Turbuhaler seems to be an effective way of treating asthma.", "Salbutamol dry powder was compared with salbutamol aerosol in 38 asthmatic patients. The study was double-blind and took place over six months. Salbutamol powder in a dose of 200 micrograms per capsule was able to control asthma as well as the aerosol, but some patients needed to increase the frequency of dosage when using the powder. The device used for powder administration, the Rotahaler, was well accepted and was preferred to the pressurized aerosol by one-third of patients. Dry powder administered by Rotahaler allows salbutamol to be given by inhalation to many patients previously using aerosols inefficiently.", "In a two-day, randomised, double-blind, double-dummy, cross-over multicenter study, the bronchodilating effect of 100 micrograms of salbutamol (CAS 18559-94-9) inhaled from a new metered dose powder inhaler (MDPI; Taifun) was compared with that of an identical dose of salbutamol inhaled from a conventional pressurised metered dose inhaler connected to a spacer (pMDI + S). Thirty-six non-smoking, adult asthmatic outpatients with a baseline forced expiratory volume in 1 s (FEV1) between 35 and 70% of the predicted value participated in the study. After inhalation of the study medication pulmonary function, FEV1 and airway resistance (R(aw)), blood pressure (BP), and heart rate (HR) were measured up to 6 h. Area under the FEV1 vs. time curve (AUCFEV1) was used as the primary efficacy parameter, and the 90% confidence intervals (CI) were used to judge clinical equivalence. Other efficacy parameters were used in supportive analyses as secondary parameters. Both treatments produced a clear improvement in pulmonary function. The mean +/- SD AUCFEV1 were 893 +/- 281 and 889 +/- 2761.min after MDPI and pMDI + S, respectively. The 90% CI for the relative efficacy of the MDPI is from 98 to 103% of that of the pMDI + S. Also the other efficacy parameters gave similar results without significant differences: the mean +/- SD values of percent increase in FEV1 were 47.2 +/- 19.3 and 44.7 +/- 20.8, the maximum absolute value of FEV1 were 2.87 +/- 0.77 and 2.86 +/- 0.77, the maximum percent decrease in R(aw) 53.2 +/- 20.5 and 55.0 +/- 19.1, and the minimum absolute value of R(aw) 0.27 +/- 0.11 and 0.30 +/- 0.12 kPa.s.l-1 for the MDPI and pMDI + S, respectively. The salbutamol doses had no significant effect on BP or HR, and were equally well tolerated. Furthermore, 57.5% of the patients preferred the MDPI, 35% the pMDI + S, and 7.5% considered that there was no difference between the devices. In conclusion, this study demonstrates that the new MDPI is as effective and safe a device as a conventional pMDI connected to a spacer in administering inhaled salbutamol for asthmatic patients. Further, most patients considered the MDPI easier to handle, and preferred it over the pMDI + S.", "An open, crossover and randomized study was carried out to compare the safety and efficacy of salbutamol inhaled using the dry-powder inhaler Turbuhaler, and using a pressurized metered-dose inhaler (pMDI). Twelve patients with moderate to severe asthma, aged 47-68 years, were included in the study. On two separate days, patients received a total dose of 1600 micrograms of salbutamol administered in a cumulative dose fashion: 100, 100, 200, 400 and 800 micrograms at 3-min intervals. Salbutamol inhaled via Turbuhaler caused a larger decrease in serum potassium concentration than did salbutamol inhaled via pMDI. The estimated relative dose potency of the hypokalaemic effect of salbutamol Turbuhaler vs salbutamol pMDI was 2.0 with a 95% confidence interval of 1.3-3.6. Turbuhaler caused a small (but statistically significantly greater than with pMDI) increase in heart rate, QTc interval and tremor. Blood pressure was unaffected by the treatments. No adverse events of clinical relevance were reported. The estimated relative dose potency of the bronchodilating effect (FEV1) of salbutamol Turbuhaler vs salbutamol pMDI was 3.0 with a 95% confidence interval of 1.8-5.8. In conclusion, salbutamol inhaled via Turbuhaler was more potent and seemed to have a better therapeutic ratio than salbutamol inhaled via pMDI. Both treatments were equally well tolerated.", "Reversibility after administration of an inhaled bronchodilator is not always demonstrable in patients with asthma. Bronchodilator aerosol-induced bronchoconstriction has also been reported to occur in some patients.\n Fifteen selected patients showing < 10% improvement in forced expiratory volume in one second (FEV1) when tested with four doses of salbutamol (0.1 mg/dose) or terbutaline (0.25 mg/dose) from a pressurised metered dose inhaler (MDI) participated in two randomised, double blind studies. They received 2.0 mg terbutaline (4 x 2 doses of 0.25 mg) or a corresponding placebo from an MDI connected to a 750 ml spacer, and 1.0 mg (2 x 0.5 mg) terbutaline or placebo from a multidose dry powder inhaler free of additives (Turbohaler).\n Inhalation of placebo MDI resulted in a mean (SD) decrease in FEV1 of 20.5 (14.1)% (range -42.9% to +2.6%). In 14 patients inhalation of 2.0 mg terbutaline MDI with spacer resulted in < 10% improvement (mean increase 3.1 (6.0)%). One mg of terbutaline via a Turbohaler resulted in improvements in FEV1 of > 15% in eight patients (mean increase 16.0 (9.7)%). The improvement was < 10% in four patients. Use of placebo Turbohaler did not affect airway calibre (mean change 0.2 (2.9)%).\n Additives of MDIs may cause bronchoconstriction in some patients with asthma. In these patients inhalation from a pressurised metered dose inhaler is more likely to decrease the bronchodilator response than inhalation from an additive-free inhaler. The frequency of this phenomenon is unknown.", "Several breath-activated multidose powder devices for inhaled anti-asthma drugs are now available. Some of these inhalers have been argued to give higher drug deposition in the airways than conventional pressurized metered dose inhalers (pMDI). The aim of the present study was to compare the efficacy and safety of salbutamol given via pMDI or Turbuhaler (both 100 microgram per inhalation). Adult asthmatic patients of either sex (n = 22) and with reversible airflow obstruction were included in a randomized, placebo-controlled study. On the study days, salbutamol was given with increasing doses (200 to 3,200 microgram cumulative) or placebo, via pMDI or Turbuhaler. A dose-related increase in FEV1 was observed after administration of salbutamol given via either device, versus placebo. The improvement in FEV1 was similar whether salbutamol was given via pMDI or Turbuhaler, at microgram equivalent doses. After a total cumulative dose of 3,200 microgram, mean FEV1 for Turbuhaler was 2.98 (change from baseline of 23.1%), for pMDI 2.93 (change from baseline of 23.6%), and for placebo 2.36 (change from baseline of 0. 42%). Changes in potassium, glucose, and heart rate did not show any significant differences between pMDI and Turbuhaler. We conclude that the efficacy of salbutamol is comparable when the drug is given via the Turbuhaler or pMDI.", "Twenty-one adult asthmatic patients participated in a trial to compare the clinical equivalence of a single dose of salbutamol inhaled either from a novel multiple dose powder inhaler (MDPI), Easyhaler, or from a conventional metered dose inhaler (MDI). The trial was carried out as a randomized, double-blind, crossover study. The study involved 2 study days with a 6-hour follow-up period of spirometric indices. In addition, blood pressure and heart rate were measured immediately before each lung function test. Our data indicate that salbutamol treatment with the MDPI achieves values which are equivalent to those achieved with the conventional pressurized MDI as regards improving pulmonary function and tolerability. The mean maximum forced expiratory volume in 1 s (FEV1) after the powder dose was 2.44 +/- 0.96 liters and after the aerosol dose 2.45 +/- 0.93 liters. The mean area under the curve of absolute FEV1 values was 822 +/- 340 and 829 +/- 335, respectively. The mean percent change from the baseline in FEV1, forced vital capacity and peak expiratory flow following administration of the preparations was of equal magnitude in both cases. The treatments tested had no effect on blood pressure or heart rate and were well tolerated. A further important finding was that most patients found the MDPI easier or no more difficult to use than the conventional MDI and this probably facilitates the transition from pressurized MDIs to the novel MDPI.", "Forty-three children from 3-16 years of age suffering from moderate bronchial asthma completed a double-blind cross-over study on the clinical effect of inhaled salbutamol (Ventoline) powder (0.2 mg/dosis) compared with spray (0.1 mg/dosis) over two 4-week periods. Both administrations gave significant improvement in air flow meter (AFM) results. There was no significant difference between the periods on active powder or spray regarding daily symptom scores, adjuvant medication or AFM values. The powder caused cough in four children but in 12 of 28 children it was considered as easy or easier to accept as the spray; nine of these 12 children were younger than 10 years of age. It is concluded that salbutamol inhaled as a powder is a useful alternative when using a spray is difficult or unwanted.", "Nineteen patients with asthma completed an open, randomized, crossover study in which 0.5 mg terbutaline sulphate was administered either via Turbuhaler or via the metered dose inhaler (MDI) for 2-week periods. The clinical effect of the two treatment forms was comparable; both provided adequate bronchodilator therapy. Patients also considered Turbuhaler and MDI equally effective, with a small preference for the MDI. Turbuhaler seems to be a valuable alternative to bronchodilator MDI therapy.", "This study compares the safety and efficacy of HFA 134a salbutamol sulfate (Airomir in the 3M CFC-free system [3M Pharmaceuticals]) and CFC 11/12 salbutamol (Ventolin [Allen & Hanburys]) in a cumulative dose-response (1, 1, 2, 4, 8 inhalations at 30-min intervals) study in asthmatic patients.\n Randomized, single-blind, two-period cross-over study.\n Twenty-four stable mild to moderate asthmatics.\n At all cumulative inhalations, the changes in FEV1 (absolute, percent, and percent predicted) and FVC were equivalent. There was also no significant difference in heart rate, serum potassium level, BP, 12-lead ECG, Holter monitor recordings, or adverse events. Both HFA 134a salbutamol sulfate and CFC 11/12 salbutamol displayed a significant dose-response for FEV1, FEF25-75%, FVC, serum potassium, heart rate, and systolic BP.\n HFA 134a salbutamol sulfate and CFC 11/12 salbutamol produced clinically and statistically similar airway responses and side effects. These results indicate that HFA 134a salbutamol sulfate would be a safe and effective substitute for CFC 11/12 salbutamol.", "Twenty patients with asthma were studied. They were given either fenoterol powder or fenoterol MDI for 2-week periods using a double-blind cross-over design. Identical doses of fenoterol (0.2-0.4 mg 2-4 times daily) were given to an individual patient throughout the 4-week study period. Both forms of treatment produced an almost identical bronchodilation, and there were no statistically significant differences in symptoms or side effects. It is concluded that fenoterol powder and fenoterol aerosol are equally effective.", "In this study the bronchodilating effect of salbutamol (CAS 18559-94-9) after administration a single-dose (100 micrograms) from a novel multiple dose powder inhaler (MDPI; Easyhaler) and from a conventional metered dose inhaler (MDI) was compared. Forty adult asthmatic patients participated in a double-blind, randomized, cross-over, multicenter study with double-dummy technique. The study comprised two study days with a 4-h follow-up period of spirometric indices and measurements of blood pressure and heart rate. Both the powder and aerosol treatments caused a clear increase in spirometric parameters. The mean (SD) maximum forced exspiratory volume in one second (FEV1) after powder delivery was 2.82 (1.13) l and after aerosol 2.77 (1.03) l. The mean percentual change from the baseline in FEV1 was equal after both preparations. The mean area under the curve (AUC) of the absolute FEV1 values was 616 (264) and 609 (240) l x min after the powder and aerosol delivery, respectively. The treatments had no clinically significant effects on blood pressure or heart rate and were equally well tolerated. Thus the clinical effects indicate therapeutical bioequivalence of the powder and aerosol treatments. Furthermore, most patients found the handling of the MDPI device easier than or equal to that of the conventional MDI, which in all probability increase the patient compliance, which is one of the corner stones in the inhalation therapy of bronchial asthma.", "Two studies are presented, with the aim of establishing the dose potency ratio for salbutamol given via Turbuhaler and via a pressurized metered-dose inhaler (pMDI). Both studies were of a double-blind, randomized design. Outpatients with mild-to-moderate chronic reversible airway obstruction were given single doses of salbutamol administered via Turbuhaler and via pMDI. Efficacy and safety variables were measured before and during 6 h after each dose. The first study was a four-way crossover study including 12 patients. The salbutamol doses given were: 50, 100 and 2x100 microg via Turbuhaler and 2x100 microg via pMDI (Ventolin). The study showed that 2x100 microg of salbutamol inhaled via Turbuhaler is more potent than 2x100 microg salbutamol inhaled via a pMDI, and that 100 microg salbutamol via Turbuhaler is at least as potent as 2x100 microg salbutamol inhaled via a pMDI. The second study including 50 patients was a placebo-controlled five-way crossover, study. Two doses of salbutamol via Turbuhaler, 50 and 2x100 microg, and via pMDI, 100 and 2x200 microg, were given. There was a dose-dependent response in forced expiratory volume in one second (FEV1) for both inhalers. Adjusted for differences in baseline FEV1 values, the estimated relative dose potency for Turbuhaler versus pMDI was 1.98:1 (95% confidence interval 12-3.2). These studies showed that the same bronchodilating effect can be achieved when half the dose of salbutamol given via a conventional pressurized metered-dose inhaler is given via Turbuhaler.", "This study was designed to compare the bronchodilatatory effect of terbutaline inhaled through Turbuhaler (TH) or pressurized metered-dose inhaler (pMDI) in young asthmatics, and to assess the possible relationship between patients' inspiratory capacity and bronchodilatation for both devices. One hundred and eighteen asthmatics (aged 4 10/12-20 6/12 years) with bronchial obstruction (mean Vmax 50%: 59.5% pred, SD 17.8% pred) were allocated at random to two groups of 59 patients to inhale 0.5 mg terbutaline either by TH or by pMDI (and placebo by dummy of the other device). In- and expiratory spirometry and bodyplethysmography were conducted before and 10 min after inhalation. Bronchodilatation was effective [change in airways resistance (delta RAW) -50%, change in forced expiratory volume in 1 s (delta FEV1)+15%, delta Vmax 50% or 25% + 25% of baseline] in 41 of 59 patients with pMDI (69.5%) and 33 of 59 patients with TH (55.9%). The effect on Vmax 50% was significantly better with pMDI than with TH. Turbuhaler users with higher inspiratory flow [forced inspiratory volume in 1 s (FIV1), forced inspiratory flow at 50% vital capacity (FIF50)] reached better bronchodilatation, while bronchodilatatory effect was not correlated with inspiratory performance in MDI users. Peak inspiratory flow (PIF) did not correlate well with bronchodilatation by TH. When using TH for bronchodilatation, the effectiveness of terbutaline depends upon the degree of inspiratory capacity. This can lead to impaired bronchodilatatory effect in subgroups of obstructive young asthmatics with low inspiratory flow. In contrast, when using a pMDI, inspiratory capacity does not seem to influence the effectiveness of terbutaline.", "Comparison of the bronchodilator response to an albuterol novel dry powder inhaler (DPI) (Clickhaler [CH]; ML Laboratories PLC; St. Albans, UK) activated at various inspiratory flow rates and to an albuterol pressurized metered-dose inhaler (pMDI) by patients with moderate to moderately severe stable asthma.\n Randomized, double-blind, placebo-controlled comparison of the bronchodilator response to albuterol DPI (200 microg) at inspiratory flow rates of approximately 15, 30, and 60 L/min in patients with stable asthma with demonstrated reversibility to albuterol. Active (albuterol via pMDI inhaled at 30 L/min) and placebo controls were included.\n Single center study at the chest/allergy unit of a teaching hospital in Canada.\n Sixteen patients with moderate to moderately severe stable asthma.\n Efficacy end points were FEV1, FVC, FEV1/FVC, maximum expiratory flow, and forced expiratory flow between 25% and 75% of vital capacity. Safety end points included heart rate, BP, and tremor. There was no significant difference between the bronchodilator response to albuterol via the CH at 15, 30, and 60 L/min inspiratory flow rate and, at all flow rates, no significant difference was found comparing albuterol CH with the pMDI. All of the techniques for delivering albuterol provided significantly better bronchodilatation than placebo. Adverse events were minimal and did not differ between CH and pMDI or between the various flow rates inhaled through the CH.\n A novel passive albuterol DPI (CH) provides a similar bronchodilator response at 15, 30, and 60 L/min inspiratory flow rates compared with a pMDI used optimally.", "Salbutamol in a powder aerosol from the Rotahaler insufflator was compared, with equal doses of the conventional pressurized aerosol by dose-response curves and in a 1 month open trial, in the treatment of asthma patients with good inhalation technique. Results were not significantly different in either study. A further group of asthma patients, who were known to be incapable of using pressurized aerosols effectively, were shown to benefit from treatment with the Rotahaler. This device should increase the value of the sympathomimetic drugs to the minority of asthma patients who cannot use conventional aerosols correctly.", "Turbuhaler is a ready-loaded multiple dose inhaler which does not require co-ordination between release of dose and inhalation. 57 children with asthma participated in this clinical trial to compare the clinical effect and acceptance of terbutaline sulphate via Turbuhaler with that of metered dose inhaler (MDI). The trial consisted of two parts. In the first part of the study, which made use of a double-blind cross-over design, the clinical effect and number of treatment occasions with Turbuhaler were compared with those of MDI. In the second part, which was open, all patients were treated with Turbuhaler for 2 weeks. At the end of this period the patients were asked to make a subjective assessment of effect and to state their preference. There was no difference in clinical effect and number of treatment occasions between Turbuhaler and MDI. A majority of the patients thought Turbuhaler had the best effect and was easy to use." ]

[ "380367", "9469682", "9217519", "2686478", "16728906", "14512476", "15231557", "11476123", "1348161", "21537720", "16387219", "9892313", "1673123", "9248875" ]

[ "Acute high-dose parenteral haloperidol treatment of psychosis.", "A double-blind study of lorazepam versus the combination of haloperidol and lorazepam in managing agitation.", "Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective, double-blind, emergency department study.", "Efficacy of combinations of intramuscular antipsychotics and sedative-hypnotics for control of psychotic agitation.", "Risperidone versus haloperidol, in combination with lorazepam, in the treatment of acute agitation and psychosis: a pilot, randomized, double-blind, placebo-controlled trial.", "Rapid tranquillisation for agitated patients in emergency psychiatric rooms: a randomised trial of midazolam versus haloperidol plus promethazine.", "Rapid tranquillisation of violent or agitated patients in a psychiatric emergency setting. Pragmatic randomised trial of intramuscular lorazepam v. haloperidol plus promethazine.", "A double-blind, randomized comparison of the efficacy and safety of intramuscular injections of olanzapine, lorazepam, or placebo in treating acutely agitated patients diagnosed with bipolar mania.", "Alprazolam as a neuroleptic adjunct in the emergency treatment of schizophrenia.", "Rapid tranquilization for agitated patients in emergency psychiatric rooms: a randomized trial of olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone.", "Randomized clinical trial comparing intravenous midazolam and droperidol for sedation of the acutely agitated patient in the emergency department.", "Intramuscular flunitrazepam versus intramuscular haloperidol in the emergency treatment of aggressive psychotic behavior.", "Parenteral lorazepam versus parenteral haloperidol for the control of psychotic disruptive behavior.", "Efficacy of lorazepam and haloperidol for rapid tranquilization in a psychiatric emergency room setting." ]

[ "After 2 days of drug-free observation, 20 newly admitted psychotic patients received 20-35 mg of haloperidol intravenously and 20 patients received 30-40 mg of diazepam intravenously. Posttreatment ratings at 4 and 24 hours with the Brief Psychiatric Rating Scale and the Clinical Global Impressions revealed significant improvement in both groups but no significant differences between the two treatments.", "To compare the utility of intramuscular lorazepam (LZ) with the combination of intramuscular haloperidol (HDL) and LZ to control acutely agitated behavior.\n Randomized double-blind comparison.\n Psychiatric emergency service of a large, university-affiliated, municipal hospital.\n Twenty subjects treated on the psychiatric emergency service.\n Patients received an injection of either LZ 2 mg (11 patients) or HDL 5 mg plus LZ 2 mg (9 patients). The Overt Aggression Scale (OAS), visual analog scales reflecting agitation and hostility, and the Clinical Global Impressions (CGI) severity scale were administered at baseline and 30, 60, 120, and 180 minutes after the injection.\n Planned data comparisons included categoric assignment of patients as improved, as defined by decreases in outcome measures 60 minutes after the injection, as well as continuous variables up to 180 minutes after the injection. A significantly greater percentage of subjects receiving combined treatment improved on the specific measures 60 minutes after dosing (p<0.05). Kaplan-Meier survival analyses showed significant between-group differences in survival curves plotted for the entire study period (p<0.05). Repeated measures analyses of variance studying group differences showed that both groups improved over time, but between-group differences were not significant. The powers of these analyses were low due to the small sample. No serious adverse effects occurred in either treatment group.\n Our results suggest superior efficacy for HDL-LZ over LZ alone. Categoric tests of improvement at 60 minutes provided the strongest evidence of group differences.", "Rapid tranquilization is a routinely practiced method of calming agitated psychotic patients by use of neuroleptics, benzodiazepines, or both in combination. Although several studies have examined the efficacy of the three approaches, none have compared these treatments in a prospective, randomized, double-blind, multicenter trial. Ninety-eight psychotic, agitated, and aggressive patients (73 men and 25 women) were prospectively enrolled during an 18-month period in emergency departments in five university or general hospitals. Patients were randomly assigned to receive intramuscular injections of lorazepam (2 mg), haloperidol (5 mg), or both in combination. Patients in each treatment group received 1 to 6 injections of the same study drug within 12 hours, based on clinical need. They were evaluated hourly after the first injection until at least 12 hours after the last. Efficacy was assessed on the Agitated Behavior Scale (ABS), a modified Brief Psychiatric Rating Scale (MBPRS), Clinical Global impressions (CGI) scale, and an Alertness Scale. Effective symptom reduction was achieved in each treatment group with significant (P < .01) mean decreases from baseline at every hourly ABS evaluation. Significant (P < .05) mean differences on the ABS (hour 1) and MBPRS (hours 2 and 3) suggest that tranquilization was most rapid in patients receiving the combination treatment. Study event incidence (side effects) did not differ significantly between treatment groups, although patients receiving haloperidol alone tended to have more extrapyramidal system symptoms. The superior results produced by the combination treatment support the use of lorazepam plus haloperidol as the treatment of choice for acute psychotic agitation.", "The combination of haloperidol, 5 mg, and lorazepam, 4 mg, was both effective and safe for managing agitated behavior in an open trial with acutely psychotic patients. The combination also appeared to be superior to its individual components when studied in a randomized, nonblind trial. The principle of the combined use of antipsychotics and sedative-hypnotics was further tested by comparing two new combinations: thiothixene, 5 mg, and lorazepam, 4 mg, versus haloperidol, 5 mg, and phenobarbital sodium, 130 mg. These combinations had comparable efficacy and safety, and the level of transquilization approached that produced by the haloperidol-lorazepam combination in the preceding studies.", "To compare oral risperidone and intramuscular (IM) haloperidol, both in combination with IM lorazepam, in the management of acute agitation and psychosis in the medical emergency department.\n In this prospective, randomized, placebo-controlled, double-blind study of 30 patients presenting to the emergency department with acute agitation and/or psychosis, three groups of 10 patients received oral and IM medications: 1) 2 mg oral risperidone and 2 mg IM lorazepam; 2) 5 mg oral haloperidol and 2 mg IM lorazepam; 3) oral placebo and 2 mg IM lorazepam. Each treatment group received both an injection and a tablet to reduce treatment group variability. Patients were evaluated using the Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Syndrome Scale (PANSS) before receiving medication and at 30 and 90 minutes after medication was administered. The intergroup mean percent reductions in rating scale scores were compared using ANOVA, chi-square, and Kruskal-Wallis tests.\n There were no statistically significant differences among the groups at any point. The two groups receiving an antipsychotic plus lorazepam showed a trend towards increased symptom reduction compared with the group receiving lorazepam alone, although this trend was not statistically significant.\n Lorazepam alone was as effective as lorazepam plus haloperidol or lorazepam plus risperidone in this small trial. While not statistically significant, a trend toward better outcomes with combined treatment warrants further study.", "To compare two widely used drug treatments for people with aggression or agitation due to mental illness.\n Pragmatic, randomised clinical trial.\n Three psychiatric emergency rooms in Rio de Janeiro, Brazil.\n 301 aggressive or agitated people.\n Open treatment with intramuscular midazolam or intramuscular haloperidol plus promethazine.\n Patients tranquil or sedated at 20 minutes. Secondary outcomes: patients tranquil or asleep by 40, 60, and 120 minutes; restrained or given extra drugs within 2 hours; severe adverse events; another episode of agitation or aggression; needing extra visits from doctor during first 24 hours; overall antipsychotic load in first 24 hours; and not discharged by two weeks.\n 151 patients were randomised to midazolam, and 150 to haloperidol-promethazine mix. Follow up for the primary outcome was available for 298 (99%): 134/151 (89%) of patients given midazolam were tranquil or asleep after 20 minutes compared with 101/150 (67%) of those given haloperidol plus promethazine (relative risk 1.32 (95% confidence interval 1.16 to 1.49)). By 40 minutes, midazolam still had a statistically and clinically significant 13% relative advantage (1.13 (1.01 to 1.26)). After 1 hour, about 90% of both groups were tranquil or asleep. One important adverse event occurred in each group: a patient given midazolam had transient respiratory depression, and one given haloperidol-promethazine had a grande mal seizure.\n Both treatments were effective. Midazolam was more rapidly sedating than haloperidol-promethazine, reducing the time people are exposed to aggression. Adverse effects and resources to deal with them should be considered in the choice of the treatment.", "The pharmacological management of violence in people with psychiatric disorders is under-researched.\n To compare interventions commonly used for controlling agitation or violence in people with serious psychiatric disorders.\n We randomised 200 people to receive intramuscular lorazepam (4 mg) or intramuscular haloperidol (10 mg) plus promethazine (25-50 mg mix).\n At blinded assessments 4 h later (99.5% follow-up), equal numbers in both groups (96%) were tranquil or asleep. However, 76% given the haloperidol-promethazine mix were asleep compared with 45% of those allocated lorazepam (RR=2.29,95% CI 1.59-3.39; NNT=3.2,95% CI 2.3-5.4). The haloperidol-promethazine mix produced a faster onset of tranquillisation/sedation and more clinical improvement over the first 2 h. Neither intervention differed significantly in the need for additional intervention or physical restraints, numbers absconding, or adverse effects.\n Both interventions are effective for controlling violent/agitated behaviour. If speed of sedation is required, the haloperidol-promethazine combination has advantages over lorazepam.", "There are no rapid-acting intramuscular formulations of atypical antipsychotics available for quickly calming an agitated patient with bipolar disorder. In this study, 201 agitated patients with bipolar mania were randomly assigned to receive one to three injections of the atypical antipsychotic olanzapine (10 mg, first two injections; 5 mg, third injection), the benzodiazepine lorazepam (2 mg, first two injections; 1 mg, third injection), or placebo (placebo, first two injections; olanzapine, 10 mg, third injection) within a 24-hour period. Agitation was measured at baseline, every 30 minutes for the first 2 hours, and at 24 hours after the first injection using the Positive and Negative Syndrome Scale-Excited Component subscale and two additional agitation scales. At 2 hours after the first injection, patients treated with olanzapine showed a significantly greater reduction in scores on all agitation scales compared with patients treated with either placebo or lorazepam. At 24 hours after the first injection, olanzapine remained statistically superior to placebo in reducing agitation in patients with acute mania, whereas patients treated with lorazepam were not significantly different from those treated with placebo or olanzapine. Furthermore, no significant differences among the three treatment groups were observed in safety measures, including treatment-emergent extrapyramidal symptoms, the incidence of acute dystonia, or QTc interval changes. These findings suggest that intramuscular olanzapine is a safe and effective treatment for reducing acute agitation in patients with bipolar mania.", "While neuroleptics remain the mainstay of drug intervention in the emergency management of psychosis, a variety of agents have received study as alternatives or adjuncts to these drugs in an attempt to improve the safety and efficacy of acute treatment. The purposes of this study were to investigate the efficacy and safety of alprazolam as a neuroleptic adjunct for schizophrenic patients in psychotic relapse and to clarify the effects of combination treatment on specific aspects of the psychotic process.\n Twenty-eight acutely psychotic patients with schizophrenia who were admitted to an emergency psychiatric service were randomly assigned to treatment with either haloperidol and alprazolam or haloperidol with placebo under double-blind conditions. Drug administration lasted 72 hours.\n Both groups improved significantly. The combination-treated group required significantly less medication and had 56% fewer dystonic reactions. The addition of alprazolam was most effective for symptoms of excitement and uncooperativeness, particularly in the initial hours of treatment.\n The combination of alprazolam and haloperidol seems to be the most effective for agitated patients, particularly in the first 48 hours of treatment. It may also result in fewer dystonic reactions.", "To compare the effectiveness of intramuscular olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone as the first medication(s) used to treat patients with agitation and aggressive behavior.\n One hundred fifty patients with agitation caused by psychotic or bipolar disorder were randomly assigned under double-blind conditions to receive olanzapine, ziprasidone, haloperidol plus midazolam, haloperidol plus promethazine or haloperidol alone. The Overt Agitation Severity Scale, Overt Aggression Scale and Ramsay Sedation Scale were applied within 12 hours after the first dosage.\n All medications produced a calming effect within one hour of administration, but only olanzapine and haloperidol reduced agitation by less than 10 points, and only olanzapine reduced aggression by less than four points in the first hour. After twelve hours, only patients treated with haloperidol plus midazolam had high levels of agitation and aggression and also more side effects. Ziprasidone, olanzapine and haloperidol alone had more stable results for agitation control, while ziprasidone, haloperidol plus promethazine and olanzapine had stable results for aggression control.\n Olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol were effective in controlling agitation and aggression caused by mental illness over 12 hours. Although all the drugs had advantages and disadvantages, haloperidol plus midazolam was associated with the worst results in all the observed parameters.", "We compare intravenous midazolam and droperidol for the onset of sedation of acutely agitated patients in the emergency department (ED).\n This was a double-blind, randomized, clinical trial set in the ED of a university teaching hospital. Subjects were adults, acutely agitated because of mental illness, intoxication, or both, who received midazolam or droperidol, 5 mg intravenously, every 5 minutes until sedated. We analyzed time to sedation using survival analysis, median times to sedation, and proportions sedated at 5 and 10 minutes.\n Seventy-four patients received midazolam; 79 patients, droperidol. Survival analysis showed no difference in time to sedation (hazard ratio 0.86; 95% confidence interval [CI] 0.61 to 1.23), P=.42. Median time to sedation was 6.5 minutes for midazolam (median dose 5 mg) and 8 minutes for droperidol (median dose 10 mg), P=.075 (effect size 1.5 minutes; 95% CI 0 to 4 minutes). At 5 minutes, 33 of 74 (44.6%) patients from the midazolam group were adequately sedated compared with 13 of 79 (16.5%) patients from the droperidol group, a difference of 28.1% (95% CI 12.9% to 43.4%; P<.001). By 10 minutes, 41 of 74 (55.4%) from the midazolam group were sedated compared to 42 of 79 (53.2%) from droperidol, a difference of 2.2% (95% CI -14.9% to 19.3%; P=.91). Eleven adverse events occurred in the midazolam group and 10 in the droperidol group. Three patients required active airway management (3 patients with assisted ventilation and 1 patient intubated); all received midazolam.\n There is no difference in onset of adequate sedation of agitated patients using midazolam or droperidol. Patients sedated with midazolam may have an increased need for active airway management.", "The authors examined the efficacy of intramuscular flunitrazepam compared with intramuscular haloperidol for the immediate control of agitated or aggressive behavior in acutely psychotic patients.\n Twenty-eight actively psychotic inpatients, aged 20-60 years, who were under treatment with neuroleptic agents were selected for the study. Each was randomly assigned on a double-blind basis to receive either 5 mg i.m. of haloperidol (N=13) or 1 mg i.m. of flunitrazepam (N=15) during an aggressive event. Verbal and physical aggression was measured over time with the Overt Aggression Scale. Patients were also rated with the Brief Psychiatric Rating Scale and the Clinical Global Impression scale.\n Both flunitrazepam and haloperidol exhibited acute antiaggressive activity. This beneficial effect, as assessed by the Overt Aggression Scale, was obtained within 30 minutes.\n Intramuscular flunitrazepam may serve as a convenient, rapid, safe, and effective adjunct to neuroleptics in reducing aggressive behavior in emergency psychiatric settings.", "In a double-blind, prospective study, 2 mg of intramuscular lorazepam and 5 mg of intramuscular haloperidol were equally effective in controlling aggression, agitation, and assaultive behavior. Although lorazepam and haloperidol produced an equivalent mean decrease in aggression, significantly more subjects who received lorazepam had a greater decrease in aggression ratings than haloperidol recipients; this effect was independent of sedation. Lorazepam produced significantly fewer extrapyramidal symptoms. These data support the current clinical practice of using lorazepam (alone, or in combination with a neuroleptic) for control of acute aggressive and assaultive behavior.", "The efficacy of a benzodiazepine was compared with that of a neuroleptic for the rapid tranquilization of patients presenting at a psychiatric emergency room service. Thirty-seven highly agitated patients exhibiting psychotic symptoms were randomly assigned to receive either 2 mg lorazepam or 5 mg haloperidol as needed every 30 min for 4 h. Administration route was either intramuscular injection or oral concentrate. Symptom ratings were conducted each hour using double-blind procedures. Both medications reduced symptom ratings on the Brief Psychiatric Rating Scale and Global Clinical Impression of Overall Symptom Severity Scale. Global Clinical Impression scores for the two medication groups did not differ significantly either at baseline or at 4 h after entry into the study. However, Global Clinical Impression scores of patients in the lorazepam group were less severe at intermittent ratings. The groups did not differ on the Brief Psychiatric Rating Scale at any rating time. No differences were found either in the number of doses administered or in the administration route selected. Given the potential for severe extrapyramidal symptoms developing hours or days after a single dose of haloperidol, lorazepam may provide an excellent alternative for the rapid tranquilization of the acutely agitated psychotic patient in the emergency room setting." ]

[ "9171125", "17698432", "10449846", "11905866", "17943385", "9322475", "8994987", "15227690", "11360058", "15075657", "8351603", "7577282", "9294270", "16773005", "11353965", "9014667", "8957970", "9479725", "11965463", "12859305" ]

[ "Laparoscopic cholecystectomy using abdominal wall retraction. Hemodynamics and gas exchange, a comparison with conventional pneumoperitoneum.", "Randomized trial of low-pressure carbon dioxide-elicited pneumoperitoneum versus abdominal wall lifting for laparoscopic cholecystectomy.", "Randomized comparison between low-pressure laparoscopic cholecystectomy and gasless laparoscopic cholecystectomy.", "Randomized comparison of conventional carbon dioxide insufflation and abdominal wall lifting for laparoscopic cholecystectomy.", "Laparoscopic cholecystectomy with carbon dioxide pneumoperitoneum is safe even for high-risk patients.", "Splanchnic and renal deterioration during and after laparoscopic cholecystectomy: a comparison of the carbon dioxide pneumoperitoneum and the abdominal wall lift method.", "Postoperative drowsiness and emetic sequelae correlate to total amount of carbon dioxide used during laparoscopic cholecystectomy.", "Randomized clinical trial of the effect of pneumoperitoneum on cardiac function and haemodynamics during laparoscopic cholecystectomy.", "Randomized comparison of conventional and gasless laparoscopic cholecystectomy: operative technique, postoperative course, and recovery.", "Abdominal wall lift versus positive-pressure capnoperitoneum for laparoscopic cholecystectomy: randomized controlled trial.", "A prospective randomized trial comparing pneumoperitoneum and U-shaped retractor elevation for laparoscopic cholecystectomy.", "Conventional pneumoperitoneum compared with abdominal wall lift for laparoscopic cholecystectomy.", "Hormone-cytokine response. Pneumoperitoneum vs abdominal wall-lifting in laparoscopic cholecystectomy.", "Comparison between intraperitoneal CO2 insufflation and abdominal wall lift on QT dispersion and rate-corrected QT dispersion during laparoscopic cholecystectomy.", "Hemodynamic and pulmonary changes during open, carbon dioxide pneumoperitoneum and abdominal wall-lifting cholecystectomy. A prospective, randomized study.", "Randomized comparison of the neuroendocrine response to laparoscopic cholecystectomy using either conventional or abdominal wall lift techniques.", "Gasless laparoscopic cholecystectomy: comparison of postoperative recovery with conventional technique.", "Comparison of pneumoperitoneum and abdominal wall lifting as to hemodynamics and surgical stress response during laparoscopic cholecystectomy.", "Gasless laparoscopic cholecystectomy is not more time-consuming.", "Pneumoperitoneum versus abdominal wall lift: effects on central haemodynamics and intrathoracic pressure during laparoscopic cholecystectomy." ]

[ "Disadvantages related to CO2 pneumoperitoneum have led to development of the abdominal wall retractor (AWR), a device designed to facilitate laparoscopic surgery without conventional pneumoperitoneum (15 mmHg CO2). We investigated the effects of the AWR on hemodynamics and gas exchange in humans. We also investigated whether the use of an AWR imposed extra technical difficulties for the surgeon. A pilot study revealed that cholecystectomy without low-pressure pneumoperitoneum was technically impossible.\n A prospective randomized controlled trial: Twenty patients undergoing laparoscopic cholecystectomy were randomly allocated into group 1: AWR with low-pressure pneumoperitoneum (5 mmHg), or group 2: conventional pneumoperitoneum (15 mmHg).\n Surgery using the AWR lasted longer, 72 +/- 16 min (mean +/- SD) vs 50 +/- 18 min compared with standard laparoscopic cholecystectomy. There were no differences between the groups with respect to hemodynamic parameters, although a small reduction of the cardiac output was observed using conventional pneumoperitoneum (from 3.9 +/- 0.7 to 3. 2 +/- 1.1 l/min) and an increase during AWR (from 4.2 +/- 0.9 to 5.2 +/- 1.5 l/min). Peak inspiratory pressures were significantly higher during conventional pneumoperitoneum compared to AWR. A slight decrease in pH accompanied by an increase in CO2 developed during pneumoperitoneum and during the use of the AWR. In both groups arterial PO2 decreased.\n The results indicate that the view was impaired during use of the AWR and therefore its use was difficult and time-consuming. Possible advantages of this devices' effects on hemodynamics and ventilatory parameters could not be confirmed in this study.", "Two alternative surgical techniques for elective laparoscopic cholecystectomy (LC), low-pressure insufflation of the peritoneal cavity and abdominal wall lifting (AWL), have been developed over time to minimize the disadvantages associated with CO2-elicited pneumoperitoneum. To the best of our knowledge, the 2 methods have seldom been compared as regards their relative advantages and disadvantages.\n Eighty patients scheduled for elective LC were randomized into either a low-pressure (8 mmHg) CO2 insufflation method (LPLC) group, or a gasless technique using a subcutaneous abdominal wall lifting device (GLC group). The duration of the surgical procedure, the surgical results including level of postoperative pain, and perioperative cardiopulmonary function changes experienced by the members of both groups were compared.\n Laparoscopic surgery was completed for all but 1 patient from each group due to an inadequate surgical-site exposure. There was no mortality for study participants, and no major complications were noted for members of either group. The LPLC group evidenced a shorter surgical duration as compared to the GLC group (77 +/- 28 minutes vs. 98 +/- 27 minutes, respectively; p < 0.01) and a lower incidence of postoperative shoulder pain (2/38 vs. 8/39, respectively; p < 0.05), although significant differences in intraoperative pulmonary function were noted (an increased PaCO2, Pet CO2 and peak-airway pressure and decreased arterial blood pH; p < 0.01) for the LPLC group compared to the GLC group.\n Both alternative methods for this type of surgery appeared feasible and safe for LC. Low-pressure CO2 pneumoperitoneum had a shorter surgical duration and less postoperative shoulder pain compared to the GLC technique, but did not feature any other advantage over the AWL technique with regard to impact on cardiopulmonary function.", "Laparoscopic cholecystectomy using low-pressure pneumoperitoneum (8 mmHg) minimizes adverse hemodynamic effects, reduces postoperative pain, and accelerates recovery. Similar claims are made for gasless laparoscopy using abdominal wall lifting. The aim of this study was to compare gasless laparoscopic cholecystectomy to low-pressure cholecystectomy with respect to postoperative pain and recovery.\n Thirty-six patients were randomized to low-pressure or gasless laparoscopic cholecystectomy using a subcutaneous lifting system (Laparotenser).\n The characteristics of the patients were similar in the two groups. The procedure was completed in all patients in the low-pressure group, but two patients in the gasless group were converted to pneumoperitoneum. There were no significant differences in postoperative pain and analgesic consumption, but patients in the gasless group developed shoulder pain more frequently (50% vs 11%, p < 0.05). Gasless operation took longer to perform (95 vs 72.5 min, p = 0.01).\n Gasless and low-pressure laparoscopic cholecystectomy were similar with respect to postoperative pain and recovery. The gasless technique provided inferior exposure and the operation took longer, but the technique may still have value in high-risk patients with cardiorespiratory disease.", "Gasless laparoscopy using abdominal wall lifting (AWL) has been developed in an attempt to avoid the adverse effects of carbon dioxide pneumoperitoneum that may occur in conventional laparoscopy. However, lifting has been criticized for its poor operative space and surgical invasiveness. This study compared the AWL method with conventional CO2 pneumoperitoneum for laparoscopic cholecystectomy with respect to operation performance, postoperative course, and stress response.\n During a 6-month period, 95 patients with symptomatic gallstones were randomly assigned to receive laparoscopic cholecystectomy with conventional CO2 pneumoperitoneum (CO2 group; N = 47) or the AWL method (AWL group; N = 48). Operative results and operative time were recorded. Cardiopulmonary functions were assessed, and arterial blood gases were analyzed during surgery. Urinary cortisol, vanillylmandelic acid, metanephrines, and nitrogen loss; serum complement 3, C-reactive protein, and interleukin-6; postoperative pain; and the presence of nausea and vomiting were assessed for 48 hours after surgery. Postoperative time to recovery of flatus, tolerance of a full oral diet, and full activity were also determined.\n Only three significant differences were found. First, intraoperative ventilatory function deteriorated significantly less in the AWL group. Second, arterial blood gas determinations and capnography showed a greater decrease in intraoperative arterial pH and compliance with CO2 retention and an increase in peak airway pressure in the CO2 group (P < 0.05), reflecting poorer ventilatory performance. Third, preparation time and total operating time were significantly greater with the AWL method (P < 0.05).\n Although AWL required a longer operation time, our results suggest that the technique may still have value in high-risk patients with cardiorespiratory diseases.", "Because of absorbed carbon dioxide (CO(2)) and elevated intraabdominal pressure (IAP), CO(2) pneumoperitoneum (CO(2)PP) has potentially harmful intraoperative circulatory and ventilatory effects. Although not clinically significant for healthy patients, these effects are assumed to be deleterious for patients with a high risk for anesthesia (American Society of Anesthesiology [ASA] 3 and 4) and significant cardiopulmonary, renal, or hepatic diseases. The authors assessed CO(2)PP-related adverse effects by comparing ASA 3 and 4 patients who underwent laparoscopic cholecystectomy (LC) with or without CO(2)PP.\n A total of 20 successive ASA 3 and 4 patients who underwent LC were randomized into CO(2)PP (n = 10) and abdominal wall elevator (Laparolift) (n = 10) groups. The parameters for perioperative hemodynamics, ventilation, perfusion of intraabdominal organs, and blood chemistry were recorded periodically from before the induction of the anesthesia until postoperative day 2 and compared between the groups.\n Mean age, height, weight, the proportional number of ASA 3 vs ASA 4 patients, the volume of perioperative fluid loading, and the dose of analgesics did not differ significantly between the groups. The length of the operation was 49.9 +/- 10.6 min for the CO(2)PP group and 50.6 +/- 17.2 min for Laparolift group (nonsignificant difference). The mean central venous pressure (CVP) 30 min after insufflation was higher (12.3 +/- 4.8 vs 7.9 +/- 3.7 mmHg) and the (Gastric Mucosal pH) pHi at the end of the operation was lower (7.29 +/- 0.07 vs 7.35 +/- 0.04) in the CO(2)PP group than in the Laparolift group (p < 0.05). Later, CVP and pHi did not differ significantly. Other parameters of hemodynamics including oxygenation, perfusion, and blood chemistry did not differ significantly.\n For LC for patients with an ASA 3 and 4 risk for anesthesia, no significant adverse effects could be attributed to CO(2 )pneumoperitoneum. For high-risk patients, preoperative preparation and active perioperative monitoring are essential for safe anesthesia for LC with or without CO(2)PP.", "Carbon dioxide (CO2) pneumoperitoneum together with an increased intraabdominal pressure (IAP) induces a hemodynamic stress response, diminishes urine output, and may compromise splanchnic perfusion. A new retractor method may be less traumatic. Accordingly, 30 ASA physical status I or II patients undergoing laparoscopic cholecystectomy were randomly allocated to a CO2 pneumoperitoneum (IAP 12-13 mm Hg) (control) or to a gasless abdominal wall lift method (retractor) group. Anesthesia and intravascular fluids were standardized. Direct mean arterial pressure (MAP), urine output, urine-N-acetyl-beta-D-glucosaminidase (U-NAG), arterial blood gases, gastric mucosal PCO2, and intramucosal pH (pHi) were measured. Normoventilation was instituted in all patients. MAP increased (P < 0.001) only with CO2 pneumoperitoneum. Minute volume of ventilation had to be increased by 35% with CO2 insufflation. PaCO2 was significantly higher (P < 0.05) for 3 h postoperatively in the control group. Diuresis was less (P < 0.01) and U-NAG levels (P < 0.01) higher in the control group. The pHi decreased after induction of pneumoperitoneum up to three hours postoperatively and remained intact in the retractor group. We conclude that the retractor method for laparoscopic cholecystectomy ensures stable hemodynamics, prevents respiratory acidosis, and provides protection against biochemical effects, which reveal the renal and splanchic ischemia caused by CO2 insufflation. Implications: A mechanical retractor method (gasless) was compared with conventional CO2 pneumoperitoneum for laparoscopic cholestectomy. The gasless method ensured stable hemodynamics, prevented respiratory acidosis, and provided protection against the renal and splanchnic ischemia seen with CO2 pneumoperitoneum.", "After laparoscopy with carbon dioxide (CO2) insufflation early postoperative recovery is often complicated with drowsiness and postoperative nausea and vomiting (PONV).\n 25 ASA I-II patients undergoing elective laparoscopic cholecystectomy under standardized anaesthesia were studied in a randomized, prospective study. The conventional CO2 pneumoperitoneum was compared with the mechanical abdominal wall lift (AWL) method with minimal CO2 insufflation with special reference to postoperative recovery.\n Postoperative drowsiness was of a significantly longer duration with the conventional method (p < 0.001) compared with the AWL technique. There was a positive correlation with the total amount of CO2 used and the duration of drowsiness (r = 0.75, p < 0.01). PONV was seen significantly more often in patients with CO2 insufflation of more than 121 (p < 0.05).\n Avoiding excessive CO2 is beneficial for smoother and more uneventful recovery after laparoscopic cholecystectomy.", "Conventional laparoscopic cholecystectomy (CLC) with carbon dioxide pneumoperitoneum may cause major cardiovascular changes. The aim of this study was to evaluate the effect of carbon dioxide pneumoperitoneum and positional changes on haemodynamics and cardiac function in patients assigned randomly to CLC or gasless laparoscopic cholecystectomy (GLC).\n Fifty patients with American Society of Anesthesiologists physical status I and II were randomly allocated to CLC (28 patients) or GLC (22). Left ventricular end-diastolic and end-systolic diameters, fractional shortening and cardiac output were determined by transoesophageal echocardiography. Measurements were performed before (phase 1) and 10 and 30 min (phases 2 and 3 respectively) after pneumoperitoneum or abdominal wall traction, and after desufflation or release of abdominal wall traction (phase 4) in supine, Trendelenburg and reverse Trendelenburg positions.\n Mean diastolic diameter, systolic diameter, mean arterial pressure and heart rate were significantly higher, and fractional shortening was significantly lower, with carbon dioxide pneumoperitoneum than with the gasless procedure during phases 2 and 3. There were no significant differences in cardiac output between the two groups.\n Carbon dioxide pneumoperitoneum was associated with increased preload and afterload in patients undergoing laparoscopic cholecystecomy. It also decreased heart performance (fractional shortening), but did not affect cardiac output.\n Copyright 2004 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.", "The positive CO2 pneumoperitoneum needed to create the working space for laparoscopic surgery induces cardiovascular, neuroendocrine, and renal changes. Concern about these pathophysiologic changes has led to the introduction of a gasless technique. Fifty consecutive patients with symptomatic gallstones were randomized to conventional (CLC) or gasless laparoscopic cholecystectomy (GLC), with special reference to overall patient satisfaction, technical difficulties, duration of surgery, postoperative pain, and recovery. The overall exposure of the operative field was extremely poor in the GLC group, whereas the duration of surgery, steps involved in the cholecystectomy technique, length of hospital stay, and postoperative pain score did not differ significantly. After discharge, the median time to complete relief of pain tended to be shorter in the gasless group (5 days [range 1 to 15]) vs. the conventional group (8 days [range 1 to 15]). The period to return to normal activity was shorter in the GLC group (6 days [range 1 to 15]) compared to the CLC group (8.5 days [range 1 to 15]) (P = 0.031). No differences were found in terms of fatigue, dizziness and nausea, and overall satisfaction with the outcome. This study demonstrates a significantly shorter convalescence after laparoscopic cholecystectomy by means of the gasless technique compared to the conventional CO2 technique. Exposure of the operative field was less than optimal using the gasless technique.", "To compare intraoperative cardiac function, postoperative cognitive recovery, and surgical performance of laparoscopic cholecystectomy with abdominal wall lift (AWL) versus positive-pressure capnoperitoneum (PPCpn).\n AWL has been proposed as an alternative approach to PPCpn to avoid adverse cardio-respiratory changes. However, the workspace obtained with the AWL is less optimal than PPCpn and previous studies documenting delayed postoperative recovery of consciousness following PPCpn have not assessed mental alertness despite its importance.\n Forty operations were randomized into AWL and PPCpn. A standard anesthetic protocol was followed. Cardiac indices were measured with an esophageal Doppler machine. An auditory vigilance test was used to measure alertness level following extubation. All operations were videotaped and human reliability assessment techniques were used to identify surgical errors.\n There was a significant reduction in cardiac output during the first 20 minutes following CO2 insufflation in the PPCpn group, whereas in the AWL group it did not exhibit any significant change. Patients in AWL arm had better vigilance scores at 90 and 180 minutes following extubation compared with the PPn group (P < 0.05). Significantly more surgical errors were observed during surgery with AWL than with PPCpn (7.1 +/- 1.1; versus 2.9 +/- 0.4; P = 0.001).\n The AWL approach avoids fall in cardiac output associated with PPCpn during laparoscopic surgery and is associated with a more rapid recovery of postoperative cognitive function compared with PPCpn. However, AWL increases the level of difficulty in the execution of the operation.", "Between April and August 1991, 83 Japanese patients with symptomatic gallstones underwent laparoscopic cholecystectomy in our clinics. A prospective randomized trial was carried out to examine the safety, efficacy, and complications of the two techniques, pneumoperitoneum vs an elevating method using a U-shaped retractor. Forty-two patients were randomly allocated to the pneumoperitoneum (P) group and 41 to the U-shaped retractor (U) group. These two groups were well matched with respect to age, sex, etiology, and the severity of the chronic cholecystitis. Laparoscopic resection was successful for 88.1% (37/42) in the P group and 100% (41/41) in the U group. In patients with a severe fibrotic gallbladder, the rate of success was significantly higher (P < 0.05) in the U group (100%, 6/6) than in the P group (11.8%, 1/6). In the moderately inflamed group, the operation time (mean +/- SD) was significantly (P < 0.01) less in the U group (58.7 +/- 22.7) than in the P group (87.3 +/- 18.3). With the U-shaped retractor the usual surgical instruments can be used, and a rapid and safer laparoscopic cholecystectomy can be carried out. We prefer this approach to a pneumoperitoneum for patients with an inflamed gallbladder as hospital stay and pain are minimal.", "We have compared, in a randomized study, conventional carbon dioxide pneumoperitoneum with abdominal wall lift in 25 patients undergoing laparoscopic cholecystectomy. Intra-abdominal pressure (IAP) (11 (SD 2) mm Hg vs 2.7 (9) mm Hg) (P < 0.01) and total amount of carbon dioxide used (40 (23) litre vs 9 (7) litre) (P < 0.001) were significantly less with abdominal wall lift. Pulmonary compliance was significantly greater (P < 0.01) in the abdominal wall lift group throughout operation. During the first 15 min of insufflation, arterial pressures were lower with abdominal wall lift (P < 0.05). In the conventional pneumoperitoneum group, femoral vein pressure increased (P < 0.01) and remained elevated for 3 h in the recovery room. Postoperative drowsiness was of significantly longer duration in the conventional pneumoperitoneum group than in the abdominal wall lift group (98 (46) min vs 13 (34) min) (P < 0.01). Postoperative nausea and vomiting and right shoulder pain occurred more often in patients with conventional pneumoperitoneum (P < 0.05). We conclude that the benefits of abdominal wall lift may be attributed to avoiding excessive carbon dioxide and high IAP.", "Changes in blood hormone and cytokine were investigated in patients who underwent laparoscopic cholecystectomy via insufflation (CO2 group) vs those who had abdominal wall-lifting (Air group).\n Seventeen female patients with cholecystolithiasis were randomly divided into two groups. Peripheral blood samples were obtained during perioperative period, and plasma hormone levels (ACTH, cortisol) and serum cytokine levels (TNFalpha, IL-1beta, IL-6, IL-10) were measured.\n The number of circulating lymphocytes significantly decreased at 1 h after surgery in both groups, but the decrease in the CO2 group was significantly smaller than that in the Air group. There was no significant difference in hormone elevation between groups. Serum concentrations of IL-6 and IL-10 in the Air group were significantly higher than in the CO2 group.\n CO2 insufflation may reduce cytokine production in laparoscopic cholecystectomy.", "This study compared the effect of intraperitoneal CO2 insufflation with abdominal wall lift on RR interval, QT interval, the rate-corrected QT (QTc) interval, QT dispersion (QTD), and the rate-corrected QTD (QTcD) using computerized measurement during laparoscopic cholecystectomy. Thirty patients scheduled for laparoscopic cholecystectomy were randomly assigned to 2 groups: intraperitoneal CO2 insufflation (CO2 group) or abdominal wall lift (lift group). A 12-lead electrocardiogram was monitored to measure parameters. The RR interval, QT interval, and QTc interval did not change significantly during the study in both groups. The QTD and QTcD in the CO2 group increased significantly during CO2 insufflation, and were significantly higher than those of the lift group. Statistically significant increases of QTD and QTcD, which are associated with an increased risk of arrhythmias and cardiac events, occur during CO2 insufflation, and QTD and QTcD in the CO2 group were significantly higher than those of the lift group.", "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.", "Increase in plasma renin activity and noradrenaline concentration occur in response to carbon dioxide insufflation during laparoscopic cholecystectomy. In a randomized study the conventional carbon dioxide pneumoperitoneum was compared with the abdominal wall lift method for laparoscopic cholecystectomy, with special reference to neuroendocrine changes and renal function. The total mean(s.d.) volume of carbon dioxide insufflated was 42(23) litres with the conventional method and 9(7) litres with abdominal wall lift (P < 0.001). Mean(s.d.) intra-abdominal pressure after 15 min of insufflation was 11(2) and 3(9) mmHg respectively (P < 0.01). In the conventional group mean(s.d.) plasma renin activity increased slightly from 5.5(2.1) to 6.1(2.0) ng ml-1 during the first 55 min of laparoscopic cholecystectomy. In the abdominal wall lift group plasma renin activity decreased from 5.3(2.7) to 3.8(0.9) ng ml (P < 0.01 between the groups). Plasma antidiuretic hormone concentration increased similarly in both groups. Diuresis was significantly less with conventional pneumoperitoneum during the first 35 min of the operation compared with the abdominal wall lift method (P < 0.001). There were significant increases in plasma noradrenaline concentration in both groups (P < 0.001), but the increase was slightly higher in the conventional group during the first 15 min of insufflation. The abdominal wall lift method with minimal carbon dioxide insufflation was associated with smaller neuroendocrine responses and better preservation of renal function compared with conventional carbon dioxide pneumoperitoneum.", "We have compared, in a randomized study in 26 patients, immediate and late postoperative recovery after elective laparoscopic cholecystectomy using the gasless, mechanical abdominal wall lift method with conventional carbon dioxide pneumoperitoneum. After the gasless method, tracheal extubation was performed significantly earlier than after the conventional method (P < 0.01). End-tidal carbon dioxide concentrations were significantly higher after pneumoperitoneum for 30 min after operation (P < 0.01). In the conventional group, deviation in Maddox-Wing recordings from preoperative values remained at a significantly higher level during the 3-h recovery room period (P < 0.01). There was a positive correlation between the total amount of carbon dioxide used and duration of drowsiness (r = 0.61, P < 0.001) and the Maddox-Wing deviation (r = 0.62, P < 0.001). Postoperative nausea and vomiting, and right shoulder pain occurred less often after the gasless method (P < 0.05). Late recovery criteria (ability to drink, void and walk) in patients in the gasless group were fulfilled approximately 7 h earlier than in those in the pneumoperitoneum group (P < 0.01). Gasless laparoscopic cholecystectomy resulted in more uneventful and faster immediate and late postoperative recovery than conventional carbon dioxide pneumoperitoneum.", "Impairments in hemodynamics during pneumoperitoneum (PP) have been noted. This study compared changes in hemodynamics and surgical stress response with PP and abdominal wall lifting (AWL) during laparoscopic cholecystectomy.\n Twenty patients with symptomatic cholecystolithiasis were assigned to PP (n = 10) or AWL (n = 10). Cardiac output (CO), stroke volume (SV), and ejection fraction (%EF) were measured by transesophageal echocardiography. Clearances of para-aminohippurate (CPAH) and sodium thiosulfate (CSTS) were determined as measures of renal function. Levels of interleukin-6, C-reactive protein, white cell count, and neutrophil elastase were evaluated as indicators of surgical stress.\n In the PP group, CO, SV, and %EF were depressed significantly during pneumoperitoneum. Immediately after and 15 min after insufflation, the CPAH and CSTS were decreased by 78.0% and 73.8%, respectively. None of the hemodynamic parameters changed significantly in the AWL group. Surgical stress response was not different significantly between the two groups.\n In contrast to pneumoperitoneum, AWL did not alter cardiac function or renal hemodynamics. AWL may be useful in patients with cardiovascular or renal disorders.", "Although abdominal wall retraction is said to be advantageous in laparoscopic cholecystectomy (LC), many surgeons have found that, when this option is chosen, more time is needed to prepare for and carry out the surgical procedure. Our aim was to determine the time required for surgical preparation and operation in patients undergoing LC with carbon dioxide (CO2) pneumoperitoneum (CO2 PP) vs abdominal wall retraction (AWR).\n We performed a prospective randomized study of a CO2 PP LC group (n = 19) vs an AWR LC group (n = 15). Demographic data were collected preoperatively. LC was performed with either CO2 PP (12 mmHg) or AWR (6-10 kps). Two phases were considered: (a) time employed to create the surgical field (phase 1) and (b) operating time (phase 2). The chi-square test was used to compare the medians of the two groups.\n The two groups were homogeneous. Phase 1 required 35 min in the CO2 PP group vs 25 min in the AWR group (p = 0.24). Phase 2 required 60 min in both groups (p = 0.76).\n We found no statistically significant difference between the PP CO2 and AWR groups in either time spent to create the surgical field or actual operating time.", "It has been shown repeatedly that laparoscopic cholecystectomy using pneumoperitoneum (CO2 insufflation) may be associated with increased cardiac filling pressures and an increase in blood pressure and systemic vascular resistance. In the present study, the effects on the central circulation during abdominal wall lift (a gasless method of laparoscopic cholecystectomy) were compared with those during pneumoperitoneum. The study was also aimed at elucidating the relationships between the central filling pressures and the intrathoracic pressure.\n Twenty patients (ASA I), scheduled for laparoscopic cholecystectomy, were randomised into two groups, pneumoperitoneum or abdominal wall lift. Measurements were made by arterial and pulmonary arterial catheterization before and during pneumoperitoneum or abdominal wall lift with the patient in the horizontal position. Measurements were repeated after head-up tilting the patients as well as after 30 min head-up tilt. The intrathoracic pressure was monitored in the horizontal position before and during intervention using an intraesophageal balloon.\n After pneumoperitoneum or abdominal wall lifting there were significant differences between the two groups regarding MAP, SVR, CVP, CI, and SV. Analogous to previous studies, in the pneumoperitoneum group CVP, PCWP, MPAP, and MAP as well as SVR were increased after CO2 insufflation (P < 0.01), while CI and SV were not affected. In contrast, in the abdominal wall lift group, CI and SV were significantly increased (P < 0.01), as was MAP (P < 0.01), while CVP, PCWP, MPAP, and SVR were not significantly affected. There was a significant difference in intraesophageal pressure between the two groups. In the pneumoperitoneum group, the intraesophageal pressure was increased by insufflation (P < 0.01) while, in the abdominal wall lift group, it was unaffected. In the pneumoperitoneum group the mean increases in cardiac filling pressures were of the same magnitude as the mean increase in the intraesophageal pressure.\n In healthy patients, abdominal wall lift increased cardiac index while pneumoperitoneum did not. Cardiac filling pressures and systemic vascular resistance were increased by pneumoperitoneum but unaffected by abdominal wall lift. The recorded elevated cardiac filling pressures during pneumoperitoneum may be only a reflection of the increased intra-abdominal pressure." ]

[ "932064", "7462278", "8891982" ]

[ "Capsulodesis of the metacarpophalangeal joint of the thumb in children with cerebral palsy.", "A dynamic approach to the thumb-in palm deformity in cerebral palsy.", "Treatment of spastic thumb-in-palm deformity: a modified extensor pollicis longus tendon rerouting." ]

[ "A deformity of hyperextension of the metacarpophalangeal joint of the thumb occurring in thirteen children with spastic cerebral palsy was corrected by capsulodesis of the joint. The technique involves shifting the metacarpal attachment of the volar plate more proximally in the metacarpal. When combined with selective release of the involved intrinsic muscles and selective transfer of the extrinsic motors, when indicated, the thumb is brough away from the palm and its function and appearance are improved. Moreover, there is not risk to growth of the thumb such as might follow arthrodesis in a growing child. Results were satisfactory except in two athetoid patients, in whom some of the intial correction was lost, but even their thumbs did not revert into hyperextension. In five patients, for reasons not entirely clear, the previously flexed interphalangeal joint had better extension postoperatively. This improved the function of the thumb, because the broad pulp of the thumb could then be used firmly against the side of the index finger.", "One hundred and sixty-five different surgical procedures were performed for the correction of thumb deformities in fifty-six patients with spastic cerebral palsy at Gillette Children's Hospital, St. Paul, Minnesota, between 1967 and 1975. The quality of voluntary muscle control and sensibility were the most important factors in predicting the success of operation. In the past, thumb deformities were classified on the basis of the static position of the thumb, but rational treatment decisions can be made only by a careful assessment of the patient's hand and thumb function. Using various combinations of releases, tendon transfers, and joint stabilizations, measurable and predictable improvement in function was achieved in all fifty-six patients whose records were analyzed.", "Fourteen patients (15 hands) with spastic thumb-in-palm deformities were treated with a modified technique of extensor pollicis longus tendon rerouting. Twelve patients obtained satisfactory correction of their deformities. Although functional improvement was not always anticipated, it was achieved to some degree in 12 patients. Extensor pollicis longus tendon rerouting can provide satisfactory correction of severe thumb-in-palm deformity especially when combined with other procedures such as metacarpophalangeal joint arthrodesis and thumb intrinsic muscle release. The modified rerouting technique can be done with a single incision and allows easy adjustment of tension." ]

[ "11375358", "12173729", "9589648", "3282895", "12149599", "7734015", "9540025", "9540024", "10372249", "9428831", "8082525", "14693413", "10528419", "7555508", "9135927", "9283792", "7979840", "11919121", "9653595", "9625287", "8697309", "1954810", "10937515", "10369427", "7733122", "7556806", "11268714", "8458189" ]

[ "The synergistic effect of miglitol plus metformin combination therapy in the treatment of type 2 diabetes.", "Dose-dependent efficacy of miglitol, an alpha-glucosidase inhibitor, in type 2 diabetic patients on diet alone: results of a 24-week double-blind placebo-controlled study.", "Advantages of alpha-glucosidase inhibition as monotherapy in elderly type 2 diabetic patients.", "Effectiveness of acarbose, an alpha-glucosidase inhibitor, in uncontrolled non-obese non-insulin dependent diabetes.", "Acarbose improves indirectly both insulin resistance and secretion in obese type 2 diabetic patients.", "The efficacy of acarbose in the treatment of patients with non-insulin-dependent diabetes mellitus. A multicenter controlled clinical trial.", "Chronic treatment of African-American type 2 diabetic patients with alpha-glucosidase inhibition.", "Long-term titrated-dose alpha-glucosidase inhibition in non-insulin-requiring Hispanic NIDDM patients.", "A randomized double-blind trial of acarbose in type 2 diabetes shows improved glycemic control over 3 years (U.K. Prospective Diabetes Study 44)", "Efficacy of 24-week monotherapy with acarbose, metformin, or placebo in dietary-treated NIDDM patients: the Essen-II Study.", "Efficacy of 24-week monotherapy with acarbose, glibenclamide, or placebo in NIDDM patients. The Essen Study.", "Is acarbose equivalent to tolbutamide as first treatment for newly diagnosed type 2 diabetes in general practice? A randomised controlled trial.", "[Non-insulin-dependent diabetes mellitus associated with nonalcoholic liver cirrhosis: an evaluation of treatment with the intestinal alpha-glucosidase inhibitor acarbose].", "Reduction of glycosylated hemoglobin and postprandial hyperglycemia by acarbose in patients with NIDDM. A placebo-controlled dose-comparison study.", "The efficacy and safety of miglitol therapy compared with glibenclamide in patients with NIDDM inadequately controlled by diet alone.", "Glibenclamide, but not acarbose, increases leptin concentrations parallel to changes in insulin in subjects with NIDDM.", "Long-term efficacy and safety of acarbose in the treatment of obese subjects with non-insulin-dependent diabetes mellitus.", "Effects of dietary treatment alone or diet with voglibose or glyburide on abdominal adipose tissue and metabolic abnormalities in patients with newly diagnosed type 2 diabetes.", "An Asian multicenter clinical trial to assess the efficacy and tolerability of acarbose compared with placebo in type 2 diabetic patients previously treated with diet. Asian Acarbose Study Group.", "European study on dose-response relationship of acarbose as a first-line drug in non-insulin-dependent diabetes mellitus: efficacy and safety of low and high doses.", "Influence of 16-week monotherapy with acarbose on cardiovascular risk factors in obese subjects with non-insulin-dependent diabetes mellitus: a controlled, double-blind comparison study with placebo.", "Therapeutic potentials of acarbose as first-line drug in NIDDM insufficiently treated with diet alone.", "Effect of acarbose on insulin sensitivity in elderly patients with diabetes.", "Will acarbose improve the metabolic abnormalities of insulin-resistant type 2 diabetes mellitus?", "Multicenter, placebo-controlled trial comparing acarbose (BAY g 5421) with placebo, tolbutamide, and tolbutamide-plus-acarbose in non-insulin-dependent diabetes mellitus.", "Comparison of miglitol and glibenclamide in diet-treated type 2 diabetic patients.", "Comparison of acarbose and gliclazide as first-line agents in patients with type 2 diabetes.", "Long-term effect of acarbose on glycaemic control in non-insulin-dependent diabetes mellitus: a placebo-controlled double-blind study." ]

[ "To investigate the efficacy and safety of miglitol in combination with metformin in improving glycemic control in outpatients in whom type 2 diabetes is insufficiently controlled by diet alone.\n In this multicenter, double-blind, placebo-controlled study, 324 patients with type 2 diabetes were randomized, after an 8-week placebo run-in period, to treatment with either placebo, miglitol alone, metformin alone, or miglitol plus metformin for 36 weeks. The miglitol was titrated to 100 mg three times a day and metformin was administered at 500 mg three times a day. The primary efficacy criterion was change in HbA(1c) from baseline to the end of treatment. Secondary parameters included changes in fasting and postprandial plasma glucose and insulin levels, serum triglyceride levels, and responder rate.\n A total of 318 patients were valid for intent-to-treat analysis. A reduction in mean placebo-subtracted HbA(1c) of -1.78% was observed with miglitol plus metformin combination therapy, which was significantly different from treatment with metformin alone (-1.25; P = 0.002). Miglitol plus metformin also resulted in better metabolic control than metformin alone for fasting plasma glucose (-44.8 vs. -20.4 mg/dl; P = 0.0025), 2-h postprandial glucose area under the curve (-59.0 vs. -18.0 mg/dl; P = 0.0001), and responder rate (70.6 vs. 45.52%; P = 0.0014). All therapies were well tolerated.\n In type 2 diabetic patients, miglitol in combination with metformin gives greater glycemic improvement than metformin monotherapy.", "A double-blind randomised study was performed to compare the dose-effect and dose-tolerability relationships between the alpha-glucosidase inhibitor miglitol in doses of 25 mg, 50 mg, 100 mg and 200 mg all t.i.d. vs placebo t.i.d. in patients with Type 2 diabetes mellitus on diet only.\n After a 6-week placebo run-in period 468 patients with a fasting blood glucose > or = 7 mmol/l as well as a HbA1c between 6.1% and 10.4% were randomised for a 24-week treatment period.\n The results of 465 patients were valid for safety analysis and of 384 patients for the efficacy analysis. In the placebo group the HbA1c level increased by 0.40+/-1.46% as compared with baseline. The decrease in the mean HbA1c values (corrected for differences in baseline values) was significant and dose-dependent for all miglitol groups compared with placebo, being -0.46% (95% CI: -0.91%, -0.01%) in the 25 mg group, -0.45% (95% CI: -0.90%, -0.003%) in the 50 mg group, -0.84% (95% CI: -1.31%, -0.37%) in the 100 mg group and -1.26% (95% CI: -1.76%, -0.76%) in the 200 mg group. Blood glucose levels following a standardised breakfast tolerance test were significantly and dose-dependently lower for all the miglitol doses at 12 and 24 wk of treatment compared to baseline: in comparison with baseline maximum blood glucose increased by 4% with placebo and decreased by 7%, 14%, 24% and 33% with miglitol 25 mg, 50 mg, 100 mg and 200 mg t.i.d. respectively. The same pattern was seen with postprandial maximal serum insulin levels which decreased by 8% under placebo and by 17%, 26%, 25% and 35% with the 25 mg to 200 mg doses of miglitol. The adverse events reported were mainly of gastrointestinal nature, mostly being flatulence, diarrhoea and abdominal pain and the incidence increased with increasing dose. Although the side effects were not serious, they were troublesome, leading to a considerable drop-out rate increasing with dose.\n The alpha-glucosidase inhibitor miglitol in Type 2 diabetic patients on diet alone decreases both HbA1c levels and postprandial glucose and insulin levels in a dose-dependent manner. Gastrointestinal side effects also showed dose-dependency. Combination of efficacy and safety results leads to the conclusion that the optimal dose of miglitol will be in the range of 50 to 100 mg t.i.d.", "The objective of this study was to determine the safety, efficacy, and tolerability of the alpha-glucosidase inhibitor miglitol vs. the sulfonylurea glyburide in the treatment of elderly patients with type 2 diabetes mellitus, inadequately controlled by diet alone. This was a double-blind, randomized, placebo-controlled, 1-yr trial of miglitol 25 mg TID and 50 mg TID compared with placebo and a titrated dose of glyburide in a parallel group comparison study conducted in 30 out-patient sites across the United States. Four hundred eleven (411) diet-treated patients age 60 yr or greater were randomized to receive either placebo TID (n = 101), miglitol 25 mg TID (n = 104), miglitol 50 mg TID (n = 102), or a once-daily dose of glyburide titrated based on fasting plasma glucose (FPG) (n = 104), for a period of 56 weeks. Efficacy was assessed by glycated hemoglobin (HbA1c), fasting and post-meal glucose, insulin, and lipid levels, and by 24-h urinary excretion of glucose and albumin. Safety and tolerability were assessed by tabulation of adverse events, periodic laboratory determinations, and home blood glucose monitoring. HbA1c treatment effects (placebo-subtracted change in HbA1c from baseline) at the 1-yr endpoint were -0.49%, -0.40%, and -0.92% in the miglitol 25 mg TID, miglitol 50 mg TID, and glyburide groups, respectively (P < 0.05- 0.01 vs. placebo). Postprandial insulin levels were significantly greater than placebo and miglitol in the glyburide group (P < 0.01). Hypoglycemia, weight gain, and both routine and serious cardiovascular events were more frequent in the glyburide group (P < 0.05-0.01 vs. placebo or miglitol groups). Diarrhea (or soft stools) and flatulence were more common in both miglitol groups than in the other two groups in a dose-dependent manner, but resulted in relatively few study dropouts. Treatment with miglitol offers the elderly type 2 diabetic patient significant reductions in daylong glycemia as measured by HbA1c. The greater HbA1c reductions seen with once-a-day glyburide occurred at a cost of significant increases in weight, insulin levels, and the incidences of clinical and subclinical hypoglycemia, which did not occur in the miglitol groups. alpha-glucosidase inhibitors are a useful and relatively safe therapeutic option in the elderly patient with type 2 diabetes.", "The effect of acarbose, an alpha-glucosidase inhibitor, on glycaemic control, was compared with placebo in a double-blind, randomised, group comparison study during 16 weeks in 20 non-obese non-insulin dependent diabetic patients in whom sulphonylurea treatment had been withdrawn. There was significant deterioration in glycaemic control as assessed by HbA1 following withdrawal of the sulphonylurea. There was no significant improvement in HbA1 between weeks 0 and 16 in either the acarbose (11.3% and 12.4% respectively) or the placebo group (10.6% and 12.2% respectively). In both the acarbose and placebo treated groups fasting glucose and insulin concentrations were unaltered. This study also suggests that acarbose was not an effective substitute for sulphonylureas in non-obese Type 2 diabetes uncontrolled by diet alone.", "Acarbose is an oral antidiabetic mainly acting on postprandial blood glucose, inhibiting alphaglucosidase. Through this mechanism, it could improve the peripheral insulin sensitivity and/or increase the insulin secretion. The aim of the present study is to assess the therapeutic efficacy of Acarbose in obese type 2 diabetic patients on both insulin resistance and insulin secretion.\n 17 obese non insulin-dependent diabetic patients, well controlled with diet alone were randomized into 2 groups: acarbose (2 x 50 mg) or placebo during 16 weeks. A glucagon test allowed to evaluate insulin secretion before and after treatment as well as a triple test (glucose-insulin-somatostatin) with indirect calorimetry allowed to evaluate insulin sensitivity.\n A significant improvement in post-prandial plasma glucose was detected only in the Acarbose group (8.0 +/- 0.5 mmol/l before vs 6.5 0.5 mmol/l after, p<0.05). Basal C-peptide secretion was similar between groups and remained unchanged after treatment. However, stimulated insulin secretion was significantly increased by 30%, p<0.05, in the Acarbose group while no change was detected in the placebo group. Interestingly, the group receiving Acarbose disclosed a 15% reduction in insulin resistance (15.0 +/- 1.8 mmol/l before vs 12.8 +/- 1.4 mmol/l after).\n Our results show that a treatment with Acarbose is efficient even in diabetic patients presenting a good glucose control without any other associated treatment. By decreasing post-prandial blood glucose, acarbose improves both insulin sensitivity and secretion.", "To evaluate the long-term efficacy of acarbose, an alpha-glucosidase inhibitor, in improving glycemic control in patients with non-insulin-dependent diabetes mellitus.\n A 1-year, multicenter, randomized, double-blind, placebo-controlled study.\n Seven university-affiliated, community-based, tertiary care diabetes clinics.\n 354 patients with non-insulin-dependent diabetes mellitus were recruited; 77 were being treated with diet alone, 83 with diet and metformin, 103 with diet and sulfonylurea, and 91 with diet and insulin. Patients in each treatment group were randomly assigned to either acarbose or placebo for 1 year. Eighty-seven percent of patients receiving acarbose and 92% of those receiving placebo were included in the efficacy analysis (n = 316).\n At baseline and at 3-month intervals, levels of hemoglobin A1c (HbA1c), fasting and postprandial plasma glucose, fasting and postprandial serum C-peptide, and fasting serum lipids were measured.\n Compared with placebo, acarbose treatment caused a significant decrease in the mean postprandial plasma glucose peak (90 minutes) in all four groups (19.0 +/- 0.4 mmol/L to 15.5 +/- 0.4 mmol/L; P < 0.001). Analysis of the postprandial plasma glucose incremental area under the curve showed that the change from baseline to the end of the treatment period differed for placebo and acarbose recipients by 4.73 mmol.h/L in the diet alone group (P < 0.001), 2.06 mmol.h/L in the metformin group (P = 0.01), 2.65 mmol.h/L in the sulfonylurea group (P < 0.001), and 3.13 mmol.h/L in the insulin group (P = 0.001). Corresponding decreases in HbA1c levels occurred; these were 0.9% in the diet alone group (P = 0.005), 0.8% in the metformin group (P = 0.011), 0.9% in the sulfonylurea group (P = 0.002), and 0.4% in the insulin group (P = 0.077). Acarbose did not significantly affect mean serum C-peptide or mean serum lipid levels.\n Acarbose improved long-term glycemic control in patients with non-insulin-dependent diabetes mellitus regardless of concomitant antidiabetic medication.", "To evaluate the long-term efficacy, safety, and tolerability of the alpha-glucosidase inhibitor miglitol in the treatment of African-American patients with type 2 diabetes.\n A total of 345 African-American type 2 diabetic patients (mean age 55.6 years, BMI 31.9 kg/m2, duration of diabetes 4.9 years, baseline HbA1C 8.7%) treated with either diet alone or sulfonylurea were randomized to 1 year of double-blind treatment with either placebo (n = 117) or miglitol (n = 228) at doses of 50 or 100 mg t.i.d., titrated based on tolerability. The primary efficacy criterion was change from baseline in HbA1C at the 6-month visit. Secondarily efficacy parameters included changes from baseline in plasma glucose and serum insulin (both fasting and 120 min after a standardized test meal), fasting lipids, and urinary albumin-to-creatinine ratio. Safety and tolerability evaluations were primarily based on reporting of adverse events and symptoms and on periodic laboratory analyses.\n Miglitol treatment was associated with a mean placebo-subtracted reduction in HbA1C from baseline of 1.19% at 6 months. Fasting and 120-min postprandial plasma glucose levels were reduced in parallel to HbA1C, in association with miglitol treatment. Significant reductions versus placebo in 120-min postprandial insulin levels, in LDL cholesterol, and in fasting triglycerides, were also seen in the miglitol group at individual study time points. Softer, more frequent stools and flatulence were significantly more common in the miglitol group. Urinary tract infections, hematuria, and herpes simplex infections were significantly more common in the placebo group.\n Miglitol treatment appears to be at least as efficacious in the African-American type 2 population as in the U.S. type 2 population at large, with comparable tolerability. alpha-Glucosidase treatment may be an important therapeutic option in these patients in view of their greater risk for microvascular complications and the accumulating body of evidence that better glucose control reduces the risk of these complications.", "To assess the long-term safety and effectiveness of a titrated dose of the alpha-glucosidase inhibitor miglitol (BAY m 1099) in Hispanic NIDDM patients.\n A 1-year double-blind randomized placebo-controlled study in which diet-treated or diet plus sulfonylurea-treated Hispanic NIDDM patients received either placebo (n = 131) or miglitol in doses of 50, 100, 150, 200 mg t.i.d. (n = 254), up-titrated and down-titrated based on tolerability. Efficacy parameters included changes from baseline in HbA1c, fasting and 2-h postprandial plasma glucose and serum insulin, fasting serum lipids, and urinary albumin-to-creatinine ratio (ACR). Safety assessments consisted primarily of tabulation of adverse events and intercurrent illnesses, and of periodic laboratory determinations.\n Reductions from baseline in HbA1c levels at the 6-month (primary efficacy) endpoint were significantly greater by 0.83% in the miglitol group than in the placebo group. HbA1c reductions in the miglitol treatment group significantly exceeded those in the placebo group by 0.63, 0.73, and 0.92% at 3, 9, and 12 months of treatment, respectively. Reductions in 120-min postprandial glucose and insulin levels were significantly greater in the miglitol group than in the placebo group at all postbaseline visits. There was little difference between treatments for changes in fasting insulin or lipid levels. Miglitol-associated reductions versus placebo in fasting plasma glucose (P = 0.0587 at 6 months) and in ACR (P = 0.0541 at 1-year) were nearly statistically significant. These efficacy results were not notably different between the 6-month endpoint, at which time the mean miglitol dose was 100 mg t.i.d., and the 1-year visit, when the mean miglitol dose was 149 mg t.i.d. Notable adverse events seen significantly more often in the miglitol group than in the placebo group were flatulence and diarrhea (or soft stools). The incidence of these gastrointestinal adverse events appeared to be dose dependent.\n Miglitol treatment of non-insulin-requiring Hispanic NIDDM patients at doses from 50 to 200 mg t.i.d. produced statistically and clinically significant reductions of HbA1c, primarily associated with reduction of glucose and insulin levels in the postprandial period, which were sustained over a year of treatment. Adverse events related to the drug's mechanism of action were common, but generally well tolerated. Doses above 100 mg t.i.d. were not associated with notably enhanced efficacy in most patients.", "To determine the degree to which alpha-glucosidase inhibitors, with their unique mode of action primarily reducing postprandial hyperglycemia, offer an additional therapeutic approach in the long-term treatment of type 2 diabetes.\n We studied 1,946 patients (63% men) who were previously enrolled in the U.K. Prospective Diabetes Study (UKPDS). The patients were randomized to acarbose (n = 973), titrating to a maximum dose of 100 mg three times per day, or to matching placebo (n = 973). Mean +/- SD age was 59 +/- 9 years, body weight 84 +/- 17 kg, diabetes duration 7.6 +/- 2.9 years, median (interquartile range) HbA1c 7.9% (6.7-9.5), and fasting plasma glucose (FPG) 8.7 mmol/l (6.8-11.1). Fourteen percent of patients were treated with diet alone, 52% with monotherapy, and 34% with combined therapy. Patients were monitored in UKPDS clinics every 4 months for 3 years. The main outcome measures were HbA1c, FPG, body weight, compliance with study medication, incidence of side effects, and frequency of major clinical events.\n At 3 years, a lower proportion of patients were taking acarbose compared with placebo (39 vs. 58%, P < 0.0001), the main reasons for noncompliance being flatulence (30 vs. 12%, P < 0.0001) and diarrhea (16 vs. 8%, P < 0.05). Analysis by intention to treat showed that patients allocated to acarbose, compared with placebo, had 0.2% significantly lower median HbA1c at 3 years (P < 0.001). In patients remaining on their allocated therapy, the HbA1c difference at 3 years (309 acarbose, 470 placebo) was 0.5% lower median HbA1c (8.1 vs. 8.6%, P < 0.0001). Acarbose appeared to be equally efficacious when given in addition to diet alone; in addition to monotherapy with a sulfonylurea, metformin, or insulin; or in combination with more complex treatment regimens. No significant differences were seen in FPG, body weight, incidence of hypoglycemia, or frequency of major clinical events.\n Acarbose significantly improved glycemic control over 3 years in patients with established type 2 diabetes, irrespective of concomitant therapy for diabetes. Careful titration of acarbose is needed in view of the increased noncompliance rate seen secondary to the known side effects.", "To compare the therapeutic potential of acarbose, metformin, or placebo as first line treatment in patients with non-insulin-dependent diabetes mellitus (NIDDM).\n Ninety-six patients with NIDDM (35-70 years of age, body mass index (BMI) < or = 35 kg/m2, insufficiently treated with diet alone, glycated hemoglobin (HbA1c; 7% to 11%) were randomized into 3 groups and treated for 24 weeks with acarbose, 3 x 100 mg/day, or metformin, 2 x 850 mg/day, or placebo. Efficacy, based on HbA1c (primary efficacy criterion), fasting blood glucose (BG) and insulin, 1 hour postprandial BG and insulin (after standard meal test), postprandial insulin increase, plasma lipid profile, and tolerability, based on subjective symptoms and laboratory values were determined every 6 weeks. Analysis of covariance was performed for endvalues with adjustment on baseline values. Ninety-four patients were valid for efficacy evaluation.\n Both active drugs showed the same improvement of efficacy criteria compared with placebo. Baseline adjusted means at endpoint were as follows: BG, fasting and 1 hour postprandial, 9.2 mM and 10.9 mM with placebo, 7.6 mM and 8.7 mM with acarbose, and 7.8 mM and 9.0 mM with metformin; HbA1c was 9.8% with placebo, 8.5% with acarbose, and 8.7% with metformin. Comparisons: acarbose versus placebo and metformin versus placebo were statistically significant, but not acarbose versus metformin. No effect on fasting insulin could be observed. Relative postprandial insulin increase was 1.90 with placebo, 1.09 with acarbose, and 1.03 with metformin. Comparisons: acarbose versus placebo and metformin versus placebo were statistically significant, but not acarbose versus metformin. With respect to lipid profile, acarbose was superior to metformin. Low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol ratio increased by 14.4% with placebo, was unchanged with metformin, but decreased by 26.7% with acarbose. Comparisons: acarbose versus placebo and acarbose versus metformin were statistically significant, but not metformin versus placebo. Slight body weight changes were observed with acarbose (-0.8 kg) and metformin (-0.5 kg), but not with placebo. Acarbose led to mild or moderate intestinal symptoms in 50% of the patients within the first 4 weeks, but in only 13.8% of the patients within the last 4 weeks.\n Acarbose and metformin are effective drugs for the first line monotherapy of patients with NIDDM. With respect to plasma lipid profile, especially HDL cholesterol, LDL cholesterol and LDL/HDL cholesterol ratio acarbose may be superior to metformin.", "To compare the different therapeutic principles of alpha-glucosidase inhibitors and sulphonylureas as first-line treatment in non-insulin-dependent diabetes mellitus (NIDDM) patients with dietary failure.\n Ninety-six NIDDM patients (35-70 years of age, body mass index [BMI] < or = 35), insufficiently treated with diet alone (HbA1c 7-9%) were randomized into three groups and treated for 24 weeks with acarbose, glibenclamide, or placebo. Efficacy, based on fasting blood glucose (BG), BG 1 h after ingestion of standard breakfast (postprandial), serum insulin, postprandial insulin increase, and HbA1c; and tolerability, based on subjective symptoms and laboratory values, were investigated every 6 weeks. Efficacy evaluation was valid for 85 patients.\n The test drugs were dosed as follows: 100 mg acarbose (A) three times a day, 1 placebo tablet three times a day, 3.5 mg glibenclamide tablets dosed 1-0-0 or 1-0-1, mean dose 4.3 mg/day. Compared with the placebo, both drugs showed the same mean efficacy on fasting BG (-1.4 mM with acarbose, -1.6 mM with glibenclamide), 1-h postprandial BG (-2.2 mM with acarbose, -1.9 mM with glibenclamide), and HbA1c (-1.1% with acarbose, -0.9% with glibenclamide); but they showed a marked difference in 1-h postprandial insulin values (-80.7 pM with acarbose, 96.7 pM with glibenclamide). The mean relative insulin increase (1-h postprandial) was 1.5 in the placebo group, 1.1 in the acarbose group, and 2.5 in the glibenclamide group. No changes in body weight could be observed. No adverse events were seen under placebo. Acarbose led to mild or moderate intestinal symptoms in 38% of patients. Glibenclamide led to hypoglycemia, which could be solved by dose reduction, in 6% of patients. No dropouts occurred in any of the treatment groups.\n Acarbose and glibenclamide are effective drugs for the monotherapy of NIDDM patients when diet alone fails. Because postprandial insulin increase has been shown to be associated with increased risk for cardiovascular disease, acarbose, which lowers pp increase, may be superior to glibenclamide, which elevates postprandial insulin increase.", "We performed a double blind randomised controlled trial in general practice to assess equivalence between tolbutamide and acarbose with respect to the effect on mean HbA(1c) in newly diagnosed patients with type 2 diabetes. Secondary objectives were to compare the effects of both treatments on fasting and post-load blood glucose and insulin levels, lipids, and adverse events. Patients were randomised to receive acarbose, titrated step-wise to a maximum of 100mg three times daily (n=48) or tolbutamide, similarly titrated to a maximum of 2000 mg in three doses (n=48). The two treatments were considered equivalent if the two-sided 90% confidence interval (CI) for the difference in mean HbA(1c) levels was within the range -0.4 to 0.4%. Results were analysed on an intention-to-treat, per-protocol and on worst-case basis. Both agents reduced the HbA(1c) percentage and fasting blood glucose levels. The difference in mean decrease of HbA(1c) was 0.6% in favour of tolbutamide (90% CI 0.3, 0.9; 95% CI 0.2, 1.0). A worst-case analysis, assuming no change in HbA(1c) for dropouts, yielded a difference in mean decrease of 0.9% (90% CI 0.6, 1.2) in favour of tolbutamide. The difference in mean decrease of fasting blood glucose was 1.0 mmol/l in favour of tolbutamide (95% CI 0.3, 1.7). There were no significant differences in post-load blood glucose, fasting and post-load insulin levels, or lipids. In the acarbose group significantly more patients (15 versus 3) discontinued therapy because of adverse effects, mostly of gastrointestinal origin. We conclude that the results of this study favour tolbutamide over acarbose as first treatment for patients with newly diagnosed type 2 diabetes.", "Non-insulin-dependent diabetes mellitus not responding to diet only in patients with non-alcoholic liver cirrhosis is characterized by high post-prandial hyperglycemia. The aim of this study was to evaluate the safety and efficacy of 24 weeks of treatment with 300 mg acarbose per day in 76 consecutive outpatients affected by type 2 diabetes and well-compensated liver cirrhosis. The study design was double-blind cross-over vs placebo. All patients tolerated both treatments well, and no significant variations in liver function tests were observed (< 5% vs pre-treatment). A significant reduction of several parameters was observed only after acarbose: fasting glycemia (19 +/- 6 vs 2 +/- 0.5%; p < 0.01), post-prandial glycemia (41 +/- 9 vs 3 +/- 0.6%; p < 0.01), mean glycemia (30 +/- 8 vs 14 +/- 5%; p < 0.01), daily glycemic variation (52 +/- 8 vs 8 +/- 1%; p < 0.01), HbA1c (16 +/- 1 vs 2 +/- 0.5; p < 0.05), incremental area of C-peptide after a standard meal (80 +/- 19 vs 200 +/- 36 ng/mL/300 min; p < 0.01). After acarbose a significant increase of intestinal voiding/week (98 vs 28%; p < 0.01) and a parallel reduction of blood ammonia levels (52 +/- 9 vs 9 +/- 5%; p < 0.01) were observed. Results clearly document the good tolerability and the absence of toxic effects of acarbose on the liver, due to a theoretic absence of both absorption by the gut and hepatic metabolism of the drug. In fact, acarbose increases peristaltic movement of the gut, stimulates the proliferation of saccharolytic bacteria and simultaneously reduces proteolytic bacterial proliferation, thus actively reducing blood ammonia levels. These unexpected effects of acarbose may be used to advantage for the treatment of type 2 diabetes mellitus in patients with well-compensated liver cirrhosis.", "To compare the safety and efficacy of three doses of acarbose (100, 200, and 300 mg three times daily) with placebo for the treatment of non-insulin-dependent diabetes mellitus (NIDDM) in patients maintained on dietary therapy alone.\n This multicenter double-blind placebo-controlled trial was 22 weeks in duration. The trial consisted of a 2-week screening period, a 4-week placebo run-in period, and a 16-week double-blind treatment period. The primary measure of drug efficacy was the mean change from baseline in HbA1c levels. Additional efficacy variables included the mean change from baseline in fasting and postprandial plasma glucose and serum insulin levels.\n After 16 weeks of treatment, acarbose-treated patients had statistically significant reductions in mean HbA1c levels of 0.78, 0.73, and 1.10% (relative to placebo) in the 100-, 200-, and 300-mg t.i.d. groups, respectively. Significant reductions in fasting and postprandial plasma glucose levels, glucose area under the time-concentration curve, and maximum glucose concentration were also observed in acarbose-treated patients. Although there were no statistically significant differences among the 100-, 200-, and 300-mg treatment groups, there was a trend toward a dose-response relationship for most plasma glucose variables that were measured. Gastrointestinal side effects (e.g., abdominal pain, flatulence, and diarrhea) and serum transaminase elevations (e.g., aspartate aminotransferase [AST] and alanine aminotransferase [ALT] were more frequently reported in the acarbose-treated patients than in the placebo-treated control patients. Transaminase elevations occurred only at the 200-, and 300-mg dosages and were readily reversible on discontinuation of treatment.\n Acarbose at doses of 100, 200, and 300 mg administered three times daily for 16 weeks significantly reduced HbA1c levels and postprandial hyperglycemia. Treatment with acarbose is a safe and effective adjunct to dietary therapy for the treatment of NIDDM.", "To compare the therapeutic effects of the alpha-glucosidase inhibitor miglitol (BAY m 1099), the sulfonylurea glibenclamide, and placebo on parameters of metabolic control and safety in patients with NIDDM that is inadequately controlled by diet alone.\n After a 4-week placebo run-in period, 201 patients in 18 centers in 4 countries were randomized in a double-blind manner to miglitol (50 mg t.i.d., followed by 100 mg t.i.d.), glibenclamide (3.5 mg q.d/b.i.d.), or placebo for 24 weeks. Efficacy criteria were changes from baseline of HbA1c, fasting and postprandial blood glucose and insulin levels, body weight, and serum triglycerides.\n Efficacy was assessed in 119 patients who completed the full protocol, and the results were similar to those obtained in 186 patients who fulfilled the validity criteria for analysis. Compared with placebo, mean baseline-adjusted HbA1c decreased by 0.75% (P = 0.0021) and 1.01% (P = 0.0001) in the miglitol and glibenclamide treatment groups, respectively. Blood glucose decreased slightly in the fasting state and considerably in the postprandial state in both treatment groups but not in the placebo group. Fasting insulin levels increased slightly (NS) in all treatment groups; however, postprandial insulin levels decreased with miglitol, while increasing markedly with glibenclamide (P = 0.0001 between all treatment groups). Gastrointestinal side effects (flatulence and diarrhea) occurred mostly in the miglitol-treated patients, while some glibenclamide-treated patients had symptoms suggestive of hypoglycemia.\n Miglitol monotherapy is effective and safe in NIDDM patients. Compared with glibenclamide, it reduced HbA1c less effectively and caused more gastrointestinal side effects. On the other hand, glibenclamide, unlike miglitol, tended to cause hypoglycemia, hyperinsulinemia, and weight gain, which are not desirable in patients with NIDDM.", "To hypothesize if glibenclamide, which increases insulin levels, also increases leptin concentrations.\n Leptin is a hormone that regulates weight in mice. In obese humans, leptin concentrations are increased, suggesting resistance to the effects of this hormone. Although short-term infusion of insulin during the hyperinsulinemiceuglycemic clamp does not increase leptin concentration, the effect of oral antidiabetic agents on leptin concentration is unknown. Differing effects can be expected, since glibenclamide acts via stimulation of insulin secretion, whereas acarbose inhibits alpha-glucosidases of the small intestine and has no direct effect on insulin levels. We examined the effect of acarbose (n = 4), glibenclamide (n = 6), and placebo (n = 6) on insulin and leptin levels during 24-h periods before and after 16 weeks of therapy.\n We observed a significant diurnal variation in leptin concentrations. This was inversely related to insulin levels during the 24-h follow-up with usual diet. Neither the placebo nor acarbose altered leptin concentrations. However, glibenclamide increased leptin concentrations parallel to insulin levels. There were only minor changes in body weight during the l6-week follow-up: decrease in the placebo group (change -0.5 kg/m2, P = 0.07) and acarbose (change -0.7 kg/m2, P = 0.046) and increase in the glibenclamide group (change 0.8 kg/m2, P = 0.27). However, individual subjects who gained weight had increases in their leptin concentrations. The diurnal variation in leptin concentrations was preserved after glibenclamide.\n Glibenclamide increases circadian leptin and insulin concentrations, whereas acarbose does not. This observation may help to explain weight gain in subjects treated with glibenclamide and stable weight in those treated with acarbose in the long run.", "Acarbose delays the release of glucose from complex carbohydrates and disaccharides by inhibiting intestinal alpha-glucosidases, attenuating postprandial increments in blood glucose and insulin. This multicenter double-blind study compared the efficacy and safety of acarbose with placebo in the treatment of obese subjects with non-insulin-dependent diabetes mellitus (NIDDM) managed by diet.\n Two hundred twelve obese subjects with NIDDM who had not received any diabetic medication for at least 12 weeks were randomized to receive acarbose or placebo. The subjects were stratified by fasting glucose level above or below 11.1 mmol/L (200 mg/dL). Based on the subject's therapeutic response and tolerance, the acarbose dosage was titrated from 50 to 300 mg three times per day. This 36-week study consisted of a 6-week pretreatment period, a 24-week double-blind treatment period, and a 6-week posttreatment period.\n Ninety-one subjects given acarbose and 98 subjects who received placebo were evaluable for efficacy. During a standard meal tolerance test at the double-blind end point, the differences between treatment groups in mean change from baseline were as follows: 0.9 mmol/L (16 mg/dL) for fasting plasma glucose level, approximately 2.8 mmol/L (50 mg/dL) for postprandial plasma glucose level, and 0.59% (P < .0001) for hemoglobin A1c concentration (for all three measurements, values decreased in the acarbose group and increased in the placebo group).\n Acarbose improved both fasting and postprandial hyperglycemia and improved overall glycemic control as measured by the hemoglobin A1c level. These findings suggest a beneficial role for acarbose in combination with diet in the treatment of obese subjects with NIDDM.", "OBJECTIVE; To examine the effects of diet and diet with voglibose or glyburide on abdominal adiposity and metabolic abnormalities in patients with type 2 diabetes.\n A total of 36 Japanese patients with newly diagnosed type 2 diabetes (50.8 +/- 8.6 years of age, BMI 24.5 +/- 3.5 kg/m(2)) and 273 normal control subjects were studied. The patients were treated for 3 months with diet alone (30 kcal/kg per day) (n = 15), diet with voglibose (n = 12), or diet with glyburide (n = 9). They underwent 75-g oral glucose tolerance testing, assessment of insulin sensitivity (SI), and acute insulin response (AIR) with intravenous glucose tolerance testing based on the minimal model, and measurement of abdominal visceral adipose tissue area (VAT) and subcutaneous adipose tissue area (SAT) by computed tomography before and after treatment.\n The diabetic patients had comparable SAT but larger VAT than the control subjects. With a mean weight loss of 2-3 kg, VAT and SAT were decreased similarly in all treatment groups. The VAT-to-SAT ratio was decreased only in the voglibose group. Glycemic control and serum lipid profiles were improved in all groups. Changes in glycemic control after diet were closely correlated with changes in VAT but not with changes in SAT. SI and AIR were unchanged in the diet group but were improved in the voglibose and glyburide groups.\n In Japanese patients with newly diagnosed type 2 diabetes who were relatively lean but had excess VAT, diet with or without voglibose or glyburide effectively reduced VAT. Decrease in VAT was closely associated with improvement of glycemic control with diet. Additional use of voglibose or low-dose glyburide had no detrimental effects on abdominal adiposity and had beneficial effects on SI and AIR.", "To assess the efficacy, safety, and tolerability of acarbose versus placebo during a 24-week treatment period in Asian type 2 diabetic patients with dietary failure.\n After a 6-week screening period, 126 multiethnic Asian type 2 diabetic patients (64 men, 62 women; mean age +/- SD, 53.4 +/- 10 years) were randomized to receive acarbose (n = 63) or placebo (n = 63). The dosage was increased from 50 mg t.i.d. at week 0 to 100 mg t.i.d. at week 4. Patients were then followed up at weeks 10, 16, and 24. At each visit, body weight, blood pressure, and metabolic indexes were measured. At weeks 0 and 24, fasting plasma glucose and insulin were measured before and 1 h after the administration of an individually tailored breakfast.\n Using the intention-to-treat analysis, there were greater reductions in (mean [95% CI]) HbA1c (-0.70 [-1.00 to -0.39] vs. -0.27% [-0.54 to 0]; P = 0.04), fasting plasma glucose (-0.37 [-0.75 to 0.02] vs. 0.41 mmol/l [-0.08 to 0.90]; P = 0.017) and 1-h plasma glucose (-0.77 [-1.44 to -0.10] vs. 0.65 mmol/l [-0.07 to 1.36]; P = 0.05) in the acarbose group compared with the placebo group. With acarbose treatment, 78% of patients achieved an HbAlc < 8% compared with 56% in the placebo group (P = 0.003). There was a greater reduction in body weight (-1.31 [-2.46 to -0.15] vs. 0.16 kg [-3.36 to 0.10]; P = 0.02) and higher incidence of flatulence (56 vs. 37%; P = 0.032) in the acarbose than in the placebo group. Using baseline HbA1c and race as covariates, there were no significant interethnic differences in treatment responses (P = 0.232 for treatment-race interaction; P < 0.001 for treatment effect). The dropout rates were similar between the two groups (acarbose, 11 of 63; placebo, 6 of 63). There were no significant laboratory adverse events in either group.\n In this multicenter study involving six ethnic groups, acarbose 100 mg t.i.d. was an effective, safe, and generally well-tolerated therapy in Asian type 2 diabetic patients with dietary failure. In some patients with troublesome gastrointestinal symptoms, a lower dosage may be necessary.", "The aim of this double-blind, placebo-controlled, multinational, five-arm study was to investigate the dose-response relationship of acarbose as a first-line drug in the treatment of type 2 diabetes (non-insulin dependent) over a range of minimal and maximal doses according to the European recommendations. The study included 495 patients from 7 countries who were insufficiently controlled with diet alone (glycosylated haemoglobin HbA1C 6.5%-9%). Acarbose, 25, 50, 100 or 200 mg t.i.d., or placebo t.i.d. was given for 24 weeks. Even a low dosage of 25 mg t.i.d. acarbose reduced fasting and postprandial blood glucose levels (1 h postprandial -11.6%; 2 h postprandial -11.3%). Acarbose in a dosage of 200 mg t.i.d. had the greatest effect on these parameters. In the placebo group the mean 2 h postprandial area under the curve (AUC) value for blood glucose was 22.6 mmol/l after 24 weeks' therapy. The mean 2 h postprandial AUC values in the patients given acarbose at doses of 25, 50, 100 and 200 mg t.i.d. were found to be 21.2, 19.6, 20.3 and 18.5 mmol/l, respectively. The corresponding HbA1C values for the placebo and acarbose groups were 7.83%, 7.37%, 7.08%, 6.98% and 6.79%. Interestingly, there was a plateau of blood glucose level at a dosage of 50-100 mg t.i.d. The frequency of flatulence decreased with the duration of drug therapy, but we could not find a linear relationship between doses of acarbose and the gastrointestinal side effects. Less than 3% of patients stopped tablet intake due to adverse events.", "nan", "Acarbose inhibits alpha-glucosidases of the small intestine and thus delays glucose release from complex carbohydrates. Therefore, its efficacy and acceptability as a first-line drug in non-insulin-dependent diabetes mellitus (NIDDM) insufficiently treated with diet alone was tested in a randomized double-blind placebo-controlled study.\n Ninety-four NIDDM subjects, aged 43-70 yr with average body mass index of 28 kg/m2 and undergoing a pretreatment period of at least 3 mo with diet alone, were treated with 100 mg acarbose three times daily or placebo for 24 wk. The patients were recruited after a 4-wk screening period of dietary reinforcement. The inclusion limits for patients termed diet not satisfactory were fasting blood glucose (FBG) greater than or equal to 7.8 mM and/or postprandial blood glucose (BG) greater than or equal to 10 mM.\n FBG was lowered in the acarbose group from 9.8 to 8.4 mM and in the placebo group from 10.2 to 9.6 mM after 24 wk (P = 0.007 vs. placebo). The most impressive therapeutic effect was a highly significant reduction of postprandial hyperglycemia for at least 5 h after the test meal (1-h postprandial BG with acarbose 10.4 mM and placebo 13.5 mM at 24 wk, P less than 0.001) accompanied by a significant decrease in HbA1 (acarbose 8.65%, placebo 9.32%, P = 0.003). Whereas C-peptide and fasting serum insulin were not significantly affected by acarbose, postprandial insulin increment was approximately 30% lower after 24 wk compared with placebo. Furthermore, acarbose significantly reduced 1-h postprandial triglyceride levels. After an initial phase of greater than 4 wk (when 76.6% in the acarbose group vs. 28% on placebo complained about flatulence, P less than 0.001), the drug was well accepted. At the end of the study, only 32% showed mild or moderate gastrointestinal sensations.\n Extrapolation shows that acarbose is an efficient and acceptable drug for the treatment of NIDDM with poor metabolic control by diet alone. It has beneficial effects on postprandial hyperinsulinemia and postprandial hypertriglyceridemia.", "To study the effect of acarbose, an alpha-glucosidase inhibitor, on insulin release and insulin sensitivity in elderly patients with type 2 diabetes.\n Elderly patients with type 2 diabetes were randomly treated in a double-blind fashion with placebo (n = 23) or acarbose (n = 22) for 12 months. Before and after randomization, subjects underwent a meal tolerance test and a hyperglycemic glucose clamp study designed to measure insulin release and sensitivity.\n After 12 months of therapy there was a significant difference in the change in fasting plasma glucose levels (0.2 +/- 0.3 vs. -0.5 +/- 0.2 mmol/l, placebo vs. acarbose group, respectively; P < 0.05) and in incremental postprandial glucose values (-0.4 +/- 0.6 vs. -3.5 +/- 0.6 mmol/l, placebo vs. acarbose group, P < 0.001) between groups. There was a significant difference in the change in HbA(1c) values in response to treatment (0.4 +/- 0.2 vs. -0.4 +/- 0.1%, placebo vs. acarbose group, P < 0.01). The change in fasting insulin in response to treatment (-2 +/- 2 vs. -13 +/- 4 pmol/l, placebo vs. acarbose group, P < 0.05) and incremental postprandial insulin responses (-89 +/- 26 vs. -271 +/- 59 pmol/l, placebo vs. acarbose group, P < 0.01) was also significantly different between groups. During the hyperglycemic clamps, glucose and insulin values were similar in both groups before and after therapy However, there was a significant difference in the change in insulin sensitivity in response to treatment between the placebo and the acarbose groups (0.001 +/- 0.001 vs. 0.004 +/- 0.001 mg/kg x min(-1) [pmol/l](-1), respectively, P < 0.05)\n Acarbose increases insulin sensitivity but not insulin release in elderly patients with diabetes.", "Individuals with type 2 diabetes mellitus (n = 105; age 36-71 years) on diet therapy alone, and with quite good glycaemic control (mean HbA1c approximately 7.0%) were randomized to receive acarbose (100 mg three times daily) or placebo for 16 weeks, and changes in clinical and metabolic parameters indicative of Syndrome X were monitored. Fasting levels of glucose, glycosylated haemoglobin (HbA1c), true insulin, proinsulin, fibrinogen and lipids were measured four times weekly, and glucose, insulin, proinsulin and triglyceride responses to a standardized 1.6 MJ breakfast were determined at 0, 1 and 2 h post meal. Analysis was on an intention-to-treat basis. Fasting levels of glucose (P < 0.0001), triglycerides (P = 0.03) and HbA1c (P = 0.003) were reduced by acarbose over the 16 weeks of treatment. The mean change in HbA1c from week 0 to 16 differed by 0.4% (P = 0.003) between the two groups. Insulin (P = 0.06), proinsulin (P = 0.07) and glucose (P < 0.0001) responses to the standard meal were reduced. These data show that acarbose reduces fasting glucose and triglyceride levels, lowers HbA1c and limits the glycaemic and insulin response to food in individuals with type 2 diabetes mellitus with Syndrome X. Pharmacological agents that improve the metabolic environment and reduce insulin resistance have the potential to limit the progression of atherogenesis associated with type 2 diabetes mellitus.", "Acarbose delays release of glucose from complex carbohydrates and disaccharides by inhibiting intestinal alpha-glucosidases, thereby attenuating postprandial increments in blood glucose and insulin. This multicenter, double-blind, placebo-controlled study compared the efficacy and safety of diet alone, acarbose, tolbutamide, and acarbose-plus-tolbutamide in non-insulin-dependent diabetes mellitus (NIDDM) patients.\n A total of 290 patients with NIDDM and fasting plasma glucose levels of at least 140 mg/dL were randomized to receive treatment TID with acarbose 200 mg, tolbutamide 250 to 1,000 mg, a combination of both drugs, or placebo. A 6-week run-in period was followed by double-blind treatment for 24 weeks, then a 6-week follow-up period.\n All active treatments were superior (P < 0.05) to placebo in reducing postprandial hyperglycemia and HbA1c levels. The ranking in order of efficacy was: acarbose-plus-tolbutamide, tolbutamide, acarbose, and placebo. The postprandial reductions in glucose were approximately 85 mg/dL for acarbose-plus-tolbutamide, 71 mg/dL for tolbutamide, 56 mg/dL for acarbose, and 13 mg/dL for placebo. Tolbutamide was associated with increases in body weight and postprandial insulin levels when taken alone, but these were ameliorated when tolbutamide was taken in combination with acarbose. Acarbose alone or in combination with tolbutamide caused significantly more gastrointestinal adverse events (mainly flatulence and soft stools or diarrhea) than tolbutamide or placebo, but these were generally well tolerated. Clinically significant elevations in hepatic transaminase levels occurred in 3 patients in the acarbose group and 2 in the acarbose-plus-tolbutamide group. Transaminase levels returned to normal when therapy was discontinued.\n Acarbose was effective and well tolerated in the treatment of NIDDM. Control of glycemia was significantly better with acarbose compared with diet alone. Acarbose-plus-tolbutamide was superior to tolbutamide alone.", "The efficacy of the new intestinal alpha-glucosidase inhibitor, miglitol, and glibenclamide were compared in a 6-month double-blind controlled protocol involving 100 non-insulin dependent diabetic patients under diet alone. HbA1c levels (initially between 7 and 11%) were reduced (p < 0.05): -0.78 +/- 0.21% after miglitol and -1.18 +/- 0.20% after glibenclamide. The difference between the two treatments was not significant, although glibenclamide appeared to be more active than miglitol at 8 (p = 0.002) and 16 weeks (p = 0.01) but not at 24 weeks. Fasting glycaemia decreased after miglitol (8.7 +/- 0.3 vs 9.6 +/- 0.3 mmol/l, p = 0.005) and after glibenclamide (8.0 +/- 0.3 vs 9.1 +/- 0.3, p = 0.007). After miglitol, a decrease was noted after breakfast (p < 0.001) and lunch (p < 0.001). The same was true for glibenclamide (p = 0.004 and p < 0.001 respectively). A significant reduction in glucose incremental area during a standard meal test was noted at the end of miglitol (p = 0.008) or glibenclamide treatment (p = 0.04). Subgroups of nonresponders to both treatments were identified (10/49 with miglitol, 9/47 with glibenclamide). Side effects were recorded in 10 patients treated with miglitol (flatulence and meteorism, diarrhoea, 1 discontinued therapy) and in 10 treated with glibenclamide (asthenia, sensation of hunger). This study indicates that miglitol is suitable for initial application in diet-resistant Type 2 diabetic patients, providing, a persistent effect and acceptable side effects.", "To compare the effect of acarbose and gliclazide on clinical findings, biochemical parameters and safety in type 2 diabetic patients insufficiently controlled with medical nutrition therapy (MNT).\n Seventy-two patients (age 35-70 years, BMI < or = 35 kg/m2), who had not taken any oral antidiabetic drug previously, were randomised into two groups after a four-week placebo period, and treated for 24 weeks with acarbose (100 mg two to three times daily) and gliclazide (40-80 mg twice daily). The study was open and 57 patients (33 males and 24 females) completed it. MNT was provided for each patient based on personal requirements as defined by a dietitian. The effect of treatment was evaluated by fasting and postprandial (PP) metabolic parameters (blood glucose, insulin and C peptide levels), HbA1c and plasma lipid levels. In addition, side-effects were recorded and clinical examinations performed.\n Both drugs were effective in reducing of HbA1c, fasting and PP blood glucose levels. However, PP serum insulin levels in the gliclazide group increased more than those in the group treated with acarbose (p = 0.007). Moreover, a small weight reduction was obtained with acarbose treatment but not with gliclazide. Lipid levels were favourably affected by both drugs. Total cholesterol levels decreased in both groups, the decrease only reaching significance in the acarbose group (p = 0.013). However, serum levels of LDL cholesterol decreased in both groups (acarbose and gliclazide, p = 0.033 and p = 0.023, respectively), but the ratio of HDL to LDL cholesterol increased in the acarbose group only (p = 0.045). Both treatments were generally well tolerated. Common complaints in the acarbose group were flatulence and meteorism (29.6%). However, 10.0% of the patients in the gliclazide group reported at least one mild hypoglycaemic episode.\n The results of the study demonstrate that acarbose and gliclazide were reasonably effective in improving metabolic control in patients insufficiently controlled with diet alone, and both treatments were well tolerated. Because of its effects on weight reduction and PP hyperinsulinaemia, acarbose may be preferred as a first-line drug, particularly in the treatment of overweight type 2 diabetic patients.", "The efficacy and safety of acarbose therapy (100 mg tds for 24 weeks) was investigated in a placebo-controlled double-blind study in patients with non-insulin dependent diabetes mellitus who could not achieve satisfactory glycaemic control by diet alone. In the acarbose group, the 2 h postprandial blood glucose and haemoglobin A1 levels decreased significantly from 14.0 mmol l-1 to 11.3 mmol l-1 and from 11.1% to 9.7%, respectively. In the placebo group, the 2 h postprandial blood glucose (14.4 mmol l-1 to 14.2 mmol l-1) and the hemoglobin A1 level (10.3% to 9.9%) showed no significant changes. A 75 g oral glucose tolerance test was performed before and after the study, the difference not being significant in either the acarbose group or the placebo group. The incidence of side-effects (mainly gastrointestinal symptoms such as flatulence and abdominal distension) was high at 78.9% in the acarbose group and 61.1% in the placebo group. However, there was no significant difference between the groups, and side-effects in the acarbose group tapered during the trial, suggesting that some at least were not related to the drug. From these findings, it was concluded that acarbose is an effective new treatment for diet treated non-insulin-dependent diabetic patients." ]

[ "6998390", "2959925", "10204127", "10848854", "1434726", "9782018", "9467607", "8861437", "2663737", "9515521", "6454249", "10357049", "7655967", "3522528", "6375599", "1353510", "7552537", "8104978", "2670608", "3408172", "2416085", "1728688", "8377241", "10753692", "2691482", "686894", "3512507", "2191752", "6084675", "6638856", "2527316", "8541198", "8201718", "3324594" ]

[ "Prophylactic antibiotics in vascular surgery. Topical, systemic, or both?", "[Antibioprevention in reconstructive arterial surgery. A double-blind study].", "A comparison of teicoplanin versus cephradine plus metronidazole in the prophylaxis of post-operative infection in vascular surgery.", "Two-year results of a randomized controlled trial of rifampicin-bonded extra-anatomic dacron grafts.", "Comparative study of cefazolin, cefamandole, and vancomycin for surgical prophylaxis in cardiac and vascular operations. A double-blind randomized trial.", "Early results of a randomized trial of rifampicin-bonded Dacron grafts for extra-anatomic vascular reconstruction. Joint Vascular Research Group.", "The rifampicin-bonded gelseal graft.", "Prophylaxis of graft infection with rifampicin-bonded Gelseal graft: 2-year follow-up of a prospective clinical trial. Italian Investigators Group.", "Controlled trial of cephradine versus cefuroxime in vascular surgery.", "Duration of antimicrobial prophylaxis in vascular surgery.", "Prevention of synthetic arterial graft infections by improved hygienic routine and dicloxacillin administration.", "Prospective, randomized, double-blind trial comparing teicoplanin and cefazolin as antibiotic prophylaxis in prosthetic vascular surgery.", "A new \"closed\" in situ vein bypass technique results in a reduced wound complication rate.", "Prophylactic Timentin in patients undergoing thoracic or vascular surgery.", "Effects of prophylactic antibiotics in vascular surgery. A prospective, randomized, double-blind study.", "Cost-effectiveness analysis of the use of chlorhexidine detergent in preoperative whole-body disinfection in wound infection prophylaxis.", "Oral ciprofloxacin versus intravenous cefuroxime as prophylaxis against postoperative infection in vascular surgery: a randomised double-blind, prospective multicentre study.", "Does the addition of pre-operative skin preparation with povidone-iodine reduce groin sepsis following arterial surgery?", "Do preoperative chlorhexidine baths reduce the risk of infection after vascular reconstruction?", "Risk factors in vascular surgical sepsis.", "Prophylactic vancomycin versus placebo in arterial prosthetic reconstructions.", "Cefuroxime versus cefazolin as prophylaxis in vascular surgery.", "Cefamandole versus cefazolin in vascular surgical wound infection prophylaxis: cost-effectiveness and risk factors.", "Intraoperative contamination of synthetic vascular grafts. Effect of glove change before graft implantation. A prospective randomised study.", "The prophylactic activity of amoxycillin/clavulanate and cefoxitin in vascular surgery--a randomized clinical study.", "Antibiotic prophylaxis in vascular surgery.", "Antibiotic prophylaxis in vascular reconstructive surgery: a double-blind placebo-controlled study.", "Vacuum drainage of groin wounds after vascular surgery: a controlled trial.", "Comparison of prophylactic antibiotic regimens in patients undergoing vascular surgery.", "The effect of cephradine prophylaxis on wound infection after arterial surgery through a groin incision.", "Prophylactic closed suction drainage of femoral wounds in patients undergoing vascular reconstruction.", "Skin closure and the incidence of groin wound infection: a prospective study.", "Randomized prospective study of angioscopically assisted in situ saphenous vein grafting.", "Single-dose v. short-term antibiotic therapy for prevention of wound infection in general surgery. A prospective, randomized double-blind trial." ]

[ "A prospective, randomized, blinded study was performed to determine whether prophylactic antibiotics would reduce the incidence of infection in peripheral vascular surgery and whether the route of antibiotic administration was important. Patients undergoing a vascular procedure with a groin incision were allocated to one of four groups with respect to prophylactic antibiotics. Group I received no antibiotic. Group II had topical cephradine instilled in their incisions prior to closure. Group III received a 24-hour perioperative course of intravenous cephradine, and Group IV received both topical and intravenous cephradine. Groin and abdominal incisional infections were significantly reduced (p < 0.01) among patients who received prophylactic antibiotics by either the topical, systemic, or combined routes of administration. No significant differences were noted among the three antibiotic groups. Profundoplasty, femoral embolectomy, and femoral aneurysm repair were each associated with an increased incidence of infection (p < 0.01). Other risk factors were only important in patients not receiving antibiotics. Either intraoperative topical antibiotics or perioperative systemic antibiotics prevent infection in peripheral vascular surgery, but antibiotic administration by both routes is unnecessary.", "Routine antibiotic prophylaxis in reconstructive vascular surgery was established on a small number of controlled trials. A comparative double-blind study of cefazolin versus placebo was conducted in 179 patients who underwent reconstructive vascular surgery over a 23 month period. The surgical procedures were divided in three groups: aorto-iliac reconstructions (112 cases) infra-inguinal reconstructions (50 cases), extra anatomic by-passes (17 cases). The arterial diseases encountered and the systemic and local conditions in favour of infection were equal in the 2 randomized groups. Among the 93 patients who received cephazolin, 13 (13.97%) developed an infection which was systemic in 1 case and local in 12 cases; 1 amputation and 1 death were observed in this group. In the placebo group 26 patients among 86 (30.23%) developed an infection, systemic in 4 cases and local in 22 cases with 1 death and 1 amputation. Statistical analysis (chi-square test) showed a significant difference in favour of the active substance. A short time massive dose of antibiotic administered in the perioperative period is the best method to reduce the incidence of infection in this type of surgery.", "A total of 272 patients were enrolled into this prospective, unblinded, randomized comparison of single-dose teicoplanin vs three doses of cephradine plus metronidazole as prophylaxis for vascular surgery at St James's and Seacroft Hospitals, Leeds, UK. In all, 71.3% of patients (194/272) were enrolled at St James's University Hospital. Patients received either a single dose of teicoplanin, 6 mg/kg i.v., or cephradine, 1 g i.v. with metronidazole, 1 g rectally, at induction of anaesthesia followed by two further 1 g doses of cephradine and metronidazole 8 and 16 hours later. There were 136 patients in each treatment group. The most common operations were femoropopliteal grafts (96) and aortic aneurysm repairs (47). In the 'intention-to-treat' analysis, primary wound infections were seen in 4.4% of patients (6/136) receiving teicoplanin and 5.9% of patients (8/136) receiving cephradine plus metronidazole (95% CI -6.7%, +3.8%). Other disturbances to wound healing occurred in 23 patients (11 in the teicoplanin and 12 in the cephradine plus metronidazole group). Secondary respiratory tract infections occurred in 17 patients (8 receiving teicoplanin and 9 receiving cephradine plus metronidazole). In the evaluable patients analysis, primary wound infections occurred in 3.5% of patients (4/114) receiving teicoplanin and 5.1% of patients (6/117) receiving cephradine plus metronidazole. Staphylococcus aureus and Proteus sp. were the most common pathogens in primary wound infections. Despite the absence of Gram-negative cover in the teicoplanin group, Gram-negative infections occurred more often in the cephradine plus metronidazole group. Surgery of the lower extremities carried the highest risk of post-operative infection. Rates of infection were significantly higher at Seacroft Hospital (P = 0.001), and significantly higher for cephradine plus metronidazole between the two hospitals (P = 0.0008). Adverse events occurred in 40 patients receiving teicoplanin (29.4%) and 39 patients receiving cephradine plus metronidazole (28.7%). In 19 patients receiving teicoplanin (14%) and 15 receiving cephradine plus metronidazole (11%) these events were considered to be related to the study drugs. The most often reported events were infections, cardiac events and vascular phenomena (haematoma or emboli). Marked changes in haematological parameters and liver function tests were noted seven days after operation in patients in each treatment group, but these resolved quickly as the effects of the operation subsided. ESR remained elevated in both groups at the six-month follow-up assessment. It is concluded from this two-centre study that a single dose of teicoplanin shows similar efficacy to a three-dose regimen of cephradine plus metronidazole as prophylaxis for wound infection in vascular surgery. Both regimens were well tolerated, and there was an equal incidence of adverse events in the two regimens, which reflected the poor general health status of this elderly study population.", "nan", "Three-hundred twenty-one adults undergoing cardiac or major vascular operations were randomized to receive intravenous cefazolin, cefamandole, or vancomycin for prophylaxis against surgical infection in a double-blind trial. All three regimens provided therapeutic blood levels throughout operation in patients studied undergoing cardiopulmonary bypass. The prevalence of surgical wound infection was lowest with vancomycin (4 infections [3.7%] versus 14 [12.3%] and 13 [11.5%] in the cefazolin and cefamandole groups, respectively; p = 0.05); there were no thoracic wound infections in cardiac operations in the vancomycin group (p = 0.04). The mean duration of postoperative hospitalization was lowest in the vancomycin group (10.1 days; p < 0.01) and highest in the cefazolin group (12.9 days). Prophylaxis with vancomycin or cefamandole, compared with cefazolin, did not prevent nosocomial cutaneous colonization by methicillin-resistant coagulase-negative staphylococci; colonization or infection with vancomycin-resistant staphylococci or enterococci was not detected. Adverse effects attributable to the prophylactic regimen were infrequent in all three groups. Eight patients given vancomycin became hypotensive during administration of a dose, despite infusion during a 1-hour period; however, slowing the rate of administration and pretreating with diphenhydramine allowed vancomycin to be resumed and prophylaxis completed uneventfully in five of the patients. We conclude that administration of vancomycin (approximately 15 mg/kg), immediately preoperatively, provides therapeutic blood levels for surgical prophylaxis throughout most cardiac and vascular operations, resulting in protection against postoperative infection superior to that obtained with cefazolin or cefamandole. Vancomycin deserves consideration for inclusion in the prophylactic regimen (1) for prosthetic valve replacement and prosthetic vascular graft implantation, to reduce the risk of implant infection by methicillin-resistant coagulase-negative staphylococci and enterococci; (2) for any cardiovascular operation if the patient has recently received broad-spectrum antimicrobial therapy; and (3) for all cardiovascular operations in centers with a high prevalence of surgical infection with methicillin-resistant staphylococci or enterococci. Guidelines for dosing and administration of vancomycin for cardiovascular surgical prophylaxis are provided.", "The aim of this study was to determine whether the routine use of an antibiotic-bonded gelatin-coated Dacron graft could reduce the incidence of prosthetic graft infection. Extra-anatomic grafts were chosen for study as they have the highest risk of graft infection. This paper reports early results up to 1 month after surgery.\n This multicentre study involved 14 vascular units in the UK. A total of 257 patients underwent extra-anatomic bypass. Patients were randomized to rifampicin bonding (1 mg/ml rifampicin soak for 15 min before graft insertion) or a control group. Routine three-dose antibiotic prophylaxis was administered to patients in both groups.\n There were 178 men and 79 women of median age 69 (range 43-92) years. Rifampicin-bonded (n=123) and control (n=134) groups were well matched for clinical details, risk factors and operative techniques. No side-effects were noted from rifampicin bonding. Only one patient (in the control group) developed a graft infection and this proved fatal. There were no significant differences between bonded and unbonded grafts in terms of perioperative mortality rate (9 and 5 per cent respectively), median hospital stay (10 days for both groups), total infective complications (15 and 21 per cent respectively) or need for postoperative antibiotics (13 and 18 per cent respectively).\n Early results from this study have not identified any significant advantage in the routine use of rifampicin bonding, but the rate of graft infection was very low (0.4 per cent). Gelatin coating alone may provide protection against infection. Definitive recommendations about the role of antibiotic bonding cannot be made until longer follow-up becomes available.", "nan", "Between March 1991 and June 1992, 600 patients were treated with mono-, bifemoral or iliofemoral arterial graft revascularization for occlusions and/or aneurysms. The patients were divided into two groups: group A (n = 296) received a Gelseal Vascutek graft immersed for 15 min before implant in a solution containing 1 mg/ml rifampicin; group B (n = 304) received an untreated Gelseal Vascutek graft. Both groups received perioperative antibiotic treatment with cephalosporins. Clinical follow-up was performed at 1, 6, 12 and 24 months after surgery to exclude signs of graft infection. Statistical analysis (X(2)) of pre-, intra- and postoperative risk factors showed both groups to be well matched. Among 600 patients treated, the 2-year follow-up showed 12 cases of graft infection (2.0%): five in group A (1.7%) and seven in group B (2.3%) (P = n.s.). All cases of graft infection originated in the groin and Staphylococcus aureus was isolated in 50% of cases. Statistical analysis (Mann-Whitney U test) showed a significant prevalence of lymphatic complications and immediate redo surgery in patients with graft infection. Of the 12 cases with infection, one was lost to follow-up, three were treated with total graft removal, six with partial graft removal and two with conservative therapy: there were no deaths. In spite of the relatively limited series and follow-up, no statistically significant difference emerged from the clinical use of vascular grafts pretreated with antibiotics.", "Two hundred and three consecutive patients undergoing acute or elective vascular reconstructions (N = 162) or amputations (N = 41) were randomized to receive either a single dose of cephradine 2 g intravenously or cefuroxime 1.5 g intravenously at induction of anaesthesia. Infective morbidity in both groups was assessed post-operatively as was therapeutic antibiotic prescribing. No significant differences in septic complications were found between patients receiving cefuroxime or cephradine. In addition, tissue penetration of each antibiotic was assessed by assay of serum and tissue specimens. Serum levels of cefuroxime were significantly less than cephradine 10 min after injection (median concentrations 115 micrograms/ml versus 182 micrograms/ml, p less than 0.01 Wilcoxon), but there were no differences in tissue penetration.", "This randomized clinical trial compares the incidence of wound infection after vascular surgery in patients who received prophylaxis using the same antibiotic as either a single-dose or a multiple-dose regimen (until the lines/drain tubes were removed, but not for more than 5 days).\n Each of the 302 patients who entered the study received ticarcillin 3.0 g/clavulanate 0.1 g (Timentin) intravenously immediately after the induction of anesthesia. Patients randomized to the multiple-dose group received an average of 14.3 doses (range 9 to 20).\n The incidence of wound infections was 18% (28 of 153) for patients in the single-dose group and 10% (15 of 149) for patients in the multiple-dose group (P = 0.04; relative risk estimate = 2.00, 95% confidence interval = -1.02 to 3.92).\n A multiple-dose antibiotic regimen, rather than single-dose therapy, provides optimal prophylaxis against wound infection for patients undergoing vascular surgery.", "30/60 patients electively reconstructed with synthetic arterial grafts were randomly treated with dicloxacillin per- and postoperatively for 6 days. Wound infections occurred in 10 of the non-treated patients. 1 of whom had a graft infection. In the dicloxacillin group no wound infection was recorded. Overgrowth with bacteria resistant to isoxazolylpenicillin was not noticed during treatment. No late infections occurred. In comparison with previous results, improved hygienic routines before, during and after operation reduced the incidence of postoperative graft infections from 15 to 3%. As postoperative infections after synthetic arterial graft implantation are serious complications, per- and postoperative antibiotic treatment seems justified as a complement to a rigorous hygienic routine.", "To compare efficacy, tolerability, and cost of antibiotic prophylaxis with teicoplanin and cefazolin in clean prosthetic vascular surgery, a randomized, prospective, double-blind study was performed at the Vascular Surgery Unit of a tertiary-care university hospital. Two-hundred thirty-eight consecutive patients undergoing elective, clean, abdominal or lower-limb prosthetic vascular surgery were allocated to receive a single intravenous dose of teicoplanin (400 mg) or cefazolin (2 g) at the induction of anesthesia. Surgical-site infections occurred in 5.9% of teicoplanin recipients (4.2% wound infection, 1.7% graft infection) and 1.7% of cefazolin recipients (1.7% wound infection, 0% graft infection) (P=0.195). Other postoperative infections occurred in 10% of teicoplanin recipients (pneumonia 7%, urinary tract infection 3%) and 12% of cefazolin recipients (pneumonia 7%, urinary tract infection 2.5%, bloodstream infections 2.5%). Overall mortality rate was 3.4% in teicoplanin recipients (4 patients) and 2.5% in cefazolin recipients (3 patients). Infective deaths occurred in one patient for each group. The two prophylactic regimens were well tolerated. Cost savings of US $52,510 favoring cefazolin were related to the lower acquisition cost (US $1034 vs US $4740) and to the shorter duration of the hospital stay (1762 days vs 1928 days). Cefazolin can still be regarded as the drug of choice for prophylaxis in clean vascular surgery.", "This prospective randomised multicentre trial was conducted to test whether a new \"closed\" technique for in situ vein bypass would result in a lower frequency of wound complications, without negative effects on patency rates and without an intolerable increase in residual arteriovenous fistulae compared to the conventional \"open\" technique.\n We have developed a new \"closed\" technique using a co-axial catheter embolisation system for intra-operative coil embolisation of side branches, in order to avoid long incisions.\n In four centres and 95 patients, 97 in situ bypasses were performed: 47 \"closed\" and 50 \"open\". Randomisation was stratified for below knee femoropopliteal bypasses (60) and femorocrural bypasses (37). Indications were disabling intermittent claudication (29), restpain (26) or ulcers and/or necrosis (42).\n Postoperative mortality was 2% (one in the \"closed\", one in the \"open\" group). A total number of 16 (34%) wound complications (grade 1, 2 and 3) occurred in the closed group compared to 36 (72%) in the open group (p < 0.05). Deep wound complications (grade 2) occurred in six patients (13%) of the \"closed\" group, compared to 15 (30%) in the \"open\" group. In both groups, three patients (6%) developed deep wound complications including the bypass area (grade 3). In the \"closed\" group, 20 patients needed additional treatment for arteriovenous fistulae, compared to four in the \"open\" group. One-year patency rates did not show a statistically significant difference: primary patency rates were 65% and 61% and secondary patency rates were 86% and 76% respectively for the \"closed\" and \"open\" group.\n These results indicate that a \"closed\" technique reduces wound complication rate, without negative effects on the short term patency rates. The \"closed\" technique results in an increased number of postoperative treatments for residual arteriovenous fistulae.", "Timentin (ticarcillin + clavulanic acid) and cefamandole were compared in 484 patients undergoing elective thoracic or vascular surgery. Two hundred and forty eight patients received three 3 g/200 mg injections of Timentin and 236 patients received three 0.75 g injections of cefamandole. The patients were evaluated at discharge. Among the 248 patients given Timentin, only six (2.4%) had a post-operative infection, while nine (3.8%) of the 236 patients given cefamandole had a post-operative infection. There was no statistically significant difference between the two treatment regimes. This comparative study shows that Timentin may be used for antibiotic prophylaxis of clean vascular or thoracic surgery.", "In a prospective, randomized, double-blind study the effects on infection rates of a 1-day and a 3-day course of cefuroxime versus placebo were studied in patients undergoing peripheral vascular surgery. During a 30-month study period 211 patients were randomized to one of three treatment groups: Group I Placebo; Group II cefuroxime 1 day; Group III cefuroxime 3 days. Cefuroxime was administered intravenously (1.5 g every 8 hours) and the first dose was given 1 hour before surgery. Wound infection rates in the three treatment groups were: Group I 16.7%; Group II 3.8% (p less than 0.05 vs placebo); Group III 4.3% (p less than 0.05 vs placebo). One graft infection occurred in 110 patients at risk (0.9%) and this occurred in the placebo group. No allergic reactions or other side effects were noted in any of the treatment groups. No cefuroxime-resistant bacteria were found in Group II or III. In conclusion, prophylactic administration of cefuroxime during 1 day significantly reduced the incidence of infectious complications following peripheral vascular surgery. Extension of the prophylaxis beyond the day of surgery offered no additional effect. The study supports the use of short-term prophylactic antibiotics in vascular surgery.", "A total of 3482 general surgical patients entered a trial in which they had a chlorhexidine or placebo detergent shower three times before elective clean wound or potentially contaminated surgery. Patients who showered with a chlorhexidine detergent (N = 1744) had a significant reduction in skin flora compared with those who showered with a placebo detergent (N = 1738). The majority of wound infections occurred outside hospital (312 outpatient infections vs. 201 inpatient infections). Wound infection rates were similar in the chlorhexidine and placebo groups (5.79% vs. 5.75% for inpatient infections and 8.54% vs. 9.38% for outpatient infections). The average hospital cost of both non-infected and infected patients was higher in the chlorhexidine group. The average cost of a non-infected chlorhexidine patient was 847.95 pounds as opposed to 804.60 pounds for a non-infected placebo patient, whilst the average cost of an infected patient was 1459.70 pounds (chlorhexidine) and 1414.22 pounds (placebo). A cross-match comparison of patients undergoing vascular surgery revealed no statistical significance in the difference between the two experimental groups. Patients were matched for age, sex, type of operation and surgeon. We conclude that preoperative whole-body disinfection with a chlorhexidine detergent is not a cost-effective treatment for reducing wound infection.", "To test the hypothesis that oral ciprofloxacin is equally effective as intravenous cefuroxime in preventing postoperative infectious complications in patients undergoing peripheral arterial surgery involving the groins.\n Prospective, randomised, double-blind multicentre study.\n 580 patients undergoing arterial surgery involving the groins were randomised to ciprofloxacin (Ciproxin, Bayer) 750 mg x 2 p.o. or cefuroxime (Zinacef, Glaxo) 1.5 g x 3 i.v. given only on the day of surgery. The primary endpoint was wound/graft infection within 30 days postoperatively. Wound infection was defined as pus.\n The wound infection rate in the ciprofloxacin group was 9.2% (27 patients) and in the cefuroxime group 9.1% (26 patients) according to intention to treat. For correct treatment the corresponding numbers were 9.5% (23 patients) and 9.7% (22 patients), respectively. There were three graft infections (0.5%). The infection rate was 7.1% (31/433) in the absence and 14.9% (22/147) in the presence of distal ulcers (p < 0.05). S. allreus was the most common bacteria isolated. Forty percent of the wound infections were localised to the groins. By multivariate analysis presence of distal ulcer was the only factor of prognostic significance.\n The infection rate was similar in the two groups. Thus, oral administration of ciprofloxacin is an attractive, cost-effective and safe alternative to prophylaxis in vascular patients capable of taking oral medication on the day of surgery.", "Sixty-four consecutive patients undergoing elective vascular surgery involving exposure of the femoral artery at the groin were randomized to one of two groups. Group A (N = 34) received twice-daily skin preparation with 10% aqueous povidone-iodine for 48 h preoperatively, while group B (N = 30) did not. Both groups were examined on a daily basis following surgery and any discharge from the wound was recorded and sent for bacteriological culture. The groups were well matched for age, sex and the type of vascular graft material used. In group A there were six (18.7%) groin wound infections and in group B there were five (17.2%). In this series of patients the addition of preoperative skin preparation with 10% povidone-iodine to standard peri-operative prophylaxis had no effect on the incidence of postoperative groin wound sepsis.", "Pathogenic organisms are frequently present on the skin of vascular patients and are a risk factor for postoperative infection. A randomised trial of preoperative antiseptic baths was performed in 64 high risk vascular patients to determine whether two chlorhexidine baths could reduce the incidence of postoperative sepsis. Although pathogenic organisms were isolated preoperatively in 35% of patients, the wound infection rate after chlorhexidine baths (26%) was greater, though not significantly, than after baths with non-medicated soap (11%). An alternative theory that infection arises via lymphatics in the limb was not confirmed when organisms could not be isolated from groin lymph nodes in a group of 35 patients. The case for preoperative antiseptic regimes in vascular surgery remains unproven.", "The risk factors for sepsis after vascular surgery were studied in 100 consecutive patients with lower limb arterial ischaemia. Patients were randomised either to a short or long course of antibiotic prophylaxis with amoxycillin/clavulanic acid combination (Augmentin). Pathogenic organisms were isolated from the skin preoperatively in 39 (36%) cases, significantly more frequently in patients with ischaemic rest pain and skin necrosis (66%) than rest pain alone (21%) (P = 0.0004) or claudication/aneurysm (11%) (P = 0.0001). All but three organisms isolated (5%) were sensitive to amoxycillin/clavulanic acid. A wound infection occurred after 21 (19%) reconstructions, significantly more frequently both in patients suffering rest pain with skin necrosis (P = 0.001) and rest pain without skin necrosis (P = 0.04) compared with claudication/aneurysm. Sixteen of the 21 patients with a wound infection had at least one organism isolated from their skin preoperatively (P = 0.0001). Twelve patients (57%) had a similar organism isolated from the skin preoperatively and from the postoperative wound infection. Reducing the course of antibiotic prophylaxis from 5 days to 3 doses did not significantly increase the infection rate. The only other significant risk factor for sepsis was increasing age of the patient. Although prophylaxis is undisputed in patients having synthetic grafts, antibiotics may not be as important in the prevention of wound sepsis as had been thought. The role of antiseptic agents requires further evaluation.", "Vascular reconstructive surgery with the placement of prosthetic material caudal to the diaphragm is occasionally associated with postoperative wound infection. These infections often lead to amputation and can be lethal. Only a few published reports contain information on the value of prophylactic antibiotic treatment with these operations, but its use is common throughout the world. To investigate this problem, a prospective, double blind, randomized study of vancomycin versus placebo in 128 vascular graft operations caudal to the diaphragm was conducted from June, 1982 to July, 1984. The difference in infection rate was significant (2 p = 0.0008) in favor of the vancomycin group. Fourteen wound infections (21.2%) were found in the placebo group, 3 of which (4.5%) were prosthesis infections. Among the 62 vancomycin-treated patients, one case of superficial wound infection (1.6%) and no cases of prosthesis infection were found. The most common pathogen was Staphylococcus aureus. The study has demonstrated that vancomycin, a narrow spectrum antibiotic, in an ultra-short regimen (one gram one hour before surgery and one gram 4 hours later) is an effective prophylactic agent against postoperative wound infection. Temporary and, in most cases, doses-related side effects were seen in 7.9% of the patients treated with vancomycin.", "Although cefazolin prophylaxis has proven efficacy in vascular surgery, Staphylococcus aureus wound infections are still an important postoperative complication. In cardiac surgery, cefazolin's susceptibility to hydrolysis by staphylococcal beta-lactamase has been proposed to account for some prophylaxis failures. To determine whether the incidence of vascular wound infections can be reduced by administering a more beta-lactamase-stable cephalosporin, we undertook a prospective, randomized trial of cefuroxime versus cefazolin. Cefuroxime was administered as a 1.5 gm dose before operation and 750 mg every 3 hours during operation. Cefazolin was given as 1 gm before operation and 500 mg every 4 hours during operation. Both agents were continued every 6 hours after operation for 24 hours. Deep wound infections developed in seven of 272 (2.6%) cefuroxime and three of 287 (1.0%) cefazolin recipients (p = 0.2). Staphylococcus aureus wound infections occurred in five cefuroxime versus two cefazolin recipients. In vitro evaluation of six of the study isolates plus an additional eight S. aureus strains from vascular wound infections showed greater susceptibility of the strains to cefazolin than cefuroxime (median minimal inhibitory concentrations of 0.5 and 2.0 micrograms/ml, respectively, p less than 0.05). Furthermore, despite its more frequent intraoperative redosing, cefuroxime exhibited lower trough serum concentrations than cefazolin. Among cefuroxime recipients, infection-associated procedures were significantly longer than infection-free procedures (p less than 0.05), suggesting that low tissue antibiotic concentrations may have contributed to the pathogenesis of these infections. In contrast, the length of the procedure was not a risk factor for infection among cefazolin recipients.(ABSTRACT TRUNCATED AT 250 WORDS)", "Recent studies of perioperative antimicrobial prophylaxis have indicated an improved efficacy of beta-lactamase-stable cephalosporins compared with cefazolin, the most commonly used prophylactic agent. Previous studies in our institution have revealed a superiority of cefamandole to cefazolin in patients undergoing heart surgery, although there was no difference between cefazolin and cefuroxime in patients undergoing peripheral vascular surgery. This study was therefore designed to compare cefamandole with cefazolin in wound infection prophylaxis in clean vascular surgery.\n The study was conducted from August 1990 through May 1992 and consisted of 893 patients with aortic or infrainguinal arterial procedures randomized to receive either cefamandole or cefazolin.\n The difference in infection rates associated with cefamandole versus cefazolin prophylaxis (3.2% vs 1.9%, respectively) was not significant (p = 0.42). A cost savings of approximately $95,000 per year at our institution favors the continued use of cefazolin over cefamandole. Risk factor analysis was carried out for preoperative and postoperative events that might have predisposed to infection. Only preoperative use of aspirin and the postoperative finding of a lymphocele correlated with a higher infection rate.\n Cefazolin continues to be the most cost-effective antibiotic for prophylaxis in clean vascular surgical procedures.", "to investigate the incidence of intraoperative graft contamination, bacterial species and the influence of change of surgeon's gloves on contamination.\n a prospective randomised study.\n forty patients had implantation of synthetic vascular grafts. All patients received intraoperative cloxacillin (2.0 g) or clindamycin (0.6 g) intravenously. The procedures were randomised to two groups: Group 1 - surgeons changed the gloves before the first contact with the vascular prosthesis and Group 2 - operation without glove change. The growth of all bacterial species from graft segments and from the gloves was recorded. The susceptibility to antibiotics was tested.\n the number of contaminated grafts was similar in the two groups. Growth of bacteria was recorded from 92.5% (37/40) of the graft segments and 33% (51/156) of glove imprints. Of the cultured species, 75% and 47%, respectively, were identified as coagulase-negative staphylococci (CNS). Twenty-eight per cent of CNS were resistant to cloxacillin, 15% to clindamycin, and 10% to cloxacillin and clindamycin. In all, 25% of the CNS strains were resistant to the prophylactic antibiotic used. In 50% of cases, the antibiogram of the CNS strain recovered from gloves agreed with that of the strain harvested from the graft.\n a high incidence of graft contamination was found which was not reduced by changing gloves. However, changing gloves did seem to reduce the number of bacterial species.\n Copyright 2000 Harcourt Publishers Ltd.", "In a randomized clinical study, 141 patients who had to undergo operations on the aorta or the main arteries received either amoxycillin/clavulanate or cefoxitin perioperatively for prophylaxis. As no wound infection occurred amoxycillin/clavulanate and cefoxitin were found to be equal in effectiveness.", "Preoperative and intraoperative antibiotic prophylaxis of infection in peripheral vascular surgery has been widely used although controlled studies have been lacking. A randomized, a prospective, double-blind study of cefazolin versus placebo during 565 arterial reconstructive operations was performed at this hospital from February 1976 through August 1977. Among the 462 patients undergoing surgery of the abdominal aorta and lower extremity vasculature, there was a highly significant difference in the infection rates: 6.8% for placebo recipients versus 0.9% for cefazolin recipients (p less than .001). Of the 18 infections, four involved vascular grafts and all four graft infections occurred in the placebo group. Over 8% of abdominal wounds of patients receiving placebo became infected versus 1.2% of cefazolin patients (p less than .05). Groin wounds were infected infrequently, 1.1% for placebo patients versus none for cefazolin patients. No infections occurred among 103 brachiocephalic procedures. Skin antisepsis was analyzed retrospectively. Infection rates were significantly higher (p less than .01) following hexachlorophene-ethanol versus a povidone-iodine skin preparation. Adverse effects of cefazolin were carefully monitored: no rash, phlebitis, or emergence of resistant strains was observed. A breif perioperative course of cefazolin and povidone-iodine skin antisepsis are recommended in vascular reconstructive surgery of the abdominal aorta and lower extremity vasculature.", "In a prospective randomized double-blind study of 141 patients referred for reconstructive vascular surgery on the abdominal aorta and the lower extremities, placebo was compared to antibiotic prophylaxis. The prophylaxis group received three doses of a combination of methicillin, 2 g and netilmicin, 200 mg. Antibiotic prophylaxis reduced postoperative wound infections as compared to placebo, i.e. 4/69 (5.8%) vs. 12/72, (16.7%) respectively (P = 0.04). No graft infections occurred. Two cases of postoperative septicaemia were seen in the placebo group, none in the antibiotic group. Among different procedures aortic-femoral bypass operations showed the highest wound infection rates. The two treatment groups were comparable with regard to all other postoperative complications registered, including nephro- and ototoxicity. The antibiotic regimen was considered safe, but had only marginal value as prophylaxis in vascular reconstructive surgery on the abdominal aorta and the lower extremities.", "A pilot study of 100 consecutive groin wounds after vascular surgery demonstrated lymph leaks in 12 per cent. Lymph leak was significantly associated with wound infection and with prolongation of in-patient stay. A controlled trial was therefore instituted to assess the influence of vacuum drainage in groin wound healing. One hundred and twenty-seven wounds were randomized to drainage (n = 65) or no drainage (n = 62) and the wounds were examined 'blind' by independent observers. No difference in the incidence of lymph leakage or wound infection was noted between the two groups. The routine use of suction drainage for groin wounds in vascular surgery is unnecessary.", "An unacceptably high infection rate in patients undergoing vascular surgery prompted two studies on these patients. The first study confirmed the problem and described antibiotic usage which was not standardized. A second double blind randomized study compared antibiotic usage in two groups of patients, receiving vein grafts or synthetic grafts. Patients receiving vein grafts were randomized either to placebo or cefazolin 2 g 1 h pre-operatively and every 6 h for 48 h. Patients receiving synthetic grafts were randomized either to cefazolin 1 g or to cefazolin 2 g 1 h pre-operatively and every 6 h for 48 h. Four of 50 vein graft patients developed a purulent discharge. Two of these infected patients received placebo and two received the cefazolin 2 g protocol. Of 90 patients receiving a synthetic graft, four became infected. Three patients were randomized to the cefazolin 1 g protocol and one to the cefazolin 2 g protocol. No statistically significant differences were observed.", "Cephradine administered prophylactically to a group of 35 patients undergoing reversed saphenous vein femoro-popliteal bypass, iliofemoral endarterectomy or profundaplasty through a groin incision, resulted in a significant reduction in the incidence of wound infection (P = 0.025; exact probability test). One gram of cephradine was given at induction of anaesthesia, followed by three postoperative doses of one gram at 6 hourly intervals. The overall wound infection rate at 7 days, as assessed by frank purulent discharge, was 15%. After cephradine prophylaxis, no infections were noted as judged on this basis, but erythema of the suture line was seen in equal numbers (40% of each group). Where the indication for operative intervention was rest pain or gangrene, the incidence of wound infection was very much increased, 80% of the infected cases being from this group.", "Prophylactic closed suction drainage has been advocated in a variety of surgical wounds, but its use in wounds involving vascular anastomoses has not been studied. Fifty patients undergoing lower extremity revascularization that required bilateral groin incisions were randomly assigned to have either the right or left side of the groin drained with a closed suction catheter. The contralateral wound was closed without drainage. Statistically there was no difference between wound closed with drains and undrained wounds in the occurrence of hematomas, seromas, lymphoceles, superficial infections, subcutaneous infections, or graft infections; although serious complications were more frequent in the drained wounds. Prophylactic closed suction drainage appears to offer no advantage over closure without drainage in wounds of the groin resulting from elective vascular operations.", "Groin wound infection is a dreaded complication of vascular surgery and may jeopardize an underlying graft. A variety of skin closures have been used and the object of this study was to prospectively determine the relationship between skin closure and wound infection. One hundred fourteen consecutive patients (70 men and 44 women) undergoing bypass surgery with a groin incision (n = 173) were randomly assigned to skin closure with subcuticular Maxon, interrupted nylon, continuous nylon, or clips following a standard two-layer closure of subcutaneous tissue. Fourteen (12%) patients had diabetes and 50 (44%) had digital ulceration and gangrene. Aortofemoral bypass was performed in 25% of the patients and infrainguinal bypass in the remaining 75%. Perioperative wound cultures were obtained before closure. Wounds were inspected and cultures repeated on postoperative days 3, 5, 7, 10, and 14. Infection was defined as a positive culture. Groin wound infection occurred in 3% of the population and graft infection in 0.6%. The type of suture did not influence the incidence of infection. This study failed to demonstrate a significant difference in the incidence of wound infection with the use of different suture materials. We conclude that suture material should be selected on the basis of surgeon preference and costs.", "A study was conducted to test the hypothesis that angioscopically assisted valve lysis and vein branch identification during in situ saphenous vein bypass would reduce technical causes of graft failure, local operative morbidity, and hospital stay.\n Patients requiring primary bypass to an infrageniculate artery were randomly assigned to undergo in situ saphenous vein bypass with valvulotomy and branch identification either under angioscopic visualization with use of short intermittent incisions (scope) or under direct vision with use of a continuous incision (no scope). Data on operative details, morbidity, hospital length of stay, and graft patency were collected prospectively and compared.\n Fifty-nine patients were enrolled (32 scope, 27 no scope). There were no significant differences between study groups in the incidence of diabetes, claudication versus critical ischemia indications for surgery, or popliteal versus infrapopliteal location of distal anastomoses. Rates of wound complications (9.3% and 3.7%), early graft occlusion (6.2% and 7.4%), and mean postoperative hospital stay (8.0 and 8.6 days) were statistically similar for the scope and no scope groups, respectively. Differences in cumulative secondary patency rates at 48 months (79% scope, 91% no scope) were also insignificant.\n Use of angioscopy to assist with preparation of the in situ vein for infrageniculate grafting appears to have no impact on local operative morbidity, hospital length of stay, or midterm graft patency.", "To investigate the effectiveness of a single-dose antibiotic regimen for preventing postoperative wound infection, a prospective, randomized double-blind trial was carried out in patients undergoing \"clean-contaminated\", \"contaminated\" or \"clean\" (vascular) surgery. Both elective and emergency operations were included. Single-dose (preoperative) prophylaxis was compared with short-term prophylaxis (1 dose preoperatively and 2 doses postoperatively). The antibiotics were penicillin, tobramycin and metronidazole in various combinations, and comparisons between single-dose and short-term prophylaxis were made with all the regimens. The incidence of wound infection was 5/277 (1.8%) in the short-term group and 9/287 (3.1%) in the single-dose group. The difference was not statistically significant. Nor was statistically significant difference found when the type of operation and the degree of contamination were considered. Single-dose antibiotic prophylaxis thus gave a low incidence of postoperative wound infection, even in \"clean-contaminated\" or \"contaminated\" cases." ]

[ "18950436", "11301086", "15767827", "14622817", "14622686", "11576803", "8537695", "15157684", "10737286", "22151568", "18443671", "16284584", "17575491", "1573287", "10959067", "17825129", "9932882", "4999453", "16482756", "9754420", "9428901", "17449988", "22151017", "11997197", "18557168" ]

[ "Titration with oxymorphone extended release to achieve effective long-term pain relief and improve tolerability in opioid-naive patients with moderate to severe pain.", "Continuous intrathecal morphine treatment for chronic pain of nonmalignant etiology: long-term benefits and efficacy.", "Safety, tolerability, and effectiveness of oxymorphone extended release for moderate to severe osteoarthritis pain: a one-year study.", "Evaluation of long-term efficacy and safety of transdermal fentanyl in the treatment of chronic noncancer pain.", "Long-term management of noncancer pain with transdermal therapeutic system-fentanyl.", "Long-term intrathecal infusion of drug combinations for chronic back and leg pain.", "Long-term intraspinal infusions of opioids in the treatment of neuropathic pain.", "Intrathecal opioid treatment for chronic non-malignant pain: a 3-year prospective study.", "Around-the-clock, controlled-release oxycodone therapy for osteoarthritis-related pain: placebo-controlled trial and long-term evaluation.", "Methadone in the intrathecal treatment of chronic nonmalignant pain resistant to other neuroaxial agents: the first experience.", "A randomized, double-blind, crossover comparison of the efficacy and safety of oral controlled-release tramadol and placebo in patients with painful osteoarthritis.", "Transdermal fentanyl versus sustained release oral morphine in strong-opioid naïve patients with chronic low back pain.", "Continuous intrathecal morphine infusion in patients with vertebral fractures due to osteoporosis.", "Long-term oral opioid therapy in patients with chronic nonmalignant pain.", "Maintenance of the long-term effectiveness of tramadol in treatment of the pain of diabetic neuropathy.", "Open-label study of the safety and effectiveness of long-term therapy with extended-release tramadol in the management of chronic nonmalignant pain.", "A prospective study of long-term intrathecal morphine in the management of chronic nonmalignant pain.", "[Long-term treatment of trigeminal neuralgia using valoron].", "Opioid switching from oral slow release morphine to oral methadone may improve pain control in chronic non-malignant pain: a nine-month follow-up study.", "[Intrathecal opioids in chronic non-malignant pain: relief and life quality].", "Intrathecal morphine pump as a treatment option in chronic pain of nonmalignant origin.", "Long-term use of controlled-release oxycodone for noncancer pain: results of a 3-year registry study.", "A Prospective, Randomized Trial of Intrathecal Injection vs. Epidural Infusion in the Selection of Patients for Continuous Intrathecal Opioid Therapy.", "Efficacy and safety of a once-daily morphine formulation in chronic, moderate-to-severe osteoarthritis pain: results from a randomized, placebo-controlled, double-blind trial and an open-label extension trial.", "Association of transdermal fentanyl and oral transmucosal fentanyl citrate in the treatment of opioid naive patients with severe chronic noncancer pain." ]

[ "Assess the effectiveness and tolerability of a program of gradual dose titration with oxymorphone extended release (ER) for treatment of moderate to severe chronic pain in opioid-naive patients.\n Open-label, nonrandomized 6-month study with a titration/stabilization period of <or=1 month followed by a 5-month maintenance period.\n Multidisciplinary pain centers in the United States.\n Adult opioid-naive patients with moderate to severe chronic pain.\n Patients were gradually titrated from a 5-mg dose of oxymorphone ER (taken every 12 hours) to a stabilized dose that provided effective pain relief and was well tolerated.\n Brief Pain Inventory Short Form questions 5 and 9, patient and physician global assessments of pain relief, adverse events (AEs), and discontinuations.\n The majority (94/126; 75%) of patients were stabilized on a dose of oxymorphone ER that provided effective pain relief with tolerable AEs. Most (81/94; 86%) required <24 days to reach a stable dose. Sixteen percent of patients in the titration period and 17% of patients in the maintenance period discontinued because of AEs possibly or probably related to oxymorphone ER. Patients completing the entire 5-month maintenance period experienced effective pain relief with significant (>50%) reductions of pain interference with quality-of-life measures. There was minimal dose escalation over the 5 months and low use of rescue medication.\n Oxymorphone ER provided effective pain relief from moderate to severe chronic pain in opioid-naive patients. Gradual titration was well tolerated, with a low rate of discontinuations caused by AEs.", "To analyze, prospectively, the long-term effects of continuous intrathecal morphine infusion therapy in 16 patients with chronic nonmalignant pain syndromes.\n Twenty-five patients with severe, chronic, nonmalignant pain that had proven refractory to conservative management were considered candidates for trial of intrathecal spinal morphine. Sixteen patients achieved more than 50% pain relief after a trial period of intrathecal morphine infusion. They were implanted with fully implantable and programmable pumps through which morphine was delivered intrathecally on a continuous basis. These patients were followed prospectively and underwent careful evaluation of their functional and mental status, and pain intensity measurements using standardized techniques before treatment and every 6 months thereafter in the follow-up period. The follow-up period ranged from 13 months to 49 months (mean 29.14 months +/- 12.44 months) for the patients who had implanted morphine pumps.\n The mean morphine dosage initially administered was 1.11 mg/day (range 0.2--6.5 mg/day); after 6 months, it was 3.1 mg/day (range 0.4--8.75 mg/day). In long-term observation, no patient had a constant dosage history. The patients who received intrathecal morphine for longer than 2 years all showed an increase in morphine dosage to more than 10 mg/day. The best long-term results were seen with deafferentation pain and mixed pain, with 75% and 61% pain reduction (visual analog scale), respectively. Nociceptive pain patients had best pain relief initially (78% pain reduction) but it tended to decrease over the follow-up period to 57% pain reduction at final follow-up. The average pain reduction for all groups after 6 months was 67.5% and at last follow-up, it was 57.5%. Ten patients were satisfied with the delivery system and eleven reported improvement in their quality of life. In two patients, morphine was not able to adequately control the pain without producing undesirable side effects requiring the addition of clonidine to their infusion medication. In this series, 12 patients were considered successes and 4 patients were considered failures. In two patients, the intrathecal opioid therapy was unable to produce satisfactory pain relief and in the other two patients the pumps had to be explanted because of intolerable side effects.\n In our experience, the administration of intrathecal opioid medications for nonmalignant pain is justified in carefully selected patients.", "A 52-week, multicenter, open-label extension study was performed to evaluate the safety, tolerability, and effectiveness of oxymorphone extended release (ER), a novel tablet formulation of oxymorphone hydrochloride, in 153 patients with moderate to severe chronic osteoarthritis-related pain. Sixty-one patients (39.9%) completed the study. Common opioid-related nonserious adverse events (AEs) caused most withdrawals. However, approximately one-half of withdrawals due to AEs were among opioid-naive patients who received placebo in a previous trial and were started on a dose of 20 mg every 12 hours, suggesting that tolerability can be improved by titrating from a lower initial dose. Mean pain scores initially decreased as previously opioid-naive patients achieved adequate pain relief, reached stable levels after the first 6 weeks, and remained stable at mild levels throughout the remainder of the study (average pain, 20-25 mm on 100-mm Visual Analog Scale). Average daily dosing remained stable throughout the study (median, 40 mg/d). At each assessment, at least 80% of patients rated their global satisfaction with oxymorphone ER as \"excellent,\" \"very good,\" or \"good.\" Oxymorphone ER provides a new 12-hour analgesic for the treatment of moderate to severe chronic osteoarthritis-related pain in patients who may require long-term opioid therapy.", "The objective of this international, multicenter, open-label trial was to assess the efficacy and safety of up to 12 months of therapy with transdermal therapeutic system (TTS) fentanyl in patients (n = 532) with chronic noncancer pain. The trial was completed by 301 (57%) of the patients. The main outcome measures were pain control assessment, global treatment satisfaction, patient preference for TTS fentanyl, and quality of life. The mean dose of transdermal fentanyl (TDF) increased from 48 to 90 microg/h during a period of 12 months. During treatment, on average 67% of patients within the efficacy analysis group (n = 524) reported very good, good, or moderate pain control. Global satisfaction (very good or good) was also stable at 42%. The majority (86%) of patients reported a preference for TDF over their previous treatment (P < .001, binomial test). Short Form 36 quality-of-life scores improved from baseline for bodily pain. The most frequent treatment-related adverse events were nausea (31%), constipation (19%), and somnolence (18%). With regard to opioid-specific adverse events (respiratory depression [< 1%], adrenal insufficiency [< 1%], drug abuse/dependence [1%], and opioid withdrawal syndrome [3%]), these were extremely rare and, with the exception of opioid withdrawal syndrome, none was considered definitively related to the treatment. Long-term treatment with TDF provided a stable degree of pain control in the majority of patients with moderate to severe chronic noncancer pain. It was preferred by the majority of patients compared with their previous opioid medication. Overall, long-term treatment with TDF was generally well tolerated, particularly in view of the low incidence of potentially serious side effects such as drug abuse/dependence and respiratory depression. However, at present, it is important that patients receiving TDF should still be subject to careful assessment and monitoring.", "Transdermal therapeutic system-fentanyl (TTS-F) has been extensively studied in cancer pain management. However, few studies have addressed the long-term management of noncancer pain, especially when it relates to neuropathic pain. A total of 529 patients were recruited into this prospective open-label study to determine the safety and effectiveness of TTS-F in relation to quality-of-life (QOL) stratified according to pain type and etiology. TTS-F significantly improves QOL within 28 days, and pain management within 48 hours. The frequency of side effects rapidly decreases over time, and patients not experiencing adequate pain management are identified within 28 days. The median duration of therapy for effective pain management was 10 months, and 90% of patients sustained such efficacy. TTS-F offers statistically significant increases in QOL-Short Form 12 (including the Physical Component Scale and Mental Component Scale measures) and pain control (Greek Brief Pain Inventory) from one time point to the next (P <.0001). These improvements are not influenced by pain type or etiology. TTS-F is a safe and effective pain management system independent of patient characteristics and demographic factors. What is of most importance is that in those patients with neuropathic pain, for whom opioids have long been thought to be ineffective, similar effectiveness is demonstrated when compared to patients with nociceptive pain.", "Continuous intrathecal infusion of analgesic drugs by implantable pumps is recognized as an established treatment option for patients with chronic pain resistant to oral or parenteral medication. Polyanalgesia, the simultaneous use of more than one intrathecal analgesic drug, is practiced relatively often, but there are only a few published clinical studies on intrathecal polyanalgesia for chronic nonmalignant pain. This pilot study represents a long-term evaluation of a treatment regimen consisting of intrathecal morphine admixed with bupivacaine, clonidine, or midazolam in patients with chronic nonmalignant back and leg pain due to degenerative lumbar spinal disease. Twenty-six adult patients have been treated by intrathecal programmable pump-controlled infusion of analgesic drugs and followed for up to 3.5 years (27 +/- 11 months). Combination of morphine with a second drug was used in 10 cases, morphine with 2 additional drugs in 12 cases, and morphine with 3 additional drugs in 4 cases. Mean daily doses at 24 months after pump implantation were 6.2 +/- 2.8 mg for morphine, 2.5 +/- 1.5 mg for bupivacaine, 0.06 +/- 0.03 mg for clonidine, and 0.8 +/- 0.4 mg for midazolam. Nineteen patients reported excellent or good long-term treatment results, 6 patients had sufficient results, and only 1 patient complained of poor therapeutic efficacy. No long-term clinical side effects of intrathecal polyanalgesia were noted. Mean morphine dose had to be increased from 1.2 mg at baseline to 5.1 mg at 24 months due to tolerance development and disease progression. This experience suggests that intrathecal polyanalgesia employing morphine combined with additional nonopioid drugs can have a favorable analgesic efficacy in patients with complex chronic pain of spinal origin, and lacks major drug-related complications.", "Long-term intraspinal infusions of opioid drugs are being increasingly utilized in patients with noncancer pain. Despite this, there is a lack of long-term information, including success and failure rates for pain relief and technical problems. During a 5-year period, 18 noncancer patients underwent implantation of programmable infusion pumps for long-term intrathecal opioid infusion. Patients had (a) neuropathic pain, (b) had failed or been ineligible for noninvasive treatments, and (c) obtained greater than 50% pain relief with intrathecal trial infusions of morphine sulfate or sufentanil citrate. A disinterested third-party reviewer evaluated patients at the most recent follow-up. Sixty-one percent (11/18) of patients had good or fair pain relief with mean follow-up 2.4 +/- 0.3 years (0.8-4.7 years). Average numeric pain scores decreased by 39% +/- 4.3%. Five of the 11 responders required lower opioid doses (12-24 mg/day morphine) and the remaining six patients required higher opioid doses (> 34 mg/day morphine). Failure of long-term pain relief occurred in 39% (7/18) despite good pain relief in trial infusions and the use of both morphine and sufentanil. Technical problems developed in 6/18 patients but appeared to be preventable with further experience. Long-term intrathecal opioid infusions can be effective in treatment of neuropathic pain but might require higher infusion doses.", "Intrathecal (IT) opioid therapy is a treatment alternative for patients with severe chronic non-malignant pain. Several uncontrolled retrospective and prospective outcome studies have suggested a benefit in chronic non-malignant pain patients, but uncertainties about patient selection in these studies weaken the results. This study evaluated long-term outcome of IT opioid therapy in chronic non-malignant pain prospectively, and included two comparative groups to improve understanding of selection criteria and relative severity of intrathecal pump recipients (PRs). The study subjects included 38 PRs while the comparative groups included 31 intrathecal candidates who either had an unsuccessful trial, or declined the IT therapy, and another group of 41 newly referred patients. The following data were analyzed at study entry, and at 6 monthly intervals for a 3-year period: Symptom Check List 90 (SLC-90), SF-36 Health survey, Beck Depression Inventory, McGill Pain Questionnaire (short form), Oswestry Disability Index, Pain Drawings and Pain rating on visual analogue scale. Data analysis suggests the study group of PRs had improvements in pain, mood, and function from baseline to 36 months. These same parameters improved among new referrals (less severe patients receiving conservative pain management) while non-recipients significantly worsened. Although PRs improved, they were still worse off at 36 months than new referrals were at baseline. The study showed that when patients with extremely severe pain problems are selected as pump candidates, they will likely improve with the therapy, but their overall severity of pain and symptoms still remains high.", "Although opioid analgesics have well-defined efficacy and safety in treatment of chronic cancer pain, further research is needed to define their role in treatment of chronic noncancer pain.\n To evaluate the effects of controlled-release oxycodone (OxyContin tablets) treatment on pain and function and its safety vs placebo and in long-term use in patients with moderate to severe osteoarthritis pain.\n One hundred thirty-three patients experiencing persistent osteoarthritis-related pain for at least 1 month were randomized to double-blind treatment with placebo (n = 45) or 10 mg (n = 44) or 20 mg (n = 44) of controlled-release oxycodone every 12 hours for 14 days. One hundred six patients enrolled in an open-label, 6-month extension trial; treatment for an additional 12 months was optional.\n Use of controlled-release oxycodone, 20 mg, was superior (P<.05) to placebo in reducing pain intensity and the interference of pain with mood, sleep, and enjoyment of life. During long-term treatment, the mean dose remained stable at approximately 40 mg/d after titration, and pain intensity was stable. Fifty-eight patients completed 6 months of treatment, 41 completed 12 months, and 15 completed 18 months. Common opioid side effects were reported, several of which decreased in duration as therapy continued.\n Around-the-clock controlled-release oxycodone therapy seemed to be effective and safe for patients with chronic, moderate to severe, osteo-arthritis-related pain. Effective analgesia was accompanied by a reduction in the interference of pain with mood, sleep, and enjoyment of life. Analgesia was maintained during long-term treatment, and the daily dose remained stable after titration. Typical opioid side effects were reported during short- and long-term therapy.", "Intrathecal drug delivery is a widely used and effective method of treatment for chronic intractable pain. Unfortunately all currently used agents can not provide adequate pain relief in all patients. A prospective study of neuroaxial methadone was performed in 24 patients, all of whom had failed treatment with multiple previous intrathecal drugs. Thirteen patients experienced improvement of their pain control with methadone, nine continued to receive this agent for 6 months with good pain relief, improved quality of life and no side effects. The final rates of methadone infusion were 2.2 times higher than preceding morphine rates. The only observed possible side effect of methadone was transient blurred vision in one patient. Methadone is a promising alternative neuroaxial agent in the treatment of chronic pain.", "To compare the efficacy and safety of controlled-release (CR) tramadol (Zytram XL, Purdue Pharma, Canada) and placebo in patients with painful osteoarthritis.\n Patients underwent analgesic washout for two to seven days before random assignment to 150 mg daily of CR tramadol or placebo, and were titrated weekly to 200 mg, 300 mg or a maximum of 400 mg once daily. After four weeks, patients crossed over to the alternate treatment for another four weeks. Plain acetaminophen was provided as a rescue analgesic. All patients who completed the crossover study were eligible to receive open label CR tramadol for six months.\n Seventy-seven of 100 randomly assigned patients were evaluable for efficacy. CR tramadol resulted in significantly lower visual analogue scale pain intensity scores (37.4+/-23.9 versus 45.1+/-24.3, P=0.0009). Western Ontario and McMaster Universities osteoarthritis index subscale scores for pain (189.0+/-105.0 versus 230.0+/-115.4; P=0.0001) and physical function (632.4+/-361.3 versus 727.4+/-383.4; P=0.0205) were significantly better with CR tramadol. Total pain and disability (22.8+/-14.5 versus 27.2+/-14.8; P=0.0004), and overall pain and sleep (104.7+/-98.0 versus 141.0+/-108.2; P=0.0005) scores in the Pain and Sleep Questionnaire were significantly lower for CR tramadol. Short-form 36 Health Survey scores were significantly better during CR tramadol treatment for the pain index (38.8+/-10.8 versus 35.6+/-9.0; P=0.0100), general health perception (46.5+/-11.2 versus 44.4+/-11.6; P=0.0262), vitality (43.1+/-13.2 versus 40.2+/-13.7; P=0.0255) and overall physical components (40.8+/-8.9 versus 37.8+/-7.7; P=0.0002). CR tramadol treatment was preferred by 55.8% of patients (P=0.0005) versus 20.8% and 23.4% of patients who chose placebo or had no preference, respectively. These improvements were sustained for up to six months, and 86.5% of patients reported at least moderate benefit from CR tramadol during long-term treatment.\n CR tramadol is effective for the management of painful osteoarthritis.", "Open, randomized, parallel group multicenter study.\n To compare the efficacy and safety of transdermal fentanyl (TDF) and sustained release morphine (SRM) in strong-opioid naïve patients with chronic low back pain (CLBP).\n Most studies of TDF and SRM have involved patients already receiving strong opioids. This is the first large-scale study focusing on strong-opioid naïve patients with CLBP.\n Adults with CLBP requiring regular strong opioid therapy received either TDF or SRM for 13 months. Starting doses were 25 microg/hr fentanyl patches every 72 hours or 30 mg oral morphine every 12 hours. Doses were adjusted according to response. Participants assessed pain relief and bowel function using weekly diaries. Other assessments, including quality of life, disease progression, and side effects, were made by patients and investigators.\n Data from 680 patients showed that TDF and SRM provided similar levels of pain relief, but TDF was associated with significantly less constipation than SRM, indicating a greater likelihood of satisfactory pain relief without unmanageable constipation for patients receiving TDF. Other ratings were similar for TDF and SRM, but TDF provided greater relief of pain at rest and at night.\n TDF and SRM provided equivalent levels of pain relief, but TDF was associated with less constipation. This study indicates that sustained-release strong opioids can safely be used in strong-opioid naïve patients.", "Vertebral fractures are the most common consequences of severe osteoporosis. The chronic pain from collapse of osteoporotic vertebrae affects quality of life (QOL) and autonomy of patients. The management of pain with oral or transdermal opiates can cause severe side effects. Continuous intrathecal administration of morphine via an implantable pump might represent an alternative therapy to conventional oral or transdermal administration of opioids and has some advantages and disadvantages for pain relief and improvement in QOL when compared with conventional opioid delivery. It is our objective to report our experience using intrathecal delivery of analgesics in a population of patients with refractory pain due to vertebral fractures.\n In 24 patients, refractory to conventional delivery of opioids, we used intrathecal analgesic therapy. To test for efficacy and improvement in QOL, we administered the visual analog scale for pain and the Questionnaire of the European Foundation of Osteoporosis (QUALEFFO). Before patients were selected for pump implantation, an intraspinal drug delivery trial was performed to monitor side effects and responses to intrathecal therapy.\n Significant pain relief was obtained in all implanted patients. Using the QUALEFFO, we observed significant improvement of all variables such as quality of daily life, domestic work, ambulation, and perception of health status, before and after 1 year after pump implantation. With intrathecal morphine infusion, none of the 24 patients required additional systemic analgesic medication. The mean morphine dose during the spinal trial was 11.28 mg/d, 7.92 mg/d at pump implantation, and 16.32 mg/d at 1-year follow-up.\n Our results show that intrathecal administration of morphine efficiently relieves the symptoms of pain and improves QOL. Continuous intrathecal administration of morphine appears to be an alternative therapy to conventional analgesic drug delivery and has advantages in those patients who have severe side effects with systemic administration of analgesics.", "In contrast to the use of opioids for the treatment of acute and chronic cancer pain, the administration of chronic opioid therapy for pain not due to malignancy remains controversial. We describe 100 patients who were chronically given opioids for treatment of nonmalignant pain. Most patients experienced neuropathic pain or back pain. We used sustained-release dihydrocodeine, buprenorphine, and sustained-release morphine. Pain reduction was measured with visual analogue scales (VAS), and the Karnofsky Performance Status Scale was used to assess the patient's function. Good pain relief was obtained in 51 patients and partial pain relief was reported by 28 patients. Only 21 patients had no beneficial effect from opioid therapy. There was a close correlation between the sum and the peak VAS values (r = 0.983; p less than 0.0001) and pain reduction was associated with an increase in performance (p less than 0.0001). The most common side effects were constipation and nausea. There were no cases of respiratory depression or addiction to opioids. Our results indicate that opioids can be effective in chronic nonmalignant pain, with side effects that are comparable to those that complicate the treatment of cancer pain.", "The objective of this study was to evaluate the efficacy and safety of tramadol in a 6-month open extension following a 6-week double-blind randomized trial.\n Patients with painful diabetic neuropathy who completed the double-blind study were eligible for enrollment in an open extension of up to 6 months. All patients received tramadol 50-400 mg/day. Self-administered pain intensity scores (scale 0-4; none to extreme pain) and pain relief scores (scale -1-4; worse to complete relief) were recorded the first day of the open extension (last day of the double-blind phase) and at 30, 90, and 180 days.\n A total of 117 patients (56 former tramadol and 61 former placebo) entered the study. On the first day of the study, patients formerly treated with placebo had a significantly higher mean pain intensity score (2. 2+/-1.02 vs. 1.4+/-0.93, P<0.001) and a lower pain relief score (0. 9+/-1.43 vs. 2.2+/-1.27, P<0.001) than former tramadol patients. By Day 90, both groups had mean pain intensity scores of 1.4, which were maintained throughout the study. Mean pain relief scores (2. 4+/-1.09 vs. 2.2+/-1.14) were similar after 30 days in the former placebo and former tramadol groups, respectively and were maintained for the duration of the study. Four patients discontinued therapy due to ineffective pain relief; 13 patients discontinued due to adverse events. The most common adverse events were constipation, nausea, and headache.\n Tramadol provides long-term relief of the pain of diabetic neuropathy.", "Tramadol ER* is a once-daily oral analgesic for management of moderate-to-moderately severe chronic pain in adults who require around-the-clock treatment of pain. This study evaluated long-term safety of tramadol ER and effectiveness outcomes in the management of chronic, nonmalignant pain.\n Patients enrolled directly for approximately 1 year of open-label tramadol ER treatment if they had chronic, nonmalignant pain (n = 919), or 'rolled over' for 38 weeks of open-label tramadol ER treatment if they completed either of two 12-week, placebo-controlled studies of tramadol ER for low back pain (n = 72) or osteoarthritis (n = 61). Tramadol ER was titrated to a dose of 300 mg once daily (patients >or= 75 years) or 300-400 mg once daily (patients < 75 years).\n A total of 257 (24%) patients completed the study. Common adverse events, regardless of treatment relationship, were nausea, dizziness (excluding vertigo), and constipation. Mean scores for current pain intensity (from 0 = no pain to 100 = extreme pain) and least, worst, and average pain intensity over the past week improved at every post-baseline visit. At each post-baseline visit, > 50% of patients provided a global assessment rating of good, very good, or excellent. Study limitations were mandatory titration to 400 mg in some patients, concomitant analgesic therapy as a confounding variable, and lack of a placebo comparator.\n Individualized dose titration and limiting once-daily therapy with tramadol ER to the maximum recommended daily dose of 300 mg may balance tolerability and analgesic effects of tramadol ER in patients with chronic, nonmalignant pain.", "To examine in a prospective manner the long-term safety and efficacy of chronic intrathecal morphine in patients with severe, nonmalignant pain refractory to less invasive modalities.\n Forty patients with severe, chronic nonmalignant pain poorly managed by systemic medications were identified as candidates for intraspinal trial of morphine. Thirty participants reported successful pain relief during trial and were implanted with an intraspinal delivery system. Standardized measures of pain and functional status were assessed before treatment was begun and at defined intervals during the subsequent 24 months. Intrathecal opioid use and pharmacological and device-related complications were also monitored.\n The participants had a mean age of 58 +/- 13 years and a mean pain duration of 8 +/- 9 years. Fifty-three percent of the study participants were women. Pain type was characterized as mixed neuropathic-nociceptive (15 of 30 patients, 50%), peripheral neuropathic (10 of 30 patients, 33%), deafferentation (4 of 30 patients, 13%), or nociceptive (1 of 30 patients, 3%). Forty-seven percent of the patients were diagnosed with failed back surgery syndrome. Significant improvement over baseline levels of visual analog scale pain was measured at each follow-up examination after implant. Overall, 50% (11 of 22 patients) of the population reported at least a 25% reduction in visual analog scale pain after 24 months of treatment. In addition, the McGill Pain Questionnaire, visual analog scale measures of functional improvement and pain coping, and several subscales of the Chronic Illness Problem Inventory showed improvement throughout the follow-up period. Pharmacological side effects were managed medically by morphine dose reduction, addition of bupivacaine, or replacement of morphine with hydromorphone. Device-related complications requiring repeat operations were experienced by 20% of the patients.\n Continuous intrathecal morphine can be a safe, effective therapy for the management of severe, nonmalignant pain among a carefully selected patient population and can result in long-term improvement in several areas of daily function.", "nan", "Twelve patients with poor pain control or unacceptable side effects during treatment with morphine were switched to methadone and followed for nine months in this open prospective study. Primary outcomes were patient preference for opioid and pain control while physical, cognitive and role functioning were secondary outcomes. The morphine dose was decreased by 1/3 daily and was replaced with an equianalgesic dose of methadone over a three-day period. During switching and a one-week dose titration period, patients were given additional methadone if required. During dose titration one patient experienced sedation requiring naloxone. Four patients were switched back to morphine due to poor pain control, drowsiness or sweating. Seven patients preferred long-term (>nine months) treatment with methadone and reported reduced pain and improved functioning while cognition was not improved. This study brings novel information on the long-term consequences for pain control, health-related quality of life and cognitive functioning with a switch from morphine to methadone in the treatment of chronic non-malignant pain.", "The use of opioids for treatment of non-malignant pain is controversial. The evaluation of pain relief and of the quality of life of 11 severely incapacitated chronic non-cancer pain patients treated with long term intrathecal infusion of opioids trought implantable pumps was performed. The mean duration of pain complaints was 5.3 years. The mean pain intensity was 8.6. In 7 patients, pain episodes lasted at least 6 hours daily. The mean duration of the therapy was 19.6 months. After the treatment the mean pain score became 3.9. In only 1 patient, the duration of pain episodes was still longer than 6 hours. Quality of life improved in 36.36% of the cases. The long term spinal opioids through implantable pumps for non-malignant pains results in pain relief but not necessarily improves the quality of life.", "Implantable pumps for the delivery of intrathecal morphine have become a common option for administering opiate medication for the management of pain in patients with terminal cancer. Options for treating chronic pain of non-malignant origin are more controversial. This study describes responses to intrathecal morphine administration for managing chronic pain in patients without an underlying malignancy.\n Eleven patients between the ages of 29 and 81 years, nine with failed back syndrome (FBS) and two with neuropathic pain (NP) from other causes, were chosen from 15 consecutive individuals referred to neurosurgery clinic. The presenting levels of pain and a functional-economic outcome level were determined for each patient. Patients were admitted to the hospital for therapeutic trials and were assessed for the appropriateness of their analgesic response and for adverse responses to the medication. A morphine pump was implanted in five males and six females who were followed for up to 3 years.\n A good to excellent analgesic response was seen in 8 (73%) patients (6 FBS; 2 NP). In the remaining three patients (27%), the analgesic response was judged poor (3 FBS). In patients with FBS, the total effective response was 67%. Two patients experienced bladder dysfunction requiring pump removal. Other adverse effects of pump placement were rare.\n The morphine pump was found to be a viable alternative in the management of failed back syndrome. Its use in long-term therapy, however, is not without limitations and should be a last choice option.", "To evaluate the outcomes associated with the use of controlled-release (CR) oxycodone for up to 3 years in the treatment of noncancer pain.\n Adult patients who previously participated in controlled trials of CR oxycodone for osteoarthritis pain, diabetic neuropathy pain, or low back pain, and who continued to require opioid analgesia for moderate or severe pain, were enrolled in an open-label, uncontrolled, registry study. Data collected over time included dose, pain severity on a numeric scale, treatment acceptability, adverse events, and descriptions of problematic drug-related behavior.\n Two hundred thirty-three patients were enrolled. When the study closed, 141, 86, and 39 patients had taken CR oxycodone for at least 1, 2, and 3 years, respectively; mean duration of treatment was 541.5 days. Among the 219 intent-to-treat patients (received at least 1 dose and provided at least 1 postdose study observation), the mean (SD, range) daily dose was 52.5 (+/-38.5, 10.0 to 293.5) mg. Before the end of month 3, 44% required an increase in total daily dose; this dropped to 23% during months 4 to 6, to 17% during months 10 to 12, and remained at approximately 10% for each time interval thereafter (range 8% to 13%). Among the large majority of patients with stable or lower dose requirements after the initial 3 months of treatment, the average pain intensity ratings were unchanged or improved for approximately 70% to 80% of patients at all subsequent time points through month 33, and for 54% (7/13 patients) at month 36. A decrease in pain was initially seen by the end of month 3, and for the majority of patients, the Average Pain Intensity score remained the same, better, or minimally worse (<3 points) for the remainder of the 3-year study period. The most common adverse events were constipation and nausea, and the incidence of these events declined over time on treatment. Investigators reported 6 cases (2.6%) of possible drug misuse but no evidence of de novo addiction was observed.\n These registry data demonstrate that a subgroup of patients with noncancer pain experienced prolonged relief with tolerable side effects and modest need for dose escalation during long-term therapy with CR oxycodone.", "The objective of this study was to compare the cost and safety of intrathecal injection (IN) vs. epidural infusion (CE) trial and to provide a preliminary assessment of the prognostic value of each in the selection of patients for long-term continuous intrathecal opioid therapy (CIOT). Thirty-seven patients with chronic nonmalignant pain who were being considered for CIOT were randomized to morphine trial by IN or CE. Analgesic response and complications were monitored throughout trial. Sixty-seven percent of IN (12/18) and 79% (15/19) of CE subjects reported good pain relief (defined as ≥ 50% pain reduction) and were implanted with a permanent infusion system. Eighty-nine percent (24/27) of subjects provided six-month CIOT follow-up data. Cost of trial and health care utilization during six months of CIOT were compared between groups. Analgesic and functional response during CIOT was also compared between IN and CE groups. The cost of IN trial was significantly less than CE trial (p < 0.001). Complications were generally mild in both groups, although opioid-related side effects tended to be more common in the IN group. Successful pain relief after six months of CIOT was reported by 10 (60%) and 14 (64%) patients who underwent IN and CE trial, respectively (p = 0.32; Fisher's exact test). There was no difference between IN and CE groups in McGill Pain rating, quality of life (VAS), mood (Profile of Mood States), or function (Sickness Impact Profile) after six months of CIOT. We conclude that intrathecal injection is a safe procedure for use in selection of patients for CIOT and is less costly than epidural infusion. Differences in pain and functional response to long-term opioids among patients selected by either trial method are not large.", "A randomized, 4-week, double-blind trial followed by an open-label extension trial assessed the efficacy and safety of a once-daily, extended-release morphine formulation (Avinza (previously referred to as Morphelan)) in 295 patients with chronic, moderate-to-severe osteoarthritis pain who had failed to obtain adequate pain relief with NSAIDs and acetaminophen. Participants received one of four treatments: Avinza 30 mg once daily (QAM or QPM), MS Contin(R) 15 mg twice daily, or placebo twice daily. Patients (n =181) received Avinza QAM or QPM during the 26-week open-label extension trial and could increase their dose to optimize pain control. Avinza and MS Contin reduced pain and improved several sleep measures versus placebo. Analgesic efficacy was comparable between Avinza and MS Contin; however, Avinza QAM demonstrated greater improvements in overall quality of sleep. The most common adverse events were constipation and nausea. The majority of AEs occurred at a similar incidence among the active treatment groups.", "Chronic noncancer pain is often undertreated.\n To assess the efficacy of fentanyl transdermal therapeutic system (TTS) associated with oral transmucosal fentanyl citrate (OTFC) for breakthrough pain in patients with chronic noncancer pain.\n A total of 215 patients with chronic (> or =6 months), severe (VAS > or = 8) noncancer pain participated in a 6-month prospective study. The starting dose of 12 microg/h fentanyl TTS was titrated in 25 microg/h increments to a visual analog scale (VAS) score < or = 4. OTFC was administered as single-unit doses of 400 microg.\n The mean (SD) VAS score decreased from 9.86 (0.35) at baseline to 2.05 (0.96) at 6 months. The percentage of patients with poor quality of sleep decreased from 99 percent at baseline to 2.8 percent at the end of the study. The percentage of patients with inadequate pain control decreased from 16.2 percent at month 1 to 2.3 percent at month 6. Pain control was achieved with the 50 microg/h dose in 48 percent of patients, the 75 microg/h dose in 18 percent, and the 100 microg/h dose in 5 percent (only two patients required >100 microg/h). The daily use of single-unit doses of OTFC decreased from 4.64 at month 1 to 2.62 at month 6. Headache, nausea/vomiting, constipation, and somnolence of mild or moderate intensity were the most common side effects. Treatment was discontinued because of nausea/vomiting in seven patients, somnolence in three, and dermatitis in two.\n Fentanyl TTS associated with OTFC for breakthrough pain is a feasible and effective strategy in opioid naïve patients with severe chronic nonmalignant pain." ]

[ "19464029", "17719940" ]

[ "Effectiveness of adenotonsillectomy in PFAPA syndrome: a randomized study.", "A randomized, controlled trial of tonsillectomy in periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome." ]

[ "To evaluate whether adenotonsillectomy leads to complete resolution in children with PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis) syndrome.\n Thirty-nine children with PFAPA syndrome were randomized to either adenotonsillectomy (surgery group; n = 19) or expectant management (control group; n = 20). All patients were then invited prospectively to record all PFAPA episodes, and were evaluated clinically every 3 months for 18 months after randomization.\n The proportion of patients experiencing complete resolution was 63% in the surgery group and 5% in the control group (P < .001). The mean (+/- standard deviation) number of episodes recorded during the study period was 0.7 +/- 1.2 in the surgery group and 8.1 +/- 3.9 in the control group (P < .001). The episodes were less severe in the surgery group.\n Adenotonsillectomy is an effective treatment strategy for children with PFAPA syndrome.", "We carried out a prospective, randomized, controlled trial to clarify the effect of tonsillectomy on the clinical course of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome.\n Twenty-six consecutive children (mean age 4.1 years) with at least 5 PFAPA attacks were recruited from 3 tertiary care pediatric hospitals during 1999-2003 and randomly allocated to tonsillectomy or follow-up alone. They were all followed up with symptom diaries for 12 months. Tonsillectomy was allowed after 6 months in the control group if the attacks recurred.\n Six months after randomization all 14 children in the tonsillectomy group and 6/12 children in the control group (50%) were free of symptoms (difference 50%, 95% confidence interval 23% to 75%, P < .001). Tonsillectomy was performed on 5/6 of the patients in the control group who still had symptoms after 6 months. The remaining unoperated child in the control group had recurrences of the fever episodes throughout the follow-up, but the symptoms became less severe, and the parents did not choose tonsillectomy.\n Tonsillectomy appeared to be effective for treating PFAPA syndrome. The fever episodes ceased without any intervention in half of the control subjects. We conclude that although the mechanisms behind this syndrome are unknown, tonsillectomy can be offered as an effective intervention for children with PFAPA." ]

[ "14560166", "7480850", "9709516", "12699021", "17350966" ]

[ "Brief psychoeducational parenting program: an evaluation and 1-year follow-up.", "The efficacy of parent training for promoting positive parent-toddler relationships.", "Evaluating a brief parental-education program for parents of young children.", "Parent training of toddlers in day care in low-income urban communities.", "Parenting intervention in Sure Start services for children at risk of developing conduct disorder: pragmatic randomised controlled trial." ]

[ "Despite recognition of the need for parenting interventions to prevent childhood behavioral problems, few community programs have been evaluated. This report describes the randomized controlled evaluation of a four-session psychoeducational group for parents of preschoolers with behavior problems, delivered in community agencies.\n In 1998, 222 primary caregivers, recruited through community ads, filled out questionnaires on parenting practices and child behavior. Parents were randomly assigned to immediate intervention or a wait-list control. The intervention comprised three weekly group sessions and a 1-month booster, the focus being to support effective discipline (using the video 1-2-3 Magic) and to reduce parent-child conflict.\n Using an intent-to-treat analysis, repeated-measures analyses of variance indicated that the parents who received the intervention reported significantly greater improvement in parenting practices and a significantly greater reduction in child problem behavior than the control group. The gains in positive parenting behaviors were maintained at 1-year follow-up in a subset of the experimental group.\n This brief intervention program may be a useful first intervention for parents of young children with behavior problems, as it seems both acceptable and reasonably effective.", "The effectiveness of a parent training program for promoting positive parent-child relationships was examined among families of 2-year-olds. Forty-six mothers and fathers and their toddlers were assigned to either an intervention or comparison group. Intervention group parents participated in a 10-week program that focused on principles for effectively interacting with their toddlers. Parents completed measures of parenting self-efficacy, depression, stress, and perceptions of their toddler's behaviors and were videotaped playing with their toddlers preintervention, postintervention, and 3 months following the intervention. Repeated measures ANOVAs showed that the parent training program led to significant increases in maternal self-efficacy, decreases in maternal stress, and improvements in the quality of mother-toddler interactions. No significant effects were found among fathers. Explanations for obtaining different outcomes for mothers and fathers are discussed and directions for future research are recommended.", "The effectiveness of a brief parental-education program for 40 families with very young children was studied. Families were assigned to either a parental-education or waiting-list control group. The parental-education program included information and strategies drawn from developmental and cognitive psychology and social learning theory. Analysis showed that participating parents significantly reduced their use of corporal and verbal punishment, changed their parenting attitudes, and improved their perceptions of their children's behavior in comparison to the control group. Effects were maintained at six weeks follow-up. Results supported tailoring parental-education programs to the unique needs of participants.", "The authors tested a 12-week parent training program with parents (n = 208) and teachers (n = 77) of 2-3-year-olds in day care centers serving low-income families of color in Chicago. Eleven centers were randomly assigned to 1 of 4 conditions: (a) parent and teacher training (PT + TT), (b) parent training (PT), (c) teacher training (TT), and (d) waiting list control (C). After controlling for parent stress, PT and PT + TT parents reported higher self-efficacy and less coercive discipline and were observed to have more positive behaviors than C and TT parents. Among toddlers in high-risk behavior problem groups, toddlers in the experimental conditions showed greater improvement than controls. Most effects were retained 1 year later. Benefits were greatest when parents directly received training.", "To evaluate the effectiveness of a parenting programme as a preventive intervention with parents of preschool children considered to be at risk of developing conduct disorder.\n Pragmatic randomised controlled trial using a block design with allocation by area.\n Eleven Sure Start areas in north and mid-Wales.\n 153 parents from socially disadvantaged areas, with children aged 36-59 months at risk of conduct disorder defined by scoring over the clinical cut off on the Eyberg child behaviour inventory. Participants were randomised on a 2:1 basis, 104 to intervention and 49 to remaining on the wait listing (control). Twenty (13%) were lost to follow-up six months later, 18 from the intervention group.\n The Webster-Stratton Incredible Years basic parenting programme, a 12 week group based intervention.\n Problem behaviour in children and parenting skills assessed by self reports from parents and by direct observation in the home. Parents' self reported parenting competence, stress, and depression. Standardised and well validated instruments were used throughout.\n At follow-up, most of the measures of parenting and problem behaviour in children showed significant improvement in the intervention group. The intention to treat analysis for the primary outcome measure, the Eyberg child behaviour inventory, showed a mean difference between groups of 4.4 points (95% confidence interval 2.0 to 6.9, P<0.001) on the problem scale with an effect size of 0.63, and a mean difference of 25.1 (14.9 to 35.2, P<0.001) on the intensity scale with an effect size of 0.89.\n This community based study showed the effectiveness of an evidence based parenting intervention delivered with fidelity by regular Sure Start staff. It has influenced policy within Wales and provides lessons for England where, to date, Sure Start programmes have not been effective.\n ISRCTN46984318." ]

[ "2661155", "3317054", "2405741", "8156252", "8618579", "7933425", "3979000", "2350875", "3516085", "12119223", "9228372", "9459113", "10789668", "8275731", "1617983", "10470753", "3039882", "3513357", "10638663", "9105072", "8565513", "3885915", "9669790", "11685297", "12649125" ]

[ "Randomized double-blind, multicenter study of prostaglandin E1 in patients with the adult respiratory distress syndrome. Prostaglandin E1 Study Group.", "High-dose corticosteroids in patients with the adult respiratory distress syndrome.", "Functional and metabolic activity of polymorphonuclear leukocytes from patients with adult respiratory distress syndrome: results of a randomized double-blind placebo-controlled study on the activity of prostaglandin E1.", "Respiratory distress syndrome in patients with advanced cancer treated with pentoxifylline: a randomized study.", "Aerosolized surfactant in adults with sepsis-induced acute respiratory distress syndrome. Exosurf Acute Respiratory Distress Syndrome Sepsis Study Group.", "Safety and potential efficacy of an aerosolized surfactant in human sepsis-induced adult respiratory distress syndrome.", "Dazoxiben in human sepsis and adult respiratory distress syndrome.", "Indomethacin treatment of human adult respiratory distress syndrome.", "Prostaglandin E1 and survival in patients with the adult respiratory distress syndrome. A prospective trial.", "A randomized phase II trial of granulocyte-macrophage colony-stimulating factor therapy in severe sepsis with respiratory dysfunction.", "A trial of antioxidants N-acetylcysteine and procysteine in ARDS. The Antioxidant in ARDS Study Group.", "Treatment with N-acetylcysteine during acute respiratory distress syndrome: a randomized, double-blind, placebo-controlled clinical study.", "Ketoconazole for early treatment of acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. The ARDS Network.", "N-acetylcysteine enhances recovery from acute lung injury in man. A randomized, double-blind, placebo-controlled clinical study.", "Antioxidant treatment with N-acetylcysteine during adult respiratory distress syndrome: a prospective, randomized, placebo-controlled study.", "Liposomal prostaglandin E1 (TLC C-53) in acute respiratory distress syndrome: a controlled, randomized, double-blind, multicenter clinical trial. TLC C-53 ARDS Study Group.", "Prevention of lower respiratory herpes simplex virus infection with acyclovir in patients with the adult respiratory distress syndrome.", "Effects of prostaglandin E1 in adult respiratory distress syndrome.", "Protective effects of N-acetylcysteine and rutin on the lipid peroxidation of the lung epithelium during the adult respiratory distress syndrome.", "Bovine surfactant therapy for patients with acute respiratory distress syndrome.", "Liposomal prostaglandin E1 in acute respiratory distress syndrome: a placebo-controlled, randomized, double-blind, multicenter clinical trial.", "Early steroid therapy for respiratory failure.", "Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial.", "A multi-centre, double-blind, placebo-controlled study of liposomal prostaglandin E1 (TLC C-53) in patients with acute respiratory distress syndrome.", "Treatment of acute respiratory distress syndrome with recombinant surfactant protein C surfactant." ]

[ "Prostaglandin E1 (PGE1) was compared to placebo in a 100-patient (50 PGE1, 50 placebo) randomized, double-blind, clinical trial to determine whether PGE1 therapy enhances survival of patients with adult respiratory distress syndrome (ARDS) when infused through a central line at 30 ng/kg/min continuously for seven days. At 30 days postinfusion, 30 PGE1 and 24 placebo patients had died. Total deaths judged to be related to the syndrome were 32 and 28 in the PGE1 and placebo groups respectively at six months. We conclude that PGE1 did not enhance survival in patients with established ARDS. PGE1 augmented the hyperdynamic circulation of these patients by reducing systemic and pulmonary vascular resistance, which resulted in a reduction of blood pressures and increased stroke volume, cardiac output, and heart rate. An improvement in oxygen availability and oxygen consumption was observed with PGE1 therapy. PGE1 was associated with an increased incidence of diarrhea (six patients in the PGE1 group vs one in the placebo group, p less than 0.05). Other adverse effects included hypotension (ten patients in the PGE1 group vs seven in the placebo group), fever (six patients in the PGE1 group vs three in the placebo group), and non-fatal dysrhythmias (ten in the PGE1 group vs five in the placebo group).", "Corticosteroids are widely used as therapy for the adult respiratory distress syndrome (ARDS) without proof of efficacy. We conducted a prospective, randomized, double-blind, placebo-controlled trial of methylprednisolone therapy in 99 patients with refractory hypoxemia, diffuse bilateral infiltrates on chest radiography and absence of congestive heart failure documented by pulmonary-artery catheterization. The causes of ARDS included sepsis (27 percent), aspiration pneumonia (18 percent), pancreatitis (4 percent), shock (2 percent), fat emboli (1 percent), and miscellaneous causes or more than one cause (42 percent). Fifty patients received methylprednisolone (30 mg per kilogram of body weight every six hours for 24 hours), and 49 received placebo according to the same schedule. Serial measurements were made of pulmonary shunting, the ratio of partial pressure of arterial oxygen to partial pressure of alveolar oxygen, the chest radiograph severity score, total thoracic compliance, and pulmonary-artery pressure. We observed no statistical differences between groups in these characteristics upon entry or during the five days after entry. Forty-five days after entry there were no differences between the methylprednisolone and placebo groups in mortality (respectively, 30 of 50 [60 percent; 95 percent confidence interval, 46 to 74] and 31 of 49 [63 percent; 95 percent confidence interval, 49 to 77]; P = 0.74) or in the reversal of ARDS (18 of 50 [36 percent] vs. 19 of 49 [39 percent]; P = 0.77). However, the relatively wide confidence intervals in the mortality data make it impossible to exclude a small effect of treatment. Infectious complications were similar in the methylprednisolone group (8 of 50 [16 percent]) and the placebo group (5 of 49 [10 percent]; P = 0.60). Our data suggest that in patients with established ARDS due to sepsis, aspiration, or a mixed cause, high-dose methylprednisolone does not affect outcome.", "Indirect and experimental evidence suggests that polymorphonuclear leukocytes, responding to an activating signal presumably related to the complement cascade activation, are involved in the pathogenesis of the adult respiratory distress syndrome (ARDS). The pathologic changes seem to be result of the polymorphonuclear leukocyte margination within the pulmonary capillary vessels and their activation with subsequent release of vasoactive peptides (thromboxane A2, prostaglandin E2) and toxic intracellular compounds. This study confirms that adherence, chemotaxis, and chemiluminescence are increased in polymorphonuclear leukocytes from patients with ARDS. Enhanced chemotactic and chemiluminescence capacities are likely specific to ARDS, whereas increased polymorphonuclear leukocyte adherence seems to be nonspecific. If increased polymorphonuclear leukocyte activation is important in the pathogenesis of ARDS, the inhibition of this phenomenon could play a therapeutic role. This double-blind prospective study was undertaken to assess if polymorphonuclear leukocyte activity is inhibited in vivo by the iv administration of prostaglandin E1 (PGE1) in patients with ARDS. A continuous infusion of PGE1 at a dose of 30 ng.kg-1.min-1 for 7 days did not modify the functional activity of polymorphonuclear leukocytes in patients with ARDS. Because hemodynamic instability was seen during infusion of this dose of PGE1, an increased dose was not tested. At the dose of PGE1 tested, no significant effect upon the function activity of polymorphonuclear leukocytes in patients with ARDS could be demonstrated.", "The inappropriate endogenous secretion of tumour necrosis factor (TNF) could play a role in the pathogenesis of acute respiratory distress syndrome (ARDS), one of the most frequent causes of death in cancer patients. Because of its capacity to inhibit TNF secretion in vitro, pentoxifylline (PTX) could be extremely useful in ARDS therapy. In this study 30 advanced cancer patients with ARDS were randomized to receive either the conventional care or conventional care plus PTX (100 mg i.v. twice a day for 7 days followed by an oral administration of 400 mg three times a day) to evaluate the efficacy of PTX in reducing TNF serum levels and in improving the symptoms of this syndrome. Serum levels of TNF were measured before and after 7 days of therapy. The percentage of patients alive at 7 days was significantly higher in the PTX-treated group than in the controls (12/15 versus 3/15; P < 0.001). The mean survival time was significantly higher in the PTX-treated group than in the controls. A clinical and/or radiological improvement was obtained in 11/15 patients treated with PTX and in only 2/15 patients in the conventional care group (P < 0.01). TNF mean levels significantly decrease in the PTX-treated group. These data confirm in vivo the capacity of PTX to inhibit TNF secretion in patients with ARDS. Moreover PTX therapy may improve the symptoms related to ARDS without particular toxic effects.", "Patients with acute respiratory distress syndrome (ARDS) have a deficiency of surfactant. Surfactant replacement improves physiologic function in such patients, and preliminary data suggest that it may improve survival.\n We conducted a prospective, multicenter, double-blind, randomized, placebo-controlled trial involving 725 patients with sepsis-induced ARDS. Patients were stratified according to the risk of death at base line (indicated by their score on the Acute Physiological and Chronic Health Evaluation [APACHE III] index) and randomly assigned to receive either continuously administered synthetic surfactant (13.5 mg of dipalmitoylphosphatidylcholine per milliliter, 364 patients) or placebo (o.45 percent saline; 361 patients) in aerosolized form for up to five days.\n The demographic and physiologic characteristics of the two treatment groups were similar at base line. The mean (+/- SD) age was 50 +/- 17 years in the surfactant group and 53 +/- 18 years in the placebo group, and the mean APACHE III scores at randomization were 70.4 +/- 25 and 70.5 +/- 25, respectively. Hemodynamic measures, measures of oxygenation, duration of mechanical ventilation, and length of stay in intensive care unit did not differ significantly in the two groups. Survival at 30 days was 60 percent for both groups. Survival was similar in the groups when analyzed according to APACHE III score, cause of death, time of onset and severity of ARDS, presence or absence of documented sepsis, underlying disease, whether or not there was a do-not-resuscitate order, and medical center. Increased secretions were significantly more frequent in the surfactant group; the rates of other complications were similar in the two groups.\n The continuous administration of aerosolized synthetic surfactant to patients with sepsis-induced ARDS had no significant effect on 30-day survival, length of stay in the intensive care unit, duration of mechanical ventilation, or physiologic function.", "To evaluate the safety and potential efficacy of aerosolized surfactant in intubated patients with adult respiratory distress syndrome (ARDS).\n A prospective, double-blind, placebo-controlled, randomized, parallel, multicenter pilot clinical trial.\n A total of 51 patients with sepsis-induced ARDS were entered into the study within 18 hours of developing sepsis or sepsis syndrome.\n Patients were randomized into four treatment groups in a 2:1:2:1 ratio, as follows: 12 hours of surfactant per day, 12 hours of 0.6% saline per day, 24 hours of surfactant per day, and 24 hours of 0.6% saline per day. Surfactant or saline was aerosolized continuously for up to 5 days using an in-line nebulizer that aerosolized only during inspiration.\n Ventilatory data, arterial blood gases, and hemodynamic parameters were measured at baseline, every 4 or 8 hours during the 5 days of treatment, 24 hours after treatment, and 30 days after treatment, at which time mortality was also assessed. Safety was evaluated throughout the 30 days of the study.\n Surfactant was administered safely in ventilated patients when given continuously throughout the 5 days using the nebulizer system. Although there were no differences in any physiological parameters between the treatment groups, there was a dose-dependent trend in reduction of mortality from 47% in the combined placebo group to 41% and 35% in the groups treated with 12 hours and 24 hours of surfactant per day, respectively.\n Aerosolized surfactant was well tolerated when administered on a continuous basis for up to 5 days; however, at the doses given, it did not result in significant improvements in patients with sepsis-induced ARDS.", "Levels of thromboxane B2 (TxB2), the stable metabolite of thromboxane A2, are elevated in human and experimental septic shock. The thromboxane synthetase inhibitor dazoxiben has improved survival and decreased pulmonary hypertension in experimental endotoxemia. A randomized prospective study of 10 patients with the clinical diagnosis of sepsis and early adult respiratory distress syndrome (hypoxemia, radiologic evidence of the syndrome, and intrapulmonary shunt greater than 20%) was performed to test the efficacy of dazoxiben in ameliorating the effects of human sepsis. Five subjects received dazoxiben and five received placebo. Dazoxiben, 100 mg, or placebo was injected intravenously every 4 hours for a maximum of 72 hours. Plasma immunoreactive TxB2 (iTxB2) levels were determined by radioimmunoassay. Before dazoxiben, the plasma iTxB2 level was 752 +/- 261 pg/ml (n = 5) and was reduced within 1 hour to 333 +/- 137 pg/ml. The plasma levels of iTxB2 remained significantly decreased with subsequent doses of dazoxiben and it was 201 +/- 67 pg/ml (n = 4) 60 hours after dosing. In contrast, placebo had no significant effect on plasma iTxB2 levels (n = 5) throughout the entire period of observation. Dazoxiben did not induce any significant changes in pulmonary or systemic vascular resistance, intrapulmonary shunting, clotting studies, or extravascular lung water. One of the five subjects in the placebo group died and two of the five subjects in the dazoxiben group died. We conclude that dazoxiben was safe and effectively lowered plasma iTxB2 levels in patients with sepsis and incipient adult respiratory distress symptom, but did not significantly alter the hemodynamic and pulmonary sequelae of established sepsis.", "The purpose of this investigation was to evaluate the magnitude and duration of changes in lung function and oxygen transport in patients with adult respiratory distress syndrome (ARDS) receiving indomethacin. Ten patients with ARDS were randomized to receive intravenously either a single 50 mg dose of indomethacin or placebo. Comparing 1 hr postinfusion levels to baseline observations in the indomethacin group, PaO2 increased to 125 +/- 13 torr from 93 +/- 8 torr, PaO2/FIO2 ratio increased to 223 +/- 24 from 160 +/- 5, and Qs/Qt dropped to 0.20 +/- 0.03 from 0.27 +/- 0.03 (all P less than 0.05). These alterations in oxygenation gradually returned to baseline levels over the ensuing 8 hr. No such changes were noted in the placebo group.", "A 7-day infusion of prostaglandin E1 (PGE1), an immunomodulator, was evaluated in a prospective, randomized, placebo-controlled, double-blinded trial in surgical patients with the adult respiratory distress syndrome (ARDS). The drug seemed to improve pulmonary function--only two PGE1 patients died with severe pulmonary failure compared with nine placebo patients (p = 0.01). Survival at 30 days after the end of the infusion--the predetermined end point of the study--was significantly better in the patients given PGE1 (p = 0.03), with 15 of 21 PGE1 patients (71%) alive at this time compared with seven of 20 placebo patients (35%). Improvement in overall survival in the PGE1 patients did not reach statistical significance (p = 0.08). Overall survival in patients initially free of severe organ failure, however, was significantly better in the PGE1 patients (p = 0.03). Of the six PGE1 patients free of severe organ failure at time of entry, all survived to leave the hospital; of the 10 placebo patients initially free of severe organ failure, four survived. The drug had no serious side effects and did not potentiate susceptibility to infection. PGE1 is a promising agent for the treatment of ARDS.", "Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates hemopoiesis and effector functions of granulocytes and macrophages and is involved in pulmonary surfactant homeostasis. We investigated whether GM-CSF therapy improved clinically diagnosed severe sepsis and respiratory dysfunction in critically ill patients. This randomized, double-blind, placebo-controlled phase II study added low-dose (3 mcg/kg) intravenous recombinant human GM-CSF daily for 5 days to conventional therapy in 10 patients, with a further eight patients receiving placebo. GM-CSF-treated patients showed improvement in Pa(O(2))/FI(O(2)) over 5 days (p = 0.02) and increased peripheral blood neutrophils (p = 0.08), whereas alveolar neutrophils decreased (p = 0.02). GM-CSF therapy was not associated with decreased 30-day survival or with increased acute respiratory distress syndrome or extrapulmonary organ dysfunction. GM-CSF therapy was associated with increased blood granulocyte superoxide production and restoration or preservation of blood and alveolar leukocyte phagocytic function. We conclude that low-dose GM-CSF was associated with improved gas exchange without pulmonary neutrophil infiltration, despite functional activation of both circulating neutrophils and pulmonary phagocytes. In addition, GM-CSF therapy was not associated with worsened acute respiratory distress syndrome or the multiple organ dysfunction syndrome, suggesting a homeostatic role for GM-CSF in sepsis-related pulmonary dysfunction.", "To determine the levels of glutathione and cysteine in patients with ARDS and examine the effect of treatment with N-acetylcysteine (NAC) and L-2-oxothiazolidine-4-carboxylate (Procysteine; Clintec Technologies Inc; Chicago [OTZ]) on these levels and on common physiologic abnormalities, and organ dysfunction associated with ARDS.\n Randomized, double-blind, placebo-controlled, prospective clinical trial.\n ICUs in five clinical centers in the United States and Canada.\n Patients meeting a predetermined definition of ARDS and requiring mechanical ventilation.\n Standard care for ARDS and I.V. infusion, every 8 h for 10 days, of one of the following: NAC (70 mg/kg, n=14), OTZ (63 mg/kg, n=17), or placebo (n=15).\n Both antioxidants effectively repleted RBC glutathione gradually over the 10-day treatment period (47% and 49% increases from baseline values for NAC and OTZ, respectively). There was no difference in mortality among groups (placebo, 40%; NAC, 36%; OTZ, 35%). However, the number of days of acute lung injury was decreased and there was also a significant increase in cardiac index in both treatment groups (NAC/OTZ [+]14%; placebo [-]6%).\n Our findings suggest that repletion of glutathione may safely be accomplished with NAC or OTZ in patients with acute lung injury/ARDS. Such treatment may shorten the duration of acute lung injury, but larger studies are needed to confirm this.", "Intravenous N-acetylcysteine (NAC) has been reported to improve systemic oxygenation and reduce the need for ventilatory support in patients with an acute lung injury. In the more serious form, namely established adult respiratory distress syndrome (ARDS) (PaO2/FIO2 < or = 200 mm Hg), we tested the hypothesis that treatment with intravenous NAC may be beneficial.\n Respiratory dysfunction was graded daily according to the need for mechanical ventilation and FIO2 and to the evolution of the lung injury score (LIS) and the PaO2/FIO2 ratio in 42 patients with established ARDS receiving either NAC 190 mg/kg/day or placebo as a continuous intravenous infusion over the first 3 days of their clinical course.\n NAC and placebo groups (22 and 20 patients, respectively) were comparable for demographic characteristics, ARDS categories, severity of illness (simplified acute physiology score [SAPS II]) LIS and PaO2/FIO2 ratio. Mortality rate was 32% for the NAC and 25% for the placebo group (difference not significant). At admission (day 1), 91% of patients in the NAC and 95% in the placebo group required ventilatory support; at days 2, 3, 5, and 7 after admission, the percentage of patients receiving ventilatory support was not significantly reduced for both groups in comparison with day 1. Moreover, there were no differences between the two groups at the same observation days. In both groups, the FIO2 was significantly lower and the PaO2/FIO2 ratio was significantly higher than the initial values during the evolution (FiO2 at day 3, P < .01 for NAC and P < .05 for placebo; PaO2/FIO2 at day 3: P < .01 for NAC and P < .02 for placebo), but this improvement was similar for both groups and, moreover, the between-group comparison was never significantly different at the various collection days. The LIS decreased significantly in NAC group between days 1 and 3 (2.23 +/- 0.62 v 1.76 +/- 0.17; P < .05), whereas no changes were observed in the placebo group; at day 5, there was a significant difference between the two groups (1.53 +/- 0.21 for the NAC v 2.15 +/- 0.19 for the placebo group; P < .05). In the prevalent sepsis category (10 patients in the NAC and 9 in the placebo group), the mortality rate, the need of ventilatory support, the intensive care unit stay, and the PaO2/FIO2 evolution did not differ significantly in both subgroups.\n In this relatively small group of patients presenting with an established ARDS subsequent to a variety of underlying diseases, intravenous NAC treatment during 72 hours neither improved systemic oxygenation nor reduced the need for ventilatory support.", "Three clinical studies have suggested that ketoconazole, a synthetic imidazole with anti-inflammatory activity, may prevent the development of acute respiratory distress syndrome (ARDS) in critically ill patients. However, the use of ketoconazole as treatment for acute lung injury (ALI) and ARDS has not been previously studied.\n To test the efficacy of ketoconazole in reducing mortality and morbidity in patients with ALI or ARDS.\n Randomized, double-blind, placebo-controlled trial conducted from March 1996 to January 1997.\n Twenty-four hospitals associated with 10 network centers in the United States, constituting the ARDS Network.\n A total of 234 patients with ALI or ARDS.\n Patients were randomly assigned to receive ketoconazole, 400 mg/d (n = 117), or placebo (n = 117), initiated within 36 hours of fulfilling study entry criteria and given enterally for up to 21 days.\n Primary outcome measures were the proportion of patients alive with unassisted breathing at hospital discharge and the number of days of unassisted breathing (ventilator-free days) during 28 days of follow-up. Secondary outcome measures included the proportion of patients achieving unassisted breathing for 48 hours or more, the number of organ failure-free days, and changes in plasma interleukin 6 (IL-6) and urinary thromboxane A2 metabolites (thromboxane B2 [TXB2] and 11-dehydro-TXB2).\n In-hospital mortality (SE) was 34.1% (4.3%) for the placebo group and 35.2% (4.3%) for the ketoconazole group (P=.85). The median number of ventilator-free days within 28 days of randomization was 9 in the placebo group and 10 in the ketoconazole group (P=.89). There were no statistically significant differences in the number of organ failure-free days, pulmonary physiology, or adverse events between treatment groups. The median serum ketoconazole level was 1.25 microg/mL and serum levels greater than 0.5 microg/mL were detected in 96% of patients assayed. Plasma IL-6, urinary TXB2, and 11-dehydro-TXB2 levels were unaffected by ketoconazole.\n In these patients with ALI or ARDS, ketoconazole was safe and bioavailable but did not reduce mortality or duration of mechanical ventilation or improve lung function. These data do not support the use of ketoconazole for the early treatment of ALI or ARDS.", "To determine the effects of intravenous N-acetylcysteine (NAC) on the development of severe adult respiratory distress syndrome (ARDS) and mortality rate in patients with mild-to-moderate acute lung injury and to analyze the duration of ventilatory support and FIO2 required as well as the evolution of the lung injury score.\n Three university hospital ICUs and one regional ICU in Switzerland.\n Sixty-one adult patients presenting with mild-to-moderate acute lung injury and various predisposing factors for ARDS received either NAC, 40 mg/kg/d, or placebo intravenously for 3 days.\n Respiratory dysfunction was assessed daily according to the need for mechanical ventilation and FIO2, the evolution of the lung injury score, and the PaO2/FIO2 ratio. The cardiovascular state, liver function, and kidney function were also monitored. Data were collected at admission (day 0), during the first 3 days, and on the day of discharge from the ICU.\n The NAC and placebo groups (32 and 29 patients, respectively) were comparable at ICU admission for severity of illness assessed by the simplified acute physiology score (SAPS) (10.8 +/- 4.6 vs 10.9 +/- 4.8) and lung injury score (LIS) (1.39 +/- 0.95 vs 1.11 +/- 1.08) (mean +/- SD). Three patients in each group developed ARDS. The 1-month mortality rate was 22 percent for the NAC group and 35 percent for the placebo group (difference not statistically significant). At admission, 22 of 32 patients (69 percent) in the NAC group were mechanically ventilated compared with 22 of 29 (76 percent) in the placebo group. At the end of the treatment period (day 3), 5 of 29 (17 percent) in the NAC group and 12 of 25 (48 percent) in the placebo group were still receiving ventilatory support (p = 0.01), The FIO2 was 0.37 less than admission value (day 0) in the NAC group, and 0.20 less in the placebo group (p < 0.04); the oxygenation index (PaO2/FIO2) improved significantly (p < 0.05) from day 0 to day 3 only in the NAC-treated group. The LIS showed a significant regression (p = 0.003) in the NAC-treated group during the first 10 days of treatment: no change was observed in the placebo group. No adverse effects were observed during the treatment with NAC.\n Intravenous NAC treatment during 72 h improved systemic oxygenation and reduced the need for ventilatory support in patients presenting with mild-to-moderate acute lung injury subsequent to a variety of underlying diseases. Development of ARDS and mortality were not reduced significantly by this therapy.", "To examine whether the antioxidant N-acetylcysteine could ameliorate the course of the adult respiratory distress syndrome (ARDS) in man.\n Randomized, double-blind, placebo-controlled study.\n Medical and surgical ICU in a regional hospital.\n Sixty-six ICU patients with ARDS.\n Patients with ARDS (PaO2/FiO2 ratio less than 250 torr) were treated with either the antioxidant N-acetylcysteine 150 mg/kg as a loading dose and then 20 mg/kg/hr, or with placebo for 6 days.\n No improvement could be demonstrated in the PaO2/FiO2 ratio in the study group as compared with the control group on any day. Pulmonary compliance was higher in the N-acetylcysteine group than in the placebo group on all days, but this difference did not reach the chosen 5% level of significance. No difference between the two groups could be demonstrated on chest radiograph or on survival rate. We documented that N-acetylcysteine acts as an anticoagulant and perhaps decreases pulmonary fibrin uptake during ARDS.\n N-acetylcysteine might be of benefit in ARDS. Before further clinical studies are started, problems with N-acetylcysteine and coagulation have to be elucidated in order to find out whether N-acetylcysteine could have a beneficial effect in the treatment of ARDS.", "To evaluate the safety and efficacy of an intravenous liposomal dispersion of prostaglandin E1 as TLC C-53 in the treatment of patients with acute respiratory distress syndrome (ARDS).\n Randomized, prospective, multicenter, double-blind, placebo-controlled, phase III clinical trial.\n Forty-seven community and university-affiliated hospitals in the United States.\n A total of 350 patients with ARDS were enrolled in this clinical trial.\n Patients were prospectively randomized in a 1:1 ratio to receive either liposomal prostaglandin E1 or placebo. The study drug was infused intravenously for 60 mins every 6 hrs for 7 days starting with a dosage of 0.15 microg/kg/hr. The dose was increased every 12 hrs until the maximal dose (3.6 microg/kg/hr) was attained or intolerance to further increases developed. Patients received standard aggressive medical/surgical care during the infusion period.\n The primary outcome measure was the time it took to wean the patient from the ventilator. Secondary end points included time to improvement of the PaO2/FIO2 ratio (defined as first PaO2/FIO2 > 300 mm Hg), day 28 mortality, ventilator dependence at day 8, changes in PaO2/FIO2, incidence of and time to development/resolution of organ failure other than ARDS.\n A total of 348 patients could be evaluated for efficacy. The distribution of variables at baseline describing gender, lung injury scores, Acute Physiology and Chronic Health Evaluation II scores, PaO2/FIO2, pulmonary compliance, and time from onset of ARDS or from institution of mechanical ventilation to the first dose of study drug was similar among patients in the liposomal prostaglandin E1 (n = 177) and the placebo (n = 171) treatment arms. There was no significant difference in the number of days to the discontinuation of ventilation in the liposomal prostaglandin E1 group compared with the placebo group (median number of days to off mechanical ventilation, 16.9 in patients receiving liposomal prostaglandin E1 and 19.6 in those administered placebo; p = .94). Similarly, mortality at day 28 was not significantly different in the two groups (day 28 mortality, 57 of 176 (32%) in the liposomal prostaglandin E1 group and 50 of 170 (29%) in patients receiving placebo; p = .55). In contrast, treatment with liposomal prostaglandin E1 was associated with a significantly shorter time to reach a PaO2/FIO2 ratio of >300 mm Hg (median number of days to reaching a PaO2/FIO2 ratio >300 mm Hg: 9.8 days in the liposomal prostaglandin E1 group and 13.7 days in patients receiving the placebo; p = .02). Among the subgroups examined, time to off mechanical ventilation was significantly reduced in patients who received at least 85% of a full dose (i.e., > 45.9 microg/kg) of liposomal prostaglandin E1 (median number of days to discontinuation of ventilation, 10.3 in the liposomal prostaglandin E1 group and 16.3 days in patients receiving placebo; p = .05). The overall incidence of serious adverse events was not significantly different in the liposomal prostaglandin E1 (40%) or placebo-treated (37%) groups. Drug-related adverse events of all kinds were reported in 69% of the patients receiving liposomal prostaglandin E1 compared with 33% of the placebo group, with hypotension and hypoxia (occurring in 52% and 24% of the liposomal prostaglandin E1-treated patients, respectively, and 17% and 5% of the placebo-treated patients, respectively) being noted most frequently.\n In the intent-to-treat population of patients with ARDS, treatment with liposomal prostaglandin E1 accelerated improvement in indexes of oxygenation but did not decrease the duration of mechanical ventilation and did not improve day 28 survival.", "Herpes simplex virus (HSV) type I commonly occurs in the lower respiratory tract (LRT) of seriously ill patients, particularly those with the adult respiratory distress syndrome (ARDS), but it is not known whether HSV is a benign mucosal colonizer or a pathogen. The aims of this study were to determine whether the antiviral agent acyclovir could prevent this occurrence, and if so, whether prevention improved the outcome. Forty-five patients with ARDS underwent double-blind randomization into a treatment group (22 subjects) who received prophylactic acyclovir intravenously, 5 mg/kg every 8 h, and a control group (23 subjects). Upper and lower respiratory secretions were examined for the presence of HSV before randomization and twice weekly thereafter. Seven patients were excluded because of HSV detection prior to treatment. There were no significant differences between the remaining 17 acyclovir and 21 control patients in age, sex, distribution of primary diagnostic categories, and severity of primary illness. Only 1 patient (6%) in the acyclovir group developed HSV after treatment compared with 15 (71%) in the control group (p less than 0.001), but there was no improvement in the acyclovir group in the severity of respiratory failure, the duration of ventilator support (acyclovir, 20 +/- 19 days; control, 14 +/- 11 days), or mortality (acyclovir, 8 of 17, 47%; control, 9 of 21, 43%). We conclude that acyclovir is effective in preventing the high incidence of HSV in patients with ARDS, but that this prevention does not improve outcome. Routine prophylaxis of HSV is not recommended.", "Prostaglandin E1 (PGE1, Prostin VR) in doses of 30 ng/kg . min was studied in two series of severely ill surgical patients with adult respiratory distress syndrome (ARDS). First the drug was administered in an initial trial in six patients; then a prospective, randomized, blinded trial was conducted in 10 studies on nine patients. PGE1 markedly decreased pulmonary artery pressure, pulmonary and systemic vascular resistance indexed, and venous pressures, while increasing cardiac output, arterial PO2 (PaO2), oxygen delivery, and oxygen consumption when compared with the baseline preinfusion control values and with the response of the placebo-treated control series. The PGE1 responses were greater in patients whose ARDS was primarily attributed to the postoperative state with or without sepsis and least in patients with cirrhosis. The data are consistent with the concept that the drug reduces vasoconstriction primarily in the pulmonary circulation but also in the systemic circulation; improved PaO2 usually follows the hemodynamic effect. We conclude that PGE1 may be a useful adjunctive therapy for ARDS.", "This study investigates the effects of N-acetylcysteine (NAC) and rutin on the lung oxidative burden of patients with early adult respiratory distress syndrome (ARDS). The protection was evaluated by measuring expired ethane and malondialdehyde (MDA), and oxidized (GSSG) and reduced glutathione (GSH) in the epithelial lining fluid of 36 patients who developed ARDS less than 24 hours before enrollment in the study. The patients were randomly assigned to 3 groups, receiving 250 mL 5% dextrose in water (group 1), NAC 50 mg/kg body weight in 5% dextrose (group 2), and NAC 50 mg/kg + rutin 5 mg/kg in 5% dextrose (group 3). Ethane and MDA concentrations were significantly reduced in the treatment groups after day 6. GSH was 30% increased in the treatment groups. No significant variations were observed in the control group until day 9. The trial confirms that NAC and rutin are efficient in protecting the lungs of patients with ARDS.", "Lung surfactant is deficient in patients with acute respiratory distress syndrome (ARDS). We performed a randomized, prospective, controlled, open-label clinical study of administration of a bovine surfactant to patients with ARDS to obtain preliminary information about its safety and efficacy. Patients received either surfactant by endotracheal instillation in addition to standard therapy or standard therapy only. Three different groups of patients receiving surfactant were studied: patients receiving up to eight doses of 50 mg phospholipids/kg, those receiving up to eight doses of 100 mg phospholipids/kg, and those receiving up to four doses of 100 mg phospholipids/kg. Outcome measures included ventilatory support parameters, arterial blood gases, organ system failures, bronchoalveolar lavage (BAL) analyses, immunologic analyses, survival, and adverse events during the 28-d study period. Fifty-nine study patients were evaluable; 43 in the surfactant group and 16 in the control group. The FI(O2) at 120 h after treatment began was significantly decreased only for patients who received up to four doses of 100 mg phospholipids/kg surfactant as compared with control patients (p = 0.011). Mortality in the same group of patients was 18.8%, as compared with 43.8% in the control group (p = 0.075). The surfactant instillation was generally well tolerated, and no safety concerns were identified. This pilot study presents preliminary evidence that surfactant might have therapeutic benefit for patients with ARDS, and provides rationale for further clinical study of this agent.", "To evaluate the safety and efficacy of liposomal prostaglandin E1 (TLC C-53) in the treatment of patients with the acute respiratory distress syndrome (ARDS).\n Randomized, prospective, multicenter, double-blind, placebo-controlled, phase II clinical trial.\n Eight community and university-affiliated hospitals in the United States.\n Twenty-five patients with ARDS.\n Patients were prospectively randomized in an unbalanced ratio within each site to receive either TLC C-53 (n = 17) or placebo (n = 8). Study drug was infused intravenously over 60 mins every 6 hrs for a 7-day period, starting at a dose of 0.15 micrograms/kg/hr. The dose was increased every 12 hrs until the maximal dose (3.6 micrograms/kg/hr) was attained, intolerance to further increases developed, or invasive monitoring was discontinued. Patients received standard, aggressive, medical/surgical care throughout the trial.\n Outcome measurements were Pao2/FI0(2), dynamic pulmonary compliance, ventilator dependence on day 8, and 28-day all-cause mortality rate. At baseline, the distribution of variables describing Lung Injury Scores, Acute Physiology and Chronic Health Evaluation II scores, Pao2/FI0(2), pulmonary compliance, and time from onset of ARDS to first dose of study drug was similar between patients in the TLC C-53 and placebo treatment groups. On day 8, all eight patients given placebo required mechanical ventilation, while eight of 17 patients given TLC C-53 were healthy enough to be removed from the ventilator (p = .03). Improvement in PaO2/FIO2 during the initial 8-day study period was greater in patients receiving TLC C-53. This trend achieved statistical significance on day 3, when the increase in PaO2/FIO2 from baseline was 82.5 +/- 14.6 in the TLC C-53 group compared with 28.3 +/- 22.1 in the placebo group (p = .05). By day 8, lung compliance also increased from baseline significantly more in TLC C-53 patients than in placebo patients (5.7 +/- 1.7 vs -1.5 +/- 1.8 mL/cm H2O; p = .01). The 28-day mortality rate was 6% (1/17 patients) in the TLC C-53 group and 25% (2/8 patients) in the placebo group (p = .23). Drug-related adverse events were reported in 82% of the patients receiving TLC C-53 compared with 38% of the placebo group, with half of the adverse events in the TLC C-53 group being localized infusion site irritation. TLC C-53 was hemodynamically well tolerated, with transient hypotension occurring in three patients.\n In patients with ARDS, TLC C-53 was associated with improved oxygenation, increased lung compliance, and decreased ventilator dependency.", "We performed a randomized double-blind trial to determine the usefulness of early methylprednisolone therapy for patients with pulmonary failure. We selected 81 acutely ill, mechanically ventilated patients at high risk for adult respiratory distress syndrome (ARDS). Thirty-nine patients received methylprednisolone, 30 mg/kg, every six hours for 48 hours; 42 patients received mannitol placebo. All patients were given a positive end-expiratory pressure of 5 cm H2O, monitored with pulmonary artery catheters, and treated for their primary disease processes. Twenty-five steroid-treated patients (64%) and 14 placebo-treated patients (33%) developed ARDS. Early infectious complications occurred in 30 steroid-treated patients (77%) and 18 placebo-treated patients (43%). There were no significant differences in factors predisposing to ARDS, ventilatory requirements, or days of intensive care. These results do not support the use of methylprednisolone for ARDS. Steroids failed to improve pulmonary function and were associated with an increased infection rate. Intensive pulmonary and general supportive care remain the preferred therapy for ARDS.", "No pharmacological therapeutic protocol has been found effective in modifying the clinical course of acute respiratory distress syndrome (ARDS) and mortality remains greater than 50%.\n To determine the effects of prolonged methylprednisolone therapy on lung function and mortality in patients with unresolving ARDS.\n Randomized, double-blind, placebo-controlled trial.\n Medical intensive care units of 4 medical centers.\n Twenty-four patients with severe ARDS who had failed to improve lung injury score (LIS) by the seventh day of respiratory failure.\n Sixteen patients received methylprednisolone and 8 received placebo. Methylprednisolone dose was initially 2 mg/kg per day and the duration of treatment was 32 days. Four patients whose LIS failed to improve by at least 1 point after 10 days of treatment were blindly crossed over to the alternative treatment.\n Primary outcome measures were improvement in lung function and mortality. Secondary outcome measures were improvement in multiple organ dysfunction syndrome (MODS) and development of nosocomial infections.\n Physiological characteristics at the onset of ARDS were similar in both groups. At study entry (day 9 [SD, 3] of ARDS), the 2 groups had similar LIS, ratios of PaO2 to fraction of inspired oxygen (FIO2), and MODS scores. Changes observed by study day 10 for methylprednisolone vs placebo were as follows: reduced LIS (mean [SEM], 1.7 [0.1] vs 3.0 [0.2]; P<.001); improved ratio of PaO2 to FIO2 (mean [SEM], 262 [19] vs 148 [35]; P<.001); decreased MODS score (mean [SEM], 0.7 [0.2] vs 1.8 [0.3]; P<.001); and successful extubation (7 vs 0; P=.05). For the treatment group vs the placebo group, mortality associated with the intensive care unit was 0 (0%) of 16 vs 5 (62%) of 8 (P=.002) and hospital-associated mortality was 2 (12%) of 16 vs 5 (62%) of 8 (P=.03). The rate of infections per day of treatment was similar in both groups, and pneumonia was frequently detected in the absence of fever.\n In this study, prolonged administration of methylprednisolone in patients with unresolving ARDS was associated with improvement in lung injury and MODS scores and reduced mortality.", "To evaluate the safety of liposomal PGE1 (TLC C-53) in patients with acute respiratory distress syndrome (ARDS), and determine its efficacy in improving oxygenation and reducing ventilator dependency.\n A multi-centre, randomized, double-blind, placebo-controlled clinical study.\n Thirty-one hospitals in six European countries.\n One hundred two patients with ARDS.\n Patients were randomized in a 2:1 ratio to receive infusions of either the study drug TLC C-53 or placebo. Infusions were given over 60 min every 6 h for 7 days. The dose of study drug started at 0.6 microg/kg per h, rising over 24 h to a maximum dose of 1.8 microg/kg per h.\n Seventy patients received the study drug and 32 placebo. Sixty-nine patients (47 treatment, 22 placebo) completed the study protocol. Patients were monitored for changes in the PaO2/FIO2 ratio, changes in lung compliance, time to off-ventilator and 28-day mortality, in addition to basic haematological and haemodynamic parameters. There were no significant differences in demographics and baseline characteristics between the two groups. There were no differences in the time to off-ventilation (16 days with treatment, 16.6 days with placebo, p=0.94) or in 28-day mortality (30% with treatment, 28% with placebo, p=0.78). There was a difference in the time to achieve a PaO2/FIO2 ratio above 300 in favour of TLC C-53 (10.3 versus 26.5 days) but this was not statistically significant (p=0.23).\n TLC C-53 was generally well-tolerated but failed to reduce mortality or duration of mechanical ventilation.", "We performed a phase I/II trial in North America of a recombinant surfactant protein C-based surfactant (Venticute) as treatment for the acute respiratory distress syndrome. Patients were prospectively randomized to receive either standard therapy or standard therapy plus one of two doses of exogenous surfactant given four times over 24 hours. Surfactant administration was well tolerated. No significant treatment benefit was associated with surfactant treatment. Bronchoalveolar lavage of treated patients at 48 hours reflected the presence of exogenous surfactant components, did not show evidence of improved surface tension lowering function, and had interleukin-6 concentrations that were significantly lower than control group values, consistent with an antiinflammatory treatment effect. The presence of exogenous surfactant was not detected in lavage fluid obtained at 120 hours. Future studies might rationally employ larger surfactant doses and a more prolonged dosing schedule." ]

[ "12638027", "12511760", "6141377", "15960563", "17303766", "8202964", "10926942", "3729755", "15814161" ]

[ "Early fluoxetine treatment of post-stroke depression--a three-month double-blind placebo-controlled study with an open-label long-term follow up.", "Cognitive behavioral psychotherapy for depression following stroke: a randomized controlled trial.", "Nortriptyline treatment of post-stroke depression: a double-blind study.", "Double-blind comparison of sertraline and placebo in stroke patients with minor depression and less severe major depression.", "Motivational interviewing early after acute stroke: a randomized, controlled trial.", "Effective treatment of poststroke depression with the selective serotonin reuptake inhibitor citalopram.", "Fluoxetine in early poststroke depression: a double-blind placebo-controlled study.", "Antidepressant therapy after stroke. A double-blind trial.", "An evaluation of efficacy and safety of reboxetine in elderly patients affected by \"retarded\" post-stroke depression. A random, placebo-controlled study." ]

[ "Poststroke depression is a frequent psychiatric complication after stroke that may have strong negative impact on rehabilitation therapy and functional recovery. This study was conducted to show the efficacy and safety of early treatment with the selective serotonin reuptake inhibitor fluoxetine in post-stroke depressed patients.\n This double-blind, randomized placebo-controlled study was of patients within two weeks after stroke. Moderate to severe depressed patients (determined by Hamilton Depression Scale (HDS) > 15, the Beck Depression Inventory (BDI) and the Clinical Global Impression (CGI) Scale) were randomized to receive either 20 mg/d fluoxetine or placebo for 3 months. Beside the psychiatric assessment, patients were evaluated by use of the Scandinavian Stroke Scale (SSS), the Mini-Mental-State-Examination (MMSE) and the Barthel-Index (BI). An open-label long-term follow up was done 18 months after the initial assessment.\n 54 depressed patients of an inpatient population of 242 consecutive stroke patients aged 25 to 85 years entered the trial within the first two weeks post-stroke. 50 patients completed the trial per-protocol. The initial severity of depression was comparable in the two groups (mean baseline HDS score 32.8 in the fluoxetine vs. 30.3 in the placebo group), as were neurological symptom severity and demographic parameters. Significant improvement was seen in both groups within 4 weeks of treatment, whereas no advantages of fluoxetine could be observed at this time. This indicates a high degree of spontaneous recovery during early rehabilitation therapy. BDI scores of patients treated with fluoxetine further decreased until the follow-up at 12 weeks, whereas the scores increased again in the placebo group. This depressive relapse of the placebo patients after the end of most rehabilitation efforts was evident at a long-term follow-up 18 months after inclusion, when patients who had been treated with fluoxetine were significantly less depressed. No side effects of fluoxetine treatment were detected.\n The advantages of fluoxetine were obvious at the follow-up 18 months after inclusion, but could not be demonstrated within the first three months of controlled treatment. The multitude of therapeutic efforts that take place in the early phase of rehabilitation might have facilitated spontaneous recovery from depression and might have hindered benefits of antidepressant treatment to become obvious. Fluoxetine treatment was well tolerated and safe.", "There is inconclusive evidence of the effectiveness of psychological interventions for depression after stroke. We report the results from a randomized controlled trial of cognitive behavioral therapy (CBT).\n Stroke patients admitted to hospital were invited to complete mood questionnaires 1, 3 and 6 months after stroke. Patients who were depressed were invited to take part in a trial and randomly allocated to receive CBT (n=39), an attention placebo intervention (n= 43), or standard care (n=41). Outcome assessments were undertaken at 3 and 6 months after recruitment, on the Beck Depression Inventory, Wakefield Depression Inventory, Extended Activities of Daily Living scale, London Handicap Scale, and a rating of satisfaction with care.\n There were no significant differences between the groups in patients' mood, independence in instrumental activities of daily living, handicap, or satisfaction with care.\n CBT in the treatment of depression following stroke was found to be ineffective in this study. However, because of the small sample size, method of recruitment, and selection criteria, further randomized trials are required.", "The efficacy of nortriptyline in the treatment of post-stroke depression was assessed by a double-blind study in thirty-four patients. Half of the patients had major depression. There was a significantly greater improvement in depression in patients treated with nortriptyline than in a similar group of placebo-treated patients. Depression was measured by the Hamilton depression scale, Zung depression scale, present state examination, and an overall depression scale. Successfully treated patients had serum nortriptyline levels in the therapeutic range. Post-stroke depressions are common, severe, and longstanding, and the demonstrated efficacy of nortriptyline provides an important addition to the treatments available for stroke patients.", "Poststroke depression is a frequent condition and important to treat. The aim of this trial was to study the efficacy and tolerability of sertraline.\n In 4 Swedish stroke centers, 123 patients (aged 70.7 +/- 9.9 years) were enrolled during the period September 1998 to January 2001 in a randomized, double-blind, placebo-controlled 26-week trial, at a mean of 128 +/- 97 days (range, 3-375 days) after stroke, if they fulfilled DSM-IV criteria of major depressive episode (N = 76) or minor depressive disorder (N = 47). The primary efficacy variable was a change in depression assessed by the Montgomery-Asberg Depression Rating Scale. The Emotional Distress Scale (EDS) was administered and the occurrence of emotionalism and quality of life (QoL) were assessed, as well as neurologic recovery. Efficacy analyses were intention-to-treat, short-term (week 6) and long-term (week 26).\n Of the 123 patients, 62 were treated with sertraline (50-100 mg/day) and 61 with placebo. Both groups improved substantially, with no differences between the treatments, either for major depressive episode or minor depressive disorder, or for short- or long-term antidepressant effect and neurologic outcome. EDS revealed a better outcome with sertraline at week 6 (p < .05). At week 26, the improvement in QoL was better in sertraline patients (p < .05) and there was a trend for emotionalism (p = .07). No serious side effects were seen.\n Poststroke depression as measured by a conventional depression rating scale improved over time irrespective of treatment. Positive effects specific to sertraline were identified in emotional distress, emotionalism, and QoL. The study indicates that poststroke emotional reactions comprise depression and other domains susceptible to pharmacologic therapy.", "The purpose of this study was to determine whether motivational interviewing, a patient-centered counseling technique, can benefit patients' mood 3 months after stroke.\n A single-center, open, randomized, controlled trial was conducted at a single hospital with a stroke unit. Subjects consisted of 411 consecutive patients on the stroke register who were over 18 years of age and who did not have severe cognitive and communication problems that would prevent them from taking part in an interview; were not known to be moving out of the area after discharge; and were not already receiving psychiatric or clinical psychology intervention. All patients received usual stroke care. Patients in the intervention group received 4 individual, weekly sessions of motivational interviewing with a trained therapist in addition to usual stroke care. The primary outcome was the proportion of patients with normal mood at 3 months poststroke measured by the 28-item General Health Questionnaire (normal, <5; low > or=5) using a mailed questionnaire.\n Eighty-one of 207 (39.1%) patients in the control group and 100 of 204 (49.0%) patients in the intervention group had normal mood at follow up. A significant benefit of motivational interviewing over usual stroke care (OR: 1.60, 95% CI: 1.04 to 2.46, P=0.03) was found.\n Our results suggest motivational interviewing leads to an improvement in patients' mood 3 months after stroke.", "The aim of the study was to investigate the efficacy and safety of the selective serotonin reuptake inhibitor citalopram in treating poststroke depression, since available treatments are usually poorly tolerated.\n A 6-week double-blind, placebo-controlled trial was undertaken. Diagnosis and outcome were determined using the Hamilton Depression Scale, and unwanted effects were measured using the UKU side effect rating scale. Sixty-six consecutive depressed patients from an unselected population of 285 stroke patients aged 25 to 80 years entered the trial 2 to 52 weeks after stroke. They were assigned to equally sized treatment and placebo groups. The initial level of depression was comparable in the two groups (mean baseline Hamilton Depression scores, 19.4 and 18.9, respectively). Demographic parameters were also comparable in the two groups.\n Significantly greater improvement was seen in patients treated with citalopram (10 to 40 mg/d) for 3 and 6 weeks, both when including all patients (intention-to-treat analysis, P < .05) and excluding patients who dropped out during the first 3 weeks (efficacy analysis, P < .005). Half of the 28 patients who entered the trial 2 to 6 weeks after stroke recovered within 1 month, independent of the treatment given. This indicates a high degree of spontaneous recovery in the early phase after stroke. In contrast, recovery was infrequent in placebo group patients who became depressed 7 weeks or more after stroke. No serious side effects related to the treatment were detected; those present were mild and usually transient.\n This trial demonstrates that the selective serotonin reuptake inhibitor citalopram offers an advantageous new treatment of poststroke depression that is both safe and effective.", "Early poststroke depression (PSD) is a frequent and specific entity that impairs the rehabilitation and functional recovery of hemiplegic patients. This trial was designed to study the efficacy and tolerance of fluoxetine (FLX) in the treatment of early PSD.\n This was a multicenter, double-blind, placebo-controlled study. Recent hemiplegic patients (<3 months) suffering from major depressive disorder (determined by International Classification of Diseases, 10th Revision, and Montgomery-Asberg Depression Rating Scale [MADRS] >19) were randomized to receive either 20 mg/d fluoxetine (FLX) or placebo for 6 weeks. Patients were evaluated by use of the Motricity Index, Mini-Mental State Examination, Functional Independence Measure, and MADRS. Statistical analysis was performed by using an intent-to-treat approach comparing the 2 groups at day 0 (baseline) and days 15, 30, and 45 (end point).\n Of 121 patients screened, 31 were included in the study, 16 in the FLX group and 15 in the placebo group. There were no significant differences in baseline characteristics among the 2 groups. The FLX-treated patients compared with placebo-treated patients demonstrated significant improvement in mean MADRS scores at end point (11.8+/-6. 7 [mean+/-SD] versus 18.7+/-10.0, respectively; P=0.05). FLX-treated patients compared with placebo-treated patients also demonstrated greater response rate (62.5% versus 33.3%, respectively) and greater mean decrease of MADRS (16.6 versus 8.4, respectively; P=0.02). There were no differences in motor, cognitive, or functional improvement and no significant side effects after FLX treatment, except for a patient with a moderate and transient increase of transaminases.\n FLX is an efficacious and well-tolerated treatment for early PSD. Further research is needed to evaluate the efficacy and safety of long-term treatment in this population.", "Twenty-seven inpatients participating in a stroke rehabilitation program were randomized to receive either placebo or trazodone hydrochloride (Desyrel) beginning a mean (+/- SEM) of 44 +/- 4 days after stroke. The target dosage was 200 mg/d. Patients with either a clinical diagnosis of depression or abnormal Zung depression scores showed a consistent trend toward greater improvement in Barthel activities of daily living (ADL) scores with trazodone than with placebo. An abnormal dexamethasone suppression test result was associated with significant improvement in the Barthel ADL scores of patients receiving trazodone (38 +/- 6 vs 20 +/- 6 for placebo). Patients with stroke and evidence of depression are therefore likely to benefit from treatment with trazodone.", "Depression occurs frequently in post-stroke patients and appears to be associated with an impairment in their rehabilitation and functional recovery. Although selective serotonin reuptake inhibitors (SSRI) are often used in post-stroke depression (PSD), it has been observed that only a subset of patients is responsive to this treatment. Other patients respond to tricyclic antidepressants or MAO inhibitors, which, however, may not have a favorable profile of safety and tolerability in post-stroke patients. In this double-blinded, placebo-controlled study, we evaluated the efficacy and tolerability of the noradrenaline reuptake inhibitor, reboxetine, in a subset of PSD patients classified as affected by \"retarded\" depression. Reboxetine (4 mg, twice daily, for 16 weeks) was administered to patients that developed depression after a single ischaemic or hemorrhagic stroke. We assessed the severity of depressive symptoms by the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS). HDRS and BDI scores (mean+/-S.D.) at baseline were, respectively, 24+/-1.31 and 19.87+/-1.46 in the placebo group, 24.06+/-1.52 and 20.56+/-2.16 in the reboxetine group. After 16 weeks, HDRS and BDI mean scores were respectively 22.73+/-2.4 and 18.4+/-3.33 in the placebo group, 9.26+/-2.15 and 8.06+/-3.43 in the reboxetine group [p<0.01 versus the respective baseline (paired t-test); (#)p<0.01 versus retarded depressed patients treated with placebo (one-way analysis of variance (ANOVA) applied to the difference from baseline, associated with Dunnett's t-test to isolate the differences)]. Reboxetine showed a good efficacy, safety and tolerability in PSD patients affected by \"retarded\" depression. We conclude that reboxetine is well tolerated and may be a useful therapeutic option in PSD patients with \"retarded\" depression." ]

[ "10430197", "2677863", "9824184", "8333483", "12712108", "2014850", "9215169", "7369252", "6374098", "12237643", "1945214", "9988808" ]

[ "The effect of indomethacin tocolysis in preterm labour on perinatal outcome: a randomised placebo-controlled trial.", "Efficacy and safety of indomethacin versus ritodrine in the management of preterm labor: a randomized study.", "A comparative study of ketorolac (Toradol) and magnesium sulfate for arrest of preterm labor.", "Efficacy and safety of indomethacin compared with magnesium sulfate in the management of preterm labor: a randomized study.", "A double-blind randomized study of fetal side effects during and after the short-term maternal administration of indomethacin, sulindac, and nimesulide for the treatment of preterm labor.", "Randomized comparative trial of indomethacin and ritodrine for the long-term treatment of preterm labor.", "Lack of effect of antenatal indomethacin on fetal cerebral blood flow.", "The inhibition of premature labor with indomethacin.", "Further study of the inhibition of premature labor by indomethacin. Part II double-blind study.", "A prospective randomized safety trial of celecoxib for treatment of preterm labor.", "A randomized double-dummy comparison between indomethacin and nylidrin in threatened preterm labor.", "A randomized double-blind study comparing the fetal effects of sulindac to terbutaline during the management of preterm labor." ]

[ "To determine whether indomethacin tocolysis in preterm labour is associated with a better perinatal outcome than placebo.\n A randomised placebo-controlled trial.\n Two university teaching hospitals with level three neonatal intensive care units.\n Women in preterm labour with intact membranes between 23 and 30 weeks of gestation.\n Random allocation to tocolysis with indomethacin (50 mg followed by 25 mg 6 hourly for 48 hours) or placebo in a double-blind fashion.\n The primary outcome, perinatal mortality or severe neonatal morbidity, was defined as perinatal death, necrotising enterocolitis, bronchopulmonary dysplasia, intraventricular haemorrhage or peri-ventricular leucomalacia. Data were analysed using odds ratios (OR) and 95% confidence intervals (95% CI).\n Between March 1995 and February 1996, 34 women (39 babies) were recruited. The baseline characteristics of the two groups were similar. No patient was lost to follow up. In the indomethacin group, gestation was prolonged by > 48 hours in 13/16 (81%) of women vs 10/18 (56%) in the placebo group. The incidence of perinatal mortality or severe neonatal morbidity was not significantly different between the groups, but occurred in twice as many babies in the indomethacin group as in the placebo group--6/19 (32%) vs 3/20 (15%) OR (95% CI) 2.62 (0.44-18.8). There was one perinatal death, of a baby delivered at 24 weeks of gestation. This occurred in the indomethacin group.\n There is no evidence that indomethacin tocolysis is beneficial, and further trials are needed to assess the impact of indomethacin tocolysis in preterm labour.", "One hundred six patients in preterm labor with intact amniotic membranes and gestational age less than or equal to 32 weeks were randomized to receive either ritodrine hydrochloride or a 48-hour course of indomethacin for tocolysis. The relative efficacy, maternal and neonatal safety, and costs were evaluated to determine which may be the more appropriate first-line pharmacologic agent used to manage preterm labor. Fifty-four patients and 52 patients were randomized to receive ritodrine hydrochloride or indomethacin, respectively. Ritodrine hydrochloride and indomethacin were equally effective in inhibiting uterine contractions and delaying delivery. Delivery was delayed for at least 48 hours in 83 and 94%, and for at least 7 days in 70 and 75% of patients receiving ritodrine or indomethacin, respectively. Tocolysis with indomethacin was associated with no maternal side effects, whereas tocolysis with ritodrine hydrochloride was associated with a 24% incidence of serious cardiovascular and metabolic adverse effects prompting discontinuation of the drug. There were no differences in outcome between the infants exposed to indomethacin versus ritodrine hydrochloride when delivered either remote from therapy or during therapy, except for a statistically higher serum glucose in the infants exposed to ritodrine hydrochloride when delivered during tocolytic therapy. There were no cases of premature closure of the ductus arteriosus or pulmonary hypertension. Tocolysis with indomethacin was 17 times less costly than tocolysis with ritodrine hydrochloride. For gestations less than or equal to 32 weeks complicated by preterm labor, indomethacin may be an appropriate alternative as a first-line tocolytic agent.", "We evaluated the efficacy and safety of ketorolac (Toradol).\n In this prospective trial, 88 women in confirmed preterm labor at < or =32 weeks' gestation were randomized to receive magnesium sulfate given as an initial 6 g intravenous bolus followed by continuous infusion therapy (2 to 6 g/hr) or intramuscularly administered ketorolac (60 mg loading dose) followed by 30 mg every 6 hours for a maximum of 24 hours.\n The study groups were similar with respect to age, parity, cervical status, and gestational age on admission. Ketorolac was more rapid (2.71 hr+/-2.16) in the arrest of preterm labor than was magnesium sulfate (6.22 hr+/-5.65). No patient required discontinuance of either drug due to adverse effects. There was no difference in the incidence of neonatal complications between the two groups.\n In gestations with preterm labor at <32 weeks, ketorolac appears to be an appropriate first-line tocolytic agent.", "Our purpose was to evaluate the relative efficacy and safety of indomethacin versus magnesium sulfate in the management of preterm labor in pregnancies < 32 weeks of gestation.\n Eligible patients admitted with singleton pregnancies and idiopathic preterm labor between August 1988 and October 1989 were randomized by sealed envelopes to receive either indomethacin or intravenous magnesium sulfate.\n Of 101 eligible patients 49 were randomized to receive indomethacin. The two study groups were similar in regard to a number of entry variables, including gestational age, cervical examination, and contraction frequency. Indomethacin was as effective as magnesium sulfate in delaying delivery > 48 hours, 90% versus 85%, and together with oral terbutaline in extending the gestation, 22.9 versus 22.7 days. Tocolysis with magnesium sulfate was discontinued in eight (15%) patients because of maternal side effects, in contrast to none in the indomethacin group, p < 0.05.\n For gestations < 32 weeks indomethacin may be considered an appropriate alternative to magnesium sulfate as a first-time tocolytic agent.", "The purpose of this study was to establish whether nimesulide causes fewer fetal side effects than indomethacin or sulindac after short-term maternal exposure for tocolysis.\n This was a double-blind, double-dummy prospective randomized study with three drug treatment groups (n = 10 per group) that were comprised of subjects who were at 28 to 32 weeks of gestation with preterm contractions. The subjects were treated in the delivery suites of two busy inner-city teaching hospitals; the intervention consisted of 48 hours of treatment and with 72 hours of follow-up observation with indomethacin 100 mg (twice daily), sulindac 200 mg (twice daily), or nimesulide 200 mg (twice daily). The amniotic fluid index, hourly fetal urine production, and ductal Doppler pulsatility index observations were monitored before the treatment and at 4, 24, 48, 72, and 120 hours after the treatment was started. The statistical analysis used repeated measures analysis of variance, Bonferroni test, and Bland-Altman agreement. Significance assumed when the probability value was <.05.\n Each drug caused a significant reduction in all three observations over the 48-hour treatment period, which recovered to pretreatment levels by 72 hours after treatment. There were no significant differences among drugs for any of these effects.\n Nimesulide causes similar short-term fetal side effects to indomethacin and sulindac.", "A randomized prospective trial was performed to compare the efficacy and safety of ritodrine and indomethacin in the long-term treatment of preterm labor. Forty patients with intact membranes in preterm labor at 23 to 34 weeks' gestation were randomized to receive either intravenous ritodrine or oral indomethacin as the first-line tocolytic agent. Successful intravenous ritodrine therapy was followed by oral terbutaline therapy, and indomethacin-treated patients continued to receive oral indomethacin. Treatment failures were defined as progressive preterm labor or patient intolerance, and these patients were treated with intravenous magnesium sulfate. Ritodrine and indomethacin were equally successful in delaying preterm birth as defined by interval to delivery, gestational age at delivery, delivery delayed greater than 7 days, attainment of 35 weeks of gestation, percentage of patients who required magnesium sulfate therapy, percentage of patients who were readmitted with premature rupture of membranes, absence of recurrent preterm labor, and infant birth weight. More than 80% of mothers who received ritodrine voiced complaints of beta-sympathomimetic side effects, and one patient discontinued treatment as the result of intolerance. There were minimal patient complaints with indomethacin use. No statistically significant differences were noted in neonatal outcome as defined by Apgar scores, umbilical cord pH, intensive care days, ventilator days, or neonatal deaths. However, three cases of primary pulmonary hypertension were observed in the indomethacin group. We had not previously observed this problem with short-term (24 to 48 hours) indomethacin therapy.", "Our purpose was to investigate fetal cerebral blood flow and the incidence of intraventricular hemorrhage in patients undergoing tocolysis with either indomethacin or magnesium sulfate at < 30 weeks' gestation.\n Consenting patients at < 30 weeks' gestation with preterm labor were randomized to receive indomethacin or magnesium sulfate tocolysis. Magnesium sulfate was administered intravenously with an 8 gm loading dose given over the first hour, 4 gm over the second hour, and then a maintenance infusion of 2.5 gm per hour. The infusion was continued for approximately 12 hours after the cessation of uterine contractions. Patients randomized to receive indomethacin were given an initial dose of 50 to 100 mg orally or per rectum, followed by 25 to 50 mg orally every 4 to 6 hours for 24 to 48 hours. Oral tocolytic agents were not used after successful tocolysis. Betamethasone was administered to all patients. Patients underwent fetal cerebral Doppler studies during tocolytic therapy and at least 24 hours after completion of the treatment.\n Twelve patients were randomized to receive indomethacin and twelve patients were randomized to receive magnesium sulfate. Twenty-one fetuses underwent cerebral Doppler studies in triplicate during and after therapy. The mean gestational age at tocolysis was 27.5 +/- 1.9 weeks for the indomethacin group and 26.4 +/- 1.6 weeks for the magnesium sulfate group (p = 0.14). The middle cerebral artery resistance index for fetuses during indomethacin treatment was 0.73 +/- 0.09, whereas the resistance index after therapy was 0.75 +/- 0.05 (p = 0.49). The resistance index during magnesium sulfate tocolysis was 0.79 +/- 0.04 and after therapy it was 0.76 +/- 0.04 (p = 0.18). There was no significant difference in the resistance index between the groups on or off therapy. In addition, the incidence of intraventricular hemorrhage was similar in both groups.\n These results suggest that indomethacin does not significantly affect fetal cerebral blood flow. If antenatal indomethacin in the preterm fetus increases the risk of intraventricular hemorrhage, it would appear to be by another mechanism.", "We administered indomethacin orally for the treatment of premature labor in a prospective, randomized, double-blind fashion, and all infants were followed up. Indomethacin was significantly more effective than placebo in inhibition of premature labor during a 24-hour course of therapy, with treatment failure during therapy occurring in only one of 15 indomethacin-treated patients compared to nine of 15 placebo-treated patients (p less than 0.01). Mean plasma concentrations of indomethacin were approximately 0.8 micrograms/ml at both 4 and 12 hours after administration. Mean plasma levels of 15-oxo-13,14-dihydroprostaglandin F2 alpha (PGFM) were similar in the two groups before treatment, decreased markedly in the indomethacin group by 4 hours, and were not detected at 12 hours in all but the one indomethacin-treated patient who was delivered within 24 hours. Patients in the placebo group who were delivered prematurely had higher pretreatment PGFM levels (mean +/- SE, 83 +/- 18 pg/ml, n = 9) than the patients who responded to placebo (25 +/- 6 pg/ml, n = 6) (p less than 0.05). There was no difference between the indomethacin and placebo groups with respect to gestational age at delivery, birth weight, and neonatal morbidity and deaths. In particular, we found no evidence of premature closure of the ductus arteriosus, pulmonary hypertension, or increase in bleeding problems among the infants exposed to indomethacin in utero. Although no difference in neonatal outcome was observed in this small number of patients, it would seem prudent still to consider indomethacin as an experimental therapy.", "In the etiology of premature labor prostaglandins fulfill a significant role. It is known that indomethacin is a strong inhibitor of prostaglandin synthesis. The effect of indomethacin on premature labor was studied in a prospective randomized double-blind study in 36 patients. Eighteen patients received indomethacin and eighteen received placebo. 200-300 mg of indomethacin was the total dosage in a 24 hours period. The activity of the uterus was monitored with a cardiotocograph. The mean duration of pregnancy and the mean birth weight in indomethacin group (36.4 weeks, 2833 g) were both significantly greater (p less than 0.001) than that in placebo group (31.2 weeks, 2028 g). In the indomethacin group 3 children weighted less than 2500 g compared with 14 in placebo group. In 15 of 18 indomethacin treated patients (83.3%) premature labor was arrested after indomethacin treatment compared with 4 of 18 in the placebo group (22.2%). The indomethacin group had a mean 1 minute APGAR score of 9.3 +/- 0.2 whereas the placebo group showed a score of 7.8 +/- 0.5 (p less than 0.01). Three infants died from respiratory distress syndrome; one in the indomethacin group (1810 g) and two in the placebo group (600 and 1450 g). Autopsies in the infants demonstrated a typical picture of pulmonary atelectasis and hyaline membranes. There was no evidence of premature closure of the ductus arteriosus or pulmonary hypertension. 2 mothers in the indomethacin group suffered minor discomfort i.e. nausea, vomiting and vertigo.(ABSTRACT TRUNCATED AT 250 WORDS)", "We compared the safety of celecoxib, a selective cyclo-oxygenase-2 inhibitor, with the safety of the nonselective cyclo-oxygenase inhibitor indomethacin, when it was administered for treatment of preterm labor.\n In a randomized, double-blind, placebo-controlled trial, 24 pregnant women in preterm labor at 24 to 34 weeks of gestation received either indomethacin or celecoxib for 48 hours. Clinical assessment, fetal sonography, and Doppler blood flow studies of the fetal ductus arteriosus were performed daily.\n Mean maximum ductal flow velocity was significantly elevated over baseline (82.9 +/- 4.6 cm/s vs 111.14 +/- 14.3 cm/s; P =.02) after 24 hours of indomethacin, but not celecoxib. Both medications were associated with a transient decrease in amniotic fluid volume, with a greater effect by indomethacin. The medications were equally effective in the maintenance of tocolysis. There were no significant maternal or neonatal adverse events.\n In this initial evaluation, the safety of short-term celecoxib in women with preterm labor was superior to that of indomethacin.", "We compared the tocolytic effect of indomethacin and nylidrin in a prospective double-blind trial in which the appearance of the tocolytic treatment (always intravenous infusion and rectal suppositories/oral capsules) was identical to the subjects. Sixty healthy women in imminent preterm labor between 25-34 weeks of singleton gestation were included. Thirty of these women received indomethacin (concomitantly with placebo infusion), with doses as follows: day 1, 100-mg rectal suppository followed by two oral capsules (50 mg) at 8-hour intervals; days 2 and 3, three 50-mg oral capsules each day. Thirty women received intravenous nylidrin (concomitantly with rectal/oral placebo), initiated with the dose of 50 micrograms/minute and continued at the dose of 100-150 micrograms/minute for a maximum of 3 days. Preterm labor was arrested for 24, 48, and 72 hours in 100, 96, and 90%, respectively, of subjects in the indomethacin group, compared with 100, 76, and 73% of women in the nylidrin group; the difference was significant (P less than .05) at 48 hours. Women progressed beyond 37 gestational weeks more commonly (P less than .05) with indomethacin (21 of 30, 70%) than with nylidrin (13 of 30, 43%). Indomethacin treatment was accompanied by maternal side effects 20% of the time, significantly less commonly (P less than .001) than with nylidrin (83%). The neonatal outcome was similar in the two study groups. We conclude from this double-dummy technique trial that indomethacin is more effective and better tolerated than nylidrin in arresting imminent preterm labor.", "The object of this study was to compare the fetal effects of sulindac and terbutaline used in the management of preterm labor on the ductus arteriosus, middle cerebral artery, renal artery, umbilical artery, fetal urine production, and amniotic fluid index.\n In a randomized, double-blind study 20 patients with preterm labor and no evidence of fetal structural anomalies or intra-amniotic infection received either sulindac (200 mg orally every 12 hours for 6 doses) or terbutaline (5 mg orally every 4 hours) for 72 hours of therapy. All medications were administered from identical blister packs. Opaque glucose base tablets were given at 4-hour intervals in the sulindac treatment arm to mimic the dosing interval in the terbutaline arm of the study. The Doppler pulsatility indices for the ductus arteriosus, middle cerebral artery, renal artery and umbilical artery and also the fetal urinary output were obtained at baseline and 5, 12, 24, 48, and 72 hours after the medication was started. Doppler data were analyzed within each group with raw data and between groups with the change in pulsatility indices from baseline. Statistical analysis was performed with the Kolmogorov-Smirnov test for normality, repeated measures analysis of variance, Mann-Whitney rank sum test, and Student t test as appropriate. P <.05 (2-tailed) was used to denote statistical significance.\n There were 10 patients in each group, with no difference in gestational age between the 2 groups (32.3 vs 31.7 weeks). Sulindac was stopped in 2 patients after severe ductal constriction was noted, in 1 at 12 hours and in the other at 24 hours. One patient at 33 weeks' gestation was delivered because of fetal distress after 46 hours of sulindac therapy. When analyzed across time within groups, the pulsatility index in the ductus arteriosus decreased significantly at 12 and 24 hours in the sulindac group but not the terbutaline group. No significant differences were noted in the middle cerebral artery, umbilical artery, renal artery, or fetal urinary output within either group over time. Significant differences in the change from baseline in pulsatility index of the ductus arteriosus between the sulindac and terbutaline groups were noted at 5, 12, 24, and 48 hours. A similar effect was noted in the change from baseline in pulsatility index of the middle cerebral artery at 48 and 72 hours. There was a significant decrease in the amniotic fluid index in both groups at 24, 48, and 72 hours. The amniotic fluid index in the sulindac group was significantly lower than that in the terbutaline group at 48 and 72 hours of therapy.\n Sulindac constricted the fetal ductus arteriosus, with an effect noted within 5 hours of starting therapy. The constriction, which resolved in all cases within 48 hours of discontinuing therapy, had minimal effects on the pulsatility index of the middle cerebral artery, renal artery, and umbilical artery. Sulindac and terbutaline both resulted in a significant reduction in the amniotic fluid index, with sulindac having a greater effect." ]

[ "15546651" ]

[ "Acupuncture: a promising treatment for depression during pregnancy." ]

[ "Few medically acceptable treatments for depression during pregnancy are available. The aim of this randomized controlled pilot study was to determine whether acupuncture holds promise as a treatment for depression during pregnancy.\n Sixty-one pregnant women with major depressive disorder and a 17-item Hamilton Rating Scale for Depression (HRSD17) score >or=14 were randomly assigned to one of three treatments, delivered over 8 weeks: an active acupuncture (SPEC, N=20), an active control acupuncture (NSPEC, N=21), and massage (MSSG, N=20). Acupuncture treatments were standardized, but individually tailored, and were provided in a double-blind fashion. Responders to acute phase treatment (HRSD17 score<14 and >or=50% reduction from baseline) continued the treatment they were initially randomized to until 10 weeks postpartum.\n Response rates at the end of the acute phase were statistically significantly higher for SPEC (69%) than for MSSG (32%), with an intermediate NSPEC response rate (47%). The SPEC group also exhibited a significantly higher average rate of reduction in BDI scores from baseline to the end of the first month of treatment than the MSSG group. Responders to the acute phase of all treatments combined had significantly lower depression scores at 10 weeks postpartum than nonresponders.\n Generalizability is limited by the small sample and its relative homogeneity.\n Acupuncture holds promise for the treatment of depression during pregnancy." ]

[ "10952698" ]

[ "Randomised trial of iodine intake and thyroid status in preterm infants." ]

[ "Low levels of circulating thyroid hormones have been associated with poorer general and neurodevelopmental outcome in preterm babies and it has been speculated that the association is causal. Low levels of circulating thyroid hormone have been reported after inadequate intake of iodine in preterm infants being fed milk formula.\n To investigate whether increased iodine intake from supplemented preterm formula would improve thyroid hormone levels in preterm babies (this study) and hence improve neurodevelopmental status (planned subsequent study).\n A total of 121 preterm infants were entered into a randomised controlled trial of standard (68 microg/l) versus increased (272 microg/l) iodine in preterm formula.\n The two groups were comparable at recruitment. No evidence of an effect of the intervention on thyroid hormone levels was seen up to 41 weeks after conception.\n Calls for increased iodine content of preterm infant formulas are not justified by this study." ]

[ "1464047", "1500629", "10992533", "1626795", "8423275", "7852667", "9574880", "3131406", "6507997", "8757203", "11742269", "7842184", "10565489" ]

[ "Investigation of the tendency to wheeze in pollen sensitive patients.", "Nasal beclomethasone prevents the seasonal increase in bronchial responsiveness in patients with allergic rhinitis and asthma.", "Influence of intranasal steroids during the grass pollen season on bronchial responsiveness in children and young adults with asthma and hay fever.", "Different effects of nasal and bronchial glucocorticosteroid administration on bronchial hyperresponsiveness in patients with allergic rhinitis.", "Treatment of allergic rhinitis with intranasal corticosteroids in patients with mild asthma: effect on lower airway responsiveness.", "Effect of intranasal azelastine and beclomethasone dipropionate on nasal symptoms, nasal cytology, and bronchial responsiveness to methacholine in allergic rhinitis in response to grass pollens.", "Nasal inhalation of budesonide from a spacer in children with perennial rhinitis and asthma.", "Effects of topical nasal treatment on asthma symptoms.", "Effect of an intranasally administered corticosteroid (budesonide) on nasal obstruction, mouth breathing, and asthma.", "Once daily intranasal fluticasone propionate (200 micrograms) reduces nasal symptoms and inflammation but also attenuates the increase in bronchial responsiveness during the pollen season in allergic rhinitis.", "A double-blinded, comparative study of the effects of short preseason specific immunotherapy and topical steroids in patients with allergic rhinoconjunctivitis and asthma.", "The effects of intranasal steroids on nasal and pulmonary responses to cat exposure.", "Simultaneous treatment of rhinitis and asthma by nasal inhalation of corticosteroid from a spacer." ]

[ "We have undertaken a double blind placebo controlled study of the effect of nasal beclomethasone on the tendency to wheeze in 20 unselected hay fever sufferers, half with a history of previous seasonal wheezing. We found no difference between either bronchial hyperresponsiveness, as measured by methacholine challenge, home-monitored PEFR, nor recorded wheeze nor cough between treated and placebo groups although the numbers were small. All were allowed the antihistamine cetirizine hydrochloride 10 mg daily. Eighteen out of the 19 patients had either bronchial hyperresponsiveness (PD20 methacholine < 8 mumol or a > 2 doubling dose change in their PD20 during the pollen season). We have shown a significant positive correlation between a hay fever score (HFS) (created by taking the sum of the home scored; nasal discharge, nasal blockage, eye irritation, sneeze and antihistamine use) and peak seasonal specific IgE to mixed grass pollen (Spearman correlation coefficient 0.5 P < 0.02). There was also a positive correlation between the rise in specific IgE from pre to peak season and the HFS, correlation coefficient 0.6 P = 0.03).", "Experimental studies have demonstrated that induction of a nasal allergic reaction can lead to an increase in bronchial responsiveness (BR). To assess the clinical relevance of these experimental changes to chronic asthma, we sought to determine the effect of nasal beclomethasone dipropionate (Bdp) on BR in patients with seasonal allergic rhinitis and asthma. Eighteen subjects with histories of seasonal allergic rhinitis and asthma during the fall pollen season with positive skin tests to short ragweed and bronchial hyperresponsiveness to inhaled methacholine were assigned to receive either nasal Bdp (336 micrograms/day) or placebo for the entire ragweed season. Patients recorded daily nasal and chest symptoms, nasal blockage index, oral peak expiratory flow rates, and supplemental medication use. BR to methacholine was measured during the baseline period and 6 weeks into the ragweed season. Although the Bdp group did have a significant improvement in nasal blockage index, there was no improvement in daily asthma symptom scores, oral peak expiratory flow, or asthma medication use. However, subjects treated with Bdp were protected from the increase in BR seen in the placebo group (geometric mean PC20 placebo group: baseline = 0.70, week 6 = 0.29; Bdp group: baseline = 0.80, week 6 = 0.93; intergroup difference, p = 0.022). We conclude that nasal corticosteroid therapy can prevent the increase in BR associated with seasonal pollen exposure in patients with allergic rhinitis and asthma.", "It has been reported that intranasal corticosteroids can influence bronchial hyperresponsiveness (BHR) in asthmatic subjects with seasonal rhinitis. The purpose of the present study was to evaluate the effect of intranasal fluticasone propionate and beclomethasone dipropionate on BHR and bronchial calibre (forced expiratory volume in one second, FEV(1)) in children and young adults with seasonal rhinitis and mild asthma during two consecutive grass pollen seasons.\n In the first pollen season 25 patients aged 8-28 years were included in a double blind, placebo controlled study. The active treatment group used fluticasone aqueous spray 200 microgram once daily. In the second pollen season 72 patients aged 8-28 years participated in a double blind, placebo controlled study of a similar design to that of the previous year except that an additional treatment group of patients using beclomethasone 200 microg twice daily was included. FEV(1) was measured before and after three and six weeks of treatment; BHR to methacholine (PD(20)) was measured before and after six weeks of treatment.\n In the first season the mean (SD) logPD(20) of the patients decreased significantly both in the fluticasone group (from 2.43 (0.8) microgram to 1.86 (0.85) microgram) and in the placebo group (from 2.41 (0.42) microgram to 1.87 (0.78) microgram) without any intergroup difference in the change in logPD(20). In the second pollen season the mean logPD(20) in the fluticasone, beclomethasone, and placebo groups did not change significantly.\n Intranasal steroids did not influence BHR during two grass pollen seasons in children and young adults with seasonal rhinitis and mild asthma.", "Disorders of the upper respiratory tract, particularly allergic rhinitis, are commonly associated with bronchial hyperresponsiveness. The latter may be due to postnasal drip or to mediator or chemotactic factors into the lower airways that either directly alter airway reactivity or cause airway inflammation. The aim of this study was to compare the effect of an identical dose of nasal or bronchial corticosteroid administration on bronchial hyperresponsiveness in patients with allergic rhinitis. Eleven patients were studied. All of them were judged atopic on the basis of positive skin tests to common allergens. During control, spirometry, flow-volume curves, and specific airway conductance (SGaw) were measured. Bronchial challenges were then performed with increasing concentrations of carbachol, and dose-response curves were constructed. The concentration of carbachol that decreased SGaw by 35% from baseline (PD35) was determined by interpolating from the dose-response curve. Control measurements were repeated at 1-wk intervals to ensure that PD35 was stable in all the patients. Then the patients received for 2 wk, in a double-blind randomized crossover fashion, a topical administration of either an aerosol of 400 micrograms of beclamethasone dipropionate (B) into the nose (100 micrograms four times per day) or into the bronchi. During each trial period, identical sprays of placebo were used, the latter being administered into the nose when B was administered into the bronchi and vice versa. Measurements were then performed after 2 wk of intranasal administration and after 2 wk of intrabronchial administration.(ABSTRACT TRUNCATED AT 250 WORDS)", "The effect of treatment of allergic rhinitis with intranasal corticosteroids on lower airway responsiveness was assessed in a randomized, double-blind, placebo-controlled, crossover study. Twenty-one young patients with perennial allergic rhinitis and asthma, with documented lower airway hyperresponsiveness (PC20 methacholine < 8 mg/ml), were treated with intranasal aqueous beclomethasone dipropionate and placebo, each given for 4 weeks. Patients recorded rhinitis and asthma symptom scores and monitored peak expiratory flow rates every morning and evening. Patients recorded global assessment of rhinitis and global asthma symptom scores at the beginning and end of each treatment. PC20 methacholine was performed at baseline and at the end of each treatment period. Intranasal beclomethasone dipropionate significantly reduced global rhinitis symptom scores (p = 0.05) after 4 weeks of treatment. Global asthma scores did not change significantly (p = 0.2). Geometric mean PC20 methacholine improved significantly after 4 weeks of intranasal beclomethasone, but not after placebo (p = 0.04). Daily morning and evening rhinitis symptom scores were lower in patients treated with intranasal corticosteroids over the first 4 weeks of treatment, but carryover effect of steroids precluded comparative analysis of the second 4-week block (morning p = 0.06, evening p = 0.03). Morning asthma scores tended to decrease (p = 0.07). Evening asthma scores were significantly decreased at weeks 2 and 3 (p = 0.001, p = 0.02, respectively). No change in peak expiratory flow rate was seen. This study confirms that treatment of inflammation in the upper airways indirectly improves asthma symptoms and decreases bronchial hyperreactivity. Ignoring inflammation in the upper airway may lead to suboptimal results in asthma treatment.", "We compared the effect of nasal azelastine (0.56 mg/day), nasal beclomethasone dipropionate (BDP, 200 micrograms/day) and matched placebo on seasonal symptoms, nasal cytology, and the increase in bronchial responsiveness occurring during pollen season in a group of subjects with history of allergic rhinitis to grass pollens only.\n The study was completed by nine subjects in the azelastine group, 13 subjects in the BDP group, and 13 subjects in the placebo group. Treatments were randomly administered for 6 weeks. Each subject recorded daily nasal, eye and chest symptoms and additional treatment requirement for the entire pollen season. Each subject performed nasal lavage 4 weeks into the pollen season. Bronchial responsiveness to methacholine was measured before and 4 weeks into the pollen season. Response was expressed as provocative dose causing a 20% fall in forced expiratory volume in 1 second in micromoles.\n Azelastine-treated subjects had significantly fewer nasal symptoms during week 4 (p < 0.05), and BDP-treated subjects had fewer nasal symptoms during week 4 (p < 0.05) and week 5 (p < 0.05) compared with subjects given placebo. Both treatments significantly reduced the need for additional medications. BDP, but not azelastine, treatment significantly reduced the percent of eosinophils recovered in nasal lavage (p < 0.05). Neither azelastine nor BDP protected against the increase in bronchial responsiveness to methacholine occurring during the pollen season.\n We demonstrated that both azelastine and BDP are effective treatments for nasal symptoms of seasonal allergic rhinitis after 4 weeks of therapy. However, we were not able to demonstrate an antiinflammatory activity of nasally administered azelastine. Nasal therapy with azelastine and BDP did not block the increase in bronchial responsiveness to methacholine caused by seasonal allergen exposure.", "The standard treatment of allergic rhinitis and asthma consists of topical corticosteroids administered intranasally and inhaled through the mouth. Although this therapy is highly effective, and side-effects are few and mild, it may be possible further to improve the therapeutic index and patient compliance with the treatment. In the present study, we evaluated a nasal inhalation system used for the simultaneous treatment of rhinitis and asthma. In principle, it results in an airway deposition of the corticosteroid similar to that of inhaled allergens. Twenty-four children with perennial rhinitis and asthma inhaled budesonide through the nose from a pressurized aerosol, attached to a spacer device, in a double-blind, placebo-controlled, crossover study. Compared with placebo, budesonide treatment resulted in a significant reduction of nasal symptoms (P<0.01) and of asthma symptoms (P<0.05), and in an increase of nasal peak inspiratory flow (P < 0.001) and of oral peak expiratory flow (P=0.01). There were no differences between budesonide and placebo in local side-effects, such as dry nose, nosebleed, and hoarseness. We conclude that nasal inhalation of a corticosteroid from a spacer offers a simple and effective treatment for both rhinitis and asthma in children, but it is an open question whether the nasal inhalation system can improve the ratio of antirhinitis/antiasthma effects to side-effects.", "During the ragweed season of 1984 we studied 120 patients with hay fever; 58 had a history of asthma during the ragweed season the year before. They were divided into four treatment groups to receive nasal sprays of placebo, cromolyn sodium, flunisolide, or beclomethasone. In controlling hay fever symptoms all medications were superior to placebo; the glucocorticoids were more effective than was cromolyn sodium. Chest symptoms in the 58 patients with a history of asthma were also relieved by the topical nasal treatment. Various explanations for the beneficial effect of topical nasal treatment in asthma symptoms are conceivable. We consider the most likely to be improvement of nasal airway function. With restoration of the filtering action of the nose, less allergen would penetrate to the intrathoracic airways because of reduction in mouth breathing.", "The effect of intranasally administered corticosteroid (budesonide) on nasal symptoms, mode of respiration (nasal versus mouth breathing), and asthma was investigated in 37 asthmatic children who were mouth breathers because of chronic nasal obstruction. After a 2-wk run-in period, the children were allocated randomly to 4 wk of intranasal therapy with either budesonide (400 micrograms/day) or placebo spray. A double-blind, parallel design was used. Diaries for peak expiratory flow, asthma, and rhinitis symptom scores and degree of mouth breathing were recorded at home. Nasal eosinophilia, nasal airway resistance at a flow of 0.2 L/s (NAR0.2), and lung function at rest and after exercise challenge were assessed at the clinic immediately before and at end of the 4-wk treatment. Budesonide, when compared with placebo, significantly decreased nasal obstruction (p less than 0.05), secretion (p less than 0.01), and eosinophilia (p less than 0.02), as well as NAR0.2 (p less than 0.05) and mouth breathing (p less than 0.01). The improvement in nasal obstruction correlated closely to the changes in mouth breathing (r = 0.80, n = 17, p less than 0.001). Furthermore, intranasally administered budesonide resulted in less exercise-induced asthma (EIA) (p less than 0.02) and decreased cough and asthma severity significantly. Pulmonary mechanics were only marginally improved. The present study showed that intranasally administered budesonide is effective in the treatment of perennial allergic rhinitis. An attenuation of EIA and a tendency to less asthma after budesonide therapy suggest a decrease in bronchial reactivity, but the results gave no clear evidence of an association between nasal airway function and asthma.", "Fluticasone propionate aqueous nasal spray, a new topical corticosteroid, has been proved to be an effective treatment for seasonal allergic rhinitis.\n We studied the effect of fluticasone propionate on nasal symptoms, circulating eosinophils, and nasal inflammation in patients with seasonal allergic rhinitis after high-load pollen exposure. Moreover, we examined its efficacy in preventing the increase in bronchial responsiveness to methacholine (PD20) during the pollen season.\n We conducted a double-blind, placebo-controlled, parallel-group study in patients who had a history of allergic rhinitis in response to pollens of grass and Parietaria species and were living in northern Italy. After a run-in period of 2 weeks, 24 patients were treated with fluticasone propionate (200 micrograms, once daily), and 26 patients received matched placebo for 6 weeks, starting from the beginning of the pollen season. Assessment of efficacy was based on scores of daily nasal symptoms. Nasal lavage was performed at the end of the season, and differential cell count was expressed as percent of total cells. PD20 methacholine was measured at the beginning and end of the season and after the season had ended.\n Fluticasone propionate significantly reduced nasal obstruction, itching, and rhinorrhea. Eosinophils in blood (p < 0.01) and nasal lavage (p < 0.001) were also reduced. Moreover, fluticasone significantly attenuated the decrease in mean PD20 methacholine (from 1.95 to 0.89 mg) compared with placebo (from 1.38 to 0.37 mg: p < 0.01). After the season, no difference in PD20 methacholine was found between treatment groups.\n The results of this study indicate that fluticasone propionate is effective in decreasing nasal symptoms and eosinophil inflammation in patients with seasonal allergic rhinitis after high-load pollen exposure. Our results also demonstrate that treatment with fluticasone propionate partially prevents the increase in bronchial responsiveness provoked by the inhalation of seasonal pollens in allergic rhinitis.", "Both specific immunotherapy (SIT) and nasal steroid (NS) have been shown to effectively reduce symptoms of allergic rhinitis. Although a number of investigators have convincingly shown anti-inflammatory effects of both treatments in separate studies, few comparative studies have been performed.\n The purpose of this study was to compare the effects of preseason SIT with a standardized allergen extract and NS in seasonal allergic disease (rhinoconjunctivitis and asthma).\n We examined 41 patients allergic to birch pollen, 21 with rhinoconjunctivitis and 20 with both rhinoconjunctivitis and asthma; they were treated in a randomized, double-blinded comparative study with birch SIT and NS (budesonide 400 microg daily). Bronchial hyperresponsiveness was measured before and during the season. Changes in eosinophil number, eosinophil cationic protein, and eosinophil chemotactic activity (ECA) in peripheral blood were investigated.\n Symptoms of rhinoconjunctivitis increased significantly less in the NS-treated patients than in the SIT-treated patients during the final 2 weeks of the season (P = .03 and P = .04, respectively). Seasonal peak expiratory flow values decreased significantly only in the NS-treated patients (P = .01). In the NS-treated patients, bronchial hyperresponsiveness increased significantly during the season (P = .0001); however, SIT treatment prevented seasonal PC(20) increase in the asthmatic patients. Measurement of blood eosinophils, eosinophil cationic protein, and eosinophil chemotactic activity demonstrated significant seasonal increase only in the NS-treated asthmatic patients.\n Treatment with NS was more effective than short-course preseason SIT in reducing symptoms of rhinoconjunctivitis; however, the 2 therapies were equivalent in terms of the need for rescue medication. SIT prevented seasonal increase in bronchial hyperresponsiveness, eosinophil number, eosinophil cationic protein, and eosinophil chemotactic activity only in asthmatic patients. The mechanisms underlying bronchial hyperresponsiveness developing during allergen exposure in rhinitis might be different from those operating in asthma.", "To test the hypothesis that nasal antiinflammatory treatment can modify both upper and lower airway responses to allergen exposure, 12 cat-allergic subjects underwent 1 h cat exposure challenges at baseline, with nasal occlusion, and after 1 wk of treatment with either intranasal triamcinolone acetonide or placebo in a double-blind crossover trial. Challenges were performed in a room containing two cats with airborne Fel d I levels ranging from 35 to 37,525 ng/m3. Overall, nasal symptoms were moderately reduced by treatment (p = 0.06), with the greatest reduction occurring in the first 15 and 30 min of the challenge (p < 0.01 and p < 0.05, respectively). Mean lower respiratory symptoms were also diminished by treatment (p = 0.02), although those effects were most evident during the last 15 min of the challenge. Maximum changes in FEV1 were slightly reduced by the nasal therapy (p = 0.07), reaching statistical significance only at the 30-min intervals (p < 0.05). There were no significant differences in nasal histamine or TAME esterase levels. When challenges were repeated with nasal occlusion, no significant differences were detected in chest symptoms or FEV1 changes. We conclude that treatment with an intranasal corticosteroid led to significant reductions in both upper and lower airway responses to intense cat exposure.", "nan" ]

[ "2000278", "10021717", "8233735", "7488817", "8516091", "22025591", "2007937", "20472939", "2000109", "11965714" ]

[ "Bovine surfactant replacement therapy in neonates of less than 30 weeks' gestation: a randomized controlled trial of prophylaxis versus treatment.", "Use of surfactant for prophylaxis versus rescue treatment of respiratory distress syndrome: experience from an Italian-Bulgarian trial.", "Comparison of prophylaxis and rescue treatment with Curosurf in neonates less than 30 weeks' gestation: a randomized trial.", "Porcine surfactant replacement therapy in newborns of 25-31 weeks' gestation: a randomized, multicentre trial of prophylaxis versus rescue with multiple low doses. The French Collaborative Multicentre Study Group.", "Prophylactic administration of calf lung surfactant extract is more effective than early treatment of respiratory distress syndrome in neonates of 29 through 32 weeks' gestation.", "Randomized trial comparing 3 approaches to the initial respiratory management of preterm neonates.", "Randomized, placebo-controlled trial of human surfactant given at birth versus rescue administration in very low birth weight infants with lung immaturity.", "Early CPAP versus surfactant in extremely preterm infants.", "A comparison of surfactant as immediate prophylaxis and as rescue therapy in newborns of less than 30 weeks' gestation.", "[Administration of exogenous surfactant in premature very low birth weight infants with RDS]." ]

[ "The influence of the timing of surfactant replacement therapy for the treatment of neonatal respiratory distress syndrome was evaluated in a study of 182 neonates of less than 30 weeks' gestation who were randomly assigned prior to delivery to one of three study groups: control (dummy instillation of air given at birth), early surfactant (surfactant given at birth), or late surfactant (surfactant given at less than 6 hours of age). Subjects in the late surfactant group could avoid treatment if they had a clear chest roentgenogram and required no supplemental oxygen at a mean airway pressure of less than 7 cm of water. All treated neonates were eligible to receive up to three additional doses during the first 5 days of life. The three groups were comparable with respect to birth weight, gestational age, and other perinatal parameters with the exception of a lower cord arterial pH and 1-minute Apgar score in the early surfactant group. Of the 60 neonates randomly assigned to late treatment, 29 (48%) were deemed surfactant sufficient and thereby avoided treatment; the other 31 received their first dose at a mean age of 2.9 hours. There was a significant improvement in gas exchange during the first week of life in both surfactant groups compared with the control group, reflected by differences in fraction of inspired oxygen, arterial/alveolar PO2, and ventilation index (peak pressure x rate on the ventilator) (P less than .001). Surfactant therapy also resulted in a lower incidence of pulmonary air leak and severe chronic lung disease (defined as requirement for respiratory support beyond 36 weeks post-conceptional age). There were no differences between early and late surfactant groups in any of these parameters. The only statistically significant difference between the surfactant groups was that the early group had a higher incidence of mild chronic lung disease (respiratory support beyond 28 days of age) than the late treatment group (P less than .005). Neonates in the late treatment group were extubated earlier and had a shorter neonatal intensive care unit stay than control neonates (P less than .05), whereas those in the early group were not significantly different from control neonates in these parameters. It is concluded that replacement therapy with bovine lung surfactant extract in neonates of less than 30 weeks' gestation results in decreased oxygen and ventilatory requirements during the first week of life and a lower incidence of pulmonary air leak and severe chronic lung disease.(ABSTRACT TRUNCATED AT 400 WORDS)", "To show if surfactant applied in different social-sanitary realities as prophylaxis of respiratory distress syndrome (RDS) is equally useful and able to reduce mortality and incidence of 3-4 radiological grade RDS.\n Two neonatal intensive care units (NICU) in Italy, one NICU in Bulgaria and one NICU in Romania were involved in a randomized controlled clinical trial of prophylaxis vs rescue treatment of RDS. Babies with gestational age 26-30 wks were randomized before birth to prophylaxis in the delivery-room with 200 mg/kg of porcine surfactant (prophylaxis) or to routine assistance (control). Subsequently the babies developing RDS requiring mechanical ventilation and fraction of inspired oxygen (FiO2) > or = 0.4 to maintain PaO2 about 50 mmHg were allowed to be treated rescue with 200 mg/kg of the same surfactant. To reach end-points of reducing mortality by 40% and incidence of radiological grade 3-4 RDS a total number of 174 patients were required.\n Due to logistic, practical and social-political problems the study was interrupted after enrollment of 93 babies (61 in Italy and 32 in Bulgaria). The Romanian centre did not start the study because it was impossible in the scheduled times to equip it for mechanical ventilation of the newborn infants. Analysis done on an intention to treat basis did not show significant reductions of mortality and 3-4 radiological grade RDS, even if there was a trend towards a reduction in the babies given prophylaxis. A significantly lower number of babies given prophylaxis required a subsequent rescue treatment compared to controls (p < 0.001). There was no difference in other complications such as intraventricular haemorrhage, air-leak syndromes and infections between prophylaxis and control infants. As regards pulmonary gas exchange, the PaO2/FiO2 ratio was significantly improved in the babies given prophylaxis for the first 12 hours of life vs the controls.\n Even if the study was terminated before term, the analysis of the data shows that prophylaxis with surfactant is equally effective in different social-clinical conditions to improve pulmonary gas-exchange, especially in the first critical hours of life of premature babies.", "The aim of this randomized clinical trial was to evaluate the immediate effects of prophylactic administration of Curosurf and to compare outcomes after prophylactic or expectant management.\n Porcine surfactant (Curosurf, 200 mg/kg body weight) was administered intratracheally within 10 minutes of birth to preterm neonates with a gestational age of 26 to 29 weeks (n = 75); rescue-eligible neonates (n = 72) were initially subjected to a sham maneuver. The primary end points of the trial, evaluated at the age of 6 hours, were to obtain (1) a 40% decrease in the ratio between transcutaneous oxygen tension (tcPO2) (kPa) and fraction of inspired oxygen (FIO2), and (2) a 50% decrease in the incidence of radiologically verified respiratory distress syndrome (RDS). After 6 to 24 hours, a similar dose of surfactant was given to the neonates of both the prophylaxis and the rescue-eligible group, if they needed mechanical ventilation with an FIO2 > or = 0.6.\n At 6 hours the prophylaxis group had, in comparison with the rescue-eligible group, significantly higher tcPO2/FIO2 ratios (mean +/- SD: 39.7 +/- 15.3 vs 28.1 +/- 18.1; P < .001) and less severe RDS by radiological scoring (chi 2 = 14.9; P = .005). Severe RDS was present in 19% of the prophylactically treated neonates versus 32% in the rescue-eligible group (P < .05). The prophylaxis group needed shorter periods of FIO2 > 0.40 than the rescue-eligible neonates (P < .01), and eight neonates of the prophylaxis group (11%) versus 23 of the rescue-eligible group (32%) qualified for rescue treatment with surfactant in the interval 6 to 24 hours (P < .01). There were no differences in the incidence or severity of pneumothorax, pulmonary interstitial emphysema, cerebral hemorrhage, periventricular leukomalacia, patent ductus arteriosus, in the duration of mechanical ventilation or time in supplemental oxygen, or in mortality.\n Subgroup analysis revealed (1) that administration of corticosteroids reduced the risk of developing neonatal RDS as effectively as did surfactant prophylaxis at birth, and (2) that prophylaxis was effective especially in neonates with gestational age < 28 weeks or birth weight < 1000 g, in male neonates, and in neonates who had received no antenatal treatment with corticosteroids. Our data indicate that prophylactic treatment with surfactant should be considered in high-risk neonates fulfilling these latter criteria.", "The aim of the study was to determine if prophylaxis with multiple low doses of porcine surfactant would increase survival, without bronchopulmonary dysplasia, compared with rescue therapy, for respiratory distress syndrome in newborns of 25-31 weeks' gestation. Compared with rescue therapy (n = 122), prophylaxis (n = 134) decreased the need for oxygenation and ventilatory support within 3-72 h. It did not, however, increase survival without bronchopulmonary dysplasia (60% versus 46%) (odds ratio (OR) = 1.53, 95% confidence interval (CI) = 0.90-2.61). Furthermore, prophylaxis decreased the incidence of severe peri-intraventricular haemorrhage (3% versus 16%) (OR = 0.28, 95% CI = 0.09-0.84) and retinopathy of prematurity (2% versus 11%) (OR = 0.18, CI = 0.04-0.78). We conclude that prophylaxis did not increase survival without bronchopulmonary dysplasia. The decreased incidence of severe peri-intraventricular haemorrhage and retinopathy of prematurity after prophylaxis requires further study.", "Although numerous trials have demonstrated the efficacy of exogenous surfactant for prophylaxis or treatment of neonatal respiratory distress syndrome (RDS), optimum timing of administration remains controversial. One previous study showed that administration of calf lung surfactant extract immediately following birth, to neonates born before 30 weeks postconceptional age, was preferable to delaying administration until after development of RDS. The current study was designed to test a similar hypothesis for babies born between 29 and 32 weeks gestational age.\n One thousand three hundred ninety-eight neonates with obstetric estimates of 29 through 32 weeks' gestation were randomized to receive CLSE at birth or to wait until development of mild RDS. After exclusions for malformations and other factors, data from 1248 were analyzed.\n Prophylaxis was associated with less development of moderate RDS (7% vs 12%), less need for retreatment (5% vs 9%), less need for mechanical ventilation or supplemental oxygen during the first 4 days, and fewer deaths or less requirement for supplemental oxygen at 28 days (5% vs 9%). Although 1-minute Apgar scores were significantly lower in the prophylaxis group, the difference disappeared by the 5-minute score and there was no difference in the incidence of asphyxia-related complications. Sixty percent of the neonates assigned to early treatment received endotracheal intubation and 43% received calf lung surfactant extract at a median age of 1.5 hours. When data were analyzed by gestational age and birth weight subgroups, most of the differences could be attributable to babies born at 30 weeks or less or weighing less than 1500 g, probably because of the higher incidence of surfactant deficiency in this more immature subgroup.", "We designed a multicenter randomized trial to compare 3 approaches to the initial respiratory management of preterm neonates: prophylactic surfactant followed by a period of mechanical ventilation (prophylactic surfactant [PS]); prophylactic surfactant with rapid extubation to bubble nasal continuous positive airway pressure (intubate-surfactant-extubate [ISX]) or initial management with bubble continuous positive airway pressure and selective surfactant treatment (nCPAP).\n Neonates born at 26 0/7 to 29 6/7 weeks' gestation were enrolled at participating Vermont Oxford Network centers and randomly assigned to PS, ISX, or nCPAP groups before delivery. Primary outcome was the incidence of death or bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age.\n 648 infants enrolled at 27 centers. The study was halted before the desired sample size was reached because of declining enrollment. When compared with the PS group, the relative risk of BPD or death was 0.78 (95% confidence interval: 0.59-1.03) for the ISX group and 0.83 (95% confidence interval: 0.64-1.09) for the nCPAP group. There were no statistically significant differences in mortality or other complications of prematurity. In the nCPAP group, 48% were managed without intubation and ventilation, and 54% without surfactant treatment.\n Preterm neonates were initially managed with either nCPAP or PS with rapid extubation to nCPAP had similar clinical outcomes to those treated with PS followed by a period of mechanical ventilation. An approach that uses early nCPAP leads to a reduction in the number of infants who are intubated and given surfactant.", "A randomized, placebo-controlled trial of human surfactant given intratracheally at birth (prophylactic) versus rescue administration after the onset of severe respiratory distress syndrome (RDS) was conducted among preterm infants born at 24 to 29 weeks of gestation. Singleton fetuses were randomly assigned to receive (1) placebo (air), (2) prophylactic surfactant treatment, or (3) rescue surfactant treatment; infants of multiple births received either (1) prophylactic or (2) rescue treatment. Of 282 potentially eligible fetuses, 246 infants received treatments at birth and 200 infants had RDS. Outcomes are presented both as an intention-to-treat analysis (including infants who met exclusion criteria at or after birth) and as a full treatment protocol analysis for those infants with RDS and likely to benefit from surfactant. Preterm infants (mean 1.0 kg birth weight, 27 to 28 weeks of gestational age) randomly assigned to receive prophylactic treatment received surfactant soon after birth; those assigned to receive rescue surfactant had instillation at a mean age of 220 minutes if the lecithin-sphingomyelin ratio was less than or equal to 2.0 and no phosphatidylglycerol was detected in either amniotic fluid or initial airway aspirate, oxygen requirements were a fraction of inspired oxygen of greater than 0.5, and mean airway pressure was greater than or equal to 7 cm H2O from 2 to 12 hours after birth. Up to four treatment doses (or air) were permitted within 48 hours; approximately 60% of surfactant-treated infants required two or more doses. Surfactant-treated infants had significantly less pulmonary interstitial emphysema than placebo-treated infants (p = 0.02), but there were no other significant differences in mortality rates or morbidity. Indexes of oxygenation and ventilation were improved in surfactant recipients during the first 24 hours. An intention-to-treat analysis found no significant differences between infants given placebo and surfactant-treated infants or between prophylactic- and rescue-treated infants; an improved total mortality rate (p = 0.002) was found among surfactant-treated infants in Helsinki but not in San Diego. Among infants with RDS, the total mortality rate was significantly improved (p = 0.004) with surfactant treatment but not the proportion alive and without bronchopulmonary dysplasia at 28 days (p = 0.052), or the proportion alive and without bronchopulmonary dysplasia at 38 weeks of postconceptional age (p = 0.18) to adjust for differences in prematurity. Deaths caused by RDS or bronchopulmonary dysplasia were significantly reduced among surfactant recipients (p = 0.0001). Neither among singletons nor among multiple-birth infants was there a selective advantage to prophylactic versus rescue treatment.(ABSTRACT TRUNCATED AT 400 WORDS)", "There are limited data to inform the choice between early treatment with continuous positive airway pressure (CPAP) and early surfactant treatment as the initial support for extremely-low-birth-weight infants.\n We performed a randomized, multicenter trial, with a 2-by-2 factorial design, involving infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation. Infants were randomly assigned to intubation and surfactant treatment (within 1 hour after birth) or to CPAP treatment initiated in the delivery room, with subsequent use of a protocol-driven limited ventilation strategy. Infants were also randomly assigned to one of two target ranges of oxygen saturation. The primary outcome was death or bronchopulmonary dysplasia as defined by the requirement for supplemental oxygen at 36 weeks (with an attempt at withdrawal of supplemental oxygen in neonates who were receiving less than 30% oxygen).\n A total of 1316 infants were enrolled in the study. The rates of the primary outcome did not differ significantly between the CPAP group and the surfactant group (47.8% and 51.0%, respectively; relative risk with CPAP, 0.95; 95% confidence interval [CI], 0.85 to 1.05) after adjustment for gestational age, center, and familial clustering. The results were similar when bronchopulmonary dysplasia was defined according to the need for any supplemental oxygen at 36 weeks (rates of primary outcome, 48.7% and 54.1%, respectively; relative risk with CPAP, 0.91; 95% CI, 0.83 to 1.01). Infants who received CPAP treatment, as compared with infants who received surfactant treatment, less frequently required intubation or postnatal corticosteroids for bronchopulmonary dysplasia (P<0.001), required fewer days of mechanical ventilation (P=0.03), and were more likely to be alive and free from the need for mechanical ventilation by day 7 (P=0.01). The rates of other adverse neonatal outcomes did not differ significantly between the two groups.\n The results of this study support consideration of CPAP as an alternative to intubation and surfactant in preterm infants. (ClinicalTrials.gov number, NCT00233324.)\n 2010 Massachusetts Medical Society", "Exogenous pulmonary surfactants are administered into the trachea either to prevent respiratory distress syndrome in premature infants or to treat it. In a randomized, multicenter trial, we compared the results of surfactant therapy initiated as prophylaxis with the results of rescue therapy with surfactant.\n Before birth, 479 infants with an estimated gestational age of less than 30 weeks were randomly assigned to receive surfactant as prophylaxis (n = 235) or rescue therapy (n = 244). The infants in the prophylaxis group received a 90-mg intratracheal dose of an exogenous calf-lung surfactant extract at the time of delivery, whereas the infants in the rescue-therapy group received 90 mg of the surfactant several hours after delivery if the fractional inspiratory oxygen concentration was at least 0.40 or if the mean airway pressure was at least 0.686 kPa (7 cm of water), or both. Infants in both groups received additional doses of surfactant at intervals of 12 to 24 hours if these criteria were met.\n The proportion of infants surviving until discharge to their homes was significantly higher in the prophylaxis group than in the rescue-therapy group (88 vs. 80 percent, P = 0.028). This difference was due primarily to the longer survival of very premature infants (less than or equal to 26 weeks' gestation) in the prophylaxis group than in the rescue-therapy group (75 vs. 54 percent, P = 0.006). According to proportional-hazards regression analysis, the distribution of survival times was better for all infants in the prophylaxis group (P = 0.007) and for the subgroup of infants in the prophylaxis group who were delivered at 26 weeks' gestation or earlier (P = 0.0048). Infants in the prophylaxis group who were delivered at 26 weeks' gestation or earlier had a lower incidence of pneumothorax than similar infants in the rescue-therapy group (7 vs. 18 percent, P = 0.03).\n We found a significant advantage to the administration of the initial dose of surfactant as prophylaxis rather than as rescue therapy in very premature infants.", "A retrospective study is carried out with the aim of establishing the effect from surfactant therapy on pulmonary function, survival and complication from intensive therapy on VLBWI with RDS. 67 premature infants below 1500 grams are included in the study divided in 3 groups: I gr.--27 babies treated with Corosurf; II gr.--16 babies treated with Exosurf; III gr.--24 control babies without surfactant. The results show that in spite of relatively lower gestational age and higher incidence of inborn infection in group I, Curosurf treated babies spend shortest time on mechanical ventilation and oxygen therapy showing lower incidence of BPD, IVH and mortality rate." ]

[ "9230826" ]

[ "Interferon alfa-2a is ineffective for patients with choroidal neovascularization secondary to age-related macular degeneration. Results of a prospective randomized placebo-controlled clinical trial. Pharmacological Therapy for Macular Degeneration Study Group." ]

[ "Interferon alfa-2a has been shown to be effective as an antiangiogenic agent for several systemic human angiogenic disorders and has shown antiangiogenic activity in the laboratory.\n To evaluate the safety and efficacy of interferon alfa-2a for the treatment of choroidal neovascularization secondary to age-related macular degeneration.\n A randomized, placebo-controlled, parallel, multicenter double-blind trial was performed at 45 ophthalmic centers worldwide. Four hundred eighty-one patients were randomly assigned to 4 treatment groups: placebo or interferon alfa-2a (Roferon-A), 1.5, 3.0, or 6.0 million international units (MIU). Visual acuity testing, clinical examination, fluorescein angiography, and indocyanine green angiography were evaluated, with the primary end point being a comparison of the number of patients who experienced a loss of 3 lines or more of vision at 1 year.\n At 52 weeks, 40 (38%; 95% confidence interval, 29%-48%) of 105 placebo-treated patients had lost at least 3 lines of vision (with 12% unavailable for follow-up), compared with 142 (50%; 95% confidence interval, 44%-55%) of 286 in the 3 active treatment groups combined. The difference in proportions was not statistically significant. However, a pairwise comparison of these proportions for the placebo group vs the group that received interferon alfa-2a, 6 MIU (with 26% unavailable for follow-up), showed a statistically significant difference in favor of the placebo group (P = .02) and a nearly significant difference for the placebo vs the 1.5-MIU group (P = .05) (with 16% unavailable for follow-up), again favoring the placebo group. The 3-MIU group (with 22% unavailable for follow-up) did not show a statistically significant difference in pairwise comparison (P = .48), suggesting that a dose-response relationship was not evident.\n Interferon alfa-2a provides no benefit as a treatment for choroidal neovascularization secondary to age-related macular degeneration and may be associated with a poorer visual outcome when given at a dose of 6 MIU. However, the absence of a clear dose-response relationship raises the possibility that the observed differences result from chance." ]

[ "10412335", "7662102", "2191991", "15932378", "2021877", "1789401" ]

[ "Environmental controls in reducing house dust mites and nasal symptoms in patients with allergic rhinitis.", "Efficacy of the acaricide: acardust for the prevention of asthma and rhinitis due to dust mite allergy, in children.", "A double-blind study of the effectiveness of a high-efficiency particulate air (HEPA) filter in the treatment of patients with perennial allergic rhinitis and asthma.", "The effect of encasings on quality of life in adult house dust mite allergic patients with rhinitis, asthma and/or atopic dermatitis.", "Clinical evaluation of a double-blind dust-mite avoidance trial with mite-allergic rhinitic patients.", "Efficacy of an air-cleaning device equipped with a high efficiency particulate air filter in house dust mite respiratory allergy." ]

[ "A randomized comparison group pretest-posttest experimental design was used to quantitatively determine the effects of environmental control measures on patients with allergic rhinitis. Environmental controls included wrapping the mattress with a vinyl cover, washing the top bedding cover with 55 degrees C hot water every two weeks, removal of soft furniture, and wet cleaning of the bedroom floor every day. Thirty subjects were randomly assigned to experimental and control groups. The amount of house dust mites in dust samples collected from the bedroom floor, bedding and mattress, as well as the nasal symptoms of patients, were measured twice at one-month intervals. A significant decrease in house dust mites in dust samples and relief in patients' nasal symptoms were observed in the experimental group who had environmental controls.", "A double blind, randomized, comparative study versus placebo, was done during 6 months in 32 children, aged 4-12 years, who suffer from either allergic asthma or rhinitis or both, slept in a bedroom rich in dust mite, have well documented allergy solely to house dust mite (H.D.M.), and a condition severe enough to require continuous medication. After thorough cleaning, their bedrooms were sprayed on day 0 and day 90 with the total content of a canister containing either Acardust or Placebo. Rooms were cleaned regularly throughout the study period. Each child completed an individual daily score card (scales from 0-3) for asthma, and rhinitis symptoms, medication taken, and any additional symptoms. Peak flow was recorded twice weekly. All the children were examined every month (at the clinic) when also PFF, FEVI, doctor's and patient's opinion of clinical symptoms were recorded according to the same scale (0-3) and dust samples from child's bedroom were examined for H.D.M. antigen content. At day 0, 90 and 180, total IgE and dust mite specific IgE determination was done. At the end of the study, patient's and doctor's opinion about the spray's efficacy were recorded on a scale from 0-3. The results were in favor of Acardust for asthma, according to patient's opinion (p = 0.001), doctor's opinion (p = 0.04) and individual score cards (p = 0.03), and for nasal secretion (p = 0.01), sneezing and lacrimation (p = 0.02); concurrent medication dropped significantly (p = 0.01) in the Acardust group. No side-effects were reported. We consider Acardust a safe and valuable preventive treatment in H.D.M. allergy.", "This study was designed to assess the effectiveness of a high-efficiency particulate air (HEPA) filter in alleviating allergic respiratory symptoms. Thirty-two patients were studied who had symptomatic perennial rhinitis and/or asthma during the fall and winter months and had a positive skin test with house dust or house dust--mite extract. An ENVIRACAIRE room air cleaner was placed in the bedroom for 8 weeks. In a random manner, the active filter was used for 4 weeks and a blank filter for 4 weeks. There was an average 70% reduction in the particulate matter greater than or equal to 0.3 micron with the HEPA filter. In a double-blind design, results were assessed by analysis of the patients' symptom/medication scores and subjective evaluation. For the total study, there was no difference in the total symptom/medication scores or individual symptom scores during the placebo and active-filter periods. Analysis of the last 2 weeks of each filter period in which respiratory infection was absent demonstrated definite differences in total and individual symptoms, suggesting active-filter benefit. Patients' subjective responses also suggested benefit from the filter. The overall impression is that the HEPA filter can reduce allergic respiratory symptoms.", "Environmental control has been put forward as an integral part of the management of house dust mite (HDM) allergy in sensitized patients. To validate this statement allergic disorders involved in HDM allergy--allergic asthma, rhinitis and atopic eczema/dermatitis syndrome (AEDS)--should be taken together and studied in terms of the efficacy of environmental control. Because a generic quality of life questionnaire exceeds the border of disease, this may be used as major outcome parameter.\n To study the effects of bedding encasings in HDM allergic patients with asthma, rhinitis and AEDS.\n A total of 224 adult HDM allergic patients with rhinitis and/or asthma and/or dermatitis were randomly allocated impermeable or nonimpermeable encasings for mattress, pillow and duvet. Short form 36 (SF-36) was filled in at baseline and after 12 months. Results: Lower physical (P = 0.01) and emotional (P < 0.001) sumscores were seen in females. Also, the presence of asthma resulted in lower physical sumscore (P = 0.01). However, no effect was seen of encasings on either sumscore.\n Bedding encasings do not improve quality of life in a mixed population of subjects with combinations with rhinitis, asthma and atopic dermatitis and sensitized to HDMs.", "Inheritance and allergen exposure are key factors in the development and the course of atopic allergy, expressed as conjunctivitis, rhinitis, asthma or dermatitis. This study concerns the clinical significance of mite and mite-allergen avoidance measures based on intensive cleaning with acaricide (solidified benzylbenzoate) added (10 dwellings), and without biocidal activity (10 other homes) as a control in a double-blind trial with matched pairs. Twenty subjects with persisting rhinitic complaints were selected. They lived in 20 different dwellings and were all sensitized to pyroglyphid mites; 12 of them were also sensitized to stored product mites (Acari). Daily symptoms and medication score, guanine and dust exposure, total and mite-specific IgE in serum, eosinophilia in the blood and in the nasal smear, intracutaneous tests with house dust mite and storage mite extracts were compared in both pairs and groups. Acarological data, physiochemical aspects and exposure assessment are discussed in detail elsewhere. Symptom scores dropped significantly, as did the total IgE and exposure to dust and mite products in the acaricidal cleaner treatment group. After 1 year, the daily symptoms median was 47% (P = 0.025), total IgE was 38% (P = 0.0049), and exposure to dust and mite products (guanine exposure) was 53% (P = 0.0449) better or lower than in the controls. Intensive cleaning, without acaricidal treatment performed twice a year, resulted in clinical improvement in four out of 10 subjects, of whom none became free of complaints. In the Acarosan treatment group (cleaning + benzylbenzoate) eight out of 10 subjects improved, in three cases subjective symptoms disappeared.(ABSTRACT TRUNCATED AT 250 WORDS)", "The efficacy of an air-cleaning device equipped with a high efficiency particulate air (HEPA) filter (without further avoidance measures) was studied in patients allergic to house dust mite. The effects of the air-cleaner on indoor Dermatophagoides sp. levels, symptom score and bronchial hyperresponsiveness in nine mite-allergic patients were assessed using a cross-over controlled study. No significant effect was demonstrated on indoor Dermatophagoides sp. levels when comparing the period of air-cleaner activity (2 months) with the control period (2 months). The Dermatophagoides sp. levels in the houses studied were lower than the risk level for asthmatic attacks, making it difficult to assess any effect on asthma; however, neither bronchial hyperresponsiveness nor rhinitis symptom score were changed by air-cleaner activity. During the trial period, however the mean level of Dermatophagoides sp. allergen in the houses changed spontaneously from 4.4 micrograms/g (mean level in the first 2 trial months) to 1.75 micrograms/g of dust (second 2 months) (P less than 0.05). Owing to this change, the mean rhinitis symptom score also decreased (P less than 0.05), even if no significant correlation was demonstrated (r = 0.4 P = 0.089). HEPA filter air-cleaners appear insufficient as substitutes for standard avoidance measures in mite allergic patients." ]

[ "9638782", "11585273", "12910531", "17878129", "7299084", "16025260", "16862634", "19018255", "18025916", "9492666", "3966583", "16135469", "19349551", "17562640", "12013159", "15017450", "12065562", "12035205", "11920549", "17663615", "15939927", "15669014", "11841126", "10833696", "8564938", "14622079", "12790259" ]

[ "Reducing distress in cancer patients with an orientation program.", "Difference in patient's acceptance of early versus late initiation of psychosocial support in breast cancer.", "Cognitive-behavioral intervention for distress in patients with melanoma: comparison with standard medical care and impact on quality of life.", "Transition from treatment to survivorship: effects of a psychoeducational intervention on quality of life in breast cancer survivors.", "Late stage cancer patients: age differences in their psychophysical status and response to counseling.", "Do cancer patients benefit from short-term contact with a general practitioner following cancer treatment? A randomised, controlled study.", "Long-term telephone therapy outcomes for breast cancer patients.", "Health-related quality of life and distress in cancer patients: results from a large randomised study.", "The effects and expense of augmenting usual cancer clinic care with telephone problem-solving counseling.", "Evaluation of adjuvant psychological therapy in patients with testicular cancer: randomised controlled trial.", "Psychotherapy during radiotherapy: effects on emotional and physical distress.", "Outcomes from the Moving Beyond Cancer psychoeducational, randomized, controlled trial with breast cancer patients.", "The effects of a presurgical stress management intervention for men with prostate cancer undergoing radical prostatectomy.", "Day surgery for breast cancer: effects of a psychoeducational telephone intervention on functional status and emotional distress.", "Preventing anxiety and depression in gynaecological cancer: a randomised controlled trial.", "Telephone social support and education for adaptation to prostate cancer: a pilot study.", "Efficacy and costs of two forms of stress management training for cancer patients undergoing chemotherapy.", "Counseling women with breast cancer using principles developed by Albert Bandura.", "Helping patients with localized prostate carcinoma manage uncertainty and treatment side effects: nurse-delivered psychoeducational intervention over the telephone.", "Coping and communication-enhancing intervention versus supportive counseling for women diagnosed with gynecological cancers.", "Effect of individual psychological intervention in Chinese women with gynecologic malignancy: a randomized controlled trial.", "A randomized psychosocial intervention study on the effect of home visits on the well-being of Danish colorectal cancer patients--the INCA Project.", "Lessons learned: Outcomes and methodology of a coping skills intervention trial comparing individual and group formats for patients with cancer.", "Telephone therapy for patients with breast cancer.", "A psychoeducational nursing intervention to enhance coping and affective state in newly diagnosed malignant melanoma patients.", "Project Genesis: assessing the efficacy of problem-solving therapy for distressed adult cancer patients.", "Short-term effects of telephone therapy for breast cancer patients." ]

[ "The purpose of this study was to test a brief orientation program for reducing anxiety, depressive symptoms, and overall distress in cancer patients at their initial clinic visit. One hundred and fifty consecutively referred patients seen in an oncology outpatient clinic were randomly assigned to an intervention or usual care control group. The intervention group received a clinic tour, general information about clinic operations, and a question and answer session with an oncology counselor. Outcome measures included the State-Trait Anxiety Inventory (STAI), the Brief Profile of Mood States (POMS), the Center for Epidemiologic Studies-Depression (CES-D) Scale, and an oncology clinic questionnaire which were administered at the initial clinic visit and follow-up. There were no statistically significant clinical or demographic differences between groups at initial assessment. At follow-up, the intervention group had lower state anxiety, lower overall distress, and fewer patients reporting depressive symptoms. Patients in the intervention group demonstrated significantly more knowledge about clinic operations and greater satisfaction with care. These data provide evidence that anxiety, distress and depressive symptoms can be reduced with an orientation program. This finding has particular relevance in the early stages of diagnosis where patients may suffer symptoms of anxiety and depression.", "The present study was performed to assess the difference in acceptance of psychosocial counseling and resulting benefits between patients with breast cancer with early or late onset. In a prospective randomized controlled study conducted over 6 months, 41 women with a new diagnosis of early breast cancer (group 1) and 43 patients with advanced breast cancer (group 2) received individually tailored psychosocial support and were compared against controls. This therapy was free of charge, and the duration of support was determined by the patients' wishes and needs. Among the patients with new onset of disease acceptance of the psychosocial counseling was high, and these patients experienced significant improvements in their quality of life. In contrast, acceptance of psychosocial counseling was low in the advanced breast cancer group and the therapy did not improve quality of life over the observation period of 6 months. Early psychosocial support in patients with breast cancer meets with a high acceptance rate and improves quality of life.", "Melanoma accounts for > 79% of skin cancer-related deaths, although it accounts for only 4% of skin cancer incidence. Given the potential for lethality, it is likely that patients with melanoma may experience significant emotional distress. The current study was designed to determine the effect of a cognitive-behavioral intervention on distress and health-related quality of life (HRQOL) in patients with melanoma who had medium-to-high distress.\n Forty-eight patients who had Global Severity Index scores >or= 60 2 months after their initial visit to the multidisciplinary melanoma clinic were randomized to receive either standard care or 4 sessions of a cognitive-behavioral intervention (CBI). Repeated assessments using the Brief Symptom Inventory, the Medical Outcomes Survey Short Form-36, and the State-Trait Anxiety Inventory occurred at baseline, at 2 months, and at 6 months after intervention for both groups.\n An intent-to-treat analysis did not reveal significantly lower distress in the CBI group at 2 months or 6 months of follow-up, although differences were noted in anxiety and HRQOL. An effect-of-intervention analysis did reveal lower levels of distress in the CBI group at 2 months, with differences approaching significance at 6 months.\n The four-session CBI significantly reduced distress and improved HRQOL for a period of 2 months in patients with melanoma who had medium-to-high distress, with improved general health evident 6 months after the intervention. Some variation in results was revealed in an intent-to-treat analysis. The initial evidence from the current study showed that a brief intervention may be effective for creating change in individuals with cancer who have increased distress, although further research is needed to identify the most optimal approach for delivering the intervention.\n Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11579", "To examine the effectiveness of a psychoeducational intervention on quality of life (QOL) in breast cancer survivors in post-treatment survivorship.\n A randomized controlled trial.\n An academic center collaborating with a regional cancer center in the southeastern United States.\n 256 breast cancer survivors.\n Women were randomly assigned to the experimental or wait control group. The Breast Cancer Education Intervention (BCEI) study was delivered in three face-to-face sessions and five monthly follow-up sessions (three by telephone and two in person). The control group received four monthly attention control telephone calls and the BCEI at month 6. Data were collected at baseline, three and six months after the BCEI for the experimental group, and one month after the BCEI (at month 7) for the wait control group.\n Primary endpoints were overall QOL and physical, psychological, social, and spiritual well-being.\n No differences in QOL were reported at baseline between groups. The experimental group reported improved QOL at three months, whereas the wait control group reported a significant decline in QOL. The experimental group reported continued maintenance of QOL at six months. Although the wait control group reported improved QOL at six months, significant differences continued to exist between the groups.\n The BCEI was an effective intervention in improving QOL during the first year of breast cancer survivorship. Treatment effects were durable over time.\n Post-treatment survivorship has not been empirically studied to a large degree. The BCEI is one of the few interventions demonstrating effectiveness among survivors after primary treatment, suggesting that oncology nurses may be uniquely positioned to provide safe passage using education and support.", "Much has been written about working with dying patients. To evaluate counseling, 120 terminally ill cancer patients were randomly assigned to counseling or no counseling and studied before random assignment and at 1, 3, 6, 9, and 12 months on quality of life variables (alienation, depression, locus of control, life satisfaction, self-esteem) as well as functional status and survival. Counseled patients changed significantly in comparison to controls and in a favorable direction by 3 months. The purpose here was to see if older and younger cancer patients differed at baseline and if outcomes of counseling differed by age. Patients under age 60 were compared with those 60 and over. There was no multivariate difference at baseline but univariate differences of more disability and less life satisfaction in the older group. Overall, response to therapy was similar in old and young, with both improving.", "To investigate whether increased contact with the patient's general practitioner (GP) soon after cancer treatment can increase patient quality of life (QoL) and satisfaction with follow-up.\n A randomised controlled study with 91 patients from one Norwegian municipality. The intervention group got a 30-min invited consultation with the patient's GP and an invitation to further GP follow-up. Quality of life and patient satisfaction with diagnosis, treatment and overall care were measured with validated instruments.\n Relatives' satisfaction with care increased over 6 months in the intervention group (P = 0.018), but otherwise, there was no difference between the intervention and control groups concerning QoL, satisfaction with care or number of consultations. Patient satisfaction with care showed a tendency to increase when treatment intent was curative. Some functional QoL measures and satisfaction tended to increase during the first 6 months after treatment. Free text comments suggested that some patients appreciated the contact with their GP.\n Some cancer patients benefit from follow-up by their GP. The way to perform this kind of follow-up in primary care, and who these cancer patients are, should be further studied. Short follow-up time and an urban setting may have contributed to the lack of group differences in our study, but patients treated for cancer may have limited need for follow-up as long as they feel well and the situation remains stable.", "We present the results of a breast cancer clinical trial that tested two therapy interventions delivered by telephone. Women (N = 218) with Stages I, II, or III breast cancer were randomly assigned to breast cancer health education or emotional expression interventions, or to a standard care control condition. Outcome and process measures were obtained at baseline, 6-month and 13-month follow-ups. Oncology certified nurses conducted the therapies in six, 30-minute individual phone sessions. Women in the health education condition reported significantly better knowledge and less perceived stress compared to women in the emotional expression and control conditions. No treatment effects, however, were obtained for quality of life or mood, and all women generally improved on these measures over time. Secondary analyses showed that younger women and women with a more advanced stage of breast cancer reported significantly greater avoidant coping. The data show that telephone therapy is a viable delivery modality and that distress improves with time for most women. Overall, this study showed that neither of the two telephone interventions tested had a meaningful effect on quality of life or mood.\n Copyright 2006 John Wiley & Sons, Ltd.", "To compare the effectiveness of individual support, group rehabilitation and a combination of the two in improving health-related quality of life (HRQOL) and psychological well-being in cancer patients during 24 months after diagnosis, as compared with standard care (SC). Furthermore, to compare the study sample and a random sample of the Swedish population with regard to HRQOL. A total of 481 consecutive patients, newly diagnosed with cancer, were randomly assigned to one of the four alternatives. Data on HRQOL and psychological well-being were collected at baseline and after 3, 6, 12 and 24 months. The interventions did not improve HRQOL or psychological well-being, as compared with SC. At 3 months, the study sample reported an HRQOL comparable with the normal population. Many cancer patients are able to manage their cancer-related concerns with the support available from SC. However, it is reasonable to assume that the findings suffer from a lack of data from especially vulnerable patients and a possible Hawthorne effect. It cannot be concluded that cancer patients have no need for additional psychosocial interventions. Future projects should include screening and target interventions for those at risk for significant and prolonged psychological distress.", "This study was done to assess the effectiveness and efficiency of individualized, problem-solving counseling provided by baccalaureate nurses over the telephone to prevent the onset of depression in persons with breast, lung, or prostate cancer. Of 175 persons randomized, 149 completed the 8-month follow-up. The primary outcome measures were changes in the Jalowiec Coping Scale, the Centre for Epidemiologic Studies in Depression Scale, and the Derogotis Psychosocial Adjustment to Illness Scale. In addition, expenditures for people's use of all health and social services were computed at baseline and follow-up. Telephone counseling improved the use of more favorable coping behaviors, prevented a clinically important but not statistically significant decline into depression, and poor psychosocial adjustment in a group of people with mixed cancer. These results were associated with a greater total per person per annum expenditure for use of all other health and social services in the community compared with the control group. In a situation of limited resources and a service producing more effect for more costs, one needs either to examine what services to forgo to offer this service or to carefully target the new service to those most likely to benefit.", "To determine the efficacy of adjuvant psychological therapy in patients with testicular cancer and to compare the characteristics and psychosocial outcomes of men who agreed to participate with those who declined to participate in a randomised trial of psychological intervention.\n Newly diagnosed patients were asked to participate in a randomised trial of psychological support compared with standard medical care. Participants and non-participants completed self assessment questionnaires at baseline and at 2, 4 and 12 months.\n Testicular Tumour Unit of the Royal Marsden Hospital.\n 73 of 184 (40%) eligible patients agreed to enter the randomised trial (participants) and 81 (44%) declined to participate but agreed to complete further assessments (non-participants). 30 patients wanted no further contact with the researchers.\n Hospital anxiety and depression scale, psychosocial adjustment to illness scale, Rotterdam symptom checklist, mental adjustment to cancer scale. Only scores on the hospital anxiety and depression scale are reported for evaluating treatment efficacy.\n 111 of 184 (60%) eligible men declined to participate in the trial. Patients with stage I disease were most likely to refuse to participate. A patient was less likely to participate if he had low volume disease and was receiving no further treatment. Likelihood of participation was associated with stage of disease and with type of primary treatment (P < 0.001 for heterogeneity). Patients with early stage disease (P < 0.001) and fewer physical symptoms (P < 0.001) were less likely to participate. Psychosocial factors associated with participation included anxious preoccupation regarding disease (P = 0.01). There were no differences in outcome between participants and non-participants during follow up. Patients seemed to gain little benefit from adjuvant psychological therapy. At 2 months change from baseline favoured the treated group in the anxiety subscale (mean difference between groups -1.41 (95% confidence interval -2.86 to 0.03)). This was not sustained when adjusted for factors related to the disease. By 12 months change from baseline seemed to favour the control group (mean difference between groups 1.66 (-0.18 to 3.50)).\n Patients with testicular cancer seem to have considerable coping abilities. Those who declined to participate in the trial differed from those who participated. Those who agreed to participate may comprise the clinical group who perceive a need for psychological support. No evidence was found to indicate a need for routinely offering adjuvant psychological therapy.", "The authors determined the effects of ongoing weekly individual psychotherapy on the symptoms of patients undergoing a 6-week course of radiotherapy for cancer. Forty-eight patients were given weekly psychotherapy sessions for 10 weeks; another 52 patients served as control subjects. A statistically significant reduction was found in both emotional and \"physical\" manifestations of distress in the patients receiving psychotherapy compared with the control group. This was true regardless of gender, ward or private patient status, or knowledge of diagnosis. Patient gender and knowledge of diagnosis did affect the pattern and magnitude of the response to psychotherapy.", "Evidence suggests that the re-entry phase (ie, early period after medical treatment completion) presents distinct challenges for cancer patients. To facilitate the transition to recovery, we conducted the Moving Beyond Cancer (MBC) trial, a multisite, randomized, controlled trial of psychoeducational interventions for breast cancer patients.\n Breast cancer patients were registered within 6 weeks after surgery. After medical treatment, they completed baseline measures and were randomly assigned to standard National Cancer Institute print material (CTL); standard print material and peer-modeling videotape (VID); or standard print material, videotape, two sessions with a trained cancer educator, and informational workbook (EDU). Two primary end points were examined: energy/fatigue and cancer-specific distress. Secondary end points were depressive symptoms and post-traumatic growth. Perceived preparedness for re-entry was analyzed as a moderator of effects.\n Of 558 women randomly assigned to treatment, 418 completed the 6-month assessment and 399 completed the 12-month assessment. In analyses controlling for study site and baseline depressive symptoms, VID produced significant improvement in energy/fatigue at 6 months relative to CTL, particularly among women who felt less prepared for re-entry at baseline. No significant main effect of the interventions emerged on cancer-specific distress, but EDU prompted greater reduction in this outcome relative to CTL at 6 months for patients who felt more prepared for re-entry. Between-group differences in the primary outcomes were not significant at 12 months, and no significant effects emerged on the secondary end points.\n A peer-modeling videotape can accelerate the recovery of energy during the re-entry phase in women treated for breast cancer, particularly among those who feel less prepared for re-entry.", "PURPOSE This study assessed the short-term and long-term efficacy of a presurgical stress management intervention at reducing mood disturbance and improving quality of life (QOL) in men undergoing radical prostatectomy (RP) for prostate cancer. PATIENTS AND METHODS One hundred fifty-nine men were randomly assigned to a two-session (plus two boosters) presurgical stress management intervention (SM), a two-session (plus two boosters) supportive attention group (SA), or a standard care group (SC). Assessments occurred 1 month before surgery; 1 week before surgery; the morning of surgery; 6 weeks after surgery, and 6 and 12 months after surgery. Results Results indicated significant group differences in mood disturbance before surgery (P = .02), such that men in the SM group had significantly less mood disturbance than men in the SC group (P = .006), with no significant differences between the SM and SA or SA and SC groups. In the year after surgery, there were significant group differences on Medical Outcomes Study 36-item short form survey (SF-36) physical component summary (PCS) scores (P = .004); men in the SM group had significantly higher PCS scores than men in the SC group (P = .0009), and there were no significant differences between the SM and SA or SA and SC groups. There were no group effects on prostate-specific QOL or SF-36 mental health scores. CONCLUSION These findings demonstrate the efficacy of a brief presurgical stress management intervention in improving some short-term and long-term outcomes. If these results are replicated, it may be a useful adjunct to standard care for men with prostate cancer undergoing surgery.", "To determine the efficacy of a nursing intervention based on self-regulation theory known as the Attentional Focus and Symptom Management Intervention (AFSMI) in enhancing physical and emotional well-being in women who underwent day surgery for breast cancer.\n Randomized clinical block trial; subjects were randomly allocated to the experimental group (n = 61) or the usual care (control) group (n = 56). Subjects in the experimental group received the AFSMI during two phone sessions, at 3-4 days and 10-11 days after surgery.\n The convenience sample was drawn from five regional centers located in different geographic areas (urban and rural regions) in Quebec, Canada.\n 117 patients with primary breast cancer who underwent day surgery as part of their initial treatment for cancer.\n Data collection and nursing intervention via telephone interviews.\n Functional status and emotional distress.\n Significant differences between the experimental and control group were found at post-test on home management, total mood disturbance, confusion, and tension scores.\n The AFSMI was effective in reducing emotional distress and enhancing physical functioning.\n Findings validate the use of the self-regulation model in designing individualized nursing interventions. Redirecting attention and focusing on concrete objective features hold potential in developing other innovative nursing interventions.", "To examine the effect of counselling and relaxation intervention on psychological symptoms in patients with gynaecological cancer between the post-operative period and the six-week review.\n Randomised controlled trial.\n Fifty-three patients with gynaecological cancer.\n Three Australian tertiary referral hospitals.\n Fifty-three patients were randomised to control or intervention and completed the baseline Hospital Anxiety and Depression Scale (HADS) and General Health Questionnaire-28 (GHQ-28) questionnaires. The intervention consisted of a relaxation and counselling session performed by a senior doctor. Follow up questionnaires were completed at six weeks. Demographic and tumour data were collated independently.\n Complete data were available on 50 patients. There were no significant differences in demographic, social support or tumour characteristics between the two groups. Multivariate analysis determined that only the intervention and baseline score were significant predictors of outcome. The intervention was associated with a significant reduction in total HADS score (P = 0.002). The reduction was seen in both anxiety and moderate depression subscales (P = 0.001 and P = 0.02). The intervention was also associated with a significant reduction in total GHQ-28 score and in three of the four subscale scores (somatisation, anxiety and personality development; all P < 0.02). However, no significant difference was found in the fourth subscale of major depression.\n A relaxation and counselling intervention performed by a treating doctor reduces psychological symptoms in women with a new diagnosis of gynaecological cancer.", "To evaluate the feasibility of an intervention of telephone social support and education to increase the physical, emotional, functional, and interpersonal adaptation of men to prostate cancer.\n Prospective, random assignment to experimental or control treatments.\n Urban New Jersey.\n 17 men diagnosed with prostate cancer within four weeks of study entry. Mean age was 66 years (range = 51-78); 59% were Caucasian, 35% were African American, and 6% were American Indian.\n Subjects in the experimental group received telephone social support over a 12-month period in addition to education via mailed resource kits. The control group received education through mailed resource kits only. The Functional Assessment of Cancer Therapy Scale-General Physical, Emotional, Functional, and Social/Family Well-Being subscales; Symptom Experience Scale-Prostate; and the Relationship Change Scale were administered initially and at the end of each of the three phases; the International Index of Erectile Function Scale was administered at the end of each of the three phases. Qualitative information was gathered throughout and at the conclusion of the study.\n Physiologic, emotional, functional, and social adaptation to prostate cancer.\n Results were somewhat more favorable for the experimental group on all outcome measures; however, differences were not statistically significant. Structured interviews with 14 of 17 subjects revealed that telephone social support and education were effective in increasing adaptation to prostate cancer.\n Despite the lack of a significant difference between the experimental and treatment groups in this small sample of men, analysis of trends and interview feedback indicated that telephone social support, in addition to education through a mailed resource kit, has the potential to be beneficial by increasing access to supportive services.\n Telephone social support when supplementing patient education may assist men in adapting during the year following a prostate cancer diagnosis.", "Professionally administered psychosocial interventions have been shown to improve the quality of life of cancer patients undergoing chemotherapy. The present study sought to improve access to psychosocial interventions during chemotherapy treatment by evaluating the efficacy and costs of a patient self-administered form of stress management training that requires limited professional time or experience to deliver.\n Four hundred eleven patients about to start chemotherapy were randomly assigned to receive usual psychosocial care only, a professionally administered form of stress management training, or a patient self-administered form of stress management training. Quality-of-life assessments were conducted before randomization and before the second, third, and fourth treatment cycles. Intervention costs were estimated from both payer and societal perspectives.\n Compared with patients who received usual care only, patients receiving the self-administered intervention reported significantly (P < or = .05) better physical functioning, greater vitality, fewer role limitations because of emotional problems, and better mental health. In contrast, patients who received the professionally administered intervention fared no better in terms of quality of life than patients receiving usual care only. Costs of the self-administered intervention were estimated to be 66% (from a payer perspective) to 68% (from a societal perspective) less than the average costs of professionally administered psychosocial interventions for patients starting chemotherapy.\n Evidence regarding the efficacy and favorable costs of self-administered stress management training suggests that this intervention has the potential to greatly improve patient access to psychosocial intervention during chemotherapy treatment.", "Although researchers suggest treatments that provide patients with an active coping strategy may increase patients' sense of self-efficacy, previous studies have not measured patients' self-efficacy.\n Eighteen women receiving chemotherapy for breast cancer were randomized to efficacy-enhancing experimental (n = 10) and usual-care control (n = 8) groups. The experimental group received five interventions delivered monthly. Variables--quality of life, symptom distress, and self-care self-efficacy--were measured at baseline and at 4 and 8 months later.\n At 4 and 8 months the interaction effects for the Functional Assessment of Cancer Treatment-Breast, used to measure quality of life, ranged from small for functional concerns to large for social concerns. Interaction effects for symptom distress, measured by the Symptom Distress Scale, were large. Interaction effects for self-care self-efficacy ranged from small for Enjoying Life and Stress Reduction, medium for Stress Reduction, and large for Making Decisions.\n Interventions to promote self-efficacy may increase quality of life and decrease distress for women diagnosed with breast cancer.", "The objective of this study was to test the efficacy of an individualized uncertainty management intervention delivered by telephone to Caucasian and African-American men with localized prostate carcinoma and directed at managing the uncertainties of their disease and treatment.\n The authors delivered a psychoeducational intervention by phone to men with prostate carcinoma, with or without supplemented delivery to a close family member, that was directed at managing uncertainty and improving symptom control. One hundred thirty-four Caucasian men and 105 African-American men were assigned randomly to one of two approaches to delivering the intervention or to the control condition. Men entered the study immediately after surgical treatment or in the first 3 weeks of radiation therapy. Trained nurses delivered the intervention through weekly phone calls for 8 weeks.\n The authors found that the majority of intervention effects were from baseline to 4 months postbaseline, when treatment side effects are most intense. Both Caucasian men and African-American men who received either one of the two approaches for delivering the intervention improved in the two uncertainty management methods of cognitive reframing and problem solving. Similarly, when the intervention groups were combined, men who received the intervention also improved significantly in control of incontinence by 4 months postbaseline. Decreases in the number of treatment side effects differed by time and treatment/ ethnic group interactions as did satisfaction with sexual functioning.\n This is one of the first tests of a psychoeducational intervention among men with prostate carcinoma and was the first test that included a sufficient number of African-American men to test by ethnic group. Therefore, replication of these findings is advised.\n Copyright 2002 American Cancer Society.", "This study compared the efficacy of 2 psychological interventions, a coping and communication-enhancing intervention (CCI) and supportive counseling (SC), in reducing depressive symptoms and cancer-specific distress of women diagnosed with gynecological cancer. Demographic, medical, and psychological moderators of intervention effects were evaluated. Three hundred fifty-three women with gynecological cancer were randomly assigned to 7 sessions of CCI, 7 sessions of SC, or usual care. Intent-to-treat growth curve analyses indicated that participants assigned to CCI and SC reported lower depressive symptoms than participants assigned to usual care at the 6- and 9-month follow-ups. Women with greater than average increases in physician-rated physical symptoms and/or women who were more expressive of positive emotions benefited more from SC than women with lower than average increases in symptom scores and/or women who were less expressive of positive emotions. These findings suggest that both interventions may be effective in treating depressive symptoms among patients with gynecological cancer. Future research should evaluate whether bolstering both psychological interventions with additional intervention sessions and topics in the disease trajectory will result in persistent long-term effects.", "To evaluate the effectiveness of psychological intervention in the care of cancer patients and to determine whether routine use of individual psychological therapies is indicated.\n Patients with newly diagnosed gynecologic malignancies from August 1999 to November 2000 were recruited and randomly assigned to either a control group receiving routine medical care or to an intervention group receiving individual psychotherapy. A set of fixed-choice, self-report questionnaires assessing the patients' psychological status, quality of life, and their perceptions related to the medical consultations was completed at recruitment and then every 3 months for 18 months. Data analysis was performed according to the intention-to-treat principle by fitting the data into a linear mixed-effects model. Multivariable analyses were performed to examine the effects of confounding factors.\n One hundred fifty-five patients participated in the trial. There were no statistically significant differences between the two groups at baseline. There was a trend toward better quality of life and functional status and also improvement of the symptoms over time for both groups. No differences were found between the groups in the scores measured by any of the instruments at baseline and at any time points after the cancer diagnosis. Psychological intervention had no significant effects on the psychosocial parameters.\n Routine use of psychological therapies as given in our format has no significant effect on the patients' quality of life and psychological status.", "Home visits by health care professionals may constitute a formalized social relationship in which cancer patients can be given emotional and informational support. We aimed at studying the effect of home visits on the well-being of colorectal cancer patients. A total of 249 Danish colorectal cancer patients undergoing abdominal surgery were randomly assigned to a control group or to an intervention group. The intervention group received 10 home visits carried out by a project nurse or a medical doctor during the first 2 years after discharge. Participants were interviewed 3, 6, 12, and 24 months after discharge in order to assess well-being. Using a linear mixed model, we found no overall effect of the intervention on well-being. We recommend that future psychosocial intervention studies include baseline screening for distress and recommend testing the effect of shorter but intensive interventions carried out by trained therapists.\n Copyright 2005 John Wiley & Sons, Ltd", "Nucare, a short-term psychoeducational coping skills training intervention was evaluated in a randomized controlled clinical trial (RCT) of 225 newly diagnosed breast and colon cancer patients.\n Measures of psychosocial distress, well being and optimism were evaluated every four months during a one-year period. Patients were randomized to one of four arms: Nucare presented in an individual basis; Nucare presented in a group format; a non-directive supportive group; and a no-intervention control. The interventions were provided in five sessions of ninety minutes each.\n Patients with breast cancer who received Nucare presented in an individual format showed more significant improvements in well-being over time compared to those in the control and group arms.\n We were unable to develop functioning groups within the RCT. Partial explanations for the latter finding include the structural limitations of the RCT: the groups were small, difficult to schedule and patients indicated that they would have preferred to choose whether or not to participate in a group. The positive changes in women with breast cancer who received Nucare persisted at 12 months.", "To test the value of telephone-administered cognitive-behavioral therapy in a study of patients with breast cancer.\n Women were assigned randomly to a therapy group or an assessment-only control group.\n A tertiary cancer treatment center serving rural areas of North Dakota and Minnesota.\n Women were recruited within three to four months of stage I (n = 27) or stage II (n = 26) breast cancer diagnosis. Age ranged from 30-82 (mean = 51.5 years). Most participants (n = 35) underwent a modified radical mastectomy; 17 underwent a lumpectomy.\n Therapy involved 10 30-minute (or less) telephone sessions. Data that were collected from mailed questionnaires included psychological distress (Profile of Mood States), perceived stress, coping (Coping Response Indices-Revised), quality of life (Medical Outcome Scale), and satisfaction with therapy. Measures were completed at baseline and at 4- and 10-month follow-up intervals.\n Telephone therapy, stress, coping, and quality of life.\n With time, women in the therapy and control groups reported reduced stress and improved quality of life. However, significant reductions in some kinds of distress (anxiety, anger, depression, and confusion) were not observed. Most therapy participants liked the telephone treatment sessions but showed only modest improvement (less anxiety and confusion) compared with women in the control group.\n Most patients reported being comfortable with the telephone therapy and said that they felt better as a result of it. However, the outcome data showed that telephone therapy--as carried out in this study--produced only modest benefits. Researchers need to consider who is best for delivering such therapy.\n Providing telephone therapy to patients with breast cancer has potential benefits, and nurses may be the appropriate professionals to administer the therapy.", "The primary purpose of this study was to determine if a psychoeducational nursing intervention including (a) health education, (b) stress management, and (c) the teaching of coping skills could enhance the coping behavior and affective state of newly diagnosed Stage I/II malignant melanoma patients. The secondary purpose was to determine if this intervention could be implemented by a nurse and integrated into the overall patient care program. Sixty-one patients were randomized to a control condition or an experimental condition that received and educational manual plus 3 h of individual nurse teaching. Despite randomization, experimental patients had significantly higher baseline distress. By 3 months there was a complete reversal of the baseline trend in Profile of Mood States (POMS) total mood disturbance (TMD), suggesting that the experimental subjects were experiencing less distress over time. Between-group analysis of change scores found significant decreases in experimental subjects for POMS TMD, fatigue, and Brief Symptom Index (BSI) somatization. Within-group analysis found significant experimental decreases for BSI somatization, anxiety, grand total, General Severity Index, and Positive Symptom Distress Index as well as for POMS anxiety, fatigue, confusion, vigor, and TMD. No significant changes were found for controls. Experimental patients were using significantly fewer ineffective passive resignation coping strategies than controls at 3 months.", "The efficacy of problem-solving therapy (PST) to reduce psychological distress was assessed among a sample of 132 adult cancer patients. A second condition provided PST for both the patient and a significant other. At posttreatment, all participants receiving PST fared significantly better than waiting list control patients. Further, improvements in problem solving were found to correlate significantly with improvements in psychological distress and overall quality of life. No differences in symptom reduction were identified between the 2 treatment protocols. At a 6-month follow-up, however, patients who received PST along with their significant other reported lower levels of psychological distress as compared with members of the PST-alone condition on approximately half of the outcome measures. These effects were further maintained 1-year posttreatment.\n (c) 2003 APA", "The authors report the short-term effects of a clinical trial testing 2 telephone therapies for breast cancer patients. Women (N = 222) with breast cancer were recruited and randomly assigned to cancer education, emotional expression, or standard care. Oncology nurses conducted 6 individual 30-min-therapy phone sessions. Women in the cancer education condition reported greater perceived control than women in the standard care condition. No treatment effects were obtained for mood or quality of life. These are the 1st data from a large-scale study testing telephone therapy, and they suggest that such therapies may be ineffective. Explanations for the results include therapy type and delivery, participant characteristics, short- versus long-term results, therapy conent, and whether therapy is necessary for breast cancer patients." ]

[ "2726279", "2941056", "6763202", "8492200", "3311548", "21257263" ]

[ "Codeine 20 mg increases pain relief from ibuprofen 400 mg after third molar surgery. A repeat-dosing comparison of ibuprofen and an ibuprofen-codeine combination.", "A double-blind placebo-controlled comparison of three ibuprofen/codeine combinations and aspirin.", "Analgesic efficacy of an ibuprofen-codeine combination.", "The effect of an ibuprofen-codeine combination for the treatment of patients with pain after removal of lower third molars.", "Analgesic efficacy of two ibuprofen-codeine combinations for the treatment of postepisiotomy and postoperative pain.", "A randomised, five-parallel-group, placebo-controlled trial comparing the efficacy and tolerability of analgesic combinations including a novel single-tablet combination of ibuprofen/paracetamol for postoperative dental pain." ]

[ "A combination of 20 mg codeine base and ibuprofen 400 mg was compared with ibuprofen 400 mg in a randomised double-blind cross-over study of multiple doses in 25 patients after 2-stage bilateral third molar removal. The combination produced significantly greater pain relief and doubled the hours of minimum pain intensity and maximal relief on the day of surgery. The patients rated the combination significantly better than ibuprofen alone, and the combination was preferred by 16 of the 22 patients expressing a preference. There was no significant increase in side-effect incidence with the combination. The 30% increase in analgesic effect may be of clinical benefit, and this trial design, cross-over with multiple dosing in out-patients, may be a sensitive test for analgesics, potentially more predictive of side-effect problems than single-dose studies.", "In a double-blind, single dose study of analgesic efficacy, 165 patients who were expected to develop moderate to severe pain following the removal of an impacted mandibular third molar tooth were allocated to receive aspirin, placebo, or an increasing dose of a fixed ratio ibuprofen/codeine combination. The degree of pain experienced prior to medication was noted and the patients were asked to record the degree of pain and of pain relief hourly for the following 5 hours. The study produced clear evidence of the superior efficacy of the combinations when compared to placebo and aspirin. In addition, the high dose combination appeared to be superior with respect to pain relief and the need for additional analgesia compared to the low dose treatment. There were few side effects and only one severe reaction was reported by a patient in the high dose group. To avoid side effects it is suggested that the medium-dose combination, ibuprofen 400 mg/codeine 30 mg, is optimal.", "Subjects who had undergone dental impaction surgery and who had moderate to severe postoperative pain were given, under double-blind, randomized conditions, a single dose of either codeine 60 mg, aspirin 650 mg, ibuprofen 400 mg, aspirin 650 mg + codeine 60 mg, ibuprofen 400 mg + codeine 60 mg, or placebo. A total of 249 subjects were included in the statistical analysis. On a report form, subjects recorded pain intensity, pain relief, and side effects hourly for four hours. They also gave an overall impression at the end of the observation period. Analysis of variance and pairwise contrasts were used to analyze the data. For the sum of pain intensity differences, the total of the hourly pain relief scores, and overall impression, there was a significant analgesic effect for codeine, aspirin, and ibuprofen and no significant interaction when they were used in combination. Ibuprofen alone was statistically superior to aspirin and also achieved higher mean scores than the aspirin-codeine combination. The ibuprofen-codeine combination was the most effective treatment for every analgesic parameter, but it was not statistically superior to ibuprofen alone. The possibility exists that the ibuprofen-codeine combination peaked out the sensitivity of the model. There was no notable difference in the frequency or intensity of side effects among the treatment groups, and no subject had to withdraw due to an adverse effect. This study again confirms the superiority of ibuprofen to aspirin and suggests that ibuprofen is at least as effective as an aspirin-codeine combination. Codeine added a small amount of additional analgesia when used in combination with ibuprofen.", "A double-blind randomized crossover analgesic trial was carried out on 70 patients undergoing surgical removal of one lower third molar at each visit. The analgesic efficacy of a two-dose regimen of the combination ibuprofen-codeine, 400 to 60 mg, was compared with ibuprofen, 400 mg. Each of the two doses was taken when the patient needed pain relief and the pain intensity was measured on a visual analog scale during the 10-hour period after the first medication. Because of carryover effects between periods 1 and 2, the analysis was carried out only for period 1 according to a parallel group design. Of the 60 patients who were evaluated for analgesic effect, the mean pain reduction of dose 1 was 63% for the 29 patients given ibuprofen-codeine and 50% for the 31 patients given ibuprofen; the mean duration of effect was 7.5 and 6.3 hours, respectively. The difference in pain reduction index (pain reduction X duration of effect) between the two treatments was significant in favor of the combination, whereas the separate variables of pain reduction and duration of effect were not significantly different. The mean pain reduction was 67% after doses 1 and 2 for patients on ibuprofen-codeine and 52% for those on ibuprofen; the mean duration of effect was 9.4 and 9.2 hours, respectively. For doses 1 and 2, the difference in pain reduction index per dose between the two treatments was significant but not the difference for the separate variables, pain reduction, and duration of effect.(ABSTRACT TRUNCATED AT 250 WORDS)", "Our purpose was to compare the analgesic efficacy and safety of single oral doses of the combination of ibuprofen 400 mg plus codeine 60 mg and the combination of ibuprofen 200 mg plus codeine 30 mg with ibuprofen 400 mg alone, codeine sulfate 60 mg alone, and placebo. One hundred ninety-five patients with severe pain resulting from episiotomy, cesarean section, or gynecologic surgery completed a randomized, double-blind, stratified, parallel-group study. Patients were observed during a 4-hour period after medication. Based on the sum of the pain intensity differences (SPID), total pain relief (TOTPAR), and most of the hourly direct measures of pain and relief, both doses of the combination and ibuprofen 400 mg alone were statistically superior to placebo. Codeine 60 mg was statistically superior to placebo based on TOTPAR, the global ratings, and a few hourly measures. The mean effect of the combination of ibuprofen 400 mg plus codeine 60 mg was significantly superior to the mean effect of ibuprofen 400 mg alone 1/2, 1, and 2 hours after medication and to the mean effect of ibuprofen 400 mg alone and codeine 60 mg alone for SPID, TOTPAR, and other measures as well. The low-dose combination was significantly more effective than codeine 60 mg for a few hourly measures but was not significantly superior to ibuprofen 400 mg. Based on these findings it appears that the combination of ibuprofen 400 mg plus codeine 60 mg, particularly in the first few hours after medication, is more efficacious than its constituents.", "Combination analgesia is often recommended for the relief of severe pain. This was a double-blind, 5-arm, parallel-group, placebo-controlled, randomised, single-dose study designed to compare the efficacy and tolerability of a novel single-tablet combination of ibuprofen and paracetamol with that of an ibuprofen/codeine combination, and a paracetamol/codeine combination, using the dental impaction pain model. Subjects with at least 3 impacted third molars and experiencing moderate to severe postoperative pain were randomised to receive: 1 or 2 tablets of a single-tablet combination of ibuprofen 200mg/paracetamol 500mg; 2 tablets of ibuprofen 200 mg/codeine 12.8mg; 2 tablets of paracetamol 500mg/codeine 15mg; or placebo. Results for the primary endpoint, the sum of the mean scores of pain relief combined with pain intensity differences over 12hours, demonstrated that 1 and 2 tablets of the single-tablet combination of ibuprofen/paracetamol were statistically significantly more efficacious than 2 tablets of placebo (P<0.0001) and paracetamol/codeine (P⩽0.0001); furthermore, 2 tablets offered significantly superior pain relief to ibuprofen/codeine (P=0.0001), and 1 tablet was found noninferior to this combination. Adverse events were uncommon during this study and treatment emergent adverse events were statistically significantly less frequent in the groups taking the ibuprofen/paracetamol combination compared with codeine combinations. In conclusion, 1 or 2 tablets of a single-tablet combination of ibuprofen 200mg/paracetamol 500mg provided highly effective analgesia that was comparable with, or superior to, other combination analgesics currently indicated for strong pain. A single-tablet combination of ibuprofen 200mg/paracetamol 500mg provides highly effective analgesia, comparable or superior to other combination analgesics indicated for strong pain.\n Copyright © 2011. Published by Elsevier B.V." ]

[ "11904108", "11600554", "15855263", "3073880", "16263815", "11932277", "11238494", "15126526", "9016421" ]

[ "A 6-month randomized trial of thyroxine treatment in women with mild subclinical hypothyroidism.", "TSH-controlled L-thyroxine therapy reduces cholesterol levels and clinical symptoms in subclinical hypothyroidism: a double blind, placebo-controlled trial (Basel Thyroid Study).", "Muscle metabolism and exercise tolerance in subclinical hypothyroidism: a controlled trial of levothyroxine.", "A double-blind cross-over 12-month study of L-thyroxine treatment of women with 'subclinical' hypothyroidism.", "Neuropsychological function and symptoms in subjects with subclinical hypothyroidism and the effect of thyroxine treatment.", "Lipoprotein profile in subclinical hypothyroidism: response to levothyroxine replacement, a randomized placebo-controlled study.", "Effect of levothyroxine on cardiac function and structure in subclinical hypothyroidism: a double blind, placebo-controlled study.", "Effect of levothyroxine replacement on lipid profile and intima-media thickness in subclinical hypothyroidism: a double-blind, placebo- controlled study.", "Does treatment with L-thyroxine influence health status in middle-aged and older adults with subclinical hypothyroidism?" ]

[ "The role of thyroxine replacement in subclinical hypothyroidism remains unclear. We performed a 6-month randomized, double-blind, placebo-controlled trial to evaluate the effects of thyroxine treatment for mild subclinical hypothyroidism, defined as a serum thyroid-stimulating hormone level between 5 to 10 microU/mL with a normal serum free thyroxine level (0.8-16 ng/dL).\n We randomly assigned 40 women with mild subclinical hypothyroidism who had presented to their family practitioners to either thyroxine treatment (n = 23; 50 to 100 microg daily) or placebo (n = 17). Health-related quality of life (Hospital Anxiety and Depression scale, 30-item General Health Questionnaire), fasting lipid profiles, body weight, and resting energy expenditure were measured at baseline and 6 months.\n The most common presenting symptoms were fatigue (n = 33 [83%]) and weight gain (n = 32 [80%]). At presentation, 20 women (50%) had elevated anxiety scores and 22 (56%) had elevated scores on the General Health Questionnaire. Thirty-five women completed the study. There were no significant differences in the changes from baseline to 6 months between women in the thyroxine group and the placebo group for any of the metabolic, lipid, or anthropometric variables measured, expressed as the mean change in the thyroxine group minus the mean change in the placebo group: body mass index, -0.3 kg/m(2) (95% confidence interval [CI]: -0.9 to 0.4 kg/m(2)); resting energy expenditure, -0.2 kcal/kg/24 h (95% CI: -1.3 to 1.0 kcal/kg/24 h); and low-density lipoprotein cholesterol, -4 mg/dL (95% CI: -23 to 15 mg/dL). There was a significant worsening in anxiety scores in the thyroxine group (scores increased in 8 of 20 women and were unchanged in 2 of 20) compared with the placebo group (scores increased in 1 of 14 women and were unchanged in 6 of 14; P = 0.03). CONCLUSIONS; We observed no clinically relevant benefits from 6 months of thyroxine treatment in women with mild subclinical hypothyroidism.", "This study evaluated the effect of physiological, TSH-guided, L-thyroxine treatment on serum lipids and clinical symptoms in patients with subclinical hypothyroidism. Sixty-six women with proven subclinical hypothyroidism (TSH, 11.7 +/- 0.8 mIU/liter) were randomly assigned to receive L-thyroxine or placebo for 48 wk. Individual L-thyroxine replacement (mean dose, 85.5 +/- 4.3 microg/d) was performed based on blinded TSH monitoring, resulting in euthyroid TSH levels (3.1 +/- 0.3 mIU/liter). Lipid concentrations and clinical scores were measured before and after treatment. Sixty-three of 66 patients completed the study. In the L-thyroxine group (n = 31) total cholesterol and low density lipoprotein cholesterol were significantly reduced [-0.24 mmol/liter, 3.8% (P = 0.015) and -0.33 mmol/liter, 8.2% (P = 0.004), respectively]. Low density lipoprotein cholesterol decrease was more pronounced in patients with TSH levels greater than 12 mIU/liter or elevated low density lipoprotein cholesterol levels at baseline. A significant decrease in apolipoprotein B-100 concentrations was observed (P = 0.037), whereas high density lipoprotein cholesterol, triglycerides, apolipoprotein AI, and lipoprotein(a) levels remained unchanged. Two clinical scores assessing symptoms and signs of hypothyroidism (Billewicz and Zulewski scores) improved significantly (P = 0.02). This is the first double blind study to show that physiological L-thyroxine replacement in patients with subclinical hypothyroidism has a beneficial effect on low density lipoprotein cholesterol levels and clinical symptoms of hypothyroidism. An important risk reduction of cardiovascular mortality of 9-31% can be estimated from the observed improvement in low density lipoprotein cholesterol.", "Neuromuscular symptoms and impaired muscle energy metabolism have been described in subclinical hypothyroidism (sHT).\n The aim of the study was to evaluate the energy and substrate response to exercise in sHT patients using a standardized protocol and to test the effect of L-T(4) replacement in a double-blind, randomized, placebo-controlled fashion.\n We studied 23 sHT patients and 10 matched euthyroid controls. Oxygen uptake (VO(2)), carbon dioxide output, and heart rate were measured during incremental step-up exercise. Blood glucose, lactate, pyruvate, free fatty acid, glycerol, and beta-hydroxybutyrate concentrations were measured at rest, every 2 min during exercise, and during 20 min of recovery. The exercise protocol was repeated after 6 months of placebo or L-T(4)-restored euthyroidism.\n Maximal power output (P = 0.02) and VO(2) max (P = 0.04) were reduced in sHT, and, with increasing workload, patients achieved higher heart rates (P < 0.03) at VO(2) values equivalent to those of controls. The respiratory quotient increments were significantly higher in patients than controls (P < 0.04). Blood lactate and pyruvate and their ratio rose with a steeper slope (P < 0.0001, P < 0.001, and P < 0.01, respectively) in patients than controls. Resting plasma free fatty acid and blood glycerol levels were significantly higher in patients than controls (P < 0.0003 and P < 0.003, respectively) throughout baseline, exercise, and recovery. L-T(4) replacement, while improving neuromuscular symptoms, did not produce significant changes in the energy or substrate response to exercise.\n The response to exercise is altered both in terms of tolerance and pattern of substrate utilization in sHT patients. Restoring stable euthyroidism does not correct this defect over a 1-yr period.", "Twenty women, who had been randomly selected from women with subclinical hypothyroidism identified in a population study were treated with L-thyroxine and placebo in a double-blind cross-over design during 2 x 6 months. Three women did not complete the study, one because she moved to another part of the country, and two because of nervousness and sense of tachycardia. None of these 'drop-outs' had any objective signs of overtreatment; they had normal pulse rate and a serum T3 concentration within the reference interval. During L-thyroxine treatment serum procollagen-III-peptide concentration increased in 13 women out of the 17 women completing the study and at the end of treatment the mean concentration was significantly raised (P less than 0.001). Serum concentrations of procollagen-III-peptide then correlated with those of free thyroxine (P less than 0.01), total thyroxine (P less than 0.05), and reverse triiodothyronine (P less than 0.05). The same comparison revealed little or no effect on the concentrations of serum creatine kinase activity, transcortin or sex-hormone binding globulin. Heart rate-corrected preejection period and symptom score decreased (P less than 0.05). Four women starting with L-thyroxine showed a marked and prolonged (4-6 months) rise in thyrotrophin concentration during the subsequent placebo period, but remained clinically euthyroid. Four women (of 17) improved during therapy as judged by psychometric testing and their own rating. We could not by pretreatment observations identify these four women apart from serum free and total 3,5,3'-triiodothyronine concentrations in the lower part of the health-associated reference interval. Subclinical hypothyroidism is common among middle-aged and old women, and our findings indicate that approximately one woman in four with this 'subclinical' condition will benefit from L-thyroxine treatment.", "Our objective was to examine the relation between neuropsychological function and subclinical hypothyroidism (SHT), defined as serum TSH of 3.5-10.0 mIU/liter and normal serum free T4 and free T3 levels, and to study the effect of T4 supplementation.\n A total of 89 subjects (45 males) with SHT and 154 control subjects (72 males) were recruited from a general health survey (the fifth Tromsø study). Sixty-nine of those with SHT were included in a placebo-controlled, double-blind intervention study with T4 medication for 1 yr.\n We used fourteen tests of cognitive function, Beck Depression Inventory, General Health Questionnaire, and a questionnaire on hypothyroid symptoms.\n The mean +/- sd serum TSH in the SHT and control group were 5.57 +/- 1.68 and 1.79 +/- 0.69 mIU/liter, respectively. There were no significant differences in cognitive function and hypothyroid symptoms between the two groups, but those with SHT scored significantly better than the controls on the GHQ-30. At the end of the intervention study, serum TSH in the T4 group (n = 36) and the placebo group (n = 33) were 1.52 +/- 1.51 and 5.42 +/- 1.96 mIU/liter, respectively. T4 substitution had no effect on any of the parameters measured.\n In subjects with SHT where the serum TSH level is in the 3.5-10.0 mIU/liter range, there is no neuropsychological dysfunction, and compared with healthy controls, there is no difference in symptoms related to hypothyroidism.", "The relationship between subclinical hypothyroidism (SCH) and an atherogenic lipoprotein profile is still controversial. We measured lipoproteins in 49 SCH patients by comparison with 33 euthyroid controls. Total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDLc), apolipoprotein A(1), apolipoprotein B, and lipoprotein (a) [Lp(a)] were measured after an overnight fast. Patients were randomly assigned to levothyroxine therapy or placebo and re-evaluated after 6 months of euthyroidism. SCH patients showed significantly higher TC (P < 0.01), LDLc (P = 0.01), and apolipoprotein B (P = 0.001) levels than controls, positively correlated with baseline TSH levels (P = 0.003, P = 0.01, and P = 0.03, respectively). Elevated Lp(a) levels were significantly more frequent in SCH (P < 0.05) and associated with familial diabetes mellitus and/or coronary heart disease (P < 0.01). Levothyroxine treatment resulted in a significant decrease of both TC and LDLc concentrations (P = 0.003), in direct proportion to the respective baseline values (P < 0.05 and P < 0.01, respectively), whereas no change in Lp(a) level was observed. No changes occurred in the placebo group. In conclusion, only serum LDLc levels are increased specifically and reversibly in association with SCH. Altered Lp(a) values reflect a genetic influence rather than a reduced thyroid hormone action.", "Subclinical hypothyroidism (sHT) affects 5-15% of the general population; however, the need of lifelong L-T(4) therapy is still controversial. As myocardium is a main target of thyroid hormone action, we investigated whether sHT induces cardiovascular alterations. Twenty sHT patients were randomly assigned to receive placebo or L-T(4) therapy and were followed for 1 yr. Twenty sex- and age-matched normal subjects served as controls. Doppler echocardiography and videodensitometric analysis were performed in all subjects. Myocardium textural parameters were obtained as mean gray levels, which were then used to calculate the cyclic variation index (CVI; percent systolic/diastolic change in mean gray levels). Patients had a significantly higher isovolumic relaxation time (3.1 +/- 0.5 vs. 2.6 +/- 0.6; P < 0.03), peak A (0.77 +/- 0.16 vs. 0.56 +/- 0.13 m/s; P < 0.01), and preejection/ejection time (PEP/ET) ratio (0.72 +/- 0.05 vs. 0.57 +/- 0.06; P < 0.03) and a lower CVI (P < 0.0001) than controls. CVI was inversely related to TSH level (P < 0.0001) and PEP/ET ratio (P < 0.01). L-T(4)-treated patients showed a significant reduction of the PEP/ET ratio (P < 0.05), peak A (P < 0.05), and isovolumic relaxation time (P < 0.05) along with a normalization of CVI. Conversely, no changes were observed in the placebo-treated group. In conclusion, sHT affects both myocardial structure and contractility. These alterations may be reversed by L-T(4) therapy.", "Subclinical hypothyroidism (sHT) is associated with dyslipidemia and enhanced cardiovascular risk. We assessed carotid artery intima-media thickness (IMT, high-resolution ultrasonography) and lipoprotein profile in 45 sHT patients (aged 37 +/- 11 yr) at baseline and after 6 months of randomized, placebo-controlled L-T(4) replacement. In comparison with 32 age- and sex-matched controls, sHT patients had elevated total and low-density lipoprotein (LDL) cholesterol and ApoB levels (P = 0.002, P = 0.0007, and P = 0.01, respectively) and higher mean-IMT values (P < 0.0001). In stepwise regression analysis, mean-IMT was positively related (r(2) = 0.71, P < 0.0001) to age, TSH, and LDL cholesterol. L-T(4) replacement significantly reduced both total and LDL cholesterol (P < 0.0001 for both) and mean-IMT (by 11%, P < 0.0001). The decrement in IMT was directly related to the decrements of both total cholesterol and TSH (P = 0.02 and P = 0.0001, respectively). We conclude that early carotid artery wall alterations are present in sHT patients. Whether such IMT increase is related to an early atherosclerotic involvement of the arterial wall cannot be clearly decided on the basis of the present results. However, the fact that L-T(4) replacement therapy was able to improve both the atherogenic lipoprotein profile and intima-media thickening suggests that lipid infiltration of arterial wall may represent a major mechanism underlying IMT increase in subclinical hypothyroidism.", "To determine if health-related quality of life (HRQL) in patients of middle age and older with elevated thyroid-stimulating hormone (TSH) and normal total thyroid hormone levels-subclinical hypothyroidism-improves with L-thyroxine replacement therapy.\n Randomized, double-blind, placebo-controlled trial.\n Outpatient clinic.\n Thirty-seven patients with subclinical hypothyroidism, most with symptoms consistent with hypothyroidism, over 55 years of age.\n Placebo or L-thyroxine replacement therapy to achieve normal TSH level.\n Disease-specific and general HRQL, cognitive function, bone mineral density, lipid levels. The mean daily dose of L-thyroxine replacement in the active group was 68 +/- 21 micrograms. TSH decreased by 8.6 mIU/L (95% confidence interval [CI] 4.1 to 13.1) and T4 increased by 27.9 nmol/L (95% CI 14.8 to 41.2). There was a statistically significant improvement in a composite psychometric memory score in treated versus control patients; all other outcomes showed similar findings in the two groups. Although confidence intervals for most measures did not exclude an important improvement in HRQL with thyroid replacement, no measure of symptoms or HRQL either showed clinically important trends in favor of treatment, or approached conventional levels of statistical significance.\n In middle-aged and older patients with elevated TSH and normal T4, it may not be harmful to follow biochemical and clinical status even in the presence of nonspecific symptoms potentially associated with hypothyroidism." ]

[ "15679793", "12361896", "10510105", "16104911" ]

[ "Tamsulosin in the management of patients in acute urinary retention from benign prostatic hyperplasia.", "Randomised, placebo controlled, double blind study of alfuzosin SR in patients undergoing trial without catheter following acute urinary retention.", "Sustained-release alfuzosin and trial without catheter after acute urinary retention: a prospective, placebo-controlled.", "The economic impact of using alfuzosin 10 mg once daily in the management of acute urinary retention in the UK: a 6-month analysis." ]

[ "To evaluate the efficacy of tamsulosin compared to placebo for treating catheterized patients with acute urinary retention (AUR) caused by benign prostatic hyperplasia (BPH), by comparing the numbers of patients who voided successfully after removing their catheter.\n This was a randomized, double-blind, placebo-controlled, parallel-group, multicentre study. Men with AUR secondary to BPH were catheterized and then, if they fulfilled the entry criteria, were randomly assigned to receive either 0.4 mg tamsulosin hydrochloride in a modified-release capsule once daily, or a placebo. After up to eight doses the catheter was removed and the ability to void unaided assessed.\n In all, 149 men (mean age 69.4 years) were randomly assigned to receive tamsulosin (75) or placebo (74); eight were not evaluable, so the intent-to-treat population was 141 men. Thirty-four men taking tamsulosin and 18 taking placebo did not require re-catheterization on the day of the trial without catheter (48% and 26% respectively, P = 0.011; odds ratio 2.47, 95% confidence interval, CI, 1.23-4.97). Success using free-flow variables was also higher in the men who received tamsulosin, at 37 (52%) vs 24 (34%) on placebo (P = 0.019; odds ratio 2.34, 95% CI 1.15-4.75). Withdrawals were high (120 men, 81%), mostly because of a need for re-catheterization (89 men, 60%). Dizziness and somnolence occurred in seven (10%) and four (6%) men who received tamsulosin, and two (3%) who received placebo, but overall the incidence of adverse events was similar in the two groups. One patient died from carcinomatosis.\n Men catheterized for AUR can void more successfully after catheter removal if treated with tamsulosin, and are less likely to need re-catheterization. The side-effect profile was similar for tamsulosin and placebo, and consistent with known pharmacology. From these results tamsulosin can be recommended for treating men after catheterization for AUR, and can reduce the likelihood of the need for re-catheterization.", "Acute urinary retention caused by bladder outlet obstruction resulting from prostatic enlargement is one of the commonest causes for acute admission to urology wards. More recently, there has been a trend to commence treatment with alpha-blockers after catheterisation followed by a trial without catheter (TWOC), in the hope that surgery may be avoided in a significant proportion of patients. There is no conclusive evidence of the efficacy of this treatment. We conducted a study to evaluate the efficacy of using the alpha-blocker alfuzosin SR in patients with acute urinary retention.\n All patients presenting with acute urinary retention to our unit were included in the trial. Exclusion criteria included patients with known bladder or prostate malignancy, bladder calculi, urinary tract infections, urethral stricture or patients on alpha-blockers. A total of 81 patients consented and were randomised. Sixty-two patients completed the study. The retention volume was recorded. Trial medicine was recorded on a twice-daily dose and the first TWOC was carried out after a minimum of three doses or 36 hours after admission. TWOC was considered successful on voiding with a residual volume of <200 ml. Unsuccessful patients were recatheterised and discharged home on trial medication, and called for a second TWOC after 2 weeks. Successful patients were continued on alpha-blockers and failures were put on the operating list for TURP. Patients on active treatments were reviewed at 2 year.\n Of the 34 patients treated with alfuzosin SR, 17 (50%) resumed voiding and of the 28 patients from placebo group, 16 (57%) voided successfully. All 33 patients were continued open labelled on alfuzosin SR 5mg BD. Out of 33 patients, 13 (43%) had TURP within first year after TWOC and three died due to various medical causes. Out of remaining 17 patients, 15 attended for follow-up. The mean peak flow rate was 8.4 ml/s and the mean residual volume was 112 ml. Six patients (40%) required TURP for severe lower urinary tract symptoms (LUTS). So out of 28 patients followed at 2 year, 19 (68%) had TURP.\n These data do not support the routine use of alpha-blockers in patients with acute urinary retention. Also continuing use of alpha-blockers does not seem to prevent further requirements of TURP, although larger studies are needed to support this.\n Copyright 2002 Elsevier Science B.V.", "To establish whether the administration of sustained-release (SR) alfuzosin improves the outcome of a trial without catheter (TWOC) after an episode of acute urinary retention.\n In a prospective, randomized, placebo-controlled trial, 81 patients with acute urinary retention related to benign prostatic obstruction received either SR alfuzosin (n=40), an alpha1-selective blocker, given at a dose of 5 mg twice daily, or placebo (n=41) for 48 h. The catheter was removed after 24 h of treatment. The main outcome measurement was success or failure of the TWOC. At the end of this double-blind phase the patients were followed up on an open basis.\n After removal of the catheter, 42% of patients voided successfully, 22 of 40 (55%) with SR alfuzosin and 12 of 41 (29%) with placebo (P=0.03). The mean age of patients voiding successfully, regardless of treatment group, was 68. 4 years, whilst the mean age of those who were not successful was 72. 9 years (P=0.015). In an intention-to-treat analysis of outcome adjusted for this age difference, the benefit in favour of those receiving SR alfuzosin was not significant, but at P=0.052 there was a strong suggestion of a positive treatment effect. The observed benefit remained significant in a per-protocol analysis adjusted for age. Taken together, these results indicate that treatment with SR alfuzosin was effective and that the observed benefit was not simply the effect of age difference between the groups. Of the 34 patients who voided successfully 23 (68%) required no further intervention within a mean follow-up of 7 months.\n Treatment with SR alfuzosin is effective in improving the success rate of a TWOC after an episode of acute urinary retention, although older patients are less likely to void successfully. By reducing the numbers of men sent home with urinary catheters, such treatment may result in a reduction in the associated perioperative morbidity in those undergoing prostatic surgery, and is clearly desirable for the patients' comfort and convenience.", "To calculate the economic consequences of using alfuzosin 10 mg once daily for managing acute urinary retention (AUR) related to benign prostatic hyperplasia (BPH).\n We examined whether alfuzosin use during hospitalization for AUR and for 6 months after a successful trial without catheter (TWOC) is cost effective compared to placebo and immediate prostatectomy, from the perspective of patients managed in the National Health Service (NHS) in the UK. A decision-analysis model was developed to estimate the costs of various treatment options within the first 6 months after a first episode of AUR. Clinical data were obtained from a large randomized clinical trial comparing alfuzosin 10 mg with placebo, and from published reports. Cost data were obtained from both NHS and resource-use data gathered during the clinical trial. A Monte Carlo analysis, allowing variability in all uncertain variables of the model, was used to calculate the uncertainty surrounding the results.\n Treating patients with alfuzosin during initial hospitalization for AUR and in the first 6 months after a successful TWOC generates a cost-saving of pounds 349 relative to placebo. Savings related to immediate prostatectomy were pounds 892; both savings were significant (P < 0.05). Alfuzosin treatment was associated with a lower rate of prostatectomy after discharge from hospital after a successful TWOC.\n Treatment with alfuzosin 10 mg once daily before and after a successful TWOC has both clinical and economic benefits. It decreases the need for emergency surgery for BPH and reduces treatment costs in the first 6 months." ]

[ "11487673", "9354709" ]

[ "Randomized study to compare PTA alone versus PTA with Palmaz stent placement for femoropopliteal lesions.", "Balloon angioplasty combined with primary stenting versus balloon angioplasty alone in femoropopliteal obstructions: A comparative randomized study." ]

[ "The purpose of this study was to evaluate whether percutaneous transluminal angioplasty (PTA) combined with Palmaz stent placement provides long-term advantages compared to PTA alone after 34 months of follow-up in the femoropopliteal region.\n Thirty patients randomized to undergo PTA in combination with stent placement and 23 patients randomized to undergo PTA alone were evaluated.\n Mean follow-up (+/-SD) for the PTA group was 33.8 months (+/- 8.7) and for the Palmaz group 29.1 months (+/- 6.2), with a maximum follow-up period of 39 months for both groups. No significant differences in primary or secondary patency rates could be observed at 12 or 39 months. After 39 months, the primary patency rate for PTA alone was 68.4% and the secondary patency rate was 89.5%; the primary patency rate for PTA with stent placement was 62% and the secondary patency rate was 90%.\n The results of this study show that even after a long-term follow up of more than 3 years, PTA with stent placement in the femoropopliteal artery does not produce better results than PTA alone, although it does provide better initial luminal gain after the procedure.", "To evaluate whether balloon angioplasty combined with stenting (ST) of symptomatic femoropopliteal disease would provide better results compared with balloon angioplasty alone (BA).\n Fifty-one patients were randomized between ST (24 patients) and BA (27 patients). Follow-up comprised clinical and hemodynamic assessment and color-flow duplex ultrasound examinations.\n Residual stenosis (> or = 30% diameter reduction) occurred in three BA patients, but not in the ST patients. By life-table analysis the cumulative rate of clinical and hemodynamic success after 1 year with ST was 74% (SE 9%) and for those with BA 85% (SE 7%) (p = 0.25). The primary patency at 1 year assessed by color-flow duplex ultrasound was 62% (SE 9%) for ST-treated patients and 74% (SE 8%) for BA patients (p = 0.22). Occlusion occurred in five ST patients (21%) compared with two BA patients (7%).\n ST does not improve clinical and hemodynamic outcome compared with BA. Moreover, the occlusion rate in ST-treated patients is higher." ]

[ "3770281" ]

[ "Buphenine and threatened abortion." ]

[ "One hundred and seventy patients with threatened abortion have been studied in two groups. Group 1 of eighty-five patients were treated with the uterine muscle relaxant, buphenine hydrochloride. The second group of eighty-five patients were given placebo. Pregnancy continuation was 90.6% in group 1 and 62.3% in group 2. Only three of 22 patients with history of recurrent abortion using buphenine aborted." ]

[ "5574690", "10671705", "12690593", "10868718", "4066178" ]

[ "Perceptual training in patients with left hemiplegia.", "Comparison of remedial and compensatory interventions for adults with acquired brain injuries.", "Effectiveness of a visual attention retraining program on the driving performance of clients with stroke.", "A comparison of two approaches in the treatment of perceptual problems after stroke.", "An evaluation of perceptual retraining." ]

[ "nan", "To examine the effects of a compensatory intervention versus a remedial intervention for deficits in visual processing of adults with acquired brain injuries (ABI).\n A cognitive rehabilitation program at a large comprehensive rehabilitation hospital in the New York City metropolitan area.\n Thirty adults with ABI were matched according to severity of injury, gender, age, and time post-injury, and randomly assigned to the remedial or compensatory group.\n The remedial intervention consisted of four 45-minute sessions (once weekly) of participation in computer tasks without instruction in compensatory strategies. The compensatory intervention consisted of four 45-minute sessions of instruction in the use of three internal compensatory strategies, including verbalization, chunking, and pacing.\n Pretest/posttest measures included three functional computer tasks. Weekly measures included a computerized version of the Paced Auditory Serial Addition Task (PASAT) and two computerized matching tasks.\n Both groups exhibited statistically significant improvement of comparable degree on posttests and weekly measures. Further analysis revealed that 80% of both groups used compensatory strategies, regardless of intervention method. Those who used strategies demonstrated better performance than those who did not.\n The ability to use internal compensatory strategies may be a significant confound in research examining the effects of the various cognitive rehabilitation intervention methods.", "To compare the effectiveness of a visual attention retraining program using the Useful Field of View (UFOV) with a traditional visuoperception treatment program on the driving performance of clients with stroke.\n Randomized controlled trial.\n Rehabilitation hospital located in Quebec, Canada.\n Ninety-seven individuals referred for driving evaluation after a stroke.\n Participants were randomized to receive 20 sessions of either UFOV training of visual processing speed, divided attention, and selective attention or traditional computerized visuoperception retraining.\n Subjects were evaluated with an on-road driving evaluation, visuoperception tests, and the Test of Everyday Attention. An occupational therapist unaware of group assignment conducted all evaluations.\n Eighty-four participants completed the outcome evaluation. There were no significant differences between groups on any of the outcome measures. There was, however, almost a 2-fold increase (52.4% vs 28.6%) in the rate of success on the on-road driving evaluation after UFOV training for subjects with right-sided lesions.\n Rehabilitation that targets visual attention skills was not significantly more beneficial than traditional perceptual training in improving the outcome of an on-road driving evaluation. However, results suggest a potential improvement for subjects with right-sided lesions, indicating that training must target specific skills.", "To compare the effectiveness of the transfer of training and functional approaches in improving perceptual and functional abilities after stroke.\n Patients identified as having perceptual problems were randomly allocated to either the transfer of training approach or the functional approach for perceptual treatment. On completion of six weeks of treatment, each patient was reassessed for perceptual and functional abilities.\n Eighty inpatients on the Nottingham Stroke Unit.\n Perceptual treatment was given for 2.5 hours per week for six weeks.\n Rivermead Perceptual Assessment Battery, Barthel ADL Index and Edmans ADL index.\n There was no significant difference between the treatment groups on patient characteristics or impairments. The results also showed no significant difference between the treatment groups before and after treatment on perceptual ability total scores, individual perceptual subtest scores, or functional ability total scores (Mann-Whitney U 642.5-798.0, p > 0.05). Wilcoxon matched pairs signed ranks tests showed a significant improvement in both groups after treatment on perceptual and functional abilities (perceptual z = 6.02, p < 0.001, functional z = 6.72, p < 0.001).\n These results indicated that the improvement in perceptual abilities was equivalent using either of the two approaches. This could be due to spontaneous recovery or the effects of the Stroke Unit.", "A group of head injury and stroke patients with impairment of visual perception were randomly allocated to receive either perceptual retraining or conventional occupational therapy. No significant differences were found between the groups, either before or after 4 weeks of treatment, on measures of visual perception or on activities of daily living scale." ]

[ "4865295", "15602113", "7868850", "9347380", "1599987" ]

[ "A double-blind trial of amitriptyline/perphenazine, perphenazine and placebo in chronic withdrawn inert schizophrenics.", "Negative symptoms of schizophrenia are improved by the addition of paroxetine to neuroleptics: a double-blind placebo-controlled study.", "Adjunctive fluoxetine in the treatment of negative symptoms in chronic schizophrenic patients.", "Benefits of trazodone and mianserin for patients with late-life chronic schizophrenia and tardive dyskinesia: an add-on, double-blind, placebo-controlled study.", "Fluvoxamine improves negative symptoms in treated chronic schizophrenia: an add-on double-blind, placebo-controlled study." ]

[ "nan", "Despite the availability of atypical antipsychotics, the treatment of negative symptoms in schizophrenia remains a challenge. This study was designed to confirm the positive effect observed in our pilot study with paroxetine as augmentation to antipsychotics in the treatment of negative symptoms in chronic schizophrenia. Twenty-nine patients with chronic schizophrenia, as defined by DSM-IV, who scored at least 20 points on the negative subscale of the Positive and Negative Syndrome Scale (PANSS) were randomized for treatment with 30 mg paroxetine or placebo in a double-blind, placebo-controlled study for 12 weeks. Ratings included the PANSS, the Hamilton Rating Scale for Depression (HAM-D) and scales for extrapyramidal side-effects. An intention-to-treat analysis was based on the 25 patients who were available for at least one follow-up assessment. The last observation carried forward principle was applied. The mean score of the negative subscale of the PANSS decreased in both groups. Using an analysis of covariance, there was a significant treatment effect with paroxetine compared to placebo with respect to negative symptoms (-4.53; 95% confidence interval -9.054 to -0.015). The mean HAM-D scores remained almost constant. The study suggests the efficacy of paroxetine with respect to the treatment of negative symptoms in chronic schizophrenia.", "The effect of adjunctive fluoxetine on negative schizophrenic symptoms was evaluated in 34 chronic schizophrenic in-patients on maintenance therapy with neuroleptics. They received randomly, on a double-blind basis, fluoxetine (20 mg/day) or placebo for 12 weeks. In the fluoxetine group, three patients dropped out because of side effects. Negative symptoms, as measured by change on the Scale for Assessment of Negative Symptoms at the end point compared to baseline values, were significantly improved in fluoxetine-treated patients (p < 0.001), but not in the placebo group. Fluoxetine treatment did not influence positive schizophrenic symptoms, while it induced a slight, but statistically significant, decrease (p < 0.05) in depressive symptoms, as measured by the Hamilton Rating Scale for Depression. Unwanted effects were more common among patients receiving fluoxetine. These data suggest that the addition of fluoxetine to neuroleptic treatment may be beneficial in some schizophrenic patients with negative symptoms.", "The objective of the present study was to evaluate the efficacy of mianserin and trazodone as antidepressants with serotonin 2 antagonist properties on negative symptoms and tardive dyskinesia in elderly patients with chronic schizophrenia. In this double-blind, placebo-controlled study the dose of each drug was increased gradually, from 20 mg/day mianserin to 60 mg/day, and from 50 mg/day trazodone to 200 mg/day. Symptoms were assessed using the Brief Psychiatric Rating Scale, the Scale for Assessment of Negative Symptoms and the Abnormal Involuntary Movement Scale every week for 5 weeks. A total of 38 patients (23 men and 15 women) completed the trial. Mianserin (n = 13) and trazodone (n = 12) did not alter the Brief Psychiatric Rating Scale positive symptom factor over the 5 weeks. In the mianserin group, the Scale for Assessment of Negative Symptoms total score decreased significantly after 5 weeks. Scores of 'affective flattening and blunting' and 'alogia' scores on the Scale for assessment of Negative Symptoms decreased significantly in both treatment groups. In the trazodone group, the decrease in the Abnormal Involuntary Movement Scale total score was statistically significant at weeks 2 and 3. Results indicate that serotonergic antidepressants, when used in conjunction with neuroleptics, are safe and effective for treating negative symptoms in elderly patients with chronic schizophrenia. Results also indicated a possible beneficial effect of trazodone in treating tardive dyskinesia.", "nan" ]

[ "3475429", "1921255", "2476604", "3300841", "3570421" ]

[ "Australian National Health and Medical Research Council dietary salt study in mild hypertension.", "The influence of oral potassium citrate/bicarbonate on blood pressure in essential hypertension during unrestricted salt intake.", "Placebo-controlled trial of potassium supplements in black patients with mild essential hypertension.", "Controlled trial of long term oral potassium supplements in patients with mild hypertension.", "Double-blind, placebo-controlled trial of potassium chloride in the treatment of mild hypertension." ]

[ "Two-hundred-and-twelve untreated subjects (mean age 52.3 +/- 0.8 years; 181 males and 31 females) with a diastolic blood pressure between 90 and 100 mmHg were recruited to the study. Subjects were seen fortnightly and, after 4 pre-diet visits, were randomized into a normal diet group (A, 55 subjects), a high-potassium diet group (B, 52 subjects receiving greater than 100 mmol K+/day) a reduced-sodium diet group (C, 52 subjects receiving 50-75 mmol Na+/day) or a high-potassium and low-sodium diet group (D, 53 subjects receiving same Na+ and K+ as groups B and C). Two-hundred subjects completed the diet phase of 12 weeks. Urine sodium fell to 86 +/- 7 mmol/day in group C and 73 +/- 6 mmol/day in group D, while daily potassium excretion rose to 96 +/- 5 mmol in group B and 87 +/- 4 mmol in group C. Systolic and diastolic blood pressure fell by 3.8 +/- 1.0 and 1.6 +/- 0.6 mmHg respectively in the normal diet group. The falls in systolic and diastolic blood pressures (mmHg) in the diet phase were 7.7 +/- 1.1 and 4.7 +/- 0.7 (B), 8.9 +/- 1.0 and 5.8 +/- 0.6 (C) and 7.9 +/- 0.9 and 4.2 +/- 0.7 (D). These falls were all greater than those in the control group on an intention-to-treat analysis (P less than 0.005) but did not differ from each other. Factorial analysis confirmed that the falls in pressure attributable to the low-sodium diet and high-potassium diet were not additive.(ABSTRACT TRUNCATED AT 250 WORDS)", "In several trials, a blood pressure lowering effect of potassium chloride could be demonstrated. However, it is not known if other potassium salts are also effective. In a randomized cross-over trial, 12 patients with essential hypertension were treated for 8 weeks with placebo and 120 mmol potassium per day. Potassium was given together with 50% citrate and 50% bicarbonate as anions. Urinary potassium excretion rose from 61.8 +/- 8.1 to 166.7 +/- 21.2 mmol/24 hours during potassium supplementation. However, blood pressure and heart rate remained unchanged when compared to placebo. Non-chloride potassium salts may not be effective in lowering blood pressure in essential hypertension. Since potassium rich foods like fruits and vegetables contain potassium mostly as non-chloride salts, it appears to be premature to recommend a high dietary potassium intake as a mean to treat elevated blood pressure.", "Forty-eight black patients with mildly increased blood pressure (BP) that had not yet been subjected to treatment took part in a double-blind clinical trial of the efficacy and tolerability of oral potassium supplements (64 mmol daily) versus a matching placebo (made of starch with coating) in a 16-week study. Potassium supplements produced a significant decrease in mean supine and standing BP within 4 weeks after treatment inception. Urinary potassium excretion increased significantly in the 24 patients who received potassium supplements (p less than 0.001). No significant changes occurred in plasma sodium and potassium concentrations or in urinary excretion of sodium during the study. All patients completed the trial without experiencing any notable untoward effects. These results are consistent with the premise that oral potassium supplements may exert hypotensive effects of clinically significant degree in patients with mild hypertension.", "A 15 week randomised double blind placebo controlled trial of oral potassium supplements (48 mmol daily) was conducted in 37 patients who had mildly increased blood pressure and a normal dietary intake of sodium. After a two month run in and a one week baseline period the patients were randomly assigned to receive either potassium supplements (n = 18) or placebo (n = 19). By the third week of treatment blood pressure in the actively treated group had decreased significantly compared with that in the placebo group, though the decrease reached its maximum after 15 weeks. Urinary potassium excretion increased significantly in the group who received potassium supplements, but no significant changes were found in plasma sodium and potassium concentrations or in urinary sodium excretion. In a subgroup of 13 patients who underwent a further nine weeks of treatment with oral potassium supplements at half of the previous dose (24 mmol daily) their blood pressure, at the end of this second study period, was still significantly lower compared with their baseline value but not with that of the placebo group. These results show that moderate oral potassium supplements are associated with a long term reduction in blood pressure in patients who have mild hypertension.", "Epidemiological and experimental data suggest blood pressure-lowering effects of dietary potassium. A randomized, double-blind clinical trial was used to assess blood pressure response to orally administered potassium, 120 mEq/day, and to placebo in 101 adults with mild hypertension. Blood pressure was measured with a random-zero sphygmomanometer every 2 weeks of this 8-week trial. Systolic blood pressure in the potassium-treated group decreased by 6.4 +/- 13.7 (SD) mm Hg (p less than or equal to 0.025) compared with 0.11 +/- 13.0 mm Hg in the placebo-treated group (p = 0.96). Diastolic blood pressure in the potassium-treated group decreased by 4.1 +/- 8.3 mm Hg (p less than or equal to 0.05) compared with a 1.6 +/- 6.5 mm Hg decrease in placebo-treated subjects (p = 0.09). Baseline blood pressure of potassium-treated subjects was unexpectedly higher than that of controls. After correcting for baseline variation, blood pressure still decreased 3.4/1.8 mm Hg more in potassium recipients than in placebo recipients (p = 0.14 and 0.24, respectively). Blood pressure decreased by 19/13 mm Hg in five blacks taking potassium versus a 1/0 mm Hg increase in seven blacks taking placebo. Compliance with the potassium regimen was 91.5% by pill count; only one subject discontinued treatment because of side effects. In conclusion, 120 mEq/day of microencapsulated potassium chloride was well tolerated in adults with mild hypertension. An antihypertensive effect of potassium cannot be ruled out despite the fact that there was no statistically significant difference between potassium-treated and placebo-treated subjects after adjustment for differences in baseline blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)" ]

[ "16020076", "17655565" ]

[ "Effects of exercise on mental and physical health parameters of persons with schizophrenia.", "Yoga therapy as an add-on treatment in the management of patients with schizophrenia--a randomized controlled trial." ]

[ "Although the benefits of exercise are well documented, few published research studies have examined exercise in persons with schizophrenia. This pilot examined a 16-week walking program for outpatients diagnosed with schizophrenia (N = 10). Six-minute walking distance, body mass index, percent body fat and severity of psychiatric symptoms were measured. Experimental participants in the walking group experienced significant reductions in body fat (p = 0.03) compared to a control group not participating in the exercises during the same time period. Experimental participants also had greater aerobic fitness, lower body mass indexes, and fewer psychiatric symptoms than controls at the conclusion of the program. Research is needed to identify effective exercise interventions and feasible delivery modalities for persons with schizophrenia in community settings.", "Treatment of schizophrenia has remained unsatisfactory despite the availability of antipsychotics. This study examined the efficacy of yoga therapy (YT) as an add-on treatment to the ongoing antipsychotic treatment.\n Sixty-one moderately ill schizophrenia patients were randomly assigned to YT (n = 31) and physical exercise therapy (PT; n = 30) for 4 months. They were assessed at baseline and 4 months after the start of intervention, by a rater who was blind to their group status.\n Forty-one subjects (YT = 21; PT = 20) were available at the end of 4 months for assessment. Subjects in the YT group had significantly less psychopathology than those in the PT group at the end of 4 months. They also had significantly greater social and occupational functioning and quality of life.\n Both non-pharmacological interventions contribute to reduction in symptoms, with YT having better efficacy." ]

[ "6154024", "8160096", "15364138", "14701778", "16757720", "18091051", "11249050", "18164847", "10487566", "12829672", "9336134", "18555546", "19801201", "15158627", "19127261", "11013281", "12569292", "7673021", "6174490", "19836153", "2994386", "16446056", "21041710", "1993631", "6397578", "6171553", "1997887", "8934050", "18459180" ]

[ "The palliation of brain metastases: final results of the first two studies by the Radiation Therapy Oncology Group.", "Radiation therapy for brain metastases from lung carcinoma. Prospective randomized trial according to the level of lactate dehydrogenase.", "A randomised phase III study of palliative radiation with concomitant carboplatin for brain metastases from non-small cell carcinoma of the lung.", "Neurocognitive function and progression in patients with brain metastases treated with whole-brain radiation and motexafin gadolinium: results of a randomized phase III trial.", "Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial.", "Improved survival, quality of life, and quality-adjusted survival in breast cancer patients treated with efaproxiral (Efaproxyn) plus whole-brain radiation therapy for brain metastases.", "Results of a phase III study of early versus delayed whole brain radiotherapy with concurrent cisplatin and vinorelbine combination in inoperable brain metastasis of non-small-cell lung cancer: Groupe Français de Pneumo-Cancérologie (GFPC) Protocol 95-1.", "A phase III study of conventional radiation therapy plus thalidomide versus conventional radiation therapy for multiple brain metastases (RTOG 0118).", "Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases.", "Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and whole-brain radiation therapy in brain metastases.", "A randomized phase III study of accelerated hyperfractionation versus standard in patients with unresected brain metastases: a report of the Radiation Therapy Oncology Group (RTOG) 9104.", "A phase III study of accelerated versus conventional hypofractionated whole brain irradiation in patients of good performance status with brain metastases not suitable for surgical excision.", "Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial.", "Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial.", "A phase III trial of topotecan and whole brain radiation therapy for patients with CNS-metastases due to lung cancer.", "Treatment of brain metastases of small-cell lung cancer: comparing teniposide and teniposide with whole-brain radiotherapy--a phase III study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group.", "A prospective randomized multicentre phase III trial of fotemustine plus whole brain irradiation versus fotemustine alone in cerebral metastases of malignant melanoma.", "Results of a randomized comparison of radiotherapy and bromodeoxyuridine with radiotherapy alone for brain metastases: report of RTOG trial 89-05.", "Ultra-rapid high dose irradiation schedules for the palliation of brain metastases: final results of the first two studies by the Radiation Therapy Oncology Group.", "Randomized comparison of whole brain radiotherapy, 20 Gy in four daily fractions versus 40 Gy in 20 twice-daily fractions, for brain metastases.", "Whole brain irradiation for metastases from lung carcinoma. A clinical investigation.", "Whole-brain radiotherapy with or without efaproxiral for the treatment of brain metastases: Determinants of response and its prognostic value for subsequent survival.", "Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study.", "A randomized phase III protocol for the evaluation of misonidazole combined with radiation in the treatment of patients with brain metastases (RTOG-7916).", "Randomized trial of radiotherapy versus radiotherapy plus metronidazole for the treatment metastatic cancer to brain. A Southwest Oncology Group study.", "The palliation of brain metastases in a favorable patient population: a randomized clinical trial by the Radiation Therapy Oncology Group.", "Chemotherapy of brain metastases from lung carcinoma: a controlled randomized study.", "Final results of the Royal College of Radiologists' trial comparing two different radiotherapy schedules in the treatment of cerebral metastases.", "Primary chemotherapy for newly diagnosed nonsmall cell lung cancer patients with synchronous brain metastases compared with whole-brain radiotherapy administered first : result of a randomized pilot study." ]

[ "nan", "Since September 1980 we have been conducting a prospective randomized trial to determine the best treatment schedule for radiation therapy (XRT) on brain metastasis from lung carcinoma. The first trial (September 1980 to December 1984) was randomly allocated by two different time-dose radiotherapy schemes, i.e., 30 Gy/ten fractions/two weeks versus 50 Gy/20 fractions/four weeks. Treatment results showed no significant difference in neurological improvement and survival between the two arms and lactate dehydrogenase (LDH) as the most important prognostic factor. The present study (January 1985 to April 1992) examines two sequential trials stratified by the level of LDH enrolled 162 patients with brain metastasis from lung carcinoma.\n Whole brain dose was selected for 30 Gy/ten fractions/two weeks (group A, n = 46) or 50 Gy/20 fractions/four weeks (group B, n = 46) in the group with normal LDH and 30 Gy/ten fractions/two weeks (group C, n = 35) or 20 Gy/five fractions/one week (group D, n = 35) in the group with high LDH, while the treatment fields were shrunk at 30 Gy in group B if possible.\n The final results showed the facts that 1. the most important prognostic factor, according to Cox's multivariate analysis, was also the level of LDH in the second trial, 2. the incidence of acute side effects showed the trend toward depending upon a single dose, i.e., group A (3 Gy/fraction); 35% versus group B (2.5 Gy/fraction); 21% (p = 0.165) and group C (3 Gy/fraction); 23% versus group D (4 Gy/fraction); 45% (p = 0.044), 3. median survival time and one-year survival rates were 5.4 months and 21% in group A; 4.8 months and 17% in group B; 3.4 months and 6% in group C; and 2.4 months and 4% in group D, respectively, and survival curves showed no statistically significant difference between the two treatment groups in each LDH group, 4. improvement in neurologic function appeared to increase with total dosage escalation, i.e., 41% in group A versus 45% in group B and 35% in group C versus 21% in group D (p = 0.13).\n A short course (30 Gy/ten fractions/two weeks) is an advantageous XRT because of the short treatment time for normal LDH and neurological improvement and minor toxicity for the high LDH group, while an optional treatment may be necessary for the selected patients.", "To determine if the addition of carboplatin chemotherapy to whole brain irradiation improves response and survival in patients with brain metastases from non-small cell lung cancer (NSCLC).\n Forty-two patients with brain metastases from NSCLC and performance status ECOG 0-2 were randomised to receive either whole brain radiotherapy (WBRT) alone (20Gy in five fractions) or the same radiotherapy plus concomitant carboplatin (70 mg/m(2) intravenously for 5 days).\n The median survival was 4.4 months in the radiotherapy alone (RT) arm and 3.7 months in the combined treatment (RTC) arm (P = 0.64). The objective response rates of 10% on the RT arm and 29% on the RTC arm were not significantly different (P = 0.24). The trial was closed early because of poor accrual.\n Although no firm conclusions can be made regarding the efficacy of the combined treatment, this prospective study highlights the poor objective response rates and relatively poor symptom control despite standard treatment of brain metastases from NSCLC.", "To report the neurocognitive findings in a phase III randomized trial evaluating survival and neurologic and neurocognitive function in patients with brain metastases from solid tumors receiving whole-brain radiation therapy (WBRT) with or without motexafin gadolinium (MGd).\n Patients were randomly assigned to receive WBRT 30 Gy in 10 fractions with or without MGd 5 mg/kg/d. Monthly neurocognitive testing for memory, executive function, and fine motor skill was performed.\n Four hundred one patients were enrolled (251 with non-small-cell lung cancer, 75 with breast cancer, and 75 with other cancers); 90.5% patients had impairment of one or more neurocognitive tests at baseline. Neurocognitive test scores of memory, fine motor speed, executive function, and global neurocognitive impairment at baseline were correlated with brain tumor volume and predictive of survival. There was no statistically significant difference between treatment arms in time to neurocognitive progression. Patients with lung cancer (but not other types of cancer) who were treated with MGd tended to have improved memory and executive function (P =.062) and improved neurologic function as assessed by a blinded events review committee (P =.048).\n Neurocognitive tests are a relatively sensitive measure of brain functioning; a combination of tumor prognostic variables and brain function assessments seems to predict survival better than tumor variables alone. Although the addition of MGd to WBRT did not produce a significant overall improvement between treatment arms, MGd may improve memory and executive function and prolong time to neurocognitive and neurologic progression in patients with brain metastases from lung cancer.", "In patients with brain metastases, it is unclear whether adding up-front whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) has beneficial effects on mortality or neurologic function compared with SRS alone.\n To determine if WBRT combined with SRS results in improvements in survival, brain tumor control, functional preservation rate, and frequency of neurologic death.\n Randomized controlled trial of 132 patients with 1 to 4 brain metastases, each less than 3 cm in diameter, enrolled at 11 hospitals in Japan between October 1999 and December 2003.\n Patients were randomly assigned to receive WBRT plus SRS (65 patients) or SRS alone (67 patients).\n The primary end point was overall survival; secondary end points were brain tumor recurrence, salvage brain treatment, functional preservation, toxic effects of radiation, and cause of death.\n The median survival time and the 1-year actuarial survival rate were 7.5 months and 38.5% (95% confidence interval, 26.7%-50.3%) in the WBRT + SRS group and 8.0 months and 28.4% (95% confidence interval, 17.6%-39.2%) for SRS alone (P = .42). The 12-month brain tumor recurrence rate was 46.8% in the WBRT + SRS group and 76.4% for SRS alone group (P<.001). Salvage brain treatment was less frequently required in the WBRT + SRS group (n = 10) than with SRS alone (n = 29) (P<.001). Death was attributed to neurologic causes in 22.8% of patients in the WBRT + SRS group and in 19.3% of those treated with SRS alone (P = .64). There were no significant differences in systemic and neurologic functional preservation and toxic effects of radiation.\n Compared with SRS alone, the use of WBRT plus SRS did not improve survival for patients with 1 to 4 brain metastases, but intracranial relapse occurred considerably more frequently in those who did not receive WBRT. Consequently, salvage treatment is frequently required when up-front WBRT is not used.\n umin.ac.jp/ctr Identifier: C000000412.", "To determine whether efaproxiral, an allosteric modifier of hemoglobin, improves quality of life and quality of survival in patients with primary breast cancer and brain metastases when used as an adjunct to whole-brain radiation therapy (WBRT).\n Patients with brain metastases from breast cancer were randomly assigned to receive WBRT and either efaproxiral or no efaproxiral. The primary endpoint for this analysis was quality of life and quality-adjusted survival. Quality of life was assessed prior to initiation of WBRT and periodically in follow-up using the Spitzer Quality of Life Index (SQLI).\n A subgroup of 106 eligible breast cancer patients with baseline SQLI were randomized into this study and represent the target population discussed in this report. Treatment, age, and SQLI were significant predictors of survival. The addition of efaproxiral to WBRT reduced the death rate by 46% (P = 0.0086). Quality of life was improved in the WBRT + efaproxiral arm compared with the WBRT alone arm (P = 0.019). Quality-adjusted survival was statistically significantly improved by the addition of efaproxiral to WBRT (P = 0.001).\n Survival, quality of life, and quality-adjusted survival were all improved in breast cancer patients with brain metastases receiving efaproxiral and WBRT compared with those receiving WBRT alone.", "To determine if the timing of whole brain radiotherapy (WBRT) with respect to chemotherapy with cisplatin and vinorelbine would influence survival in patients with non-small-cell lung cancer (NSCLC) and concurrent brain metastasis.\n One hundred seventy-six patients with brain metastasis from NSCLC were included in the study between July 1995 and October 1997. All patients received chemotherapy with cisplatin 100 mg/m2 on day 1 and vinorelbine 30 mg/m2 on days 1, 8, 15, 22. Cycles were repeated every four weeks. Evaluation of response was performed after two, four or six cycles. After two cycles, chemotherapy was administered to the responders to a maximum of six cycles. Patients were randomised to receive WBRT 30 Gy/10 fx/12 days and delayed corticosteroids. (arm A) for the intracranial nonresponders, or early on day 1 to 12 during the first cycle of chemotherapy (arm B).\n One hundred seventy-one patients were eligible: eighty-six in arm A and eighty-five in arm B; none had received prior chemotherapy; seventy-six and seventy-three, respectively, were assessable for response. There was a 21% overall objective response rate (OR) (with 1 complete response and 17 partial responses) after two cycles of chemotherapy alone (arm A) and a 20% OR (with 17 partial responses) to chemotherapy and early WBRT (arm B). The intracranial OR was 27% and 33%, respectively (P = 0.12). The six months survival rate (46% and 40%) and the median survival duration (24 and 21 weeks, respectively) were not significantly different between the two arms (P = 0.83, log-rank test). The major toxicity was severe or life-threatening neutropenia (grade 4), which occurred in 35% of arm A patients and 36% of arm B patients. There were thirteen treatment-related deaths (six in arm A and seven in arm B). There was no difference between the arms for haematological and neuro-toxicities.\n These results confirm the efficacy of chemotherapy in brain metastases of NSCLC and suggest that the timing (early or delayed) of WBRT did not influence survival of NSCLC with brain metastasis treated with concurrent chemotherapy.", "To compare whole-brain radiation therapy (WBRT) with WBRT combined with thalidomide for patients with brain metastases not amenable to resection or radiosurgery.\n Patients with Zubrod performance status 0-1, MRI-documented multiple (>3), large (>4 cm), or midbrain brain metastases arising from a histopathologically confirmed extracranial primary tumor, and an anticipated survival of >8 weeks were randomized to receive WBRT to a dose of 37.5 Gy in 15 fractions with or without thalidomide during and after WBRT. Prerandomization stratification used Radiation Therapy Oncology Group (RTOG) Recursive Partitioning Analysis (RPA) Class and whether post-WBRT chemotherapy was planned. Endpoints included overall survival, progression-free survival, time to neurocognitive progression, the cause of death, toxicities, and quality of life. A protocol-planned interim analysis documented that the trial had an extremely low probability of ever showing a significant difference favoring the thalidomide arm given the results at the time of the analysis, and it was therefore closed on the basis of predefined statistical guidelines.\n Enrolled in the study were 332 patients. Of 183 accrued patients, 93 were randomized to receive WBRT alone and 90 to WBRT and thalidomide. Median survival was 3.9 months for both arms. No novel toxicities were seen, but thalidomide was not well tolerated in this population. Forty-eight percent of patients discontinued thalidomide because of side effects.\n Thalidomide provided no survival benefit for patients with multiple, large, or midbrain metastases when combined with WBRT; nearly half the patients discontinued thalidomide due to side effects.", "Multiple brain metastases are a common health problem, frequently diagnosed in patients with cancer. The prognosis, even after treatment with whole brain radiation therapy (WBRT), is poor with average expected survivals less than 6 months. Retrospective series of stereotactic radiosurgery have shown local control and survival benefits in case series of patients with solitary brain metastases. We hypothesized that radiosurgery plus WBRT would provide improved local brain tumor control over WBRT alone in patients with two to four brain metastases.\n Patients with two to four brain metastases (all < or =25 mm diameter and known primary tumor type) were randomized to initial brain tumor management with WBRT alone (30 Gy in 12 fractions) or WBRT plus radiosurgery. Extent of extracranial cancer, tumor diameters on MRI scan, and functional status were recorded before and after initial care.\n The study was stopped at an interim evaluation at 60% accrual. Twenty-seven patients were randomized (14 to WBRT alone and 13 to WBRT plus radiosurgery). The groups were well matched to age, sex, tumor type, number of tumors, and extent of extracranial disease. The rate of local failure at 1 year was 100% after WBRT alone but only 8% in patients who had boost radiosurgery. The median time to local failure was 6 months after WBRT alone (95% confidence interval [CI], 3.5-8.5) in comparison to 36 months (95% CI, 15.6-57) after WBRT plus radiosurgery (p = 0.0005). The median time to any brain failure was improved in the radiosurgery group (p = 0.002). Tumor control did not depend on histology (p = 0.85), number of initial brain metastases (p = 0.25), or extent of extracranial disease (p = 0.26). Patients who received WBRT alone lived a median of 7.5 months, while those who received WBRT plus radiosurgery lived 11 months (p = 0.22). Survival did not depend on histology or number of tumors, but was related to extent of extracranial disease (p = 0.02). There was no neurologic or systemic morbidity related to stereotactic radiosurgery.\n Combined WBRT and radiosurgery for patients with two to four brain metastases significantly improves control of brain disease. WBRT alone does not provide lasting and effective care for most patients.", "This phase III randomized trial evaluated survival as well as neurologic and neurocognitive function in patients with brain metastases from solid tumors receiving whole-brain radiation therapy (WBRT) with or without motexafin gadolinium (MGd).\n Patients were randomly assigned to 30 Gy of WBRT +/- 5 mg/kg/d MGd. Survival and time to neurologic progression determined by a blinded events review committee (ERC) were coprimary end points. Standardized investigator neurologic assessment and neurocognitive testing were evaluated.\n Four hundred one (251 non-small-cell lung cancer) patients were enrolled. There was no significant difference by treatment arm in survival (median, 5.2 months for MGd v 4.9 months for WBRT; P =.48) or time to neurologic progression (median, 9.5 months for MGd v 8.3 months for WBRT; P =.95). Treatment with MGd improved time to neurologic progression in patients with lung cancer (median, not reached for MGd v 7.4 months for WBRT; P =.048, unadjusted). By investigator, MGd improved time to neurologic progression in all patients (median, 4.3 months for MGd v 3.8 months for WBRT; P =.018) and in lung cancer patients (median, 5.5 months for MGd v 3.7 months for WBRT; P =.025). MGd improved neurocognitive function in lung cancer patients.\n The overall results did not demonstrate significant differences by treatment arm for survival and ERC time to neurologic progression. Investigator neurologic assessments demonstrated an MGd treatment benefit in all patients. In lung cancer patients, ERC- and investigator-determined time to neurologic progression demonstrated an MGd treatment benefit. MGd may improve time to neurologic and neurocognitive progression in lung cancer.", "To compare 1-year survival and acute toxicity rates between an accelerated hyperfractionated (AH) radiotherapy (1.6 Gy b.i.d.) to a total dose of 54.4 Gy vs. an accelerated fractionation (AF) of 30 Gy in 10 daily fractions in patients with unresected brain metastasis.\n The Radiation Therapy Oncology Group (RTOG) accrued 445 patients to a Phase III comparison of accelerated hyperfractionation vs. standard fractionation from 1991 through 1995. All patients had histologic proof of malignancy at the primary site. Brain metastasis were measurable by CT or MRI scan and all patients had a Karnofsky performance score (KPS) of at least 70 and a neurologic function classification of 1 or 2. For AH, 32 Gy in 20 fractions over 10 treatment days (1.6 Gy twice daily) was delivered to the whole brain. A boost of 22.4 Gy in 14 fractions was delivered to each lesion with a 2-cm margin.\n The average age in both groups was 60 years; nearly two-thirds of all patients had lung primaries. Of the 429 eligible and analyzable patients, the median survival time was 4.5 months in both arms. The 1-year survival rate was 19% in the AF arm vs. 16% in the AH arm. No difference in median or 1-year survival was observed among patients with solitary metastasis between treatment arms. Recursive partitioning analysis (RPA) classes have previously been identified and patients with a KPS of 70 or more, a controlled primary tumor, less than 65 years of age, and brain metastases only (RPA class I), had a 1-year survival of 35% in the AF arm vs. 25% in the AH arm (p = 0.95). In a multivariate model, only age, KPS, extent of metastatic disease (intracranial metastases only vs. intra- and extracranial metastases), and status of primary (controlled vs. uncontrolled) were statistically significant (at p < 0.05). Treatment assignment was not statistically significant. Overall Grade III or IV toxicity was equivalent in both arms, and one fatal toxicity at 44 days secondary to cerebral edema was seen in the AH arm.\n Although a previous RTOG Phase I/II report had suggested a potential benefit in patients with limited metastatic disease, a good Karnofsky performance status, or neurologic function when treated with an AH regimen, this randomized comparison could not demonstrate any improvement in survival when compared to a conventional regimen of 30 Gy in 10 fractions. Therefore, this accelerated hyperfractionated regimen to 54.4 Gy cannot be recommended for patients with intracranial metastatic disease.", "An accelerated prescription for whole brain irradiation (WBI) in the treatment of brain metastases has been reported to provide favourable survival in good performance status patients. Because it was not known whether this outcome represented patient selection or a radiobiologically advantageous regimen, a phase III study to compare overall survival following accelerated and conventional hypofractionated daily WBI was proposed.\n Ninety patients were randomized between 1996 and 2003 at two centres. The investigational arm received 40 Gy in 20 fractions of 2 Gy twice daily. The control arm received 20 Gy in 5 daily fractions. The study was designed to detect an increase in median survival of 1.75x. Outcome measures included acute side effects (WHO epilation score), neurological function (modified Barthel Index) and late toxicity (LENT/SOMA score for the CNS).\n Both arms of the study were balanced by RPA class. The median survival was 19 weeks in both arms. Subset analysis showed time to retreatment for intracranial relapse was 14 weeks in the control arm and 32 weeks in the accelerated arm (p=0.03). Trends for more severe epilation and improved neurological function in the accelerated arm did not reach statistical significance. Overall survival was associated with RPA class and colorectal pathology.\n Although accelerated WBI may improve local control this did not translate into improved overall survival in the patients studied.", "It is unclear whether the benefit of adding whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) for the control of brain-tumours outweighs the potential neurocognitive risks. We proposed that the learning and memory functions of patients who undergo SRS plus WBRT are worse than those of patients who undergo SRS alone. We did a randomised controlled trial to test our prediction.\n Patients with one to three newly diagnosed brain metastases were randomly assigned using a standard permutated block algorithm with random block sizes to SRS plus WBRT or SRS alone from Jan 2, 2001, to Sept 14, 2007. Patients were stratified by recursive partitioning analysis class, number of brain metastases, and radioresistant histology. The randomisation sequence was masked until assignation, at which point both clinicians and patients were made aware of the treatment allocation. The primary endpoint was neurocognitive function: objectively measured as a significant deterioration (5-point drop compared with baseline) in Hopkins Verbal Learning Test-Revised (HVLT-R) total recall at 4 months. An independent data monitoring committee monitored the trial using Bayesian statistical methods. Analysis was by intention-to-treat. This trial is registered at www.ClinicalTrials.gov, number NCT00548756.\n After 58 patients were recruited (n=30 in the SRS alone group, n=28 in the SRS plus WBRT group), the trial was stopped by the data monitoring committee according to early stopping rules on the basis that there was a high probability (96%) that patients randomly assigned to receive SRS plus WBRT were significantly more likely to show a decline in learning and memory function (mean posterior probability of decline 52%) at 4 months than patients assigned to receive SRS alone (mean posterior probability of decline 24%). At 4 months there were four deaths (13%) in the group that received SRS alone, and eight deaths (29%) in the group that received SRS plus WBRT. 73% of patients in the SRS plus WBRT group were free from CNS recurrence at 1 year, compared with 27% of patients who received SRS alone (p=0.0003). In the SRS plus WBRT group, one case of grade 3 toxicity (seizures, motor neuropathy, depressed level of consciousness) was attributed to radiation treatment. In the group that received SRS, one case of grade 3 toxicity (aphasia) was attributed to radiation treatment. Two cases of grade 4 toxicity in the group that received SRS alone were diagnosed as radiation necrosis.\n Patients treated with SRS plus WBRT were at a greater risk of a significant decline in learning and memory function by 4 months compared with the group that received SRS alone. Initial treatment with a combination of SRS and close clinical monitoring is recommended as the preferred treatment strategy to better preserve learning and memory in patients with newly diagnosed brain metastases.", "Brain metastases occur in up to 40% of all patients with systemic cancer. We aimed to assess whether stereotactic radiosurgery provided any therapeutic benefit in a randomised multi-institutional trial directed by the Radiation Therapy Oncology Group (RTOG).\n Patients with one to three newly diagnosed brain metastases were randomly allocated either whole brain radiation therapy (WBRT) or WBRT followed by stereotactic radiosurgery boost. Patients were stratified by number of metastases and status of extracranial disease. Primary outcome was survival; secondary outcomes were tumour response and local rates, overall intracranial recurrence rates, cause of death, and performance measurements.\n From January, 1996, to June, 2001, we enrolled 333 patients from 55 participating RTOG institutions--167 were assigned WBRT and stereotactic radiosurgery and 164 were allocated WBRT alone. Univariate analysis showed that there was a survival advantage in the WBRT and stereotactic radiosurgery group for patients with a single brain metastasis (median survival time 6.5 vs 4.9 months, p=0.0393). Patients in the stereotactic surgery group were more likely to have a stable or improved Karnofsky Performance Status (KPS) score at 6 months' follow-up than were patients allocated WBRT alone (43% vs 27%, respectively; p=0.03). By multivariate analysis, survival improved in patients with an RPA class 1 (p<0.0001) or a favourable histological status (p=0.0121).\n WBRT and stereotactic boost treatment improved functional autonomy (KPS) for all patients and survival for patients with a single unresectable brain metastasis. WBRT and stereotactic radiosurgery should, therefore, be standard treatment for patients with a single unresectable brain metastasis and considered for patients with two or three brain metastases.", "Brain metastases represent an important cause of morbidity in patients with lung cancer and are associated with a mean survival of less than 6 months. Thus, new regimens improving the outcome of these patients are urgently needed. On the basis of promising data raised in a phase I/II trial, we initiated an open, randomised, prospective, multicentric phase III trial, comparing whole brain radiation therapy (WBRT; 20 x 2 Gy) alone with WBRT+topotecan (RCT; 0.4 mg m(-2) day(-1) x 20). A total of 320 patients with CNS-metastases due to SCLC or NSCLC were projected. The primary end point was overall survival, whereas second end points were local response and progression-free survival. However, until the cutoff date of study completion (i.e., a study duration of 34 months), only a total of 96 (RCT:47, WBRT:49) patients had been recruited, and so an analysis was performed at that time point. Although the numbers of grade 3/4 non-haematological toxicities (besides alopecia 115 (RCT/WBRT: 55 out of 60) were evenly distributed, the 25 haematological events occurred mainly in the combined treatment arm (24 out of 1). Local response, evaluated 2 weeks after treatment, was assessable in 44 (RCT/WBRT: 23 out of 21) patients, showing CR in eight (3 out of 5), PR in 17 (11 out of 6), SD in 14 (8 out of 6) and PD in five (1 out of 4) patients (all differences n.s.). Neither OAS (RCT/WBRT: median (days)): 87 out of 95, range 3-752/4-433; HR 1.32; 95% CI (0.83; 2.10)) nor PFS (median (days)): 71 out of 66, range, 3-399/4-228; HR 1.28, 95% CI (0.73; 2.43) differed significantly. On the basis of these results and the slow recruitment, a continuation of the study did not seem reasonable. The available data show no significant advantage for concurrent radiochemotherapy for patients with lung cancer; however, the recruited number of patients is too low to exhibit a small advantage of combined treatment.", "Approximately 60% of patients with small-cell lung cancer (SCLC) develop brain metastases. Whole-brain radiotherapy (WBRT) gives symptomatic improvement in more than 50% of these patients. Because brain metastases are a sign of systemic progression, and chemotherapy was found to be effective as well, it becomes questionable whether WBRT is the only appropriate therapy in this situation.\n In a phase III study, SCLC patients with brain metastases were randomized to receive teniposide with or without WBRT. Teniposide 120 mg/m(2) was given intravenously three times a week, every 3 weeks. WBRT (10 fractions of 3 Gy) had to start within 3 weeks from the start of chemotherapy. Response was measured clinically and by computed tomography of the brain.\n One hundred twenty eligible patients were randomized. A 57% response rate was seen in the combined-modality arm (95% confidence interval [CI], 43% to 69%), and a 22% response rate was seen in the teniposide-alone arm (95% CI, 12% to 34%) (P<.001). Time to progression in the brain was longer in the combined-modality group (P=.005). Clinical response and response outside the brain were not different. The median survival time was 3.5 months in the combined-modality arm and 3.2 months in the teniposide-alone arm. Overall survival in both groups was not different (P=.087).\n Adding WBRT to teniposide results in a much higher response rate of brain metastases and in a longer time to progression of brain metastases than teniposide alone. Survival was poor in both groups and not significantly different.", "The main objective of this prospective multicentre randomized phase III study was to compare a combined regimen of fotemustine plus whole brain irradiation with fotemustine alone in terms of cerebral response and time to cerebral progression in patients with melanoma cerebral metastases. Seventy-six patients were randomized to receive either fotemustine (arm A, n = 39) or fotemustine plus whole brain irradiation (arm B, n = 37). Fotemustine was administered intravenously at 100 mg/m(2) on days 1, 8 and 15, followed by a 5 week rest period, then every 3 weeks in non-progressive patients. In arm B, concomitant whole brain irradiation was performed at a total dose of 37.5 Gy (2.5 Gy/day on days 1-5 for three consecutive weeks). Although patients who received fotemustine alone had worse prognostic factors, there was no significant difference in cerebral response (arm A, 7.4%, arm B, 10.0%) or control rates (objective responses plus stable disease) after 7 weeks (arm A, 30%; arm B, 47%) or in overall survival (arm A, 86 days; arm B, 105 days). However, there was a significant difference in favour of arm B for the time to cerebral progression (P = 0.028, Wilcoxon test). In conclusion, fotemustine plus whole brain irradiation delayed the time to cerebral progression of melanoma cerebral metastases compared with fotemustine alone but without a significant improvement in terms of objective control or overall survival.", "To determine if the addition of bromodeoxyuridine (BrdUrd) to radiotherapy prolongs survival when compared to radiotherapy alone in patients with brain metastases.\n Seventy-two patients with brain metastases were randomized to 37.5 Gy in 15 fractions of 2.5 Gy or to the same dose with BrdUrd 0.8 g/m2 per day for 4 days of each of 3 weeks. Drug treatment was begun on Thursday or Friday before the first week of radiotherapy. Patients had a Karnofsky performance score of at least 70, a neurological function classification of 1 or 2, and any primary tumor except central nervous system (CNS), leukemia, or lymphoma. The primary was absent, controlled, or under active radiotherapy. Patients were free of other metastases. They were stratified by primary site (breast, lung or other), number of metastases (single or multiple) and age (< 60 vs. > 60).\n There was no significant difference between the two treatment arms (p = 0.904). The study was open from October 1989 to March 1993 and accrued 72 patients. Only one patient in the RT only arm remains alive. The two treatment arms were balanced with respect to all stratification variables. Toxicity due to radiotherapy was similar in both arms. BrdUrd caused significant Grade 4 and 5 hematologic and skin toxicity in five patients. Two patients died due to hematologic toxicity and one from a Stevens-Johnson type skin reaction. Phenytoin played a role in the skin reactions and ranitidine was associated with the hematologic deaths. Ranitidine was eliminated, BrdUrd was discontinued after any hematologic toxicity, and no further Grade 4 or 5 toxicities were seen. The median survival was 6.12 months in the radiotherapy group and 4.3 in the BrdUrd group (p = 0.904). Patients with solitary brain metastases had significantly better survival (p = 0.031).\n BrdUrd did not enhance the efficacy of the radiotherapy regimen tested, in spite of the fact that brain metastases have shown high labeling indices. The toxicity of this schedule of BrdUrd administration was apparently increased by ranitidine and phenytoin.", "nan", "The present study compared the intracranial control rate and quality of life for two radiation fractionation schemes for cerebral metastases.\n A total of 113 patients with a Eastern Cooperative Oncology Group performance status <3; and stable (>2 months), absent, or concurrent presentation of extracranial disease were randomized to 40 Gy in 20 twice-daily fractions (Arm A) or 20 Gy in four daily fractions (Arm B), stratified by resection status. The European Organization for Research and Treatment of Cancer Quality of Life 30-item questionnaire was administered monthly during Year 1, bimonthly during Year 2, and then every 6 months to Year 5.\n The patient age range was 28-83 years (mean 62). Of the 113 patients, 41 had undergone surgical resection, and 74 patients had extracranial disease (31 concurrent and 43 stable). The median survival time was 6.1 months in Arm A and 6.6 months in Arm B, and the overall 5-year survival rate was 3.5%. Intracranial progression occurred in 44% of Arm A and 64% of Arm B patients (p = .03). Salvage surgery or radiotherapy was used in 4% of Arm A patients and 21% of Arm B patients (p = .004). Death was attributed to central nervous system progression in 32% of patients in Arm A and 52% of patients in Arm B (p = .03). The toxicity was minimal, with a minor increase in short-term cutaneous reactions in Arm A. The patients' quality of life was not impaired by the more intense treatment in Arm A.\n Intracranial disease control was improved and the quality of life was maintained with 40 Gy in 20 twice-daily fractions. This schema should be considered for better prognosis subgroups of patients with cerebral metastases.\n (c) 2010 Elsevier Inc. All rights reserved.", "Sixty-nine consecutive patients with brain metastases from lung carcinoma were randomly allocated to one of two radiation therapy schedules: 30 Gy/10 fractions/2 weeks or 50 Gy/20 fractions/4 weeks. The improvement rate for neurologic function was similar in the two groups. The median survival times for patients receiving the short course and the long course were 4 months and 3 months, respectively. The half-year survival rate was 42 per cent after the short course and 14 per cent after the long course (p less than 0.05). Performance status and lactate dehydrogenase were other factors which significantly influenced the half-year survival rate.", "To determine the prognostic factors for radiographic response and its prognostic value for subsequent survival in patients undergoing whole-brain radiotherapy (WBRT) for brain metastases.\n Five hundred fifteen eligible patients were randomized in a phase III trial evaluating WBRT and supplemental oxygen with or without efaproxiral, an allosteric modifier of hemoglobin that reduces hemoglobin oxygen-binding affinity and enhances tumor oxygenation, potentially increasing tumor radiosensitivity. Brain images were obtained at baseline and at scheduled follow-up visits after WBRT. Landmark analysis was used to assess the ability of response at selected time points to predict subsequent survival. Logistic regression was used to assess determinants of response at 3 months.\n Treatment arm, Karnofsky Performance Status, presence or absence of liver metastases, and primary site were all determinants of response at the 3-month follow-up visit, with patients in the efaproxiral arm experiencing a 67% greater odds of response at this visit (p = 0.02). Response at 3 and 6 months was a significant prognostic factor for longer subsequent survival.\n The 3-month scan is a valuable prognostic factor for subsequent survival in patients with brain metastases treated with WBRT. Patients in the efaproxiral arm had a higher response rate at 3 and 6 months than those in the control arm.", "This European Organisation for Research and Treatment of Cancer phase III trial assesses whether adjuvant whole-brain radiotherapy (WBRT) increases the duration of functional independence after surgery or radiosurgery of brain metastases.\n Patients with one to three brain metastases of solid tumors (small-cell lung cancer excluded) with stable systemic disease or asymptomatic primary tumors and WHO performance status (PS) of 0 to 2 were treated with complete surgery or radiosurgery and randomly assigned to adjuvant WBRT (30 Gy in 10 fractions) or observation (OBS). The primary end point was time to WHO PS deterioration to more than 2.\n Of 359 patients, 199 underwent radiosurgery, and 160 underwent surgery. In the radiosurgery group, 100 patients were allocated to OBS, and 99 were allocated to WBRT. After surgery, 79 patients were allocated to OBS, and 81 were allocated to adjuvant WBRT. The median time to WHO PS more than 2 was 10.0 months (95% CI, 8.1 to 11.7 months) after OBS and 9.5 months (95% CI, 7.8 to 11.9 months) after WBRT (P = .71). Overall survival was similar in the WBRT and OBS arms (median, 10.9 v 10.7 months, respectively; P = .89). WBRT reduced the 2-year relapse rate both at initial sites (surgery: 59% to 27%, P < .001; radiosurgery: 31% to 19%, P = .040) and at new sites (surgery: 42% to 23%, P = .008; radiosurgery: 48% to 33%, P = .023). Salvage therapies were used more frequently after OBS than after WBRT. Intracranial progression caused death in 78 (44%) of 179 patients in the OBS arm and in 50 (28%) of 180 patients in the WBRT arm.\n After radiosurgery or surgery of a limited number of brain metastases, adjuvant WBRT reduces intracranial relapses and neurologic deaths but fails to improve the duration of functional independence and overall survival.", "From 1979 through July 1983, 859 patients were enrolled in a Phase III RTOG Protocol (7916) evaluating the role of Misonidazole combined with radiation in the treatment of brain metastasis. Patients were randomized to one of four treatment arms (3.0 Gy x 10 fractions with or without 1 g/m2 of Misonidazole [total 10 g/m2] versus 5.0 Gy x 6 fractions with or without 2 g/m2 of Misonidazole) [total 12 g/m2]. Among the 779 analyzable cases, 63% had a lung primary and 12% had breast. Of the histologic types, 43% were adenocarcinoma and 24% were squamous cell. Seventy-eight percent had a Karnofsky of greater than 70. Of the 779 cases, 773 are dead (99%). Median survival is 3.9 months, with 60% alive at 3 months, 35% at 6 months, and 15% at 1 year. Survival was evaluated by treatment arm, Misonidazole status, and fractionation scheme; none showed any statistical significance. Favorable prognostic factors were assessed (age less than 60, Karnofsky of 70-100, controlled primary and brain metastasis only) in each treatment arm and no difference was found. Brain metastasis was cause of death in 1/3, and 19-33% of patients were retreated. Because up to 1/3 of the patients in this study died secondary to uncontrolled brain metastasis, improvement in local control remains an important goal. Until proven otherwise, the treatment of choice for the majority of patients still remains a conventional palliative course of 3.0 Gy x 10 fractions.", "One hundred sixteen eligible patients with metastatic cancer to the brain were randomized to receive either radiotherapy 3000 rad/10 fractions (treatment 1) or the same radiotherapy plus metronidazole 6 gm/m2 (treatment 2). One hundred eleven patients were either fully or partially evaluable. The response rates (CR + PR) and survival showed no significant differences between treatments. Treatment 1: CR + PR 24%, median survival 14 weeks, Treatment 2: CR + PR 27%, median survival 12 weeks. There were no differences observed in response rates based on primary tumor site, neurologic performance status, or extent of metastatic disease. Metronidazole therapy was associated with substantial nausea and vomiting but no neurotoxicity was observed. Oral metronidazole given every other day during radiation therapy provided no clinical benefit for patients with brain metastases compared to radiotherapy alone.", "nan", "A controlled randomized study was carried out to evaluate the effects of chemotherapy in patients with brain metastases from lung carcinoma. One hundred patients were randomly divided into three groups at the time of diagnosis or after surgery for metastases. Group A received radiotherapy alone; Group B received radiotherapy and chloroethylnitrosoureas (methyl-CCNU, 100-120 mg/m2, or ACNU 80-100 mg/m2, every 6-8 weeks), and Group C received radiotherapy and a combination of chloroethylnitrosoureas and tegafur (300 mg/m2, daily). Of the 100 patients, 88 could be evaluated. The reduction rates of the tumors of the patients in whom tumor was not surgically removed or not totally removed were compared. Complete resolution of the tumor was noted in 29, 69, and 63% of the patients in Groups A, B, and C, respectively. Tumor regression of greater than or equal to 50% was seen in 36, 69, and 74% of the patients in Groups A, B, and C, respectively. The difference in the response rates of Groups A and C was statistically significant (P less than 0.05). Median survival after the start of treatment for brain metastasis was 27, 30.5, and 29 weeks in Groups A, B and C, respectively. There was 1 long-term survivor (more than 5 years) in Group A, 3 in Group B, and 1 in Group C. The main cause of death was deterioration attributable to the primary lesion or systemic metastasis, and no statistical difference was noted in survival time among the groups.(ABSTRACT TRUNCATED AT 250 WORDS)", "Between February 1990 and February 1993, 25 centres in the UK recruited 544 patients into a prospective randomized trial comparing two whole-brain radiotherapy regimens (30 Gy in ten fractions over 2 weeks versus 12 Gy in two fractions on consecutive days) for the treatment of patients with symptomatic cerebral metastases. Of these patients 533 were eligible for analysis: 270 assigned to the two-fraction arm and 263 to the ten-fraction arm. The two groups were well balanced with respect to patient characteristics. Median survival was 77 days with two fractions (95% CI 68-89) and 84 days for the longer schedule (95% CI 67-102). Analysis of the survival curves showed a marginal advantage for ten fractions (P = 0.04). Performance status (P = 0.0001), site of primary tumour (P = 0.006), dose of dexamethasone (P = 0.004), age (P = 0.04) and randomization treatment (P = 0.03) were independant factors associated with survival. The classification of patients into good or poor risk groups based on these factors, excluding treatment, showed highly significant differences in survival (P < 0.0001). Predictive models suggested that any benefit attributable to the longer radiotherapy schedule was confined to those in a good prognostic group (these patients formed 22% of the study population). Radiation related side effects, other than alopecia, were seen in 12% of patients receiving two fractions and 8% of those given ten fractions. The short survival of many patients hampered the assessment of response, but overall responses were seen in 39% of those given two fractions and 44% of patients receiving ten fractions. These results suggest that any increase in survival due to longer radiotherapy treatment is confined to good prognosis patients, but, for the majority, there is no advantage and the value of radiotherapy for these patients relates purely to the possibility of control or relief of distressing symptoms.", "This randomized pilot trial investigated whether primary chemotherapy was feasible in terms of efficacy, survival, toxicity profile, and quality of life compared with whole-brain radiotherapy (WBRT) given first in chemotherapy-naive patients nonsmall cell lung cancer (NSCLC) with synchronous brain metastasis when neurologic symptoms or signs are absent or controlled by supportive care.\n After stratification by Eastern Cooperative Oncology Group performance status (ECOG PS) (0-1 vs 2), the number of intracranial metastases (<3 vs 3< or =), and the presence of extrathoracic extracranial metastasis, eligible patients were randomized to the primary chemotherapy arm or the WBRT-first arm. World Health Organization (WHO) response criteria, National Cancer Institute Common Toxicity Criteria (NCI-CTC; version 2.0), and the European Organization for Research and Treatment of Cancer (EORTC) C-30/LC-13 questionnaire were used.\n A total of 48 patients were enrolled between August 2002 and November 2005. The response rate of chemotherapy and survival outcomes in the primary chemotherapy arm were not statistically different from those in the WBRT-first arm (overall response rate, 28.0% vs 39.1%; progression-free survival, 3.6 months vs 4.4 months; overall survival, 9.1 months vs 9.9 months). There was close correlation noted between intracranial and extracranial tumor responses (k = 0.82). However, in the WBRT-first arm, grade 3 of 4 neutropenia was more frequent (79% vs 40%) during chemotherapy and 4 patients (17.4%) did not receive further chemotherapy because of early death or poor performance after WBRT. Cognitive function appeared to deteriorate during primary chemotherapy, but was also found to deteriorate after WBRT.\n Primary chemotherapy is more feasible and can be an appropriate option for patients with synchronous brain metastasis when neurologic symptoms or signs are absent or controlled. The role and timing of WBRT should be defined in further studies in this clinical setting.\n (Copyright) 2008 American Cancer Society." ]

[ "12603234", "16816060", "17654298", "10982577", "12762083", "17186421", "17473036", "16534040", "17426046", "10373999", "15020174", "8543703", "17336026", "2071729", "14581254", "8907100", "16027567", "9808825", "17454714", "11800220", "17568244", "11162323", "18188753", "16277633", "10224982", "16838818", "10446040", "9357351", "8506786", "1536333", "15367074", "15450636", "8123347", "18048633", "9396102", "18689856", "16548938", "15264976", "11399219", "12780372", "8223364", "15100337", "11817768", "12634020", "17154745", "14503897", "11072391", "10146734", "18048636", "11818305", "9046892", "16116148", "18618189", "12362011", "15533544", "18304363", "10896845", "2030195", "15152882", "18783459", "17119047", "16298723" ]

[ "A controlled trial of an expert system and self-help manual intervention based on the stages of change versus standard self-help materials in smoking cessation.", "Efficacy of telephone counseling for pregnant smokers: a randomized controlled trial.", "Telephone booster sessions for optimizing smoking cessation for patients in rehabilitation centers.", "Using radon risk to motivate smoking reduction: evaluation of written materials and brief telephone counselling.", "A pilot study of telephone-based smoking cessation intervention in asbestos workers.", "Tools for health: the efficacy of a tailored intervention targeted for construction laborers.", "Tobacco use quitline enrollment through dental practices: a pilot study.", "Benefits of telephone care over primary care for smoking cessation: a randomized trial.", "Using radon risk to motivate smoking reduction II: randomized evaluation of brief telephone counseling and a targeted video.", "Is telephone counselling a useful addition to physician advice and nicotine replacement therapy in helping patients to stop smoking? A randomized controlled trial.", "Integrating smoking cessation treatment into primary care: an effectiveness study.", "A randomized trial of self-help materials, personalized feedback, and telephone counseling with nonvolunteer smokers.", "Interactive voice response telephony to promote smoking cessation in patients with heart disease: a pilot study.", "Self-help quit smoking interventions: effects of self-help materials, social support instructions, and telephone counseling.", "Effectiveness of bupropion sustained release for smoking cessation in a health care setting: a randomized trial.", "Telephone counseling for smoking cessation: effects of single-session and multiple-session interventions.", "The effectiveness of a nursing inpatient smoking cessation program in individuals with cardiovascular disease.", "A self-help intervention for African American smokers: tailoring cancer information service counseling for a special population.", "Proactive recruitment of health plan smokers into telephone counseling.", "Effectiveness of telephone contact as an adjunct to a self-help program for smoking cessation: a randomized controlled trial in Spanish smokers.", "Improving outcomes after myocardial infarction: a randomized controlled trial evaluating effects of a telephone follow-up intervention.", "Counselor and stimulus control enhancements of a stage-matched expert system intervention for smokers in a managed care setting.", "Evaluating the effectiveness of a single telephone contact as an adjunct to a self-help intervention for smoking cessation in a randomized controlled trial.", "Smoking cessation intervention in parents of young children: a randomised controlled trial.", "Prevention of relapse in women who quit smoking during pregnancy.", "The costs and effectiveness of different benefit designs for treating tobacco dependence: results from a randomized trial.", "Evaluation of a minimal self-help smoking cessation intervention following cervical cancer screening.", "Telephone support as an adjunct to transdermal nicotine in smoking cessation.", "The effects and use of maintenance newsletters in a smoking cessation intervention.", "Brief supportive telephone outreach as a recruitment and intervention strategy for smoking cessation.", "Telephone counseling increases cessation rates among young adult smokers.", "Prenatal and postpartum smoking abstinence a partner-assisted approach.", "Randomized telephone smoking-intervention trial initially directed at blue-collar workers.", "The effectiveness and cost effectiveness of telephone counselling and the nicotine patch in a state tobacco quitline.", "Self-help interventions for older smokers.", "In-practice management versus quitline referral for enhancing smoking cessation in general practice: a cluster randomized trial.", "Evaluating the effectiveness of proactive telephone counselling for smoking cessation in a randomized controlled trial.", "A randomized trial comparing the effects of self-help materials and proactive telephone counseling on teen smoking cessation.", "The effectiveness of callback counselling for smoking cessation: a randomized trial.", "The effectiveness of personalized smoking cessation strategies for callers to a Quitline service.", "Standardized, individualized, interactive, and personalized self-help programs for smoking cessation.", "Effectiveness of implementing the agency for healthcare research and quality smoking cessation clinical practice guideline: a randomized, controlled trial.", "One-to-one: a motivational intervention for resistant pregnant smokers.", "The impact of financial incentives and a patient registry on preventive care quality: increasing provider adherence to evidence-based smoking cessation practice guidelines.", "Evaluating nicotine replacement therapy and stage-based therapies in a population-based effectiveness trial.", "Telephone counselling as an adjunct to nicotine patches in smoking cessation: a randomised controlled trial.", "Using tailored interventions to enhance smoking cessation among African-Americans at a community health center.", "Does tailoring matter? The impact of a tailored guide on ratings and short-term smoking-related outcomes for older smokers.", "Effects of frequency and duration in telephone counselling for smoking cessation.", "The SUCCESS project: the effect of program format and incentives on participation and cessation in worksite smoking cessation programs.", "Smoking cessation in hospitalized patients. Results of a randomized trial.", "Peer-delivered smoking counseling for childhood cancer survivors increases rate of cessation: the partnership for health study.", "Does outpatient telephone coaching add to hospital quality improvement following hospitalization for acute coronary syndrome?", "Evidence of real-world effectiveness of a telephone quitline for smokers.", "Does extended proactive telephone support increase smoking cessation among low-income women using nicotine patches?", "Acceptability and effectiveness of opportunistic referral of smokers to telephone cessation advice from a nurse: a randomised trial in Australian general practice.", "Free nicotine patches plus proactive telephone peer support to help low-income women stop smoking.", "Effects of a smoker's hotline: results of a 10-county self-help trial.", "Telephone counseling for population-based smoking cessation.", "The effectiveness of covering smoking cessation services for medicare beneficiaries.", "A tailored smoking, alcohol, and depression intervention for head and neck cancer patients.", "Proactive, motivationally enhanced smoking cessation counseling among women with elevated cervical cancer risk." ]

[ "To examine the population impact and effectiveness of the Pro-Change smoking cessation course based on the Transtheoretical Model (TTM) compared to standard self-help smoking cessation literature.\n Randomized controlled trial.\n Sixty-five West Midlands general practices.\n Randomly sampled patients recorded as smokers by their general practitioners received an invitation letter and 2471 current smokers agreed.\n Responders were randomized to one of four interventions. The control group received standard self-help literature. In the Manual intervention group, participants received the Pro-Change system, a self-help workbook and three questionnaires at 3-monthly intervals, which generated individually tailored feedback. In the Phone intervention group, participants received the Manual intervention plus three telephone calls. In the Nurse intervention group, participants received the Manual intervention plus three visits to the practice nurse.\n Biochemically confirmed point prevalence of being quit and 6-month sustained abstinence, 12 months after study commencement.\n A total of 9.1% of registered current smokers participated, of whom 83.0% were not ready to quit. Less than half of participants returned questionnaires to generate second and third individualized feedback. Telephone calls reached 75% of those scheduled, but few participants visited the nurse. There were small differences between the three Pro-Change arms. The odds ratio (95% confidence intervals) for all Pro-Change arms combined versus the control arm were 1.50 (0.85-2.67) and 1.53 (0.76-3.10), for point prevalence and 6-month abstinence, respectively. This constitutes 2.1% of the TTM group versus 1.4% of the control group achieving confirmed 6-month sustained abstinence.\n There was no statistically significant benefit of the intervention apparent in this trial and the high relapse of quitters means that any population impact is small.", "Reducing tobacco use in pregnancy is a public health priority. Brief smoking counseling during prenatal care is effective but generates modest cessation rates. Telephone counseling is an effective smoking cessation method that could offer pregnant women convenient access to more intensive smoking cessation counseling.\n The efficacy of proactive pregnancy-tailored telephone counseling for smoking cessation was compared with a \"best-practice\" brief-counseling control in a randomized controlled trial of 442 pregnant smokers referred by prenatal providers and a managed care plan. Trained counselors using cognitive-behavioral and motivational interviewing methods called intervention subjects throughout pregnancy and for 2 months postpartum (mean = 5 calls, mean total contact = 68 minutes). Controls received one 5-minute counseling call.\n Cotinine-validated 7-day tobacco abstinence rates in intervention and control groups were 10.0% and 7.5% at end of pregnancy (odds ratio [OR] 1.37, 95% confidence interval [CI] 0.69-2.70; number needed to treat = 40) and 6.7% versus 7.1% at 3 months postpartum (OR 0.93, 95% CI 0.44-1.99). The intervention increased end-of-pregnancy cessation rates among 201 light smokers (< 10 cigarettes/day at study enrollment) (intervention 19.1% versus control 8.4%; OR 2.58, 95% CI 1.1-6.1; number needed to treat = 9.3) and among 193 smokers who attempted to quit in pregnancy before enrollment (intervention 18.1% versus control 6.8%; OR 3.02, CI 1.15-7.94; number needed to treat = 8.8); 63% of the sample (n = 267) was in one of these subgroups.\n Proactive pregnancy-tailored telephone counseling did not outperform a brief \"best practice\" intervention among pregnant smokers. The intervention had efficacy in light smokers and in women who had attempted cessation earlier in pregnancy. Future studies should confirm whether telephone counseling benefits these groups of pregnant smokers.\n ClinicalTrials.gov, #NCT00181909.\n I.", "Smokers with smoking-related diseases who are hospitalized in rehabilitation centers should be offered smoking cessation. This is the first study evaluating whether telephone booster sessions after intensive inpatient treatment are an effective strategy. The present study was conducted in 13 rehabilitation centers for somatic disorders as a prospective multicenter study with a randomized treatment-control group design. We compared abstinence rates after hospital discharge from treatment that included a group smoking cessation program with (treatment group) and without telephone booster sessions (control group). Data from 290 smokers were analyzed. After 6 and 12 months the treatment group achieved abstinence rates twice as high as those of the control group. Men profited more from telephone booster sessions than did women. Results indicated that telephone booster sessions were highly effective (even) after an inherently intensive group program during a hospital stay. Further research should focus on the special needs of women receiving telephone counseling.", "Radon and cigarette smoking have synergistic effects on lung cancer, even when radon concentrations are relatively low. Working through an electric utility company, we sought to reach smoking households with low radon concentrations and motivate smoking cessation or prohibiting smoking in the home.\n Eligible homes (n = 714) were randomised to receive: (1) the Environmental Protection Agency's (EPA's) \"A citizen's guide to radon\"; (2) a specially developed pamphlet; or (3) that pamphlet plus brief telephone counselling.\n Utility company \"bill stuffers\" offered free radon test kits to smoking households. All households received radon test results with an explanatory cover letter. Both the specially developed pamphlet and the telephone counselling emphasised that smoking cessation or prohibiting smoking in the home were the optimal risk reduction strategies. Households were followed up at 3 and 12 months after receiving materials.\n The specially developed pamphlet and the EPA guide yielded similar outcomes. There was a non-significant trend for telephone counselling to produce greater sustained quitting than the specially developed pamphlet, and phone counselling led to significantly more new household smoking bans.\n Working through a public utility company is an efficient way to reach smoking households, and brief telephone counselling is a promising method for promoting household smoking bans and cessation in homes alerted to the risk posed by the combination of radon and smoking.", "Smoking markedly increases the risk of asbestos-related lung cancer. We conducted a randomized pilot trial of a telephone-based smoking cessation intervention in asbestos workers. Fifty-nine smokers were assigned to either a control or telephone-based smoking cessation treatment group and were followed-up at 6 months. Intent-to-treat analysis revealed a 16.7% quit rate at 6 months for the intervention group compared to 6.9% for the control group (P = 0.25). Treatment-received quit-rates were 33% for the intervention group and 6.9% for the control group (P = 0.05). The intervention group was twice as likely to use smoking cessation medicines and progressed further along the stage of change continuum compared with the control group. Incorporating telephone-based smoking cessation treatment into medical screening activities for asbestos workers is feasible and the intervention is effective in increasing quit rates at 6 months.", "Novel approaches to worksite health promotion are needed for high-risk workers who change job sites frequently, and thus may have limited access to worksite health promotion efforts. The objective of this study was to test a behavioral intervention among construction laborers.\n Using a randomized-controlled design, we tested the efficacy of a tailored telephone-delivered and mailed intervention to promote smoking cessation and increased fruit and vegetable consumption (n = 582).\n At baseline, 40% of control group participants and 45% of intervention group participants reported using any tobacco in the last seven days. At final, 8% of baseline cigarette smokers in the control group had quit, compared to 19% in the intervention group (p = 0.03). In both groups, the mean consumption of fruits and vegetables at baseline was over five servings per day. At final, the intervention group had increased consumption by approximately one and one-half servings, compared to a slight decrease in consumption in the control group (p < 0.001).\n A tailored intervention can be efficacious in promoting tobacco use cessation and increased fruit and vegetable consumption among construction laborers, a high-risk, mobile workforce.", "Time and resource constraints limit the ability of oral health care professionals to help patients quit smoking. Opportunities exist for dental providers to help patients who smoke by enrolling them in tobacco use quitlines. The authors conducted a pilot study to investigate whether such referrals were feasible and effective.\n The authors randomly assigned eight general dental practices to provide either brief counseling regarding smoking cessation or brief counseling along with referrals to a tobacco use quitline for patients receiving routine dental hygiene care who reported that they were currently smoking cigarettes.\n The authors enrolled 82 patients (60 in the tobacco use quitline group, 22 in the brief counseling group). At six months, the self-reported, seven-day point prevalence tobacco use abstinence rates were 25.0 percent (15 of 60 patients) in the tobacco use quitline group and 27.3 percent (six of 22 patients) in the brief-counseling group (P approximately 1.0). Twenty-eight (47 percent) of 60 subjects in the tobacco use quitline group completed the initial tobacco use quitline consultation. Abstinence rates among subjects in the quitline group were higher if they completed more telephone consultations.\n Referral to a tobacco use quitline by dental practices is a feasible strategy for helping patients quit smoking if efficient links between the dental practice and the tobacco use quitline can be established. Research is needed to evaluate whether it is more effective than standard clinical interventions for tobacco use cessation.\n Dental practitioners with limited time and other resources can assist patients who smoke by referring them to a tobacco use quitline.", "Brief clinician intervention and telephone counseling are both effective aids for smoking cessation. However, the potential benefit of telephone care above and beyond routine clinician intervention has not been examined previously. The objective of this study is to determine if telephone care increases smoking cessation compared with brief clinician intervention as part of routine health care.\n This 2-group, prospective, randomized controlled trial enrolled 837 daily smokers from 5 Veterans Affairs medical centers in the upper Midwest. The telephone care group (n = 417) received behavioral counseling with mailing of smoking cessation medications as clinically indicated. The standard care group (n = 420) received intervention as part of routine health care. The primary outcome was self-reported 6-month duration of abstinence 12 months after enrollment. Secondary outcomes were 7-day point prevalence abstinence at 3 and 12 months, participation in counseling programs, and use of smoking cessation medications.\n Using intention-to-treat procedures, we found that the rate of 6-month abstinence at the 12-month follow-up was 13.0% in the telephone care group and 4.1% in the standard care group (odds ratio [OR], 3.50; 95% confidence interval [CI], 1.99-6.15). The rate of 7-day point prevalence abstinence at 3 months was 39.6% in the telephone care group and 10.1% in the standard care group (OR, 5.84; 95% CI, 4.02-8.50). Telephone care compared with standard care increased the rates of participation in counseling programs (97.1% vs 24.0%; OR, 96.22; 95% CI, 52.57-176.11) and use of smoking cessation medications (89.6% vs 52.3%; OR, 7.85; 95% CI, 5.34-11.53).\n Telephone care increases the use of behavioral and pharmacologic assistance and leads to higher smoking cessation rates compared with routine health care provider intervention.", "Radon and cigarette smoking have synergistic effects on lung cancer risk. Electric utility company bill stuffers offered free radon test kits to households with at least one smoker. Participating households (n = 1364) were randomized within a 2 x 2 design to evaluate the main effects of brief telephone counseling and a targeted video on smoking cessation and the establishment of new household smoking bans. Phone counseling was associated with cessation at 3-month follow-up but neither intervention led to 12-month or sustained cessation. While neither intervention had a significant effect on new bans, there were trends in the predicted direction and the combination of the two significantly increased new bans compared with no intervention. The presence of children in the household was associated with new bans. While few households had high levels of radon, such levels were associated with radon mitigation behaviors. Together with a previous study, these results suggest radon risk is a useful and inexpensive way to engage smoking households in risk reduction behaviors, especially the institution of household smoking bans.", "The authors evaluated the incremental efficacy of telephone counselling by a nurse in addition to physician advice and nicotine replacement therapy in helping patients to stop smoking.\n The trial was conducted at the University of Ottawa Heart Institute. A total of 396 volunteers who smoked 15 or more cigarettes daily were randomly assigned to either of 2 groups: usual care (control group) and usual care plus telephone counselling (intervention group); the groups were stratified by sex and degree of nicotine dependence. Usual care involved the receipt of physician advice on 3 occasions, self-help materials and 12 weeks of nicotine replacement therapy. Telephone counselling was provided by a nurse at 2, 6 and 13 weeks after the target quit date. Point-prevalent quit rates were determined at 52 weeks after the target quit date.\n The point-prevalent quit rates at 52 weeks did not differ significantly between the control and intervention groups (24.1% v. 23.4% respectively). The quit rates did not differ significantly at the secondary measurement points of 4, 12 and 26 weeks.\n Brief physician assistance, along with nicotine replacement therapy, can help well-motivated smokers to quit. Three additional sessions of telephone counselling by a nurse were ineffective in increasing quit rates. This form of assistance may be useful in the absence of physician advice or when self-selected by patients.", "Lack of interest has been cited as a reason not to offer cessation assistance to smokers, but research suggests that smokers accept treatments offered proactively. This study assessed acceptability, utilization, and effectiveness of free smoking cessation treatment among diverse primary care patients.\n Medical assistants invited 4174 adult smokers to participate. Enrollees (1869) self-selected or were assigned to receive free nicotine patch therapy alone or in combination with the Committed Quitters(R) program, and for some, individual counseling.\n In nearly 68% of cases, patients accepted a treatment invitation; 77% of eligible smokers enrolled; 85% of these picked up free patches. Given a choice of treatments, 75% of participants elected a psychosocial treatment in addition to patch therapy. Thirteen percent of treatment initiators achieved biochemically confirmed 7-day point-prevalence abstinence at 1 year, with no significant treatment effects. Minority patients showed greater initial interest but less utilization did than White patients.\n Free, readily accessible smoking cessation treatment offered in primary care settings was accepted and used by the majority of unselected smokers of diverse racial/ethnic origins. Psychosocial treatment components did not significantly increase abstinence rates. Barriers, rather than lack of interest, may keep minority smokers from using cessation treatments.", "The incremental effects of (a) a self-help booklet alone, (b) self-help booklet with computer-generated personalized feedback, and (c) self-help booklet, personalized feedback, and outreach telephone counseling were evaluated in a population-based, nonvolunteer sample of smokers. Smokers (N = 1,137) were identified through a telephone survey of a random sample of 5,903 enrollees in a health maintenance organization and randomized to a no-treatment control group or 1 of the 3 intervention conditions. Smoking status was ascertained 3, 12, and 21 months postrandomization. Cotinine validation of self-reported cessation was obtained at the 12-month follow-up. Overall, the telephone counseling significantly increased smoking cessation at the 3-month follow-up, but not at 12 or 21 months. Among smokers who were precontemplative at baseline, telephone counseling significantly increased prevalent abstinence at 3 and 12 months and continuous abstinence at 21 months (defined as self-reported abstinence at 3, 12, and 21 months).", "A pilot study was conducted to determine the feasibility and potential efficacy of an interactive voice response (IVR) follow-up system for smokers recently hospitalized with coronary heart disease (CHD).\n Ninety-nine smokers hospitalized with CHD completed a baseline questionnaire, were provided with bedside counseling, and offered nicotine replacement therapy. They were randomly assigned to a usual care (UC) or an IVR group. The IVR group received automated telephone follow-up calls 3, 14 and 30 days after discharge inquiring about their smoking status and confidence in remaining smoke-free. When deemed necessary, they were offered additional counseling. Smoking status was determined 52 weeks after hospital discharge.\n The 52-week point prevalence abstinence rate in the IVR group was 46.0% compared to 34.7% in the UC group (OR=1.60, 95% CI: 0.71-3.60; P=.25). After adjustment for education, age, reason for hospitalization, length of hospitalization, and quit attempts in the past year, the odds of quitting in the IVR group compared to the UC group were 2.34 (95% CI: 0.92-5.92; P=.07).\n IVR is a promising technology for following CHD patients attempting to quit smoking following discharge from hospital, however, a larger trial is required to confirm its efficacy.\n IVR may enhance the timely provision of follow-up counseling for smoking cessation in patients with CHD.", "Smokers requesting self-help materials for smoking cessation (N = 2,021) were randomized to receive (a) an experimental self-quitting guide emphasizing nicotine fading and other nonaversive behavioral strategies, (b) the same self-quitting guide with a support guide for the quitter's family and friends, (c) self-quitting and support guides along with four brief counselor calls, or (d) a control guide providing motivational and quit tips and referral to locally available guides and programs. Subjects were predominantly moderate to heavy smokers with a history of multiple previous quit attempts and treatments. Control subjects achieved quit rates similar to those of smokers using the experimental quitting guide, with fewer behavioral prequitting strategies and more outside treatments. Social support guides had no effect on perceived support for quitting or on 8- and 16-month quit rates. Telephone counseling increased adherence to the quitting protocol and quit rates.", "The efficacy of bupropion hydrochloride sustained release (SR) (Zyban) for smoking cessation has been evaluated in clinical trials that included frequent in-person behavioral counseling, but not in actual practice settings.\n To determine the differential effectiveness of 2 doses of bupropion SR in combination with behavioral interventions of minimal to moderate intensity in an actual practice setting.\n Open-label randomized trial, with 1 year of follow-up.\n A large health system (Group Health Cooperative) based in Seattle.\n Adult smokers (N = 1524) interested in quitting smoking.\n Participants were randomly assigned to receive 1 of 4 combinations of bupropion SR (150 or 300 mg) and behavioral counseling (minimal or moderate intensity).\n The primary outcome measure was self-reported point-prevalence 7-day nonsmoking status at 3 and 12 months following the target quit date. Secondary outcomes included adverse and abstinence effects reported since beginning treatment with bupropion SR.\n At 3 months, a significantly higher rate of nonsmoking was observed among those receiving the larger bupropion SR dose (P=.005). At 12 months, moderate intensity counseling was associated significantly with a higher rate of nonsmoking (P=.001). At 3 months, the higher dose was associated with a significantly increased frequency of self-reported symptoms such as difficulty sleeping (P=.02), difficulty concentrating (P=.02), shakiness/tremor (P=.002), and gastrointestinal problems (P=.005)and a decreased frequency of reported desire to smoke (P=.001).\n In this actual practice setting, the combination of bupropion SR and minimal or moderate counseling was associated with 1-year quit rates of 23.6% to 33.2%. This suggests that existing health care systems can substantially decrease tobacco use rates among their enrollees if they provide these modest interventions.", "Smokers (N = 3,030) were randomized to receive 1 of 3 interventions: (a) a self-help quit kit, (b) a quit kit plus 1 telephone counseling session, or (c) a quit kit plus up to 6 telephone counseling sessions, scheduled according to relapse probability. Both counseling groups achieved significantly higher abstinence rates than the self-help group. The rates for having quit for at least 12 months by intention to treat were 5.4% for self-help, 7.5% for single counseling, and 9.9% for multiple counseling. The 12-month continuous abstinence rates for those who made a quit attempt were 14.7% for self-help, 19.8% for single counseling, and 26.7% for multiple counseling. A dose-response relation was observed, as multiple sessions produced significantly higher abstinence rates than a single session. The first week after quitting seems to be the critical period for intervention.", "Smoking is an important risk factor for cardiovascular disease (CVD), and quitting is highly beneficial. Yet, less than 30% of CVD patients stop smoking. Relapse-prevention strategies seem most effective when initiated during the exacerbation of the disease.\n A nurse-delivered inpatient smoking cessation program based on the Transtheoretical Model with telephone follow-up tailored to levels of readiness to quit smoking was evaluated on smoking abstinence and progress to ulterior stages of change.\n Participants (N = 168) were randomly assigned by cohorts to inpatient counseling with telephone follow-up, inpatient counseling, and usual care. The inpatient intervention consisted of a 1-hr counseling session, and the telephone follow-up included 6 calls during the first 2 months after discharge. The nursing intervention was tailored to the individual's stage of change. End points at 2 and 6 months included actual and continuous smoking cessation rates (biochemical markers) and increased motivation (progress to ulterior stages of change).\n Assuming that surviving patients lost to follow-up were smokers, the 6-month smoking abstinence rate was 41.5% in the inpatient counseling with telephone follow-up group, compared with 30.2% and 20% in the inpatient counseling and usual care groups, respectively (p = .05). Progress to ulterior stages of change was 43.3%, 32.1%, and 18.2%, respectively (p = .02). Stage of change at baseline and intervention predicted smoking status at 6 months.\n This tailored smoking cessation program with telephone follow-up significantly increased smoking cessation at 6 months, and progression to ulterior stages of change. The telephone follow-up was an important adjunct. It is, therefore, recommended to include such comprehensive smoking cessation programs within hospital settings for individuals with CVD.", "African Americans remain a critically underserved group for smoking cessation interventions. This study tested the effectiveness of a tailored, culturally sensitive intervention for African American smokers who called the NCI Cancer Information Service (CIS) for help to quit smoking.\n This paper presents results of a 2-year study of tailored counseling strategies among African American smokers (n = 1,422) who called four regional CIS offices in response to a radio-based media campaign in 14 communities. Callers were randomly assigned to receive either the standard CIS quit smoking counseling and guide (Clearing the Air) or counseling and a guide (Pathways to Freedom) tailored to the quitting needs and barriers of African American smokers. Callers were predominantly female (63.6%). ages 20-49 (88%), with a high school education or more (84%). Median smoking history was 17 years; median smoking rate was 20 cigarettes/day. Standard (n = 689) and Tailored (n = 733) group subjects did not differ on most baseline measures.\n On most measures, Standard and Tailored counseling/guides received similar ratings, but the Tailored guide was rated as having more appealing photos (P = 0.001) and as being more appropriate for family members (P = 0.003). Six-month follow-up with 893 subjects (response rates were 63% Standard, 62% Tailored, ns) showed significantly more quit attempts (P = 0.002) and greater use of prequitting strategies (P < 0.05) among Tailored than among Standard subjects, but no differences in self-reported 1-week abstinence (14.4% Standard, 16.2% Tailored) (ns). An opportunistic 12-month follow-up of subjects recruited in the last year of the study (n = 445) (response rates were 57% Standard, 60% Tailored, ns) showed a significantly higher quit rate (15.4% Standard, 25.0% Tailored) for Tailored subjects (P = 0.034).\n Results show promise for tailored approaches to boost quit attempts and success rates among African American smokers.\n Copyright 1998 American Health Foundation and Academic Press.", "We tested whether a 3-month beneficial effect of telephone counseling as an adjunct to the use of medications for smoking cessation was maintained through 12 months. Health plan members filling a prescription for cessation medications were randomized either to a no-contact control group or to proactive recruitment into telephone counseling. An increased point-prevalence quit rate at 3 months (33.1% vs. 27.4%, p<.05) among smokers randomized to proactive recruitment for telephone counseling was not maintained. Although at 12 months smokers in the proactive recruitment arm were more likely to report a 24-hr quit attempt, compared with control group smokers (86.7% vs. 80.8%, p = .027), we found no differences between the groups in repeated (3-month and 12-month) 7-day point-prevalence quit rates. In an analysis of predictors of quitting, age, marital status, making a lifestyle change, and the presence of household smokers were associated with repeated 3-month and 12-month point-prevalence abstinence. Offering telephone counseling to insured smokers who have filled prescriptions for cessation medications did not increase long-term quit rates. Although other variations of this approach might be tested, we suspect that it might be more useful to test innovative ways to influence the factors we identified as being most strongly predictive of lack of successful quitting.", "This study evaluated the effect of telephone counseling as an adjunct to a self-help program for smoking cessation conducted through the mail. We obtained demographic and consumption information on those smokers who requested participation in the study. These participants (N = 200) were randomized into two study groups: (1) the standard self-help group (n = 100) (median age: 35.1 years; pretreatment consumption of 28.0 cigarettes/day); (2) the self-help group receiving additional multiple-contact telephone counseling (n = 100) (median age: 36.7 years; pretreatment consumption of 27.3 cigarettes/day). At the 12-month follow-up, the carbon monoxide in expired air was used to distinguish nonsmokers from smokers. Significant differences were found in the rates of continuous abstinence in both groups for each period evaluated. In the standard self-help group, the continuous abstinence rate at the 3-month follow-up was 21%, 18% at the 6-month follow-up, and 14% at the 12-month follow-up. The telephone counseling group yielded a 48% continuous abstinence rate at the 3-month follow-up, 40% at the 6-month follow-up, and 27% at the 12-month follow-up. The results of this randomized controlled trial show that telephone counseling was an effective aid for the smoking cessation program.", "Providing information is an important part of standard care and treatment for acute myocardial infarction inpatients. Evidence exists indicating that acute myocardial infarction patients experience an information gap in the period immediately after discharge from the hospital. The aim of this study was to assess the short-term effects of a nurse-led telephone follow-up intervention to provide information and support to patients with acute myocardial infarction after their discharge from hospital.\n A prospective randomized, controlled trial with a 6-month follow-up was conducted. A total of 288 patients were allocated to either an intervention group (n=156) or a control group (n=132). The latter received routine post-discharge care. The primary endpoint measured at 3 and 6 months after discharge was the health-related quality of life using the 36-item Short Form Health Survey. Secondary endpoints included smoking and exercise habits.\n In both groups, health-related quality of life improved significantly over time on most subscales. A statistically significant difference in favour of the intervention group was found on the 36-item Short Form Health Survey Physical Health Component Summary Scale (P=0.034) after 6 months. No difference was found between the groups on the Mental Health Component Summary Scale. We found a significant difference with respect to frequency of physical activity in favour of the intervention group after 6 months (P=0.004). More participants in the intervention group than the control group had ceased smoking at the 6-month follow-up (P=0.055).\n A nurse-led systematic telephone follow-up intervention significantly improved the physical dimension of health-related quality of life in patients in the intervention group compared with usual care patients. Participation in this intervention also seemed to promote health behaviour change in patients after acute myocardial infarction.", "Previous research has demonstrated the efficacy of an interactive expert system intervention for smoking cessation for a general population. The intervention provides individualized feedback that guides participants through the stages of change for cessation. Enhancing the expert system by adding proactive telephone counseling or a stimulus control computer designed to produce nicotine fading could produce preventive programs with greater population impacts.\n Four interventions were compared: (a) the interactive expert system intervention; (b) the expert system intervention plus counselor calls; (c) the expert system intervention plus the stimulus control computer; and (d) an assessment only condition. A 4 (intervention) x 4 (occasions) (0,6,12, and 18 months) design was used. Smokers were contacted at home via telephone or mail. The initial subject pool was the 24,178 members of a managed care company. Screening was completed for 19,236 members (79.6%), of whom 4,653 were smokers; 85.3% of the smokers were enrolled.\n Thirty-eight percent were in the precontemplation stage, 45% in the contemplation stage, and only 17% in the preparation stage. At 18 months, the expert system resulted in 23.2% point prevalence abstinence, which was 33% greater than that of assessment only. The counselor enhancement produced increased cessation at 12 months but not at 18 months. The stimulus control computer produced no improvement, resulting in 20% worse cessation rates than the assessment only condition.\n The enhanced conditions failed to outperform the expert system alone. The study also demonstrated the ability of the interactive expert system to produce significantly greater cessation in a population of smokers than assessment alone.\n Copyright 2000 American Health Foundation and Academic Press.", "This study evaluated the effects of including a single brief prequit telephone counseling session in a self-help program for smoking cessation conducted through the mail, by comparison with the effects of the self-help program alone. Volunteer participants from northwestern Spain (N = 228) were randomly assigned to one of two groups: (a) the self-help-only group (n = 110, mean age = 37.4 years, pretreatment cigarette consumption = 26.5 cigarettes/day) or (b) the telephone-support group (n = 118, mean age = 36.8 years, pretreatment cigarette consumption = 27.7 cigarettes/day). Using a conservative data analysis method (missing data considered as treatment failures), we found that the point-prevalence abstinence rate was significantly higher in the telephone-support group than in the self-help-only group at the end of treatment (44.9% vs. 21.8%) and at the 3-month follow-up (39.0% vs. 26.4%). Likewise, sustained abstinence was significantly higher in the telephone-support group at the 3-month follow-up (33.9% vs. 13.6%), the 6-month follow-up (25.4% vs. 12.7%), and the 12-month follow-up (21.2% vs. 9.1%). The results of this randomized controlled trial indicate that both treatments are an effective aid for smoking cessation, and that a single brief telephone call before the quit date is a low-cost and effective procedure for improving abstinence rates in a mailed self-help program.", "To examine whether telephone counselling based on the stages of change component of Transtheoretical model of behaviour change together with educational materials could help non-motivated smoking parents of young children to cease.\n Randomised controlled trial.\n Hong Kong Special Administrative Region, PR China.\n 952 smoker fathers and mothers of Chinese children aged 5 years.\n Participants were randomly allocated into two groups: the intervention group received printed self-help materials and three-session telephone-based smoking cessation counselling delivered by trained counsellors; the control group received printed self-help materials only. A structured questionnaire was used for data collection at baseline and at 1, 3 and 6 month follow up.\n The main outcome is 7 day point prevalence quit rate at 6 months (defined as not smoking during the 7 days preceding the 6 month follow up) determined by self reports. Other secondary outcomes were self reported 24 h point prevalence quit rate and self-reported continuous quit rate and bio-chemically validated quit rate at 6 months.\n A total of 952 smoker fathers and mothers were randomized to the intervention (n = 467) and control (n = 485) groups. Most were daily smokers (92.4%) and the mean number of cigarettes smoked per day was 14.5 (SD = 8.9). By using intention-to-treat analysis, the 7 day point prevalence quit rate at 6 month follow up was significantly greater in the intervention group (15.3%; 68/444) than the control group (7.4%; 34/459) (P < 0.001). The absolute risk reduction was 7.9% (95% confidence interval: 3.78% to 12.01%). The number needed to treat to get one additional smoker to quit was 13 (95% CI: 8-26). The crude odds ratio of quitting was 2.3(95% CI: 1.5-3.5). The adjusted odds ratio was 2.1 (95% CI: 1.4-3.4) (adjusted for age, number of years smoked, and alcohol dependency).\n Proactive telephone counselling is an effective aid to promote smoking cessation among parents of young children.", "This study is an evaluation of relapse prevention interventions for smokers who quit during pregnancy.\n Pregnant smokers at 2 managed care organizations were randomized to receive a self-help booklet only, prepartum relapse prevention, or prepartum and postpartum relapse prevention. Follow-up surveys were conducted at 28 weeks of pregnancy and at 8 weeks, 6 months, and 12 months postpartum.\n The pre/post intervention delayed but did not prevent postpartum relapse to smoking. Prevalent abstinence was significantly greater for the pre/post intervention group than for the other groups at 8 weeks (booklet group, 30%; prepartum group, 35%; pre/post group, 39%; P = .02 [different superscripts denote differences at P < .05]) and at 6 months (booklet group, 26%, prepartum group, 24%; pre/post group, 33%; P = .04) postpartum. A nonsignificant reduction in relapse among the pre/post group contributed to differences in prevalent abstinence. There was no difference between the groups in prevalent abstinence at 12 months postpartum.\n Relapse prevention interventions may need to be increased in duration and potency to prevent post-partum relapse.", "This research estimated the costs and effectiveness of three different benefit designs for treating tobacco dependence: drugs only (nicotine replacement therapy patch, nasal spray, inhaler, and Zyban); drugs and counseling (drugs and proactive telephone counseling); and drugs if counseling (drugs conditional on enrollment in counseling). A sample of 393 adult smokers enrolled in a California preferred provider organization was randomly assigned to one of three study groups. After eight months, there were no significant increases in quit attempts or quit rates in the groups with covered drugs and counseling compared to the group with drug coverage only. Therefore, costs rose with no increase in quit rates when proactive telephone counseling was added to coverage of pharmacotherapy, regardless of benefit design.", "This study was undertaken to evaluate a smoking cessation intervention provided to women smokers as follow-up to cervical cancer screening.\n Women who had had a Pap test in the prior month (N = 4,053) were called to complete a survey that assessed smoking status; 580 identified smokers were randomized to receive Usual care (n = 292) or a Self-help intervention (n = 288) that included a self-help booklet, a smoking and reproductive health information card, and three telephone counseling calls. Women were followed up at 6 and 15 months post-base line.\n Cessation rates in the Usual care (UC) and Self-help (SH) groups did not differ at the 6-month (UC 10.5% vs SH 10.9%, P = 0.56) or 15-month follow-up (UC 15.5% vs SH 10.6%, P = 0.17). Among women with an abnormal Pap test result there were no differences by study group in cessation rates at 6-month (UC 9.8% vs SH 11.0%, P = 0.71) or 15-month follow-up (UC 14.6% vs SH 13.4%, P = 0.96).\n Integrating interventions into the clinical setting and involving providers at the point of care may have greater potential for capitalizing on this \"teachable moment.\"\n Copyright 1999 American Health Foundation and Academic Press.", "Transdermal nicotine patches have shown considerable promise in improving smoking cessation outcomes. The present study assessed telephone support as an adjunct to a managed care-based, single-session group orientation smoking cessation program with nicotine patch therapy.\n The unit of randomization was the orientation session (n = 35). Subjects (n = 509) were randomly assigned to a group session without telephone support, the session plus access to a toll-free help line, or the session with telephone help line plus active telephone outreach.\n Contrary to hypothesis, there were no differences between treatment conditions. Overall abstinence rates were 22% at 6 months and 21% at 1 year. Fewer than 1% of eligible subjects called the toll-free help line. An average of 3.8 of a possible 4 calls were completed in the telephone outreach condition.\n Abstinence results obtained in this program were comparable to those obtained with more extensive counseling. However, there was no evidence of benefit from telephone support beyond the initial physician-led group orientation session.", "This article evaluates the effects and use of adjuncts to a televised smoking cessation program, based on the American Lung Association's \"Freedom From Smoking in 20 Days.\" Subjects were randomized to maintenance and control conditions. The maintenance condition received newsletters with information and support addressing different stages in the cessation process and information about a telephone hotline. The maintenance condition did not increase cessation at any wave of interviewing, assessed by multiple point or point prevalence of abstinence. Those abstinent at 6 months and those who had made an attempt to stop smoking by that time were more likely to have used the newsletters and were more likely to have used the sections relevant to their cessation stage. Rates of use of the telephone hotline were low. The newsletters appear to be useful to smokers who are predisposed to use written materials.", "Formal efforts to recruit smokers into cessation programs have failed to reach large segments of the smoking population. Telephone intervention may represent a viable strategy to promote smoking cessation. An even more promising approach may be a combination of brief telephone support and outreach to identified smokers.\n Telephone support for smoking cessation was provided to four identified smoker populations in Bloomington, Minn, one of three Minnesota Heart Health Program education communities. Smokers were randomly assigned to an intervention consisting of two 15-minute telephone calls approximately 1 to 3 weeks apart or to a nonintervention control.\n At the 6-month follow-up, a significant overall effect was found in favor of the intervention condition for both self-reported and cotinine-validated quitting. Differences between intervention and control conditions were no longer significant at 18 months.\n Smokers' receptivity to telephone intervention was at least moderately encouraging. The cost of intervention could be relatively low if trained volunteers initiated telephone calls. However, more intensive telephone intervention and support may be needed to produce lasting changes in smoking prevalence.", "During June 2000-May 2001, the American Cancer Society conducted a randomized trial of telephone counseling among more than 3,500 current smokers who called to seek assistance in quitting. All eligible callers were randomized to receive either self-help booklets through the mail or booklets and up to 5 sessions of telephone counseling. Approximately 12% (420/3,522) of study participants were 18-25 years of age. Using intent to treat analyses, 3- and 6-month quit rates among both younger and older smokers were significantly higher among those who received telephone counseling than among those who received self-help booklets only. Three-month rates were 20% versus 9% for 18-25 year olds and 15% versus 10% for older adults. Results indicate that younger smokers can benefit from telephone counseling.\n ((c) 2004 APA, all rights reserved)", "A partner's provision of support and smoking status has been consistently associated with women's likelihood of smoking cessation during pregnancy and relapse in postpartum.\n A three-group randomized controlled intervention trial was conducted in 1996 to 2001, with 583 women and their partners randomized to usual care (UC), woman-only (WO), or partner-assisted (PA) intervention. Follow-ups occurred at 28 weeks of pregnancy, and 2-, 6-, and 12-months postpartum.\n Womack Army Medical Center (WAMC) at Fort Bragg in Fayetteville, North Carolina.\n Women in the UC condition received provider advice to quit and a self-help guide. The WO condition received UC components plus a late-pregnancy relapse prevention kit (booklet and gift items) and six counseling calls (three in pregnancy and three postpartum) initiated by a health advisor. Women in the PA condition received the WO intervention, and their partners received telephone counseling and a support guide emphasizing skills to help the woman build and maintain her confidence to quit smoking. Partners who smoked also received cessation aids and related counseling.\n Seven-day self-reported abstinence from smoking at each follow-up.\n Intent-to-treat analyses showed no significant differences by condition in women's reports of abstinence at any follow-up. In late pregnancy, more partners were abstinent in the PA condition (15%) than in the UC condition (5%), p =0.02.\n Partner-assisted smoking-cessation interventions need further refinement. Influencing young couples' support patterns may require more intensive and conjoint intervention. Partners who smoke could benefit from support for their cessation efforts.", "Although smoking prevalence in the United States has declined markedly in recent years, prevalence among blue-collar workers remains high and few successful methods of reaching this group have been identified. The present study was designed to test the relative efficacy of two different approaches to telephone smoking-cessation counseling for blue-collar workers. Our study built on the experience of the National Cancer Institute's Cancer Information Service (CIS) and compared the past CIS smoking-cessation counseling procedure and a modified version of the present procedure. In our trial, callers to a special telephone hotline who asked for information on smoking cessation were randomly assigned to receive counseling under one of two protocols: 1) the past CIS procedure, in which general information was given and cessation materials were sent to the callers, and 2) a version of the present CIS stage-model procedure, adapted by us for use with blue-collar workers, in which callers were given counseling specific to their stage in the smoking-cessation process. The general-information group contained 185 subjects; the stage-model group contained 197. Despite extensive efforts in the present study, it was not possible to recruit the number of blue-collar workers planned for our statistical analysis. Consequently, of a total of 382 subjects recruited, 93 (24.3%) were blue-collar workers, 181 (47.4%) were white-collar workers, and 108 (28.3%) were retired persons who worked part time, student workers, or the unemployed. Our results show no statistically significant differences in either short-term or long-term nonsmoking rates between the general-information group and the stage-model group.(ABSTRACT TRUNCATED AT 250 WORDS)", "State and national tobacco quitlines have expanded rapidly and offer a range of services. We examined the effectiveness and cost effectiveness of offering callers single session versus multisession counselling, with or without free nicotine patches.\n This 3x2 randomised trial included 4614 Oregon tobacco quitline callers and compared brief (one 15-minute call), moderate (one 30-minute call and a follow-up call) and intensive (five proactive calls) intervention protocols, with or without offers of free nicotine patches (nicotine replacement therapy, NRT). Blinded staff assessed tobacco use by phone at 12 months.\n Abstinence odds ratios were significant for moderate (OR = 1.22, CI = 1.01 to 1.48) and intensive (OR = 1.29, CI = 1.07 to 1.56) intervention, and for NRT (OR = 1.58, CI = 1.35 to 1.85). Intent to treat quit rates were as follows: brief no NRT (12%); brief NRT (17%); moderate no NRT (14%); moderate NRT (20%); intensive no NRT (14%); and intensive NRT (21%). Relative to brief no NRT, the added costs for each additional quit was $2467 for brief NRT, $1912 for moderate no NRT, $2109 for moderate NRT, $2641 for intensive no NRT, and $2112 for intensive NRT.\n Offering free NRT and multisession telephone support within a state tobacco quitline led to higher quit rates, and similar costs per incremental quit, than less intensive protocols.", "To evaluate the relative effectiveness of two self-help smoking interventions as adjuncts to a self-help manual and telephone support service (hotline) for older smokers.\n Subjects were stratified on baseline variables and randomised to one of two treatment conditions in a methods development study.\n 177 community-dwelling smokers aged 60 years and older.\n All subjects received a self-help manual and access to a smokers' telephone hotline. Subjects also received either mailings (Letters condition) or counselling telephone calls (Proactive condition) at four and eight weeks after enrollment.\n Use of the hotline and prevalence of abstinence lasting at least 48 hours (verified by a \"significant other\") were assessed at three and six months for the full sample. Seven-day abstinence was calculated for comparison with previous research. A subsample of 91 subjects was followed up at 12 months.\n Overall abstinence rates for the two conditions were in the range of typical self-help interventions. Men were more likely to be abstinent than women at follow up at three and six months. A significant gender x treatment interaction was found, with abstinence rates higher for men in the Letters condition, and women in the Proactive condition. Hotline use was high, with nearly half of subjects calling by 12 months.\n Both interventions appear promising for older smokers, but may be differentially effective for men and women. Older smokers will use a hotline; whether Letters and Proactive interventions can improve on manual and hotline effectiveness rates alone is being tested in a subsequent controlled trial.", "GPs are an important source of smoking cessation advice. This research examined whether a model encouraging GP referral of patients who smoke to a specialist service would be acceptable and effective for increased smoking cessation when compared with a model of in-practice management.\n The study design was cluster randomized controlled trial. Practices were randomized to one of two interventions, at a rate of 1:2: (i) standard in-practice GP management or (ii) referral to a quitline service. The main outcome measures were sustained abstinence of >or=1 month duration at 3-month follow-up and >or=10 months duration at 12 months, using intention to treat analysis.\n At 3-month follow-up, patients in the referral condition were twice as likely to report sustained abstinence than those in the in-practice condition [12.3% compared with 6.9%; odds ratio (OR) = 1.92 (95% confidence interval (CI) 1.17-3.13]. At 12-month follow-up, patients in the referral condition had nearly three times the odds of sustained abstinence [6.5% compared with 2.6%; OR = 2.86 (95% CI 0.94-8.71)]. The intervention effect was mediated by the amount of help received outside the practice.\n This research provided evidence that GPs referring smokers to an evidence-based quitline service results in increased cessation. The benefit is largely due to patients in the referral condition receiving more external help than patients in the in-practice condition, as they received equivalent practice-based help. Where suitable services exist, we recommend that referral become the normative strategy for management of smoking cessation in general practice to complement any practice-based help provided.", "To evaluate the effectiveness of repeated-contact proactive telephone counselling for smoking cessation in a UK setting.\n Randomized controlled trial.\n The Quitline, an established national telephone counselling service available throughout the UK.\n A total of 1,457 callers to the Quitline in 2000 and 2001 were allocated randomly to a Control group to receive usual care or to a Repeated Contact group to be offered five proactive calls in addition to usual care. MEASUREMENTS Prolonged abstinence and 24-hour point-prevalent abstinence 6 and 12 months after recruitment, quit attempts and 24-hour periods of abstinence in non-quitters.\n No significant differences were found between the Repeated Contact and Control groups on prolonged or point-prevalent abstinence. On an intention-to-treat basis, 9.5% of the Control group were abstinent for longer than 6 months at the 12-month follow-up, compared with 9.3% of the Repeated Contact group; 18.9% and 20.2%, respectively, were point-prevalent abstinent at the 6-month follow-up. Significantly more non-quitters in the Control group made a quit attempt in the first 6 months following recruitment than in the Repeated Contact group (62.6%/56.1%, P < 0.05). CONCLUSIONS Proactive telephone counselling did not significantly increase abstinence rates, and appeared to decrease quit attempts, in callers to the Quitline. A non-structured, client-led counselling protocol and insufficient pre-quit motivational counselling could account for the lack of effect.", "We conducted a 2-arm randomized trial to test the efficacy of self-help materials with or without proactive telephone counseling to increase cessation among teen smokers. Teen smokers (N = 402) recruited from 11 shopping malls and 1 amusement park in the southeastern United States were randomized to 1 of 2 groups: written self-help material plus video; or written self-help material, video, and telephone counseling. Cessation rates based on 7-day point-prevalent abstinence for the self-help and counseling arms were 11% and 16%, respectively (p = .25), at 4 months postbaseline and 19% and 21%, respectively (p = .80), at 8 months postbaseline. Sustained abstinence, reflecting 7-day abstinence at both time points, in the self-help and counseling arms was 7% and 9% (p = .59). Results suggest that minimal self-help cessation approaches that target youth have comparable success to that shown among adult smokers. However, refinements in telephone-counseling approaches may be needed to achieve the success observed in adult populations.\n Copyright 2004 American Psychological Association", "The development of acceptable, widely available and effective smoking cessation methods is central to public health strategy for tobacco control. We examined the effectiveness of a telephone callback counselling intervention, compared to the provision of self-help resources alone.\n Participants were 998 smokers calling a state-wide \"Quitline\" service randomly allocated to either callback counselling or ordinary care. The callback condition consisted of a series of brief counselling calls at strategic times in addition to ordinary care. The number of calls varied according to caller needs, and most occurred generally just before the person's quit day and in the week or two after it. The service was delivered by trained telephone counsellors.\n At the 3-month follow-up, significantly more participants in the callback group (24%) reported that they were quit, compared to those in the usual care comparison group (13%). The difference in point prevalence of smoking declined to 6% by the 12-month follow-up. Using sustained abstinence there was a significant benefit of callback counselling at 12-month follow-up. Treating dropouts as smokers reduced the overall magnitude of the effects somewhat. The benefit of callbacks was to marginally increase quit attempts and to significantly reduce relapse.\n Our findings are consistent with those of other studies demonstrating benefits of callback telephone counselling to facilitate cessation. Such counselling provides a flexible, relatively inexpensive and widely available form of cessation service. It appears to encourage a greater proportion of quit attempts and to reduce the rate of relapse among those quitting. Further research is required to determine ways to enhance effectiveness, particularly studies of how to reduce relapse.", "To assess the effectiveness of a program of computer-generated tailored advice for callers to a telephone helpline, and to assess whether it enhanced a series of callback telephone counselling sessions in aiding smoking cessation.\n Randomized controlled trial comparing: (1) untailored self-help materials; (2) computer-generated tailored advice only, and (3) computer-generated tailored advice plus callback telephone counselling. Assessment surveys were conducted at baseline, 3, 6 and 12 months.\n Victoria, Australia.\n A total of 1578 smokers who called the Quitline service and agreed to participate.\n Smoking status at follow-up; duration of cessation, if quit; use of nicotine replacement therapy; and extent of participation in the callback service.\n At the 3-month follow-up, significantly more (chi2(2) = 16.9; P < 0.001) participants in the computer-generated tailored advice plus telephone counselling condition were not smoking (21%) than in either the computer-generated advice only (12%) or the control condition (12%). Proportions reporting not smoking at the 12-month follow-up were 26%, 23% and 22%, respectively (NS) for point prevalence, and for 9 months sustained abstinence; 8.2, 6.0, and 5.0 (NS). In the telephone counselling group, those receiving callbacks were more likely than those who did not to have sustained abstinence at 12 months (10.2 compared with 4.0, P < 0.05). Logistic regression on 3-month data showed significant independent effects on cessation of telephone counselling and use of NRT, but not of computer-generated tailored advice.\n Computer-generated tailored advice did not enhance telephone counselling, nor have any independent effect on cessation. This may be due to poor timing of the computer-generated tailored advice and poor integration of the two modes of advice.", "Smokers (N = 756) were randomly assigned by stage of change to (a) standardized self-help manuals (ALA+ condition), (b) individualized manuals matched to stage (TTT condition), (c) interactive expert-system computer reports plus individualized manuals (ITT condition), or (d) a personalized condition with 4 counselor calls, stage manuals, and computer reports (PITT condition). Over 18 months, the ITT group's results more than doubled those of the ALA+ group on abstinence measures. The ALA+ and TTT conditions were equivalent over 12 months, but at 18 months the TTT condition was more effective. The ITT condition was the best or comparable with the best treatment at all follow-ups for smokers at all stages of change. Results suggest that an effective expert system has been developed, and discussion focuses on delivering this system to entire populations of smokers.", "The Agency for Healthcare Research and Quality (AHRQ) Smoking Cessation Clinical Practice Guideline recommends that all clinicians strongly advise their patients who use tobacco to quit.\n We conducted a randomized, controlled trial of the effectiveness of Guideline implementation at eight community-based primary care clinics in southern Wisconsin (four test sites, four control sites) among 2163 consecutively enrolled adult patients who smoked at least one cigarette per day and presented for nonemergency care during the baseline period (June 16, 1999, to June 20, 2000) or the intervention period (from June 21, 2000, to May 3, 2001). After collecting baseline data, staff at test sites implemented the intervention over a 2-month period. The intervention included a tutorial for intake clinicians, group and individual performance feedback for intake clinicians, use of a modified vital signs stamp, an offer of free nicotine replacement therapy, and proactive telephone counseling. Staff at control sites received only general information about the AHRQ Guideline. Self-reported abstinence from smoking was determined by telephone interviews at 2- and 6-month follow-up assessments. Hierarchical logistic regression models were used to estimate the odds ratios (ORs) for treatment assignment after adjustment for patient characteristics. All statistical tests were two-sided.\n There were no statistically significant differences in smoking cessation rates between participants at test and control sites during the baseline period. Among participants treated during the intervention period, those at test sites were more likely than those at control sites to report being abstinent at the 2-month (16.4% versus 5.8%; adjusted OR = 3.3, 95% confidence interval [CI] = 1.9 to 5.6; P<.001) and 6-month (15.4% versus 9.8%; adjusted OR = 1.7, 95% CI = 1.2 to 2.6; P =.009) follow-up assessments and to report continuous abstinence, that is, abstinence at both 2 and 6 months (10.9% versus 3.8%; adjusted OR = 3.4, 95% CI = 1.8 to 6.3; P<.001).\n Implementation of a guideline-based smoking cessation intervention by intake clinicians in primary care is associated with higher abstinence among smokers.", "The purpose of this prospective, randomized controlled study was to determine the efficacy of an intensified, late pregnancy, smoking cessation intervention for resistant pregnant smokers (n = 269). Participants received 3-5 min of counseling plus a self-help booklet at their first prenatal visit and seven booklets mailed weekly thereafter; at 28 weeks, all had been smoking in the past 28 days. The experimental group received a stage of change-based, personalized feedback letter and two telephone counseling calls using Motivational Interviewing (MI) strategies. The control group received care as usual. The 34th week cotinine data demonstrated no overall difference between groups. However, an implementation analysis suggested that 43% of women who received the full intervention (E2) were classified as not smoking compared to 34% of the control group. At 6 weeks postpartum, 27.1% of the E2 group reported being abstinent or light smokers vs. 14.6% of the controls. No differences were detected at 3 and 6 months postpartum. Results lend preliminary but very modest support for this intervention with resistant pregnant smokers. Improvements in the intervention and implementation issues are discussed.", "This study tested the effects of two organizational support processes, the provision of financial incentives for superior clinical performance and the availability of a patient (smoker) registry and proactive telephone support system for smoking cessation, on provider adherence to accepted practice guidelines and associated patient outcomes.\n Forty clinics of a large multispecialty medical group practice providing primary care services were randomly allocated to study conditions. Fifteen clinics each were assigned to the experimental conditions \"control\" (distribution of printed versions of smoking cessation guidelines) and \"incentive\" (financial incentive pay-out for reaching preset clinical performance targets). Ten clinics were randomized to receive financial incentives combined with access to a centralized patient registry and intervention system (\"registry\"). Main outcome measures were adherence to smoking cessation clinical practice guidelines and patients' smoking cessation behaviors.\n Patients' tobacco use status was statistically significant (P < 0.01) more frequently identified in clinics with the opportunity for incentives and access to a registry than in clinics in the control condition. Patients visiting registry clinics accessed counseling programs statistically significantly more often (P < 0.001) than patients receiving care in the control condition. Other endpoints did not statistically significantly differ between the experimental conditions.\n The impact of financial incentives and a patient registry/intervention system in improving smoking cessation clinical practices and patient behaviors was mixed. Additional research is needed to identify conditions under which such organizational support processes result in significant health care quality improvement and warrant the investment.", "Pharmacological interventions for smoking cessation are typically evaluated using volunteer samples (efficacy trials) but should also be evaluated in population-based trials (effectiveness trials). Nicotine replacement therapy (NRT) alone and in combination with behavioral interventions was evaluated on a population of smokers from a New England Veterans Affairs Medical Center. Telephone interviews were completed with 3,239 smokers, and 2,054 agreed to participate (64%). Participants were randomly assigned to one of four conditions: stage-matched manuals (MAN); NRT plus manuals (NRT + MAN); expert system plus NRT and manuals (EXP + NRT + MAN); and automated counseling plus NRT, manuals, and expert system (TEL + EXP + NRT + MAN). Assessments were completed at baseline, 10, 20, and 30 months. The point prevalence cessation rates at final follow-up (30 months) were MAN, 20.3%; NRT + MAN, 19.3%; EXP + NRT + MAN, 17.6%; and TEL + EXP + NRT + MAN, 19.9%. Stage-matched manuals provided cessation rates comparable with previous studies. The addition of NRT, expert system interventions, and automated telephone counseling failed to produce a further increase in intervention effectiveness.\n ((c) 2006 APA, all rights reserved).", "To investigate the effectiveness of telephone counselling as an adjunct to nicotine replacement therapy (NRT) by transdermal patch in smoking cessation.\n Randomised controlled trial.\n 854 smokers from New South Wales, aged 18 years and older, who had smoked at least 10 cigarettes per day for the past year and responded to newspaper advertisements between October 2001 and January 2002; the trial was conducted between October 2001 and August 2002.\n Random allocation to either NRT alone or NRT plus telephone counselling (5 sessions spaced according to a relapse-sensitive call schedule).\n Self-reported abstinence assessed by telephone questionnaires at 1, 2, 3 and 6 months: 28-day continuous abstinence at 3 and 6 months, and 90-day continuous abstinence at 6 months.\n 28-day continuous abstinence rates among participants receiving telephone counselling were significantly greater than among those not receiving telephone counselling at both 3 and 6 months (31.6% v 25.1%; P = 0.04 at 3 months; and 30.1% v 22.4%; P = 0.01 at 6 months). Similarly, 90-day continuous abstinence rates at 6 months were significantly greater for participants receiving counselling (26.7% v 18.6%; P = 0.004).\n Telephone counselling as an adjunct to NRT increases abstinence rates beyond the use of NRT alone.", "This prospective randomized study examined the impact of three tailored intervention approaches to increase quitting rates among African-American smokers who were clients of a community health center that serves primarily low-income and indigent persons. Smokers were randomized to one of three groups: (1) health care provider prompting intervention alone, (2) health care provider prompting intervention with tailored print communications, and (3) health care provider prompting intervention with tailored print communications and tailored telephone counseling. Among the 160 smokers who completed the study, 35 (21.8%) had quit smoking at follow-up. Smokers who received the provider prompting intervention with tailored print materials were more likely to report having quit than smokers who received the provider intervention alone (32.7% vs. 13.2%, p < 0.05). Smokers who received all three intervention components were not more likely to report having quit at follow-up than those who only received the provider intervention (19.2% vs. 13.2%). Smokers who at baseline were less educated, smoked less than half a pack of cigarettes per day, had a stronger desire to quit, felt more efficacious, and had thought about quitting were more likely to report having quit at follow-up. These results provide support for continued refinement of tailored communications to aid smoking cessation among African-American smokers.", "There is new evidence that smokers of all ages benefit from cessation of smoking. Although most older smokers, like younger smokers, prefer to quit on their own, at the time this project was started, there were no materials or programs targeted to older smokers. Using the literature, focus groups with older smokers and a national survey of older smokers, we created Clear Horizons, a self-help guide for older smokers, and a telephone counseling protocol tailored to the needs of older smokers (age 50-74). Smokers were recruited from around the United States and assigned randomly to a control guide, Clearing the Air, Clear Horizons alone or Clear Horizons and two counselor calls. Follow-up of nearly 2000 smokers was conducted by telephone 3, 6, 12 and 24 months after delivery of the self-help guides. This report focuses primarily on results at 3 months because that was the measurement for reactions to the interventions. At the 3 month interview, those in the tailored interventions rated their guides more highly than did those in the control group. They also read more of their guides and were more likely to reread them. Quit rates were significantly higher among smokers who received a combination of the tailored guide and telephone counseling. At 3 months, the combination of the guide and telephone counseling was most effective in helping smokers to quit. By 12 months, both the tailored guide alone and the tailored guide and calls groups had higher quit rates than the control guide but were not statistically different from one another.", "This study evaluates alternative protocols in telephone counselling for smoking cessation.\n The American Cancer Society enrolled 6322 clients in a randomised trial comparing three counselling formats of varying duration and frequency of contact, with or without booster sessions, and mailed self help booklets without telephone counselling.\n Participants were drawn from callers to the American Cancer Society's National Cancer Information Center seeking assistance with smoking cessation who provided informed consent and were adult daily smokers, ready to make a quit attempt within two weeks, and from states not served by an evidence based proactive telephone counselling programme.\n Six-month cessation rates (30-day point prevalence) were measured in telephone interviews.\n There was a significant counselling effect. The overall cessation rates that were yielded by a brief protocol including booster sessions were equivalent to those obtained with the American Cancer Society's standard protocol with boosters.\n Based on these findings, the abbreviated protocol with five sessions and two boosters is considered to be an option for improving cost efficiency in the delivery of this service.", "This study examined the effect of program format and incentives on participation and cessation in worksite smoking cessation programs.\n Twenty-four worksites were randomized to 6 conditions that differed in cessation program format and the use of incentives. Programs were offered for 18 months in each worksite. A total of 2402 cigarette smokers identified at baseline were surveyed 12 and 24 months later to assess participation in programs and cessation.\n A total of 407 (16.9%) of the smoker cohort registered for programs; on the 12- and 24-month surveys, 15.4% and 19.4% of the cohort, respectively, reported that they had not smoked in the previous 7 days. Registration for programs in incentive sites was almost double that of no-incentive sites (22.4% vs 11.9%), but increased registration did not translate into significantly greater cessation rates. Program type did not affect registration or cessation rates.\n Although incentives increase rates of registration in worksite smoking cessation programs, they do not appear to increase cessation rates. Phone counseling seems to be at least as effective as group programs for promoting smoking cessation in worksites.", "Few research studies have evaluated the effectiveness of smoking interventions in hospitalized patients. This randomized controlled trial compared the efficacy of 2 smoking cessation programs in patients hospitalized in 4 community hospitals in a large health maintenance organization within the San Francisco Bay Area in California.\n Patients were randomly assigned to usual care (n = 990), nurse-mediated, behaviorally oriented inpatient counseling focused on relapse prevention with 1 postdischarge telephone contact (minimal intervention, n = 473), or the same inpatient counseling with 4 postdischarge telephone contacts (intensive intervention, n = 561). The main outcome measure, smoking cessation rate, was corroborated by plasma cotinine determination or family confirmation, 1 year after enrollment.\n At 1 year smoking cessation rates were 27%, 22%, and 20% for intensive intervention, minimal intervention, and usual care groups, respectively (P = .009 for intensive vs usual care). Subgroup analyses by diagnosis revealed that the odds of cessation among patients with cardiovascular disease or other internal medical conditions were greater among those receiving the intensive intervention than among their counterparts receiving usual care (odds ratios, 1.6 and 2.0, respectively).\n A multicomponent smoking cessation program consisting of physician advice; in-hospital, nurse-mediated counseling; and multiple postdischarge telephone contacts was effective in increasing smoking cessation rates among hospitalized smokers. Hospital-wide smoking cessation programs could substantially increase the effectiveness of hospital smoking bans.", "Cancer survivors smoke at rates that are only slightly lower than the general population. This article reports on the final outcomes of Partnership for Health, a smoking cessation intervention for smokers in the Childhood Cancer Survivors Study (CCSS).\n This study is a randomized control trial with follow-up at 8 and 12 months that involved smokers (n = 796) enrolled onto the CCSS cohort. Participants were randomly assigned to either a self-help or a peer-counseling program that included up to six telephone calls from a trained childhood cancer survivor, tailored and targeted materials, and free nicotine replacement therapy. The intervention was delivered by telephone and postal service mail.\n The quit rate was significantly higher in the counseling group compared with the self-help group at both the 8-month (16.8% v 8.5%; P < .01) and 12-month follow-ups (15% v 9%; P < or = .01). Controlling for baseline self-efficacy and readiness to change, the intervention group was twice as likely to quit smoking, compared with the self-help group. Smoking cessation rate increased with an increase in the number of counseling calls. The cost of delivering the intervention was approximately 300 dollars per participant. The incremental cost-effectiveness of the intervention compared with controls was 5,371 dollars per additional quit.\n Interventions to prevent future illnesses are of critical importance to childhood cancer survivors. The Partnership for Health intervention resulted in a doubling of smoking cessation quit rates. Because of the seriousness of smoking among childhood cancer survivors, this intervention model may be appropriate as a multicomponent treatment program for survivors who smoke.", "Telephone counseling in chronic disease self-management is increasing, but has not been tested in studies that control for quality of medical care.\n To test the effectiveness of a six-session outpatient telephone-based counseling intervention to improve secondary prevention (behaviors, medication) in patients with acute coronary syndrome (ACS) following discharge from hospital, and impact on physical functioning and quality of life at 8 months post-discharge.\n Patient-level randomized trial of hospital quality improvement (QI-only) versus quality improvement plus brief telephone coaching in three months post-hospitalization (QI-plus). Data: medical record, state vital records, patient surveys (baseline, three and eight months post-hospitalization). Analysis: pooled-time series generalized estimating equations to analyze repeated measures; intention-to-treat analysis.\n Seven hundred and nineteen patients admitted to one of five hospitals in two contiguous mid-Michigan communities enrolled; 525 completed baseline surveys.\n We measured secondary prevention behaviors, physical functioning, and quality of life.\n QI-plus patients showed higher self-reported physical activity (OR = 1.53; p = .01) during the first three months, with decline after active intervention was withdrawn. Smoking cessation and medication use were not different at 3 or 8 months; functional status and quality of life were not different at 8 months.\n Telephone coaching post-hospitalization for ACS was modestly effective in accomplishing short-term, but not long-term life-style behavior change. Previous positive results shown in primary care did not transfer to free-standing telephone counseling as an adjunct to care following hospitalization.", "Telephone services that offer smoking-cessation counseling (quitlines) have proliferated in recent years, encouraged by positive results of clinical trials. The question remains, however, whether those results can be translated into real-world effectiveness.\n We embedded a randomized, controlled trial into the ongoing service of the California Smokers' Helpline. Callers were randomly assigned to a treatment group (1973 callers) or a control group (1309 callers). All participants received self-help materials. Those in the treatment group were assigned to receive up to seven counseling sessions; those in the control group could also receive counseling if they called back for it after randomization.\n Counseling was provided to 72.1 percent of those in the treatment group and 31.6 percent of those in the control group (mean, 3.0 sessions). The rates of abstinence for 1, 3, 6, and 12 months, according to an intention-to-treat analysis, were 23.7 percent, 17.9 percent, 12.8 percent, and 9.1 percent, respectively, for those in the treatment group and 16.5 percent, 12.1 percent, 8.6 percent, and 6.9 percent, respectively, for those in the control group (P<0.001). Analyses factoring out both the subgroup of control subjects who received counseling and the corresponding treatment subgroup indicate that counseling approximately doubled abstinence rates: rates of abstinence for 1, 3, 6, and 12 months were 20.7 percent, 15.9 percent, 11.7 percent, and 7.5 percent, respectively, in the remaining subjects in the treatment group and 9.6 percent, 6.7 percent, 5.2 percent, and 4.1 percent, respectively, in the remaining subjects in the control group (P<0.001). Therefore, the absolute difference in the rate of abstinence for 12 months between the remaining subjects in the treatment and control groups was 3.4 percent. The 12-month abstinence rates for those who made at least one attempt to quit were 23.3 percent in the treatment group and 18.4 percent in the control group (P<0.001).\n A telephone counseling protocol for smoking cessation, previously proven efficacious, was effective when translated to a real-world setting. Its success supports Public Health Service guidelines calling for greater availability of quitlines.\n Copyright 2002 Massachusetts Medical Society", "It is unclear whether proactive telephone support enhances smoking cessation beyond the provision of nicotine replacement therapy alone.\n We randomly assigned 330 low-income women smokers to receive either free nicotine patches (control condition) or free nicotine patches with up to 16 weeks of proactive telephone support (experimental condition). All participants were assessed by telephone at baseline and at 2 weeks, 3 months, and 6 months post-baseline to determine smoking status.\n Results revealed a significant effect for the telephone support at 3 months, with 43% of experimental versus 26% of control condition women reporting 30-day point prevalent abstinence (P = 0.002). The difference was no longer significant at 6 months. A metaanalysis conducted with five randomized studies revealed a slight but non-significant long-term benefit of proactive telephone support when added to the provision of free nicotine patches for smoking cessation.\n This is the second study to demonstrate a short-term effect for proactive telephone support added to free nicotine replacement therapy; however, neither the current study, nor the metaanalysis including the four other published trials, confirmed a longer-term benefit.", "GPs often lack time to provide intensive cessation advice for patients who smoke. This study aimed to determine the effectiveness of opportunistic referral of smokers by their GP for telephone cessation counselling by a trained nurse.\n Adult smokers (n = 318) attending 30 GPs in South Western Sydney, Australia were randomly allocated to usual care or referral to a telephone-based program comprising assessment and stage-based behavioural advice, written information and follow-up delivered by a nurse. Self-reported point prevalence abstinence at six and 12 months was compared between groups. Characteristics of patients who accepted and completed the intervention were investigated.\n Of 169 smokers randomised to the intervention, 76 (45%) consented to referral. Compared with smokers in 'pre-contemplation', those further along the stage-of-change continuum were significantly more likely to consent (p = 0.003). Those further along the continuum also were significantly more likely to complete all four calls of the intervention (OR 2.6, 95% CI: 0.8-8.1 and OR 8.6, 95% CI: 1.7-44.4 for 'contemplation' and 'preparation' respectively). At six months, there was no significant difference between groups in point prevalence abstinence (intention to treat) (9% versus 8%, p = 0.7). There was no evidence of differential intervention effectiveness by baseline stage-of-change (p = 0.6) or patient sex (p = 0.5). At 12 months, point prevalence abstinence in the intervention and control groups was 8% and 6% respectively (p = 0.6).\n Acceptance of opportunistic referral for nurse delivered telephone cessation advice was low. This trial did not demonstrate improved quit rates following the intervention. Future research efforts might better focus support for those patients who are motivated to quit. AUSTRALIAN CLINICAL TRIALS REGISTRY NUMBER: ACTRN012607000091404.", "This study tested the impact of free nicotine patches plus proactive telephone peer support to help low-income women stop smoking.\n A total of 214 Medicaid-eligible women smokers of childbearing age were randomized to receive free nicotine patches through the mail or free nicotine patches through the mail plus the provision of proactive support by telephone from a woman ex-smoker for up to 3 months. Assessments were conducted by telephone at baseline, 10 days, and 3 and 6 months after enrollment.\n At the 3-month follow-up, significantly more women in the patch plus proactive telephone support condition were abstinent (42%) compared to the patch only condition (28%) (P = 0.03). Similarly, more women in the experimental condition were abstinent at both the 10-day and 3-month assessments (32 v 19%, P = 0.02). However, differences were not found at the 6-month follow-up, suggesting that the addition of proactive telephone peer support enhanced short-term, but not long-term cessation.\n This is the first study to demonstrate a beneficial effect for the addition of proactive telephone support as an adjunct to free nicotine replacement in a low-income population.\n Copyright 2000 American Health Foundation and Academic Press.", "The effect of a smokers' hotline as an adjunct to self-help manuals was examined. Subjects were 1,813 smokers recruited from a 10-county rural and small urban area. Counties were matched on demographic characteristics and assigned to a manual only or manual plus hotline condition. Subjects were followed over an 18-month period. Hotline services included taped messages and access to paraprofessional counselors. Results show a consistent, significant hotline effect across outcome measures and follow-up periods. This effect emerged either as a main effect for the hotline or as an interaction with enrollment method such that a significant hotline effect emerged for subjects who enrolled through face-to-face methods. These findings indicate the effectiveness of the hotline in enhancing self-help quit rates.", "To examine the options for use, efficiency, and effectiveness for structuring a population-based telephone smoking-cessation service.\n Callers (n=632) to a 1-800 number were randomized in a 2 (50-minute counseling with 2/6 calls) x 2 (pamphlet/booklet) design with print only control.\n Six-month use of the service was 0.6% of adult smokers. Service promotion cost 31.02 dollars/person. Telephone counseling resulted in higher continued abstinence (5%) than did print only (1%), P<.05. Amount of print and calls did not increase cessation. Six calls resulted in lower completion rates than 2 (22% vs 56%, P<.05).\n For planning, consider 1% use, low-cost promotion, pamphlet, 50-minute initial counseling plus 2 follow-ups, and minimize call-attempts.", "To examine whether reimbursement for Provider Counseling, Pharmacotherapies, and a telephone Quitline increase smoking cessation relative to Usual Care.\n Randomized comparison trial testing the effectiveness of four smoking cessation benefits.\n Seven states that best represented the national population in terms of the proportion of those > or = 65 years of age and smoking rate.\n There were 7,354 seniors voluntarily enrolled in the Medicare Stop Smoking Program and they were followed-up for 12 months.\n (1) Usual Care, (2) reimbursement for Provider Counseling, (3) reimbursement for Provider Counseling with Pharmacotherapy, and (4) telephone counseling Quitline with nicotine patch.\n Seven-day self-reported cessation at 6- and 12-month follow-ups.\n Unadjusted quit rates assuming missing data=smoking were 10.2 percent (9.0-11.5), 14.1 percent (11.7-16.5), 15.8 percent (14.4-17.2), and 19.3 percent (17.4-21.2) at 12 months for the Usual Care, Provider Counseling, Provider Counseling + Pharmacotherapy, and Quitline arms, respectively. Results were robust to sociodemographics, smoking history, motivation, health status, and survey nonresponse. The additional cost per quitter (relative to Usual Care) ranged from several hundred dollars to $6,450.\n A telephone Quitline in conjunction with low-cost Pharmacotherapy was the most effective means of reducing smoking in the elderly.", "Smoking, alcohol use, and depression are interrelated and highly prevalent in patients with head and neck cancer, adversely affecting quality of life and survival. Smoking, alcohol, and depression share common treatments, such as cognitive behavioral therapy and antidepressants. Consequently, we developed and tested a tailored smoking, alcohol, and depression intervention for patients with head and neck cancer.\n Patients with head and neck cancer with at least one of these disorders were recruited from the University of Michigan and three Veterans Affairs medical centers. Subjects were randomized to usual care or nurse-administered intervention consisting of cognitive behavioral therapy and medications. Data collected included smoking, alcohol use, and depressive symptoms at baseline and at 6 months.\n The mean age was 57 years. Most participants were male (84%) and White (90%). About half (52%) were married, 46% had a high school education or less, and 52% were recruited from Veterans Affairs sites. The sample was fairly evenly distributed across three major head and neck cancer sites and over half (61%) had stage III/IV cancers. Significant differences in 6-month smoking cessation rates were noted with 47% quitting in the intervention compared with 31% in usual care (P < 0.05). Alcohol and depression rates improved in both groups, with no significant differences in 6-month depression and alcohol outcomes.\n Treating comorbid smoking, problem drinking, and depression may increase smoking cessation rates above that of usual care and may be more practical than treating these disorders separately.", "Current treatment guidelines recommend that all smokers be given motivational or action-oriented counseling, as is appropriate to their readiness to quit smoking. The present study assessed the acceptability and impact of a proactively delivered, motivationally tailored phone counseling program targeted to women with elevated risk for cervical cancer. Female smokers with a recent abnormal pap exam or a colposcopy were contacted and invited to participate, regardless of their interest in quitting smoking. Participants were randomly assigned to usual care (UC) or UC plus motivationally enhanced phone counseling (MEC). The intervention was well received: 79% of eligible women enrolled (n = 275), and 90% completed at least three of four calls. Participation did not vary by baseline motivation to quit. Compared with control subjects, counseling participants were more likely to seek additional treatment services and had a higher 7-day point-prevalence abstinence rate at 6 months (20% MEC vs. 12% UC, p<.05). MEC impact was sustained at 12 months, but abstinence increased among the UC group (18% MEC vs. 20% UC, p = ns). There was no difference in repeated point-prevalence abstinence at 6 and 12 months (11% MEC vs. 10% UC, p = ns). Outcomes were similar in a subgroup of 229 women who, at baseline, were interested in quitting in the next 6 months." ]

[ "4685999", "131976", "8516054", "7054760" ]

[ "Studies on dengue hemorrhagic fever. Clinical study: an evaluation of steroids as a treatment.", "Hydrocortisone in the management of dengue shock syndrome.", "Failure of high-dose methylprednisolone in established dengue shock syndrome: a placebo-controlled, double-blind study.", "Failure of hydrocortisone to affect outcome in dengue shock syndrome." ]

[ "nan", "A total of 98 patients with dengue shock syndrome admitted into Children's Hospital from February 1973 to February 1974 were randomly selected into 2 groups. A double blind controlled trial of the efficacy of pharmacologic doses of hydrocortisone hemisuccinate was carried out. The 2 groups were confirmed to be completely matched by age, sex and severity of the disease. Nine deaths occurred out of 48 cases in the steroid group (Case Fatality Rate 18.75%) and 22 deaths out of 50 cases in the non-steroid group (Case Fatality Rate 44%), the difference being statistically significant. No significant difference was detected in fluid requirements and other morbidity pattern.", "Steroids are widely used in Thailand and other dengue-endemic countries to treat severe dengue shock syndrome. This study was designed to determine whether a single high dose of methylprednisolone will reduce mortality in children with dengue shock syndrome who did not respond to simple fluid and plasma replacement therapy.\n A prospective, randomized, double-blind, controlled trial was conducted in two hospitals in Khon Kaen Thailand during June to September in 1987 and 1988. Sixty-three children with severe dengue shock syndrome were randomized into two groups; the first group received a single dose of methylprednisolone (30 mg/kg) and the second group received placebo.\n There was no significant difference in mortality between the two groups (P = .63). The mortality rate was 12.5% (4/32) in the steroid group and 12.9% (4/31) in the group that received placebo. The sequelae at 2 weeks among treatment and control survivors were not significantly different. These two groups were comparable in age, sex, severity of illness, and duration of shock at the outset of the study. The two treatment groups were similar in subsequent hospital course as determined by maximum and minimum hematocrit level and bleeding severity. The numbers of patients in each group who had liver failure and evidence of disseminated intravascular clotting defect were also comparable. Complications such as occurrence of fever after shock, pneumonia, convulsion, cardiac arrest, pulmonary hemorrhage, and positive hemoculture were not significantly different in the treatment and control groups.\n A single high dose of methylprednisolone does not reduce mortality in severe dengue shock syndrome which does not respond to conventional critical care.", "Despite the absence of a clear-cut rationale for their use, corticosteroids are widely employed in the treatment of dengue shock syndrome. Previous comparative therapeutic trials have yielded contradictory results. Resolution of this therapeutic controversy has been attempted with a double-blind evaluation of the clinical effect of steroid administration in dengue shock syndrome. Placebo or a single dose of hydrocortisone hemisuccinate, 50 mg/kg of body weight, was administered randomly to 97 physiologically treated patients with dengue shock syndrome. The severity of disease on admission to the hospital and the effectiveness of treatment were quantified by a World Health Organization scoring system. The response to therapy as measured by mortality, duration of shock, and amount of replacement fluids required was virtually identical in 47 children who were and 50 children who were not treated with steroids. The comparison groups were composed of children similar in age, sex, and severity of illness. It is concluded that hydrocortisone is of no value in the treatment of dengue shock syndrome. Reliance should be placed on appropriate supportive and physiologic therapy." ]

[ "9626225", "9196130", "11454878", "11283120", "11750840", "15226331" ]

[ "Randomized phase II study of two schedules of topotecan in previously treated patients with ovarian cancer: a National Cancer Institute of Canada Clinical Trials Group study.", "Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer.", "Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan.", "Clinical evidence for topotecan-paclitaxel non--cross-resistance in ovarian cancer.", "A randomised trial of oral versus intravenous topotecan in patients with relapsed epithelial ovarian cancer.", "Topotecan compared with no therapy after response to surgery and carboplatin/paclitaxel in patients with ovarian cancer: Multicenter Italian Trials in Ovarian Cancer (MITO-1) randomized study." ]

[ "As topotecan is S-phase-specific, its efficacy is likely schedule-dependent. Therefore, a randomized study using a \"pick the winner\" design was undertaken to compare two schedules in patients with recurrent ovarian cancer.\n Patients with recurrent epithelial ovarian cancer previously treated with no more than two separate regimens of chemotherapy, one of which had to be platinum-containing, were randomized to either topotecan 1.5 mg/m2 intravenously (i.v.) over 30 minutes daily for 5 days repeated every 21 days (arm A, the standard arm), or topotecan 1.75 mg/m2 as a 24-hour infusion once a week for 4 weeks repeated every 6 weeks (arm B, the experimental arm).\n Sixty-six patients were eligible and 63 were assessable for response. The response rate in arm A was 22.6% (95% confidence interval [CI], 9.6% to 41.2%), which was significantly superior to that in arm B, 3.1% (95% CI, 0.1% to 16%) (P = .026). The regimens were not equitoxic, with 94% of patients on arm A experiencing grade 3 or 4 granulocytopenia as opposed to 52% on arm B.\n The weekly 24 hour infusion of topotecan at 1.75 mg/m2 was ineffective in relapsed ovarian cancer. The daily-times-five schedule remains the schedule of choice. As the regimens were not equitoxic, one cannot differentiate between an ineffective schedule and an ineffective dose as the reason for the differing response rates. However, the degree of myelotoxicity that already occurs will preclude any substantially higher dosing with the weekly regimen.", "Topotecan and paclitaxel were evaluated in a randomized, multicenter study of patients with advanced epithelial ovarian carcinoma who had progressed during or after one platinum-based regimen.\n Patients received either topotecan (1.5 mg/m2) as a 30-minute infusion daily for 5 days every 21 days (n = 112) or paclitaxel (175 mg/m2) infused over 3 hours every 21 days (n = 114). Patients had bidimensionally measurable disease and were assessed for efficacy and toxicity.\n Response rate was 23 of 112 (20.5%) in topotecan-treated patients and 15 of 114 (13.2%) in paclitaxel-treated patients (P = .138). Disease stabilization for at least 8 weeks was noted in 30% of patients with topotecan and 33% of patients with paclitaxel. Median durations of response to topotecan and paclitaxel were 32 and 20 weeks, respectively (P = .222) and median times to progression were 23 and 14 weeks, respectively (P = .002). Median survival was 61 weeks for topotecan and 43 weeks for paclitaxel (P = .515). Response rates for topotecan and paclitaxel were 13.3% versus 6.7% (P = .303) in resistant patients (not responded to prior platinum-based therapy or progressed within 6 months of an initial response) and 28.8% versus 20.0% (P = .213) in sensitive patients (progressed > 6 months after response). Neutropenia was significantly more frequent on the topotecan arm 79% versus paclitaxel arm 23% (P < .01). It was short-lasting and noncumulative in both arms. Nonhematologic toxicities were generally mild (grades 1 to 2) for both agents.\n Topotecan has efficacy at least equivalent to paclitaxel manifested by the higher response rate and significantly longer time to progression.", "To compare the efficacy and safety of pegylated liposomal doxorubicin (PLD) and topotecan in patients with epithelial ovarian carcinoma that recurred after or didn't respond to first-line, platinum-based chemotherapy.\n Patients with measurable and assessable disease were randomized to receive either PLD 50 mg/m(2) as a 1-hour infusion every 4 weeks or topotecan 1.5 mg/m(2)/d for 5 consecutive days every 3 weeks. Patients were stratified prospectively for platinum sensitivity and for the presence or absence of bulky disease.\n A total of 474 patients were treated (239 PLD and 235 topotecan). They comprised the intent-to-treat population. The overall progression-free survival rates were similar between the two arms (P =.095). The overall response rates for PLD and topotecan were 19.7% and 17.0%, respectively (P =.390). Median overall survival times were 60 weeks for PLD and 56.7 weeks for topotecan. Data analyzed in platinum-sensitive patients demonstrated a statistically significant benefit from PLD for progression-free survival (P =.037), with medians of 28.9 for PLD versus 23.3 weeks for topotecan. For overall survival, PLD was significantly superior to topotecan (P =.008), with a median of 108 weeks versus 71.1 weeks. The platinum-refractory subgroup demonstrated a nonstatistically significant survival trend in favor of topotecan (P =.455). Severe hematologic toxicity was more common with topotecan and was more likely to be associated with dosage modification, or growth factor or blood product utilization.\n The comparable efficacy, favorable safety profile, and convenient dosing support the role of PLD as a valuable treatment option in this patient population.", "A large, randomized study comparing the efficacy and safety of topotecan versus paclitaxel in patients with relapsed epithelial ovarian cancer showed that these two compounds have similar activity. In this study, a number of patients crossed over to the alternative drug as third-line therapy, ie, from paclitaxel to topotecan and vice versa. We therefore were able to assess the degree of non-cross-resistance between these two compounds.\n Patients who had progressed after one platinum-based regimen were randomized to either topotecan (1.5 mg/m(2)/d) x 5 every 21 days (n = 112) or paclitaxel (175 mg/m(2) over 3 hours) every 21 days (n = 114). A total of 110 patients received cross-over therapy with the alternative drug (61 topotecan, 49 paclitaxel) as third-line therapy.\n Response rates to third-line cross-over therapy were 13.1% (8 of 61 topotecan) and 10.2% (5 of 49 paclitaxel; P =.638). Seven patients who responded to third-line topotecan and four patients who responded to paclitaxel had failed to respond to their second-line treatment. Median time to progression (from the start of third-line therapy) was 9 weeks in both groups, and median survival was 40 and 48 weeks for patients who were receiving topotecan or paclitaxel, respectively. The principal toxicity was myelosuppression; grade 4 neutropenia was more frequent with topotecan (81.4% of patients) than with paclitaxel (22.9% of patients).\n Topotecan and paclitaxel have similar activity as second-line therapies with regard to response rates and progression-free and overall survival. We demonstrated that the two drugs have a degree of non-cross-resistance. Thus, there is a good rationale for incorporating these drugs into future first-line regimens.", "A multicentre, randomised study was carried out in Europe, South Africa and North America to compare the activity and tolerability of oral versus intravenous (i.v.) topotecan in patients with relapsed epithelial ovarian cancer. Patients who had failed first-line therapy after one platinum-based regimen, which could have included a taxane, were randomised to treatment with either oral (p.o.) topotecan, 2.3 mg/m(2)/day or i.v. topotecan 1.5 mg/m(2)/day for 5 days every 21 days. Patients were stratified by prior paclitaxel exposure, interval from previous platinum therapy and tumour diameter. 266 patients were randomised. Response rates were 13% orally (p.o.) and 20% (i.v.) with a complete response in 2 and 4 patients, respectively. The difference in the response rates was not statistically significant. Median survival was 51 weeks (p.o.) and 58 weeks (i.v.) with a risk ratio of death (p.o. to i.v. treatment) of 1.361 (95% confidence interval (CI): 1.001, 1.850). Median time to progression was 13 weeks (p.o.) and 17 weeks (i.v.). The principal toxicity was myelosuppression although grade 3/4 neutropenia occurred less frequently in those receiving oral topotecan. Toxicity was non-cumulative and infectious complications were relatively infrequent. Non-haematological toxicity was generally mild or moderate. The incidence of grade 3/4 gastrointestinal events was slightly higher for oral than i.v. topotecan. Oral topotecan shows activity in second-line ovarian cancer and neutropenia may be less frequent than with the i.v. formulation. A small, but statistically significant, difference in survival favoured the i.v. formulation, but the clinical significance of this needs to be interpreted in the context of second-line palliative treatment. Oral topotecan is convenient and well tolerated and further studies to clarify its role are ongoing.", "Topotecan is an active second-line treatment for advanced ovarian cancer. Its efficacy as consolidation treatment after first-line standard chemotherapy is unknown.\n To investigate whether topotecan (1.5 mg/m(2) on days 1 through 5, four cycles, every 3 weeks) prolonged progression-free survival (PFS) for patients responding to standard carboplatin (area under the curve 5) and paclitaxel (175 mg/m(2) administered as a 3-hour infusion in six cycles; CP), a multicenter phase III study was performed with an 80% power to detect a 50% prolongation of median PFS. Patients were registered at diagnosis and randomized after the end of CP.\n Two hundred seventy-three patients were randomly assigned (topotecan, n = 137; observation, n = 136), with a median age of 56 years. Stage at diagnosis was advanced in three fourths of patients (stage III in 65% of patients; stage IV in 10%); after primary surgery, 46% had no residual disease and 20% were optimally debulked. After CP, 87% reached a clinical complete response, and 13% achieved a partial response. Neutropenia (grade 3/4 in 58% of the patients) and thrombocytopenia (grade 3 in 21%; grade 4 in 3%) were the most frequent toxicities attributed to topotecan. There was no statistically significant difference in PFS between the arms (P =.83; log-rank test): median PFS was 18.2 months in the topotecan arm and 28.4 in the control arm. Hazard ratio of progression for patients receiving topotecan was 1.18 (95% CI, 0.86 to 1.63) after adjustment for residual disease, interval debulking surgery, and response to CP.\n The present analysis indicates that consolidation with topotecan does not improve PFS for patients with advanced ovarian cancer who respond to initial chemotherapy with carboplatin and paclitaxel." ]

[ "10943575", "11559453", "16307962", "20384388", "16135578" ]

[ "A comparative investigation of contraceptive reliability, cycle control and tolerance of two monophasic oral contraceptives containing either drospirenone or desogestrel.", "Evaluation of a unique oral contraceptive in the treatment of premenstrual dysphoric disorder.", "Treatment of premenstrual dysphoric disorder with a new drospirenone-containing oral contraceptive formulation.", "Effects of oral contraceptives containing ethinylestradiol with either drospirenone or levonorgestrel on various parameters associated with well-being in healthy women: a randomized, single-blind, parallel-group, multicentre study.", "Efficacy of a new low-dose oral contraceptive with drospirenone in premenstrual dysphoric disorder." ]

[ "To assess the contraceptive reliability, cycle control and tolerance of a new monophasic oral contraceptive (Yasmin) containing 30 microg ethinylestradiol and 3 mg drospirenone and compare it with a preparation containing an equal dose of ethinylestradiol combined with 150 microg desogestrel (Marvelon).\n A multicenter, open-label, randomized study was carried out in 26 European centers. Contraceptive efficacy, cycle control and tolerance (including body weight, blood pressure and heart rate) were assessed over 26 cycles, plus a 3-month follow-up period.\n Of 900 women who were randomized, 887 started treatment and 627 completed the 26 cycles plus follow-up (310 in the ethinylestradiol/drospirenone group and 317 in the ethinylestradiol/desogestrel group). Both study preparations were found to be effective with regard to contraceptive reliability and cycle control was good. There were six pregnancies (three in each group), but none were considered to have been the result of method failures. The subjective and objective tolerances were good in both groups. A statistically significant difference was found in body weight changes between the two groups. While there was an increase in mean body weight in the ethinylestradiol/desogestrel group from cycle 5 onward, the mean body weight per cycle in the ethinylestradiol/drospirenone group was slightly below the baseline value throughout the study. The incidence ofpremenstrual symptoms was higher in the ethinylestradiol/drospirenone group than in the ethinylestradiol/desogestrel group during the 6 months prior to the study, but lower during treatment. The rates ofdysmenorrhea were identical under both treatments but the symptoms were more often mild and less often severe in the ethinylestradiol/drospirenone group.\n The combination of 30 microg ethinylestradiol combined with 3 mg drospirenone provides effective oral contraception and good cycle control, and is well tolerated. Ethinylestradiol/drospirenone had a more favorable effect on body weight than ethinylestradiol/desogestrel, with the mean body weight remaining lower than baseline for the majority of the women.", "Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS). This is the first trial of a unique oral contraceptive containing a combination of drospirenone (DRSP, 3 mg) and ethinyl estradiol (EE, 30 microg) for the treatment of PMDD. DRSP is a spironolactone-like progestin with antiandrogenic and antimineralocorticoid activity. Spironolactone has been shown to be beneficial in PMS, whereas oral contraceptives have shown conflicting results. In this double-blind, placebo-controlled trial, 82 women with PMDD (Diagnostic and Statistical Manual of Mental Disorders, 4th ed. [DSM IV]) were randomized to receive DRSP/EE or placebo for three treatment cycles. The primary end point was change from baseline in luteal phase symptom scores as assessed on the Calendar of Premenstrual Experiences (COPE) scale. Patients treated with DRSP/EE showed a numerically greater change from baseline compared with those treated with placebo on each of the 22 COPE items and each of the 4 symptom factors. Between-group differences in symptom improvement reached statistical significance in factor 3 only (appetite, acne, and food cravings, p = 0.027). The secondary end points, Beck Depression Inventory (BDI) and Profile of Mood States (PMS), were consistent with the primary end point in that patients treated with the oral contraceptive showed a numerically greater improvement from baseline compared with those treated with placebo. The results of this study show a consistent trend in the reduction of symptoms that suggested a beneficial effect of DRSP/EE for the treatment of PMDD, despite limitations of the study design.", "This multicenter, double-blind, placebo-controlled crossover study evaluated the efficacy of a new oral contraceptive (OC) formulation containing drospirenone 3 mg and ethinyl estradiol (EE) 20 mug in treating symptoms of premenstrual dysphoric disorder (PMDD).\n The OC formulation or placebo was administered for 24 days in a 28-day cycle (24/4), rather than the usual 21-day active treatment, 7-day inert-pill regimen. Participants (N=64) were randomized to either study treatment for three cycles and then after a washout period of one treatment-free cycle switched to the alternate treatment.\n The mean decrease from baseline for total Daily Record of Severity of Problems (DRSP) scores while using drospirenone/EE was significantly greater than for placebo (-12.47, 95% CI=-18.28, -6.66; p<.001). A positive response (i.e., a score of 1 or 2 in the Clinical Global Impressions-Improvement scale) occurred in 61.7% and 31.8% of subjects while taking drospirenone/EE and placebo, respectively (p=.009).\n Drospirenone/EE, given in a 24/4 regimen, was superior to placebo for improving symptoms associated with PMDD.", "The combined oral contraceptive Yasmin (drospirenone 3 mg plus ethinylestradiol 30 microg [DRSP 3 mg/EE 30 microg]) has been shown to be a well tolerated and effective combination that provides high contraceptive reliability and good cycle control. Furthermore, DRSP 3 mg/EE 30 microg has been shown to have a positive effect on premenstrual symptoms and well-being/health-related quality of life, and to improve the skin condition of women with acne. To date, however, there have been relatively few studies that have compared the effects of DRSP 3 mg/EE 30 microg on the general well-being of women with those of other oral contraceptives.\n To compare the impact of DRSP 3 mg/EE 30 microg with that of levonorgestrel 150 microg/EE 30 microg (LNG 150 microg/EE 30 microg; Microgynon 30) on various parameters associated with well-being in healthy female subjects.\n This was a randomized, single-blind, parallel-group, multicentre study conducted using 21/7-day regimens of DRSP 3 mg/EE 30 microg and LNG 150 microg/EE 30 microg over seven cycles. Efficacy parameters included: changes in Menstrual Distress Questionnaire (MDQ) normative T scores; the proportion of subjects with acne; and menstrual symptoms. Cycle control and subjective well-being parameters were also assessed.\n Treatment with DRSP 3 mg/EE 30 microg had similar beneficial effects on symptoms of water retention and impaired concentration to LNG 150 microg/EE 30 microg, but was significantly better in alleviating negative affect symptoms during the menstrual phase (median difference in MDQ T score -3; p = 0.027; Wilcoxon rank sum test). The proportion of subjects with acne decreased from approximately 55% to approximately 45% in the DRSP 3 mg/EE 30 microg group, but remained static at approximately 60% in the LNG 150 microg/EE 30 microg group. Somatic and psychological symptoms occurred at the greatest intensity and for most subjects during the menstrual phase of the cycle in both groups.\n Both drugs had similar cycle control parameters with a tendency towards reduced bleeding with continued use. More subjects in the DRSP 3 mg/EE 30 microg group reported improved physical well-being (60% vs 46%; p = 0.035; chi-squared [chi2] test). Emotional well-being was reported improved in 61% and 51% of DRSP 3 mg/EE 30 microg and LNG 150 microg/EE 30 microg users, respectively (p = 0.1190; chi2 test). Adverse events were typical of oral contraceptive use and did not give rise to any safety concerns. Both products had similar beneficial effects on symptoms of water retention and impaired concentration, but DRSP 3 mg/EE 30 microg was significantly better in alleviating negative affect symptoms during the menstrual phase. The proportion of subjects with acne decreased in the DRSP 3 mg/EE 30 microg group but not in the LNG 150 microg/EE 30 microg group. More subjects in the DRSP 3 mg/EE 30 microg group reported improved physical well-being compared with the LNG 150 microg/EE 30 microg group.", "To compare the efficacy of a new low-dose oral contraceptive pill (OCP) formulation with placebo in reducing symptoms of premenstrual dysphoric disorder.\n This multicenter, double-blind, randomized clinical trial consisted of 2 run-in and 3 treatment cycles with daily symptom charting; 450 women with symptoms of premenstrual dysphoric disorder were randomized to either placebo or an OCP formulation containing drospirenone 3 mg and ethinyl estradiol 20 microg. Hormones were administered for 24 days, followed by 4 days of inactive pills (24/4).\n Scores on the total Daily Record of Severity of Problems decreased by -37.49 in the drospirenone/ethinyl estradiol group and by -29.99 in the placebo group (adjusted mean difference -7.5, 95% confidence interval [CI] -11.2 to -3.8; P < .001 by rank analysis of covariance). Mood symptom scores were reduced by -19.2 and -15.3 in active-treatment and placebo groups, respectively (adjusted mean difference -3.9, 95% CI -5.84 to -2.01; P = .003); physical symptom scores were reduced by -10.7 and -8.6 in active-treatment and placebo groups, respectively (adjusted mean difference -2.1, 95% CI -3.3 to -0.95; P < .001); and behavioral symptom scores were reduced by -7.7 and -6.2 in active-treatment and placebo groups, respectively (adjusted mean difference -1.5, 95% CI -2.251 to -0.727; P < .001). Response, defined as a 50% decrease in daily symptom scores, occurred in 48% of the active-treatment group and 36% of the placebo group (relative risk 1.7, 95% CI 1.1 to 2.6; P = .015) and corresponds to a number-needed-to-treat of 8 patients.\n A 24/4 regimen of drospirenone 3 mg and ethinyl estradiol 20 mug improves symptoms associated with premenstrual dysphoric disorder.\n I." ]

[ "9171045", "8229622", "9650873", "11908370", "1507038", "11806476", "10530095", "8884648", "12146537", "11699736", "9238885", "11908374", "9049794", "10048641", "7608846", "8144734", "11999936", "1930697", "8144738", "2768537", "1061599", "11830911", "12887341", "8841896", "9793284", "9238880", "14125027", "14326700", "8941832", "11686812", "9487840", "5217396", "8267871", "7699607", "2778601" ]

[ "Efficacy of a new electronic toothbrush in removing bacterial dental plaque in young adults.", "Evaluation of a counter-rotational powered brush in patients in supportive periodontal therapy.", "The effects of an ultrasonic toothbrush on plaque accumulation and gingival inflammation.", "Comparison of gingivitis and plaque efficacy of a battery-powered toothbrush and an ADA-provided manual toothbrush.", "A comparative clinical study of the safety and efficacy of three toothbrushes.", "Safety, efficacy and acceptability of a new power toothbrush: a 3-month comparative clinical investigation.", "A 3-month clinical investigation comparing the safety and efficacy of a novel electric toothbrush (Braun Oral-B 3D Plaque Remover) with a manual toothbrush.", "Efficacy of a sonic toothbrush on inflammation and probing depth in adult periodontitis.", "Six-month comparison of powered versus manual toothbrushing for safety and efficacy in the absence of professional instruction in mechanical plaque control.", "The safety and efficacy of a children's power toothbrush and a manual toothbrush in 6-11 year-olds.", "A thirty-day evaluation of the Rowenta Dentiphant powered toothbrush in children for safety and efficacy.", "Comparative efficacy of Colgate Actibrush battery-powered toothbrush and Colgate Plus (manual) toothbrush on established plaque and gingivitis: a 30-day clinical study in New Jersey.", "Assessment of the effect of an oscillating/rotating electric toothbrush on oral health. A 12-month longitudinal study.", "A comparative study of the Philips HP 735, Braun/Oral B D7 and the Oral B 35 Advantage toothbrushes.", "Clinical evaluation of the efficacy and safety of a new sonic toothbrush.", "The long-term effect of an oscillating/rotating electric toothbrush on gingivitis. An 8-month clinical study.", "Powered vs manual tooth brushing in fixed appliance patients: a short term randomized clinical trial.", "Clinical evaluation of the Plak Trac toothbrush.", "Comparison of a manual and a new electric toothbrush for controlling plaque and gingivitis.", "Comparison of manual and power toothbrushing, with and without adjunctive oral irrigation, for controlling plaque and gingivitis.", "Oral hygiene instruction in children using manual and electric toothbrushes. Benefits after six months.", "The effectiveness of an ionic toothbrush in the removal of dental plaque and reduction on gingivitis in orthodontic patients.", "Efficacy of plaque removal and learning effect of a powered and a manual toothbrush.", "Comparison of a sonic and a manual toothbrush for efficacy in supragingival plaque removal and reduction of gingivitis.", "A practice-based randomised controlled trial of the efficacy of an electric and a manual toothbrush on gingival health in patients with fixed orthodontic appliances.", "The clinical effect of a newly designed electric toothbrush on supragingival plaque, gingivitis and gingival bleeding.", "POWER VERSUS HAND BRUSHING: EFFECT ON GINGIVITIS.", "A CLINICAL STUDY OF HAND AND ELECTRIC TOOTHBRUSHING.", "Clinical evaluation of an ionic toothbrush in the removal of established plaque and reduction of gingivitis.", "Efficacy of manual and powered toothbrushes (I). Effect on clinical parameters.", "Effectiveness of the Sonicare sonic toothbrush on reduction of plaque, gingivitis, probing pocket depth and subgingival bacteria in adolescent orthodontic patients.", "A study on the uninstructed use of an electric toothbrush.", "A comparison of the Braun Oral-B Plaque Remover (D5) electric and a manual toothbrush in affecting gingivitis.", "Clinical evaluation of the effect of an ultrasonic toothbrush on plaque, gingivitis, and gingival bleeding: a six-month study.", "The effect of a new electric toothbrush on supragingival plaque and gingivitis." ]

[ "Although a high level of oral cleanliness is essential for long-term maintenance of dental health, many people cannot maintain good oral hygiene consistently. A new electronic toothbrush has been developed that induces a small electric charge onto tooth surfaces. This charge damages electrostatic bonding of plaque proteins to tooth surfaces; thus, plaque removal is enhanced while the toothbrush is used. Young men were issued identical toothbrushes; some were electrically active. Plaque levels were assessed at baseline, and after two and four weeks, concurrently with oral-hygiene instruction and professional prophylaxis. The electrically active toothbrushes demonstrated better plaque removal than the inactive toothbrushes. This better performance was statistically significant linguopalatally, indicating that significantly more plaque was removed where mechanical access was poorest. Thus, the electrical activity of this toothbrush significantly enhances plaque removal where toothbrushing access is limited.", "In order to evaluate the effectiveness of a counter-rotational powered brush (CRPB) during the supportive periodontal therapy (SPT) phase of periodontal treatment, 40 treated patients in SPT but with insufficient plaque control were randomly divided into equal experimental or control groups. All subjects used the same toothpaste, but the CRPB group did not use any interproximal aids. Gingivitis (MGI), plaque, and bleeding on probing (BOP) were scored at baseline and 1, 3, and 6 months prior to prophylaxis in conjunction with regular SPT visits. While both groups improved from baseline, CRPB use achieved significantly lower mean plaque scores and BOP at 6 months as analyzed by repeated measures ANOVA. The CRPB also showed consistent statistically superior percentage changes from baseline resulting in a general 50% improvement in clinical conditions compared to a 20 to 25% improvement for control oral hygiene methods. CRPB use resulted in at least a 50% improvement from baseline twice as often as did the control. The results of this study demonstrate more substantial and consistent improvement in periodontal conditions and plaque control effectiveness with the CRPB than the control methods that included interproximal hygiene aids. It appears that the CRPB may be a useful adjunct in maintaining reduced plaque levels and favorable gingival conditions in patients in the SPT phase of periodontal therapy.", "The purpose of this study was to evaluate the effectiveness of an ultrasonic toothbrush to reduce plaque and gingival inflammation when compared to a manual toothbrush. 62 healthy adult patients with a plaque index of at least 2.0, a 50% bleeding index and at least 16 natural teeth participated in this study. 31 patients were randomly assigned to the manual toothbrush group (group A) and 31 were assigned to an ultrasonic toothbrush group (group B). The Turesky et al. plaque index (PI), Eastman bleeding index, and Loe & Silness gingival index (GI) were performed at baseline, 15, and 30 days at the beginning of each appointment (pre-brushing). Patients then brushed with their assigned toothbrush and a post-brushing plaque index was recorded. Kruskal-Wallis one-way analysis of variance (ANOVA) was performed to determine between group differences on the parameters of all clinical indices. Results of the pre-brushing plaque index in group B were significantly lower at 15 and 30 days compared to group A. The post-brushing plaque index demonstrated no statistically significant between or within group differences. Both groups demonstrated significant within group reductions in GI and BI from baseline to 15 days and from 15 to 30 days, however, no between group differences were noted. The results of this study support the ability of an ultrasonic toothbrush to significantly remove plaque and reduce inflammation as well as a manual toothbrush over a 30 day period.", "This examiner-blind clinical study evaluated the efficacy of a new battery-powered toothbrush with oscillating head (Colgate Actibrush) on established gingivitis and plaque at 15 days and again at 30 days, as compared to a control manual toothbrush (American Dental Association [ADA]-provided toothbrush, full head, soft bristles). A total of 63 participants completed the study. They were stratified into two balanced groups according to their mean baseline prebrushing plaque scores and were randomly assigned to use the battery-powered test toothbrush or the manual control toothbrush. Participants were instructed to brush their teeth twice daily (mornings and evenings) for 1 minute with their assigned toothbrush for the 30-day duration of the study. Gingivitis and plaque (pre- and postbrushing) examinations were conducted by the same dental examiner at baseline, after 15 days, and again after 30 days. The Colgate Actibrush demonstrated a significantly greater reduction of plaque (46.53%) and gingivitis (18.57%) when compared to the ADA-provided toothbrush after 30 days of use. Additionally, a comparison of the plaque scores for the battery-powered toothbrush at 15 and 30 days shows a continued reduction in plaque of more than 25% for a cumulative difference from baseline of 73%. These results support the conclusion that the new battery-powered toothbrush is clinically superior in plaque removal efficacy and gingivitis efficacy to the manual toothbrush, and continues to significantly improve plaque scores even up to 30 days of use.", "This single (examiner) blind, randomized, 4-week study compared the safety and efficacy of a new electric toothbrush (experimental) regarding plaque removal and reducing gingivitis with two other brushes, an electric brush (control electric) and a manual toothbrush (control hand). Ninety-six subjects with 1) a minimum of 15 suitable teeth in acceptable occlusion; 2) a minimum gingivitis score of 0.9; and 3) a minimum plaque score of 1.8 were entered into the study. The subjects were randomly assigned to one of 3 groups: a control hand group (31 subjects), an experimental group (32 subjects), and a control electric group (33 subjects). Device use instructions were given according to the manufacturer's recommendations. Two examiners separately determined either gingival scores or plaque scores at baseline and 4 weeks. In regard to gingivitis, use of all 3 brushes for the study period showed statistically significant improvements in gingivitis scores (P values less than 0.01) within each of the 3 groups. Between group analyses of covariance showed that of the 3 groups, the control hand group improvement was better than both the experimental and the control electric groups (P less than 0.05). When interproximal gingivitis scores were analyzed separately, similar improvements were noted. Regarding effectiveness of plaque removal during a single brushing event at the initial and final visits, each of the 3 brushes was effective in reducing plaque for every tooth surface scored (P values less than 0.01). However, between group analyses of covariances showed that the experimental group was better than the other two (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)", "To compare the safety and efficacy of a new power toothbrush (Braun Oral-B D17) with an ADA reference manual toothbrush.\n 110 healthy subjects, 18-65 yrs of age, with a mean plaque index of > or = 1.80 and a gingival index of > or = 1.00, were enrolled in this 3-month, randomized, parallel-group, examiner-blind study. Oral soft and hard tissues were examined for safety, and plaque, gingivitis and bleeding were measured to evaluate efficacy. Measurements were made at baseline and after 1 and 3 months of product use. Following the baseline visit and randomization, subjects were instructed to brush twice daily for 2 mins with their assigned brush.\n 101 subjects completed the study with evaluable data for all time periods, 52 in the D17 group and 49 in the manual group. None of the nine withdrawals from the study were related to product use and no product-related adverse effects were reported. There was no clinically significant soft or hard tissue abrasion observed at any time point in either group. After 1 and 3 months, significant reductions from baseline in whole mouth and interproximal plaque, gingivitis and bleeding were observed in both groups. A comparison of the two groups revealed that the whole mouth and approximal plaque indices were reduced to a significantly greater extent in the D17 group after both 1 and 3 months. The whole mouth gingival index was also reduced to a greater extent in the D17 group at 1 and 3 months, but a difference in the approximal gingival index was only apparent after 3 months. With respect to the bleeding index, there was a significant difference between the two groups for the whole mouth at both 1 and 3 months, but the differences in favor of the D17 for approximal values did not achieve statistical significance. In conclusion, the D17 was found to be safe and had increased efficacy with respect to reduction of plaque and gingivitis, compared with a manual toothbrush.", "To compare the efficacy and safety of a novel electric toothbrush (Braun Oral-B 3D Plaque Remover) with a standard reference ADA manual toothbrush.\n 114 subjects were included in a 3-month randomized, parallel group, examiner-blind study and divided into two groups: 3D users and manual toothbrush users. Subjects were instructed to brush twice daily for 2 minutes. Evaluation of oral soft and hard tissue for safety, plaque, gingivitis and bleeding was conducted prior to the start of product use (at baseline), at days 14 and 35, and at 3 months.\n 105 subjects (55 3D users and 50 manual toothbrush users) completed the study. At days 14, 35 and at 3 months both groups showed reductions from baseline in whole mouth plaque, gingivitis and bleeding that were statistically significant (P < 0.005), except in the case of plaque at day 35 in manual toothbrush users. At 3 months, reductions for whole mouth plaque, gingivitis and bleeding were 15%, 16% and 65%, for 3D users and 8%, 12% and 56%, for manual toothbrush users, respectively. Group differences were significant (P < 0.05) in favor of the 3D with respect to plaque reduction for the whole mouth and for interproximal and anterior lingual sites at all three time periods. With respect to gingivitis, reductions for the whole mouth and interproximal and posterior lingual sites at 3 months were significantly greater in the 3D group. There was no clinically significant soft or hard tissue abrasion in either group. In conclusion, the 3D electric toothbrush was found to be safe and had increased efficacy with respect to reduction of plaque and gingivitis compared to a manual toothbrush.", "This single-blind, 8-week study compared the efficacy of a sonic toothbrush and a manual brush in 40 patients with adult periodontitis. Qualitative clinical indices and quantitative laboratory methods were used to monitor the periodontal status of 3 pockets 5 to 7 mm deep in each subject. Patients were randomly assigned either a sonic or manual toothbrush. The two groups were comparable with respect to age, gender, and anatomical location of the test sites. Data were collected from all sites at baseline and at 2, 4, and 8 weeks. Over the 8-week period, both groups showed significant improvements in the clinical indices used. Descriptive statistics indicated the sonic brush group had greater improvement than the manual group in the clinical parameters (gingival index, bleeding index, probing depth, and clinical attachment level). Gingival crevicular fluid (GCF) flow was significantly lower in the sonic brush group (P = 0.018). Considerable variation was present in the levels detected for both inflammatory cytokines tested, however, concentration of interleukin-1 beta was significantly lower in the GCF of sonic group patients (P = 0.05), while concentration of interleukin-6 was significantly reduced in both groups (P < or = 0.05) (t tests). Under these conditions, there is some evidence to suggest that the sonic toothbrush is more beneficial in resolving inflammation in patients with moderate periodontal disease.", "Reports suggest powered toothbrushing may provide some clinical benefit over manual tooth-brushing, but most studies have been of short duration with subjects trained in toothbrush use. The aim was to determine if the oscillating-rotating powered brush (PB) could safely provide clinical benefits over and above a manual brush (M) in subjects with no formal instruction or experience in powered brush use.\n This 6-month, single-masked, parallel design, randomized clinical trial compared the PB with an American Dental Association (ADA)-accepted soft-bristle manual brush in a non-flossing gingivitis population (n = 157). Subjects were given written instructions but no demonstration on toothbrush use at baseline. Efficacy was assessed by changes in gingival inflammation, plaque, calculus, and stain, while changes in clinical attachment levels and recession measurements provided safety data. A prophylaxis was provided after baseline assessment. The 6-month plaque index (PI) was recorded immediately post-brushing after covert timing of the subjects, and correlation analyses were run to assess the relationship of brushing time to PI. Paired t tests, analysis of variance (ANOVA), and analysis of covariance (ANCOVA) were used to assess within and between treatment group differences for PB (n = 76) versus M groups (n = 81).\n Measures of inflammation showed a statistically significant drop for both brushes at 3 and 6 months. Mean overnight full-mouth PI scores were significantly lower at 3 months for the PB (1.57) compared to the M group (1.80), P = 0.0013. Immediate post-brushing PI at 6 months was also significantly lower for the PB (1.10) versus M (1.39) (P= 0.0025). There was an overall negative correlation for PI and brushing time (r = -0.377, P= 0.0001). Mean calculus index (CI) scores were lower for the PB at 3 (P= 0.0304) and 6 months (P = 0.0078), while no significant differences in stain were observable. Clinical attachment level and recession measurements showed no significant between-group changes from baseline for either brush on canine teeth or on teeth with recession at baseline.\n The oscillating-rotating toothbrush safely provides clinical benefits in plaque and calculus reduction over a manual brush even in subjects with no formal oral hygiene instruction.", "To evaluate and compare the oral hard and soft tissue safety and the plaque-removing efficacy of a children's power toothbrush (Braun Oral-B Kids' Power Toothbrush-D10) and a manual toothbrush in children from a general population.\n Seventy children aged 6-11 yrs were enrolled into a single-blind, randomized, parallel-design study. At baseline, oral hard and soft tissues were evaluated and plaque was assessed on buccal and lingual surfaces of all fully erupted permanent and primary teeth using the Turesky Modification of the Quigley-Hein Plaque Index. Eligible subjects were randomized to use either a Braun Oral-B children's power toothbrush (D10) or a manual toothbrush for the duration of the study. Subjects were instructed to brush their teeth at home twice daily for 1 min each day for the 30-day study period. At baseline and after 15 and 30 days, plaque was assessed following 12-18 hrs of no oral hygiene. In addition, at each visit single-use plaque removal was evaluated after subjects had brushed their teeth for 1 min under supervision. Oral hard and soft tissues were assessed for safety before and after the supervised 1-min brushing at each visit.\n There were no pre-brushing oral hard and soft tissue abnormalities or post-brushing changes in oral tissues in either group. There were statistically significant reductions in mean plaque index for the whole mouth (P< 0.006), buccal surfaces (P < 0.0001) and anterior teeth (P< 0.008) from day 0 to day 30 in the D10 group, but not in the manual group. Greater mean changes in whole mouth plaque reduction were seen for the D10 group as compared to the manual group at days 15 and 30 (P< 0.05). Results from the single-use supervised brushing at each visit revealed that reductions in mean whole mouth plaque were statistically significant in both groups at each visit (P< 0.0001). There was statistically significantly greater plaque removal after a single brushing at day 0 in the D10 group compared with the manual group (P< 0.002), but the difference was not significant at days 15 and 30.", "A thirty-day clinical trial was undertaken with second grade school children to assess the safety and efficacy of a new battery-powered toothbrush (Rowenta Dentiphant) compared to the manual Oral-B 20 toothbrush. The children from four class rooms were individually and randomly assigned to use either product for the thirty days. The children reported to school having not brushed the morning of each assessment at baseline, 15 days and 30 days. Following the gingivitis assessment and given a pre-brushing plaque assessment, the children were instructed on the use of the toothbrush as they then brushed their teeth for a timed 1 minute out of sight of the examiners. The children were then reassessed for plaque removal. The results demonstrated that the children using the Rowenta powered toothbrush became used to the brush and improved their cleaning efficiency during the study. By week two, the buccal plaque scores for the Rowenta brush were significantly lower (p < 0.05) compared to the Oral-B 20 group. By week four the Rowenta subjects had significantly lower buccal and lingual plaque scores after brushing, while the Oral-B 20 subjects had significantly lower buccal scores after toothbrushing, but no significant difference was found after brushing on lingual surfaces for plaque removal. On total plaque area scores, the Rowenta group was significantly lower (p < 0.01) than the Oral-B 20 group at both two and four weeks. The Rowenta group had a 10% reduction in plaque area after brushing comparing baseline to four weeks. The Oral-B group demonstrated no percentage difference in after brushing plaque scores from baseline to four weeks. On gingivitis, the Rowenta group had significantly lower buccal and lingual mean scores compared to the Oral-B 20 group at week two, and lingual mean scores compared to the Oral-B 20 group at week four. The Rowenta group demonstrated a 27% decrease in lingual gingivitis scores compared to baseline, while the Oral-B group had an 11% decrease in lingual gingivitis scores from baseline to four weeks. Total gingivitis scores for the Rowenta group were significantly lower (p < 0.01-0.001) at both weeks two and four compared to the Oral-B 20 group, with percentage declines from baseline to four weeks being 22% and 12%, respectively. The Rowenta Dentiphant toothbrush was found to be safe to use. On total plaque and gingivitis reduction, the Rowenta Dentiphant toothbrush was found to be significantly superior to the Oral-B 20 manual toothbrush by two weeks of use and this continued to the conclusion of the study.", "The objective of this 30-day clinical study, conducted in harmony with American Dental Association guidelines, was to evaluate the efficacy of a new battery-powered toothbrush (Colgate Actibrush) relative to a manual toothbrush (Colgate Plus Diamond Head Toothbrush, Full Head, Soft Bristle) in the control of supragingival plaque and gingivitis. A total of 110 adult men and women from the Northern New Jersey area were entered into the study and stratified into 2 balanced groups according to baseline plaque and gingivitis scores. Participants were instructed to brush twice daily (morning and evening) for 1 minute with their assigned toothbrush and a commercially available toothpaste (Colgate Cavity Protection Great Regular Flavor Fluoride Toothpaste). Examinations for plaque and gingivitis were conducted by the same dental examiner at baseline, after 15 days, and again after 30 days of product use. All 110 participants complied with the protocol and completed the 30-day clinical study. At the 30-day examinations, the group using the Colgate Actibrush battery-powered toothbrush exhibited a statistically significant greater reduction in plaque (26.7%) and in gingivitis (25.8%) than did the group who used the Colgate Plus Diamond Head Toothbrush. The results of this 30-day clinical study support the conclusion that the Colgate Actibrush battery-powered toothbrush provides a clinically superior level of efficacy for the control of supragingival plaque and for the control of gingivitis when compared with a manual toothbrush.", "The aim of this 12-month parallel design controlled clinical trial was to assess the effect of the Braun Oral-B Plak Control electric toothbrush on supragingival plaque and gingival health, and to compare it with a conventional soft manual toothbrush (Jordan). A total of 111 patients aged between 20 and 63 years, from a general population, with bleeding on probing at 30% or more of all sites examined were entered into the study. At baseline, immediately after periodontal examination, all volunteers received a thorough scaling of their teeth. Volunteers in both groups were told to brush their teeth for 2 min 2 x a day. Oral hygiene instruction was given at the start of the study and was not repeated. At 3, 6 and 12 months, assessments were carried out by a single clinician who was not aware which group the volunteers belonged to. Analysis of results demonstrated that over the 12 months of the study, the Braun Oral-B Plak Control was significantly more effective in improving gingival health than the manual toothbrush. There was, however, no difference between the 2 groups in terms of plaque removal, with the number of sites with visible plaque decreasing by a similar amount in both groups. In conclusion, results indicate that the Braun Oral-B Plak Control toothbrush is safe and more effective than a manual toothbrush in improving gingival health.", "The aim of this 3-group, 3-treatment, single-blind, parallel group study was to evaluate and compare the efficacies of the Philips/Jordan HP 735 powered toothbrush, the Braun/Oral B D7 powered toothbrush and the Oral B Advantage B35 manual toothbrush in a cohort of 75 young adults (18-25 years). Following an appointment for screening, full mouth mean (+/-sd) modified Turesky plaque index (PI) and Löe & Silness gingival index (GI) were recorded at baseline. After 24 h abstinence from all oral hygiene measures, PI was recorded and each subject was given one of the test brushes with detailed instructions for use. The subject then brushed under supervision for 90 s, during which time mean (+/-sd) toothbrushing forces (TBF) were recorded. PI were recorded immediately after supervised brushing and the subjects were then discharged for 6 weeks to use the allocated toothbrush at home. After 6 weeks, PI, GI and TBF were again recorded. Comparisons between the brushing groups for all parameters, at baseline, 24 h and 6 weeks were tested using ANCOVA. There were no significant differences for PI and GI between groups at baseline, or for PI following supervised brushing at 24 h. After 6 weeks subjects using the powered brushes had lower mean PI (+/-sd) scores than those using manual brushes but the differences were significant only at interproximal sites; HP 735 1.44 (0.52), D7 1.44 (0.53), B35 1.75 (0.51) (p=0.05). At 6 weeks, mean (+/-sd) GI were; HP 735 1.49 (0.21), D7 1.61 (0.21), B35 1.64 (0.22) (p=0.033). Mean GI scores for the HP 735 group were similar at baseline and at 6 weeks although for the other brushes, the GI scores actually increased over this period. Mean (+/-sd) TBF (grammes/force) at baseline and 6 weeks respectively for the brushes were; HP 735 233 (205), D7 159 (58), B35 279 (122) (p=0.026): HP 735 194 (86), D7 141 (57), B35 297 (113) (p=0.0001). The within-group variability for the HP 735 TBF reduced considerably over 6 weeks, a likely consequence of the click-force threshold feature of this brush.", "The efficacy and safety of a new sonic toothbrush were studied in this single-blind study. The sonic toothbrush combines acoustic vibrations and dynamic fluid activity surrounding the bristles with direct mechanical scrubbing of tooth surfaces. Fifty-one subjects were randomly assigned to either the sonic or the manual toothbrush. Plaque scores were assessed before and after a 2-minute brushing at baseline and 1, 2, and 4 weeks. Gingivitis and sulcular bleeding scores were also taken at each evaluation. To assess long-term safety, 29 subjects returned after 6 months of product use. Repeated measures analysis of variance of the total mean plaque score indicated a significant difference between the devices over time (P < 0.01), with the sonic toothbrush demonstrating a greater level of plaque removal on all tooth surfaces. On average, the plaque reduction from the baseline score for the sonic toothbrush was 3 times greater than the manual brush. However, when broken down by dental region, the sonic toothbrush demonstrated an improved level of plaque removal ranging from 1.5 to 11.9 times better than the manual brush, with the greatest improvement in the interproximal and lingual areas. Both the gingivitis and sulcular bleeding scores exhibited a similar, significant reduction (P < 0.005) over time for both devices with an approximate 17% decrease in the gingivitis index and a 33% decrease in sulcular bleeding sites. Safety assessment after 6 months of use indicated no soft tissue abnormalities which could be attributed to the products.(ABSTRACT TRUNCATED AT 250 WORDS)", "The purpose of this study was to evaluate the safety and efficacy of the Braun Plak Control for the removal of supragingival plaque and improving gingival health in a long-term clinical trial, and to compare it to regular manual toothbrush. Assessed were plaque accumulation, amount of gingival inflammation, gingival bleeding on probing, and calculus. In total, 77 young individuals were selected on the basis of having 'moderate gingivitis'. They were monitored over 8 months and divided among 2 groups; a control group that used a manual toothbrush and a test group that used the Braun Plak Control. The clinical assessments were repeated after 1, 2, 5, and 8 months. At baseline, subjects were handed their assigned toothbrushes together with written oral hygiene instructions. They were instructed to brush for at least 2 min. 1 month after baseline examinations, all subjects received a professional prophylaxis and oral hygiene instruction from an experienced dental hygienist. Plaque removal was reinforced at the 2-and 5-month examination. In conclusion, results indicate that the Braun Plak Control is a safe and efficient home care device. At the end of this trial, this electric toothbrush proved to be more effective than a regular manual toothbrush.", "Sixty-three orthodontic patients wearing upper and lower fixed appliances were randomly assigned to use either a powered toothbrush fitted with a modified orthodontic brush head (Braun Oral-B Plaque Remover 3D) or a manual toothbrush (Reach Compact Medium). A trained hygienist instructed each patient on the proper use of the allocated brush. Measurements of plaque and gingival health were made at baseline, at four weeks, and at eight weeks. Data for each group were analyzed using paired t-tests. Patients using the powered toothbrush showed a significant reduction in percentage interdental bleeding scores from baseline to four weeks (-12.7, P = .003) and this was still apparent at eight weeks (-8.6, P = .028), although there were no statistically significant changes in either plaque or gingivitis scores for this group. Those patients using a manual toothbrush showed a significant reduction in mean plaque score from baseline (four weeks = -0.18, P = < .001; eight weeks = -0.12, P = .016), but gingivitis scores were only reduced significantly at four weeks. In this group, interdental bleeding scores reduced significantly at four weeks (P = .028), but were not significantly different from baseline at eight weeks (P = .0319). When the two patient groups were compared using two sample t-tests, there were no significant differences in any of the parameters measured at any time point in the study. Over an eight-week period, there were no measurable differences between the powered toothbrush with modified orthodontic brush head and a manual toothbrush with respect to mean change in plaque, gingivitis, or interdental bleeding scores when used by patients wearing fixed appliances.", "Three separate studies have been conducted to evaluate the clinical safety and efficacy of the Plak Trac mechanical toothbrush. In an exaggerated use study, volunteers used the product a minimum of five times a day for eight days. Soft tissue evaluations were conducted before and at various times after use of the Plak Trac brush throughout the study. No tissue irritation related to product use was observed or reported at any time in the study. In a thirty-day at-home use study the Plak Track brush was compared to the Colgate ADA-approved manual toothbrush. Plak Trac was consistently more effective than the Colgate brush on plaque removal, at higher statistical levels. Both brushes were effective in decreasing the gingival index during the study. In a one-time use test, Plak Trac, Interplak, and the Oral B 35 manual brush were evaluated for plaque removal efficacy. All brushes significantly reduced both smooth surface and interproximal plaque scores. On total smooth surfaces Plak Trac was significantly more effective than the Interplak brush.", "In the present clinical trial, the effect on existing plaque and gingivitis of a new electric toothbrush (ET) was compared to that of a manual toothbrush (MT). 40 medical students, age 18-30 years, participated. Plaque index (PlI) and gingival index (GI) were recorded at 6 sites at all teeth. At baseline, a PlI and GI > 1 were required. The participants were at random allocated to a group using either ET or MT and were instructed only to use the assigned toothbrush, brushing each morning and evening for 2 min. No oral hygiene instruction was given. Re-examination was done after 1, 2 and 6 weeks. In the MT group, a minor decrease in mean PlI was found after 6 weeks (all sites: from 1.2 to 1.1, approximal sites: from 1.4 to 1.2). The corresponding figures in the ET group were: 1.2 to 0.6 and 1.4 to 0.8. After 6 weeks, the % of sites with visible plaque with MT was: 24% (all sites) and 30% (approximal sites) and with ET 8% and 9%, respectively. With MT, mean GI was unchanged after 6 weeks compared to baseline, whereas with ET, the changes were from 1.1 to 0.9 (all sites) and from 1.1 to 1.0 (approximal sites). The % of sites with GI score > or = 2 had not changed after 6 weeks with MT (all sites: 11%, approximal sites: 13%). With ET, these results were 3% and 4%, respectively.", "We compared the effects of four oral hygiene methods (manual tooth-brushing, power toothbrushing, manual toothbrushing plus irrigation, and power toothbrushing plus irrigation) on plaque and periodontal disease. These methods were tested both when used alone and when used in conjunction with professional mechanical oral hygiene. 108 subjects were clinically assessed for plaque, stain, gingival inflammation, bleeding to probing, probing depth and attachment loss, and randomly assigned to one of the 4 oral hygiene groups. Subjects were carefully instructed in the use of their assigned method and asked to discontinue all other forms of oral hygiene. After 3-months, subjects returned for re-examination and full-month professional mechanical oral hygiene care. 3 months later, subjects returned for a final oral examination. All subjects kept a diary of use of their assigned method and were called every 2 weeks to monitor discomfort, provide reinforcement and answer questions. Results showed that all the oral hygiene methods were equally effective in reducing plaque and stain accumulation, gingival bleeding, bleeding to probing ratio and the % of pockets 4 mm or deeper. None of the oral hygiene methods was associated with injury to soft or hard tissues.", "nan", "This investigation was undertaken to determine if an ionic toothbrush was effective at removing plaque and reducing gingivitis in patients wearing orthodontic appliances. Fifty-two orthodontic patients were randomly assigned to one of two groups and completed a six-week double-blind study. Group 1 consisted of the test group using the ionic toothbrush with an active battery; group 2 consisted of the control group using the ionic toothbrush with an inactive battery. The plaque and gingival indices were measured at baseline, two weeks, and six weeks. The findings demonstrated that the active ionic toothbrush was no more effective at plaque removal and gingivitis reduction than the inactive toothbrush. Although the active toothbrush did effectively remove plaque and reduce gingivitis over the course of six weeks, it showed no significant improvement over the same toothbrush that contained an inactive battery. It was observed that the ionic toothbrush effectively reduced plaque and gingivitis regardless of the presence or absence of an active battery. The clinical findings demonstrated that an active ionic toothbrush was no more effective in removing plaque and reducing gingivitis in patients with orthodontic appliances than an inactive ionic toothbrush.", "Subjects with high plaque and gingivitis scores can profit most from the introduction of new manual or powered tooth brushes. To improve their hygiene, not only the technical characteristics of new brushes but also the learning effect in efficient handling are of importance.\n : The present study compared the efficacy in plaque removal of an electric and a manual toothbrush in a general population and analysed the learning effect in efficient handling.\n Eighty healthy subjects, unfamiliar with electric brushes, were divided into two groups: group 1 used the Philips/Jordan HP 735 powered brush and group 2 used a manual brush, Oral-B40+. Plaque index (PI) and gingival bleeding index (GBI) were assessed at baseline and at weeks 3, 6, 12 and 18. After each evaluation, patients abstained from oral hygiene for 24 h. The next day a 3-min supervised brushing was performed. Before and after this brushing, PI was assessed for the estimation of the individual learning effect. The study was single blinded.\n Over the 18-week period, PI reduced gradually and statistically significantly (p<0.001) in group 1 from 2.9 (+/-0.38) to 1.5 (+/-0.24) and in group 2 from 2.9 (+/-0.34) to 2.2 (+/-0.23). From week 3 onwards, the difference between groups was statistically significant (p<0.001). The bleeding index decreased in group 1 from 28% (+/-17%) to 7% (+/-5%) (p<0.001) and in group 2 from 30% (+/-12%) to 12% (+/-6%) (p<0.001). The difference between groups was statistically significant (p<0.001) from week 6 onwards. The learning effect, expressed as the percentage of plaque reduction after 3 min of supervised brushing, was 33% for group 1 and 26% for group 2 at week 0. This percentage increased at week 18 to 64% in group 1 and 44% in group 2 (difference between groups statistically significant: p<0.001).\n The powered brush was significantly more efficient in removing plaque and improving gingival health than the manual brush in the group of subjects unfamiliar with electric brushes. There was also a significant learning effect that was more pronounced with the electric toothbrush.", "A new sonic electric toothbrush (Sonicare) and a traditional manual toothbrush were compared for efficacy in removing supragingival plaque and reducing gingival inflammation in a 12-week, single-blind clinical trial. 60 subjects with a gingival index (GI) of > 1.5 and no probing depths > 5 mm were randomly assigned to use either the manual or sonic brush, instructed in its use, and asked to brush each morning and evening for 2 minutes. Plaque scores were taken at baseline and at 1, 2, 4, and 12 weeks using the Turesky modification of the Quigley-Hein plaque index. Gingival inflammation was assessed by the GI, bleeding tendency score, presence or absence of bleeding on probing, volumetric measurements of gingival crevicular fluid (GCF), and aspartate aminotransferase (AST) levels in GCF. Repeated measures multivariate analyses of variance were used to detect time- and device-dependent differences for all clinical assessments between the 2 groups over the 5 visits. Both types of brush were effective in removing supragingival plaque. The sonic brush was statistically superior, on a percentage reduction basis, in removing supragingival plaque from the dentition taken as a whole (F-statistic; p = 0.012) and was particularly better in hard-to-reach areas such as posterior teeth (F-statistic; p = 0.003) and interproximal sites (F-statistic; p = 0.004). Both devices were equally effective in reducing gingival inflammation. The sonic brush exhibited less tendency to cause gingival abrasion than the manual brush (1 incident with sonic, 5 incidents with manual), confirming the safety of this product as an oral hygiene device.", "The aim of the present study was to evaluate the efficacy of an electric toothbrush with a specially designed orthodontic brush head compared with a manual toothbrush in controlling plaque and gingivitis in patients with fixed orthodontic appliances over an 8-week period in a dental practice setting.\n This was a randomised controlled, single blind, stratified, parallel group trial conducted in two specialist orthodontic dental practices by a specialist orthodontist. Group 1 comprised 41 subjects who used the electric toothbrush and Group 2 consisted of 43 subjects who brushed with a manual toothbrush around the orthodontic appliance for a timed 2 minutes twice daily for 8 weeks. Plaque around the fixed appliance attachments was measured using an orthodontic modification to the Silness and Loe plaque index, while gingival condition was scored using the gingival index and Eastman interdental bleeding index.\n There was baseline balance for all clinical variables (p > 0.05). Both groups had significantly less plaque after 8 weeks than at baseline (p < 0.001) but the group using the electric brush also had significantly less interdental gingival bleeding, as determined by the Eastman interdental bleeding index both at week 4 (p < 0.001) and week 8 (p = 0.004). The majority of subjects (n = 54, 64.3%) preferred the electric toothbrush.\n In conclusion, the results from this study would suggest that use of an electric toothbrush with an orthodontic brush head may be of benefit in promoting gingival health in fixed orthodontic appliance patients; however, the long-term effects (over at least 6 months) need to be evaluated.", "A clinical study was carried out in an attempt to assess the efficacy of a newly designed electric toothbrush compared to a conventional manual toothbrush using the American Dental Association's protocol for evaluating toothbrushes. An Oral-B 35 manual toothbrush, which served as the control, was compared to the Plaq & White125 electric toothbrush. Examinations were performed by two calibrated examiners at baseline, day 15 and day 30. Examinations included the gingival index, plaque index and bleeding index. Mean indices were calculated and compared between the two brushes using the repeated measures multiple analysis of variance. No statistically significant differences between the mean indices on the three examination days were observed following the use of the manual or the electric toothbrushes. The results of this study demonstrate that the electric toothbrush was numerically more effective than the manual toothbrush in reducing supragingival plaque levels, either before or after brushing, at each examination date compared to baseline plaque values. However, this difference was not statistically significant. This and other findings concluded that the Plaq & White toothbrush is comparable to the control ADA-accepted toothbrush.", "nan", "nan", "The clinical effectiveness of a manual ionic toothbrush in the removal of dental plaque and the reduction of gingivitis was evaluated. A double-blind study evaluated the effect of a small, imperceptible electric current on established dental plaque and gingivitis during toothbrushing. Sixty-four adults completed the study. Gingivitis and plaque scores were determined at baseline and after 3 and 6 months. The baseline indices of the two groups were well balanced. At each examination, the participants were instructed how to hold the toothbrush properly and reminded to change brush heads every 4 weeks. Statistically significant improvements in Löe Gingival Index scores were observed from baseline to 6 months between the control and test groups and within the test group. The Quigley-Hein Plaque Index scores also showed a significant improvement from baseline to 6 months between the control and test groups and within the test group.", "The purpose of the present investigation was to compare manual (Crest Complete) and powered toothbrushing (Braun Oral-B 3D Plaque Remover) for their ability to affect clinical parameters of periodontal diseases.\n 48 periodontal maintenance subjects completed this single-blind 6-month longitudinal study. Subjects had a minimum of 20 natural teeth excluding third molars and >10% of sites (approximately 17 sites) with pocket depth > or =4 mm and/or >10% sites with attachment level >4 mm. At baseline, subjects received full mouth clinical measurements (168 sites) to determine mean Plaque Index, Gingival Index, pocket depth and attachment level and % of sites exhibiting BOP. Subjects were then randomly assigned to one of two groups. The control group (N=26) used a manual toothbrush while the test group (N=22) used a powered toothbrush. Subjects received instruction in oral hygiene and used their assigned toothbrush twice daily according to instruction. Follow-up clinical assessments were performed at 3 and 6 months. Significance of differences in clinical measures over time was determined using the Quade test and between brushing groups at each time point using the Mann-Whitney test.\n Mean pocket depth, mean plaque index and % of sites exhibiting BOP showed significant reductions from baseline to 3 and 6 months in both groups. Mean probing attachment level and mean Gingival Index were significantly reduced in the powered brushing group only. There was a significant positive correlation between plaque reduction and reduction in other clinical parameters in both brushing groups. The majority of subjects showed improvements in clinical parameters at 6 months, although a greater proportion of subjects in the powered group showed a reduction in Plaque Index (77% versus 65%) and in % sites exhibiting BOP (82% versus 69%). Mean pocket depth and mean attachment level showed significantly greater reductions between baseline and 6 months in lingual and mandibular areas in the powered group.\n Both manual and powered toothbrushes reduced pocket depth, plaque index and BOP. The powered toothbrush significantly reduced mean gingival index and probing attachment level. The greatest benefit of the powered brush was at mandibular and lingual surfaces.", "The Sonicare sonic toothbrush and a traditional manual toothbrush were compared for efficacy in improving periodontal health in young orthodontic patients with existing gingival inflammation. A 4-week, single-blind clinical trial was employed. Twenty-four subjects, ages 11-17 years, who were fully bonded and banded with fixed orthodontic appliances were selected. Subjects were randomly assigned to use either the manual or the Sonicare toothbrush, instructed in its use, and asked to brush each morning and evening for 2 minutes. Plaque index, gingival index, percentage of sites which bled on probing, pocket depth, and total gram-negative bacteria in a subgingival plaque sample were assessed at baseline and 4 weeks around the banded teeth. The results demonstrate that the Sonicare brush was significantly more effective than the manual brush in all clinical parameters. Sonicare was statistically superior to the manual brush in supragingival plaque reduction (57% vs. 10%, respectively; p < 0.001). Gingival Index scores fell by 29 percent in the Sonicare group, but only 3 percent in the manual group. Reduction of bleeding on probing was significantly greater in the Sonicare group than in the manual group (p < 0.001). The Sonicare group decreased from 78% bleeding sites at baseline to 24.5% after 1 month. In the manual group there was only a slight reduction in bleeding on probing (70% of sites at baseline and 64.6% sites after 1 month). Mean pocket depths were significantly reduced compared to baseline values in both the Sonicare and the manual groups (p < 0.001). Pocket depth reduction in the Sonicare group was, however, significantly greater than in the manual group (28% vs. 6%, respectively: p < 0.001). Total gram-negative bacteria in subgingival plaque samples from banded test teeth of a subset of patients were reduced in the Sonicare group (p < or = 0.05), but increased in the manual group. These results clearly demonstrate that the Sonicare sonic toothbrush is superior to a manual toothbrush in improving periodontal health in adolescent orthodontic patients with existing gingivitis.", "nan", "This three-month clinical trial was designed to compare the effect of an electric and a manual toothbrush on reducing primarily gingivitis and secondarily, plaque, in a cohort of 70 healthy adults. After baseline evaluation of gingivitis, soft tissue trauma, and plaque, patients were randomly assigned to one of the two experimental groups, shown an instructional tooth brushing videotape, and had their teeth cleaned. Soft tissue trauma was again scored at 2 weeks. At 12 weeks all three clinical parameters were again evaluated. The results showed statistically significant reductions (baseline vs. 3-month) in both whole mouth (p = 0.003) and interproximal (p = 0.008) gingivitis scores for the electric toothbrush group. No significant reduction at three months compared to baseline was seen for the manual brush group. When gingivitis reductions were compared over the three-month test period, the electric brush was significantly better than the manual toothbrush in both whole mouth (p = 0.0007) and interproximal (p = 0.002) gingivitis reduction. No increase in soft tissue trauma and no significant differences in plaque reductions were seen for either toothbrush.", "This study evaluated the long-term effect of an ultrasonic toothbrush used as part of a daily oral hygiene regimen on supragingival plaque, gingivitis, and gingival bleeding. Compared with a conventional toothbrush, the ultrasonic toothbrush was significantly more effective in reducing plaque formation (p < 0.05), removing plaque (p < 0.05), and reducing gingivitis (p < 0.05) during the 6-month study period.", "This study tested the effectiveness of a rechargeable electric toothbrush, Interplak, in removing supragingival plaque and resolving gingivitis. Forty adults with gingivitis were randomly assigned to either a \"manual\" or \"electric\" group. Detailed oral hygiene instructions were given and a blind examiner assessed plaque scores before and after brushing, toothbrush abrasion, and gingival inflammation at baseline, 1, 2, and 4 weeks. Subjects using the electric brush had significantly lower (P less than 0.05) mean plaque and gingival inflammation scores. The electric group's plaque scores fell from 77% at baseline to 28% (before brushing) and 14% (after brushing) at 4 weeks; the manual group's dropped from 75% to 50% and 30% (before and after brushing, respectively). The mean G.I. for the electric group fell from 1.65 at baseline to 1.28 at 4 weeks, while the manual group's scores decreased from 1.65 to 1.43. The results suggest that the electric brush removed supragingival plaque and resolved gingivitis better than the manual brush over a 28-day period. However, a telephone survey conducted 6 months later indicated that most subjects were not using the device twice a day as they had during the study." ]

[ "12527541", "10318337", "11189671" ]

[ "In-home respite intervention reduces plasma epinephrine in stressed Alzheimer caregivers.", "Respite services for caregivers: research findings for service planning.", "\"Special steps\": an effective visiting/walking program for persons with cognitive impairment." ]

[ "Some excess morbidity and mortality in Alzheimer caregivers (CGs) may be related to chronic activation of the sympatho-adrenal-medullary (SAM) system. Authors tested the efficacy of an in-home respite intervention to reduce peripheral markers of SAM activation and psychological distress in spousal caregivers of patients with Alzheimer disease.\n Caregivers were classified as Vulnerable (n = 27) or Non-Vulnerable (n = 28). Vulnerable CGs were those with a severe mismatch between caregiving demand and help received in the preceding 6 months. CGs had plasma catecholamine levels sampled at rest and in response to a stressor (speech task) before and 1 month after a 2-week in-home respite intervention. Self-reported symptoms of anxiety and depression were also obtained.\n ANOVA revealed a group x treatment interaction: At the 1-month follow-up, plasma epinephrine declined significantly in the vulnerable caregivers who received respite, but rose in those who were wait-listed. No effect was found for norepinephrine, heart rate, blood pressure, or psychological symptoms.\n Findings suggest that an in-home respite program may reduce SAM activation independent of psychological symptoms. To the extent that sympathetic activation mediates pathophysiological events, these results suggest an approach that may reduce morbidity and mortality in certain caregivers.", "A demonstration respite project for caregivers of older people with Alzheimer's disease was evaluated by a randomized experiment. Three hundred and sixteen volunteer primary caregivers were offered respite services and 315 completed the research portion without the offer of respite. The research indicated that even before the demonstration most families had some respite help in place. Of all those offered respite, 58% availed themselves of the offer. During the project year experimental and control subjects were equal in using slightly more services and there was no evidence that formal services had substituted for informal.", "A program for elderly persons with cognitive impairment and their caregivers was evaluated for its effectiveness and efficiency with regard to caregiver burden, sense of coherence, satisfaction, and cost to the health-care system. The program consisted of a weekly 2-hour visit and walk by volunteers. During a 9-month period in 1997, all eligible referrals were randomly assigned to receive the service immediately (experimental group) or be placed on a waiting list to receive it 6 weeks later (control group). Eleven caregivers/recipients formed the experimental group; 10 caregivers/recipients formed the control group. All completed questionnaires at randomization and at 6-week follow-up. Perceived burden decreased by 8% only for the caregivers in the experimental group (F = 6.8, p = .02). They indicated that they appreciated the respite and support and that the care recipient enjoyed the visit/walk. Although this study was short in duration and small in sample size, improvements were noted in perceived caregiver burden and caregivers expressed satisfaction with the program. The program did not result in additional health and social-service expenditures." ]

[ "1503915", "2868074", "8520164", "3513684", "6293073", "2260873", "1098764" ]

[ "A randomised trial of second-line hormone vs single agent chemotherapy in tamoxifen resistant advanced breast cancer.", "A randomized trial in postmenopausal patients with advanced breast cancer comparing endocrine and cytotoxic therapy given sequentially or in combination. The Australian and New Zealand Breast Cancer Trials Group, Clinical Oncological Society of Australia.", "Effects of medroxyprogesterone acetate therapy on advanced or recurrent breast cancer and its influences on blood coagulation and the fibrinolytic system.", "Combination chemotherapy compared to tamoxifen as initial therapy for stage IV breast cancer in elderly women.", "[Management of advanced breast cancer in post-menopausal women. A comparative trial of hormonal therapy, chemotherapy, and a combination of both].", "[A randomized trial of endocrine therapy, chemotherapy, and chemo-endocrine therapy in advanced breast cancer].", "Combined androgen and antimetabolite therapy of advanced female breast cancer. A report of the cooperative breast cancer group." ]

[ "Sixty patients with advanced breast cancer unresponsive to tamoxifen have been randomised to receive four course of mitozantrone, 14 mg m-2 (n = 30) intravenously every 3 weeks (9 weeks total) or megesterol acetate, 160 mg bd (n = 30). One in three patients (11 from each group) had substantial disease control for a minimum period of 6 months i.e., lack of progression; seven patients (23%) showed objective response to mitozantrone compared to four (13%) receiving megesterol. Non-progressive disease occurred in all sites, including visceral metastases and receptor negative patients. There were no significant differences between treatment groups in the median time (5 months each) to disease progression response duration or survival (13 months megesterol, 11 months mitozantrone) from commencing second-line therapy. Toxicity was considerably higher in the mitozantrone group. Second-line hormonal therapies can produce similar therapeutic results as those achieved from a short course of a 'short option' single agent cytotoxic in patients who were previously thought hormone insensitive. Provided that the patient does not have life threatening disease a trial of megesterol acetate is worth consideration in that it does not prejudice subsequent response to combination cytotoxic chemotherapy.", "A prospective randomized clinical trial was performed in 339 postmenopausal patients with advanced breast cancer. Two single modality treatment sequences, doxorubicin plus cyclophosphamide (AC) followed on failure by tamoxifen (TAM), and TAM followed by AC, were compared with combined modality chemo-endocrine therapy (TAM plus AC). The response rate to initial TAM (22.1%) was inferior to that for AC (45.1%), and for TAM plus AC (51.3%). However, patients randomized to the sequence TAM followed by AC showed a 42.5% overall tumor response to sequential protocol therapy, similar to the 46.9% for those randomized to AC followed by TAM. Furthermore, survival in all three arms was almost identical. Adverse prognostic factors for survival were liver metastases, short disease-free interval, poor performance status, and prior adjuvant chemotherapy. In no subgroup was significantly better survival associated with initial cytotoxic therapy. Endocrine therapy followed on failure by cytotoxics is appropriate for postmenopausal patients with advanced breast cancer.", "The effects of medroxyprogesterone acetate (MPA) therapy on advanced or recurrent breast cancer and its influence on blood coagulation and the fibrinolytic system were compared among three different therapy regimens consisting of cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) + MPA and CAF or MPA alone. A clinical response was observed in 42.9% (9/21) of the patients for CAF + MPA, 36.4% (8/22) for CAF and 23.8% (5/21) for MPA alone. No marked thrombosis or its prodromal condition was observed in any group. The effects on the test values for blood coagulation and the fibrinolytic system did not significantly change in the CAF group. However, both AT-III and protein C significantly increased above the normal ranges in the CAF+MPA and MPA groups. Increases in factor X, plasminogen, and alpha 2-plasmin inhibitor/plasmin complex (PIC) and decreases in fibrinogen, tissue plasminogen activator, and D-dimer, were all observed in the MPA and CAF + MPA groups, especially in the MPA group, although these changes remained within the normal ranges. The data indicated that MPA has various influences on blood coagulation and the fibrinolytic system, but these changes did not suggest activation of the blood coagulation system.", "In a randomized crossover study, 181 patients over the age of 65 with recurrent breast cancer received either tamoxifen or cyclophosphamide, methotrexate, and fluorouracil (CMF). After progression on tamoxifen, a hormone withdrawal period was required. Because of altered pharmacokinetics with aging, creatinine clearance was used in calculating the dose of CMF. Response rates were 45% on tamoxifen and 38% on CMF, with median durations of 10.4 and 7.9 months, respectively. Survival rates tended to favor tamoxifen as the initial treatment even in estrogen-receptor-negative patients. Additional disease control with hormone withdrawal occurred in 23% of patients, and this benefit was highly correlated with prior hormone response. We conclude that initiation of hormone therapy rather than CMF chemotherapy is justified in almost all situations in elderly patients, and combination chemotherapy, is safe and useful after hormone failure if modified on the basis of renal dysfunction.", "A randomized trial was done in 98 post-menopausal women with breast cancer. Hormonal receptors had not been assayed in any patient. Patients were given hormonal therapy with tamoxifen and drostanolone propionate (n = 34), or chemotherapy with the CMF protocol (n = 30), or a combination of both (n = 34). The results are in favour of hormonal therapy alone, which gave the best immediate objective responses, the least adverse side-effects, and possibly improved survival rates.", "A randomized trial of endocrine therapy (adreno-oophorectomy, H), chemotherapy (FAC, C), chemoendocrine therapy (FAC + tamoxifen, H'C, or FAC + adreno-oophorectomy, HC) was performed in 114 advanced breast cancer patients from September, 1979 to December, 1983, and 106 were evaluable. The response to H, C, H'C, and HC was shown to be 33% (10/30), 54% (14/26), 59% (17/29), and 76% (16/21), respectively. There was a significantly higher response rate in HC group than H group. Higher but not significantly different response was obtained by H'C as compared with H. There were no significant differences in the overall survival among the treatment arms. However, patients treated with H survived longer (greater than 5 years). These results suggest that higher response obtained by chemotherapy, alone or in combination with endocrine therapy does not seem to contribute to the prolongation of survival of the patients.", "A clinical trial of androgen and antimetabolite therapy of advanced female breast cancer was conducted in 110 patients by the Cooperative Breast Cancer Group. An objective regression rate of 20% was achieved in women receiving oral testolactone, 6% in patients given intravenous fluorouracil alone, and 14% when the androgen and antimetabolite were administered together. This randomized trial according to the CBCG protocol did not produce the high regression rate noted previously in a nonrandomized, nonprotocol evaluation of these drugs." ]

[ "11920905", "17134598" ]

[ "The effect of fast reporting by amnio-PCR on anxiety levels in women with positive biochemical screening for Down syndrome--a randomized controlled trial.", "Amniocentesis results: investigation of anxiety. The ARIA trial." ]

[ "To study the effect of fast reporting by polymerase chain reaction on amniotic fluid cells (amnio-PCR) on anxiety levels in women with positive biochemical screening for Down syndrome.\n Between May 2000 and April 2001, 60 screen-positive women were randomized before amniocentesis into either having (group A) or not having (group B) fast-reporting by amnio-PCR. Anxiety levels were measured by the Spielberger State-Trait Anxiety Inventory just prior to amniocentesis, three days (when PCR results were known to group A) and three weeks (when standard karyotype results were known to both groups) afterwards.\n Two women were excluded because in one woman amnio-PCR showed trisomy 21 and the other miscarried shortly after amniocentesis. The state-anxiety scores increased over the three-week period after being informed of the positive-screen result in both groups. The trait- and state-anxiety scores at all points did not differ between the two groups.\n In contrast to the general belief, fast reporting by amnio-PCR did not alleviate anxiety in women who are screen-positive for Down syndrome.\n Copyright 2002 John Wiley & Sons, Ltd.", "The Amniocentesis Results: Investigation of Anxiety (ARIA) trial tested two hypotheses: first, that giving amniocentesis results out on a fixed date alters maternal anxiety during the waiting period, compared with a policy of telling parents that the result will be issued 'when available' (i.e. a variable date), and secondly, that issuing early results from a rapid molecular test alters maternal anxiety during the waiting period, compared with not receiving any results prior to the karyotype. The effects of the two interventions on anxiety 1 month after receiving karyotype results were also examined.\n A multi-centre, randomised, controlled, open fixed sample, 2 x 2 factorial design trial, with equal randomisation.\n Twelve hospitals in England offering amniocentesis as a diagnostic test for Down's syndrome.\n A total of 226 women who had had an amniocentesis were randomised between June 2002 and July 2004. Eight women with abnormal results or test failure were excluded post-randomisation.\n Issuing karyotype results on a prespecified fixed date, rather than issuing them as soon as they became available and issuing karyotype results alone, or subsequent to issuing results from a rapid molecular test for the most common chromosomal abnormalities.\n Average anxiety during the waiting period, calculated using daily scores from the short version of the Spielberger State-Trait Anxiety Inventory (STAI). Recalled anxiety, measured 1 month after receiving karyotype results, using a rating scale. Anxiety at the 1-month follow-up, measured using the short-form STAI.\n There was no evidence that giving out karyotype results on a fixed or on a variable date altered maternal anxiety during the waiting period. However, the analysis only had sufficient power to detect a moderate to large effect. Issuing early results from a partial, but rapid, test reduced maternal anxiety during the waiting period, compared with receiving only the full karyotype results. This was a moderate to large effect. In addition, group differences in recalled anxiety reflected fairly closely the differences in anxiety women had experienced while waiting for results. One month after receiving normal karyotype results, anxiety was low in all groups, but women who had been given rapid test results were more anxious than those who had not. This was a small to moderate effect.\n Since there are no clear advantages in anxiety terms of issuing karyotype results as soon as they become available, or on a fixed date, women could be given a choice between them. Rapid testing was a beneficial addition to karyotyping, at least in the short term. This does not necessarily imply that early results would be preferred to comprehensive ones if women had to choose between them. There should be further research, including more qualitative studies, into the causes, characteristics and consequences of anxiety associated with prenatal testing. The effects of different testing regimes on short- and long-term anxiety, on the preferences of women and on the relationship between anxiety and preference should be investigated. More research is needed on the ways in which information might be used to minimise anxiety in different testing regimes. Further research is also required into the policy implications of incorporating individual preferences for different testing regimes into prenatal testing programmes." ]

[ "11461738", "12475466", "17848651" ]

[ "Propranolol treatment of congestive heart failure in infants with congenital heart disease: The CHF-PRO-INFANT Trial. Congestive heart failure in infants treated with propanol.", "Delisting of infants and children from the heart transplantation waiting list after carvedilol treatment.", "Carvedilol for children and adolescents with heart failure: a randomized controlled trial." ]

[ "Infants with congenital heart disease and left-to-right shunts may develop significant clinical symptoms of congestive heart failure in spite of therapy with digoxin and diuretics. We investigated the effects of beta-blockade in infants with severe heart failure.\n We performed a prospective, randomized, open monocenter trial in infants treated with digoxin and diuretics (n=10) in comparison to 10 infants receiving additional beta-blocker therapy. After 17 days on average beta-blocker treated infants (propranolol:1,6 mg/kg/day) improved significantly with respect to Ross heart failure score (3.3+/-2.3 vs. 8.3+/-1.9, P=0.002), lower renin levels (338+/-236 vs. 704+/-490 microU/l, P=0.008) and lower mean heart rates in Holter ECG (118+/-10 vs. 142+/-11 beats/min, P<0.001). While digoxin and diuretic treated infants had unchanged mean heart rate (149+/-8 vs. 148+/-10 beats/min), less decrease of symptoms (Ross Score: 8.5+/-1.7 vs. 6.8+/-2.3, P=0.02) but a significant increase of renin levels (139+/-102 vs. 938+/-607 microU/l, P=0.001).\n Additional propranolol treatment but not digoxin and diuretics alone can effectively reduce clinical symptoms of heart failure in infants with congenital heart disease, who suffer from increased neurohormonal activation.", "We performed a prospective, randomized, double-blind, placebo-controlled study of carvedilol effects in children with severe, chronic heart failure (HF), despite the use of conventional therapy.\n Little is known about the effects of carvedilol in youngsters with chronic HF and severe left ventricular (LV) dysfunction.\n We conducted a double-blind, placebo-controlled study of 22 consecutive children with severe LV dysfunction. The children had chronic HF and left ventricular ejection fraction (LVEF) <30%. Patients were randomly assigned to receive either placebo (8 patients) or the beta-blocker carvedilol (14 patients) at 0.01 mg/kg/day titrated up to 0.2 mg/kg/day, followed-up for six months.\n During the follow-up and the up-titration period in the carvedilol group, four patients died and one underwent heart transplantation. In patients receiving carvedilol evaluated after six months, a significant increase occurred in LVEF, from 17.8% (95% confidence interval [CI], 14.1 to 21.4%) to 34.6% (95% CI, 25.2 to 44.0%); p = 0.001. Modified New York Heart Association (NYHA) functional class improved in nine patients taken off the transplant waiting list. All nine patients were alive at follow-up. In the placebo group, during the six-month follow-up, two patients died, and two underwent heart transplantation. Four patients persisted with HF symptoms (NYHA functional class IV). No significant change occurred in LVEF or fractional shortening.\n Carvedilol added to standard therapy may reduce HF progression and improve cardiac function, allowing some youngsters to be removed from the heart transplantation waiting list.", "Although beta-blockers improve symptoms and survival in adults with heart failure, little is known about these medications in children and adolescents.\n To prospectively evaluate the effects of carvedilol in children and adolescents with symptomatic systemic ventricular systolic dysfunction.\n A multicenter, randomized, double-blind, placebo-controlled study of 161 children and adolescents with symptomatic systolic heart failure from 26 US centers. In addition to treatment with conventional heart failure medications, patients were assigned to receive placebo or carvedilol. Enrollment began in June 2000 and the last dose was given in May 2005 (each patient received medication for 8 months).\n Patients were randomized in a 1:1:1 ratio to twice-daily dosing with placebo, low-dose carvedilol (0.2 mg/kg per dose if weight <62.5 kg or 12.5 mg per dose if weight > or =62.5 kg), or high-dose carvedilol (0.4 mg/kg per dose if weight <62.5 kg or 25 mg per dose if weight > or =62.5 kg) and were stratified according to whether each patient's systemic ventricle was a left ventricle or not.\n The primary outcome was a composite measure of heart failure outcomes in patients receiving carvedilol (low- and high-dose combined) vs placebo. Secondary efficacy variables included individual components of this composite, echocardiographic measures, and plasma b-type natriuretic peptide levels.\n There was no statistically significant difference between groups for the composite end point based on the percentage of patients who improved, worsened, or were unchanged. Among 54 patients assigned to placebo, 30 improved (56%), 16 worsened (30%), and 8 were unchanged (15%); among 103 patients assigned to carvedilol, 58 improved (56%), 25 worsened (24%), and 20 were unchanged (19%). The rates of worsening were lower than expected. The odds ratio for worsened outcome for patients in the combined carvedilol group vs the placebo group was 0.79 (95% CI, 0.36-1.59; P = .47). A prespecified subgroup analysis noted significant interaction between treatment and ventricular morphology (P = .02), indicating a possible differential effect of treatment between patients with a systemic left ventricle (beneficial trend) and those whose systemic ventricle was not a left ventricle (nonbeneficial trend).\n These preliminary results suggest that carvedilol does not significantly improve clinical heart failure outcomes in children and adolescents with symptomatic systolic heart failure. However, given the lower than expected event rates, the trial may have been underpowered. There may be a differential effect of carvedilol in children and adolescents based on ventricular morphology.\n clinicaltrials.gov Identifier: NCT00052026." ]

[ "35869", "7020176", "11698275", "17272503", "19695955" ]

[ "Antihuman thymocyte globulin for prophylaxis of graft-versus-host disease. A randomized trial in patients with leukemia treated with HLA-identical sibling marrow grafts.", "Failure of early administration of antithymocyte globulin to lessen graft-versus-host disease in human allogeneic marrow transplant recipients.", "Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO).", "Bone marrow transplantation for severe aplastic anemia: a randomized controlled study of conditioning regimens.", "Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial." ]

[ "nan", "nan", "One hundred nine patients with hematologic malignancies, undergoing bone marrow transplants (BMT) from unrelated donors, were randomized in 2 consecutive trials to receive or not to receive antithymocyte globulin (ATG) in the conditioning regimen, as follows: (A) 54 patients (median age, 28 years; 39% with advanced disease) were randomized to no ATG (n = 25) versus 7.5 mg/kg rabbit ATG (Thymoglobulin; Sangstat, Lyon, France) (n = 29); (B) 55 patients (median age, 31 years, 71% with advanced disease) were randomized to no ATG (n = 28) versus 15 mg/kg rabbit ATG (n = 27). Grade III-IV graft-versus-host disease (GVHD) was diagnosed in 36% versus 41% (P =.8) in the first and in 50% versus 11% (P =.001) in the second trial. Transplant-related mortality (TRM), relapse, and actuarial 3-year survival rates were comparable in both trials. In fact, despite the reduction of GVHD in the second trial, a higher risk for lethal infections (30% vs 7%; P =.02) was seen in the arm given 15 mg/kg ATG. Extensive chronic GVHD developed overall more frequently in patients given no ATG (62% vs 39%; P =.04), as confirmed by multivariate analysis (P =.03). Time to 50 x 10(9)/L platelets was comparable in the first trial (21 vs 24 days; P =.3) and delayed in the ATG arm in the second trial (23 vs 38 days; P =.02). These trials suggest that (1) 15 mg/kg ATG before BMT significantly reduces the risk for grade III-IV acute GVHD, (2) this does not translate to a reduction in TRM because of the increased risk for infections, and (3) though survival is unchanged, extensive chronic GVHD is significantly reduced in patients receiving ATG.", "The addition of antithymocyte globulin (ATG) to a regimen of high-dose cyclophosphamide has been advocated to enhance engraftment after allogeneic bone marrow transplantation (BMT) for severe aplastic anemia (SAA). In a prospective clinical trial, 134 patients were randomly assigned to receive cyclophosphamide alone or in combination with ATG. All patients received T-cell-replete bone marrow from an HLA-matched sibling. With a median follow-up of 6 years, the 5-year probabilities of survival were 74% for the cyclophosphamide alone group and 80% for the cyclophosphamide plus ATG group (P = .44). Graft failure and graft-versus-host disease (GVHD) rates were similar in both groups. With the survival rates achieved, this study is not adequately powered to detect significant differences between the 2 treatment groups. In conclusion, the results of allogeneic BMT for SAA have improved over time related to advances in supportive care. The addition of ATG to the preparative regimen did not significantly improve the outcome.", "Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic haematopoietic cell transplantation from unrelated donors. Anti-T-cell globulins (ATGs) might lower the incidence of GVHD. We did a prospective, randomised, multicentre, open-label, phase 3 trial to compare standard GVHD prophylaxis with ciclosporin and methotrexate with or without anti-Jurkat ATG-Fresenius (ATG-F).\n Between May 26, 2003, and Feb 8, 2007, 202 patients with haematological malignancies were centrally randomly assigned using computer-generated centre-stratified block randomisation between treatment groups receiving ciclosporin and methotrexate with or without additional ATG-F. One patient in the ATG-F group did not undergo transplantation, thus 201 patients who underwent transplantation with peripheral blood (n=164; 82%) or bone marrow (n=37; 18%) grafts from unrelated donors after myeloablative conditioning were included in the full analysis set, and were analysed according to their randomly assigned treatment (ATG-F n=103, control n=98). The primary endpoint was severe acute GVHD (aGVHD) grade III-IV or death within 100 days of transplantation. The trial is registered with the numbers DRKS00000002 and NCT00655343.\n The number of patients in the ATG-F group who had severe aGVHD grade III-IV or who died within 100 days of transplantation was 12 and 10 (21.4%, 95% CI 13.4-29.3), respectively, compared with 24 and nine (33.7%, 24.3-43.0) patients, respectively, in the control group (adjusted odds ratio 0.59, 95% CI 0.30-1.17; p=0.13). The cumulative incidence of aGVHD grade III-IV was 11.7% (95% CI 6.8-19.8) in the ATG-F group versus 24.5% (17.3-34.7) in the control group (adjusted hazard ratio [HR] 0.50, 95% CI 0.25-1.01; p=0.054), and cumulative incidence of aGVHD grade II-IV was 33.0% (n=34; 95% CI 25.1-43.5) in the ATG-F group versus 51.0% (n=50; 95% CI 42.0-61.9) in the control group (adjusted HR 0.56, 0.36-0.87; p=0.011). The 2-year cumulative incidence of extensive chronic GVHD was 12.2% (n=11; 95% CI 7.0-21.3) versus 42.6% (n=34; 95% CI 33.0-55.0; adjusted HR 0.22, 0.11-0.43; p<0.0001). There were no differences between treatment groups with regard to relapse, non-relapse mortality, overall survival, and mortality from infectious causes.\n The addition of ATG-F to GVHD prophylaxis with ciclosporin and methotrexate resulted in decreased incidence of acute and chronic GVHD without an increase in relapse or non-relapse mortality, and without compromising overall survival. The use of ATG-F is safe for patients who are going to receive a haematopoietic cell transplantation from matched unrelated donors.\n Fresenius Biotech GmbH." ]

[ "16608559" ]

[ "Effect of body-oriented psychological therapy on negative symptoms in schizophrenia: a randomized controlled trial." ]

[ "In order to improve the treatment of medication-resistant negative symptoms in schizophrenia, new interventions are needed. Neuropsychological considerations and older reports in the literature point towards a potential benefit of body-oriented psychological therapy (BPT). This is the first randomized controlled trial specifically designed to test the effectiveness of manualized BPT on negative symptoms in chronic schizophrenia.\n Out-patients with DSM-IV continuous schizophrenia were randomly allocated to either BPT (n=24) or supportive counseling (SC, n=21). Both therapies were administered in small groups in addition to treatment as usual (20 sessions over 10 weeks). Changes in negative symptom scores on the Positive and Negative Symptom Scale (PANSS) between baseline, post-treatment and 4-month follow-up were taken as primary outcome criteria in an intention-to-treat analysis.\n Patients receiving BPT attended more sessions and had significantly lower negative symptom scores after treatment (PANSS negative, blunted affect, motor retardation). The differences held true at 4-month follow-up. Other aspects of psychopathology and subjective quality of life did not change significantly in either group. Treatment satisfaction and ratings of the therapeutic relationship were similar in both groups.\n BPT may be an effective treatment for negative symptoms in patients with chronic schizophrenia. The findings should merit further trials with larger sample sizes and detailed studies to explore the therapeutic mechanisms involved." ]

[ "12849805", "7836512" ]

[ "Monitoring of in vitro fertilization-embryo transfer cycles by ultrasound versus by ultrasound and hormonal levels: a prospective, multicenter, randomized study.", "Ultrasonic control without hormone determination for ovulation induction in in-vitro fertilization/embryo transfer with gonadotrophin-releasing hormone analogue and human menopausal gonadotrophin." ]

[ "To determine whether cycle monitoring using both serum E(2) and ultrasound findings yields superior clinical pregnancy rates during IVF-embryo transfer (ET) compared to monitoring with ultrasound alone.\n Prospective, randomized, multicenter, patient-blinded study.\n Four assisted conception units in the United Kingdom.\n Two hundred ninety-seven women believed to be normal responders undergoing IVF treatment.\n Patients were randomly allocated on day 7 of stimulation to one of the two hCG administration criteria: [1] the E(2)-to-follicle > or =11 mm ratio was between 250 and 500 pmol/L/follicle and at least 2 follicles reached a mean diameter of 18 mm or [2] at least 2 follicles reached a mean diameter of 18 mm and the endometrium thickness was > or =8 mm.\n Duration and cumulative dose of recombinant human FSH, total number of growing follicles, oocytes retrieved, number and quality of embryos, pregnancy rates, and ovarian hyperstimulation syndrome (OHSS) rates.\n Two hundred ninety-seven patients were randomized to one of the two criteria groups. Of these, 288 (97%) received urinary (u)-hCG (143 in group A and 145 in group B). One hundred three women in group A (72%) met both criteria for hCG administration. Pregnancy and OHSS rates were similar (34.3% vs. 31.4% and 4.9% vs. 4.1%, respectively).\n The addition of E(2)/follicle criteria to ultrasound monitoring of IVF cycles in normal responders seldom changes the timing of hCG, and does not increase pregnancy rates or the risk of OHSS.", "A total of 114 patients admitted to an in-vitro fertilization-embryo transfer programme for the first time, were randomly assigned to the study group or controls. Gonadotrophin-releasing hormone analogue (GnRHa) and human menopausal gonadotrophin (HMG) were used for ovulation induction. The study patients were followed up merely by ultrasonography and the controls by ultrasonography and serum determinations of oestradiol, progesterone and luteinizing hormone (LH). There was no significant difference in the duration and total amount of HMG used for ovulation induction (10.9 versus 11.5 days and 34.8 versus 37.9 ampoules, respectively). The number of oocytes retrieved (11.7 versus 13.4) and the numbers of embryos replaced (2.6 versus 2.8) and cryopreserved (1.9 versus 3.3) were also similar. Pregnancy rates were similar. Pregnancy rate per ovum retrieval was 22.2 versus 25% and per embryo transfer 27.2 versus 26.5%. Oestradiol patterns were also similar. The rate and severity of ovarian hyperstimulation syndrome were virtually identical. We conclude that 'ultrasound-only' monitoring of ovulation induction in IVF cycles treated by GnRHa-HMG in the long protocol is as effective and safe as the conventional ultrasound and hormone determination, but far simpler, swifter and more cost-effective." ]

[ "7853434", "3518625", "10589921", "3054035", "9716056", "8052810", "2675757", "8617528", "9139555", "8047805", "4574641", "2694343", "11099086", "2201742" ]

[ "Double-blind comparison of oral gentamicin and nalidixic acid in the treatment of acute shigellosis in children.", "Comparative efficacies of single intravenous doses of ceftriaxone and ampicillin for shigellosis in a placebo-controlled trial.", "Single dose of azithromycin or three-day course of ciprofloxacin as therapy for epidemic dysentery in Kenya. Acute Dysentery Study Group.", "Therapy for shigellosis. I. Randomized, double-blind trial of nalidixic acid in childhood shigellosis.", "Randomised comparison of ciprofloxacin suspension and pivmecillinam for childhood shigellosis.", "Comparative efficacy of pivmecillinam and cotrimoxazole in acute shigellosis in children.", "Comparison of single-dose treatment with norfloxacin and standard 5-day treatment with trimethoprim-sulfamethoxazole for acute shigellosis in adults.", "Comparative efficacy of furazolidone and nalidixic acid in the empirical treatment of acute invasive diarrhea: randomized clinical trial.", "Treatment of shigellosis: V. Comparison of azithromycin and ciprofloxacin. A double-blind, randomized, controlled trial.", "Comparison of pivmecillinam and nalidixic acid in the treatment of acute shigellosis in children.", "Comparative efficacy of nalidixic acid and ampicillin for severe shigellosis.", "A randomized, controlled, single-blind study comparing furazolidone with trimethoprim-sulfamethoxazole in the empirical treatment of acute invasive diarrhea.", "Oral ciprofloxacin vs. intramuscular ceftriaxone as empiric treatment of acute invasive diarrhea in children.", "Therapy for shigellosis. II. Randomized, double-blind comparison of ciprofloxacin and ampicillin." ]

[ "To compare the efficacy of oral gentamicin with nalidixic acid in the treatment of acute shigellosis, we studied, in a double blind-trial, 79 comparable children with bloody diarrhoea of less than 72 h duration. Of them Shigella spp. were isolated in 71 patients. Patients were randomly assigned to receive either gentamicin 30 mg/kg/day or nalidixic acid 60 mg/kg/day, both given orally in four equal doses for 5 days. Stool frequency differed significantly between the groups from day two until completion of the study. Treatment failure was observed in 14 (42 per cent) patients receiving oral gentamicin compared to none of those with nalidixic acid-sensitive strains of Shigella spp. (P = 0.0002). Although all the shigella isolates were sensitive to gentamicin in vitro, 19 (58 per cent) patients on gentamicin therapy failed to eliminate shigella organisms from stool, compared to none in the nalidixic acid treated group infected with nalidixic acid-sensitive Shigella spp. (P < 0.001). One patient in each group had a bacteriological relapse. We conclude that gentamicin given orally was therapeutically ineffective in the treatment of acute shigellosis.", "To evaluate ceftriaxone for the treatment of shigellosis, 94 adult males with acute dysentery were randomly assigned to receive ceftriaxone (1 g), ampicillin (4 g), or saline placebo intravenously in single doses in a double-blind design. Stool cultures were positive for Shigella dysenteriae in 52 patients, S. flexneri in 38 patients, and other species in 4 patients. Both ceftriaxone and ampicillin caused reductions in the mean duration of fever and the means of daily stool frequency 2 to 4 days after therapy versus placebo (P less than 0.05). The ability of ceftriaxone to reduce stool frequency during 6 days after treatment was significant in patients with S. flexneri infections (P less than 0.05), whereas S. dysenteriae infections were relatively refractory to improvement by both antibiotics. Neither drug had a significant effect on overall duration of diarrhea, blood in stool, or tenesmus. Ampicillin reduced the mean duration of positive stool cultures after treatment from 2.6 days in the placebo group to 1.1 days (P less than 0.05), whereas ceftriaxone did not affect the duration of Shigella sp. excretion. These results indicate that single intravenous doses of ceftriaxone and ampicillin caused some clinical improvement in acute shigellosis but only ampicillin exerted a bacteriological effect on Shigella sp. excretion.", "nan", "We compared nalidixic acid, 55 mg/kg/day, with ampicillin, 100 mg/kg/day, both given orally for 5 days, in the treatment of children with dysentery caused by shigellosis. All patients entered into the study had illness of less than 72 hours' duration and no prior allopathic drug therapy. Treatment was randomized and administered in double-blind fashion. Patients initially treated with ampicillin who were infected with a Shigella strain resistant to ampicillin were considered as a separate group (ampicillin-R). All isolates were susceptible to nalidixic acid. Similar percentages of patients treated with nalidixic acid (26/32, 81%) and with ampicillin (17/22, 77%) were clinically cured by the end of therapy; the rate in ampicillin-R (3/14, 21%) patients was significantly lower (p less than 0.001). Stool frequency in patients treated with nalidixic acid was significantly less than for ampicillin-treated or ampicillin-R patients during the final 3 study days. All patients treated with nalidixic acid and ampicillin had Shigella eradicated from their stool by day 3, compared with 77% (10/13) of ampicillin-R patients (p less than 0.05, ampicillin-R vs nalidixic acid or ampicillin). We conclude that nalidixic acid is an effective alternative to ampicillin in the treatment of shigellosis caused by nalidixic acid-susceptible strains.", "Infections caused by multiply resistant Shigella species are a major cause of childhood morbidity and mortality in Third World countries. The fluoroquinolone agent ciprofloxacin is active in vitro against these strains of bacteria, but has not been routinely used to treat acute childhood infections because of concern that quinolones may cause arthropathy in children. We undertook a randomised double-blind study to test the effects of ciprofloxacin treatment in children with shigella dysentery.\n We compared the efficacy and toxic effects of ciprofloxacin suspension (10 mg/kg every 12 h for 5 days, maximum individual dose 500 mg) with those of pivmecillinam tablets (15-20 mg/kg every 8 h for 5 days, maximum individual dose 300 mg). We enrolled 143 children aged 2-15 years with dysentery of 72 h or less duration. Patients stayed in hospital for 6 days, and were followed up 7, 30, and 180 days after hospital discharge. Joint symptoms and function were assessed daily for 6 days. Clinical success was defined as the absence of frank dysentery on day 3, and on day 5 no bloody-mucoid stools, one or no watery stool, six or fewer total stools, and no fever. If no shigella were isolated from faecal samples on day 3 or thereafter, treatment was judged bacteriologically successful.\n 13 patients were excluded since they did not meet eligibility criteria; 10 withdrew before day 5. Thus 120 patients (60 in each group) completed the study. Treatment was clinically successful in 48 (80%) of 60 patients who received ciprofloxacin and in 39 (65%) of 60 patients who received pivmecillinam (p=0.10). Treatment was bacteriologically successful in all of the patients receiving ciprofloxacin, and in 54 (90%) of the patients receiving pivmecillinam (p=0.03). Joint pain after treatment began in 13 (18%) of 71 patients who received ciprofloxacin and 16 (22%) of 72 patients who received pivmecillinam (p>0.2), and no patient had signs of arthritis.\n In our trial, ciprofloxacin suspension and pivmecillinam had the same clinical efficacy. Ciprofloxacin had greater bacteriological efficacy and was not associated with the development of arthropathy. We conclude that ciprofloxacin is an effective and safe drug for use in multiply resistant childhood shigellosis.", "In a prospective randomized double-blind trial, pivmecillinam was compared with cotrimoxazole (TMP-SMX), both given orally for a period of 5 days, for the treatment of 59 children with shigellosis. 29 patients were treated with pivmecillinam and 30 with cotrimoxazole. 14% of shigella organisms isolated were resistant to pivmecillinam and 21% to TMP-SMX. The diarrhea persisted for a mean (+/- SD) period of 74 +/- 24.8 h in the pivmecillinam-treated patients versus 73.8 +/- 34 h in the TMP-SMX-treated patients. Duration of fever, positive stool culture, visible blood, occult blood, and pus cells in the stools were similar for both treatment groups. Five patients (17%) in the pivmecillinam group and 4 patients (13%) in the cotrimoxazole group fulfilled the clinical criteria that defined treatment failure. One patient (3.4%) in the pivmecillinam group and 2 (6.6%) in the TMP-SMX group evidenced recurrence of the diarrheal symptoms at the follow-up visit. No major drug-related side effects were observed in either group. We concluded that pivmecillinam is equivalent to cotrimoxazole in the treatment of shigellosis in children.", "Shigellae have been shown to be highly susceptible to new quinolone agents, with average MICs for 90% of isolates of less than 0.1 microgram/ml. Because these agents also reach high concentrations in the stool after a single dose, the effectiveness of a single 800-mg dose of norfloxacin and of 5-day treatment with trimethoprim-sulfamethoxazole (TMP-SMX) were compared in a randomized trial. Patients with clinical dysentery received one of these treatment regimens, and clinical data and follow-up culture results were analyzed for patients whose stool culture on presentation grew shigellae. When 55 patients with shigellosis (26 treated with TMP-SMX, 29 treated with norfloxacin) whose bacterial isolates were susceptible to the antibiotic given were compared by treatment group, no significant differences were seen in days of illness (mean, 2.5 +/- 0.65 days with TMP-SMX and 2.0 +/- 0.47 days with norfloxacin; P = 0.200) or number of unformed stools after starting treatment (mean, 9.7 +/- 2.37 stools with TMP-SMX and 7.6 +/- 3.19 stools with norfloxacin; P = 0.312). Resistance in vitro to TMP-SMX was seen in 15% of Shigella isolates, whereas none was resistant to norfloxacin. Bacteriologic failure was found in 1 patient among 24 receiving TMP-SMX and in none of 25 patients receiving norfloxacin. One single dose of norfloxacin was as effective as 5 days of treatment with TMP-SMX in these adults with shigellosis.", "Efficacy of furazolidone and nalidixic acid was compared in a randomized trial involving 72 children with acute invasive diarrhea. Thirty six children received furazolidone (7.5 mg/kg/day) and 36 children received nalidixic acid (55 mg/kg/day). Clinical characteristics of the two treatment groups were comparable on admission. Of these, 34 children in furazolidone treated group and 29 children in nalidixic acid treated group completed the full course of treatment and were analyzed finally for clinical efficacy. Clinical cure was observed in 29(85.3%) children treated with furazolidone and 29(100.0%) children treated with nalidixic acid. Nalidixic acid treated group had statistically significantly higher cure rate (p = 0.039) as compared to furazolidone treated group. However, 85% cure rate in furazolidone treated group may be potentially useful for the treatment of acute invasive diarrhea because of decreasing efficacy of nalidixic acid against shigellosis in many countries.", "Treatment of shigellosis is currently limited by the high prevalence of multidrug-resistant strains of Shigella.\n To determine the efficacy of azithromycin in the treatment of shigellosis.\n Randomized, double-blind clinical trial.\n Diarrhea treatment center in Dhaka, Bangladesh.\n 70 men with shigellosis that had lasted 72 hours or less.\n Patients stayed in the hospital for 6 days. Thirty-four patients were randomly assigned to receive 500 mg of azithromycin on study day 1, followed by 250 mg once daily for 4 days; 36 patients were assigned to receive 500 mg of ciprofloxacin every 12 hours for 5 days.\n Clinical treatment failure was considered to have occurred if frank dysentery persisted for 72 hours after therapy began or if on study day 5 a patient had more than six stools, had any bloody-mucoid stools, had more than one watery stool, or had an oral body temperature exceeding 37.8 degrees C. Bacteriologic treatment failure was considered to have occurred if Shigella strains could be isolated from a stool sample after study day 2. Therapy was considered either clinically or bacteriologically successful in patients who completed therapy and did not meet criteria for failure.\n Therapy was clinically successful in 28 (82%) patients who received azithromycin and 32 (89%) patients who received ciprofloxacin (difference, -7% [95% Cl, -23% to 10%]). Therapy was bacteriologically successful in 32 (94%) patients receiving azithromycin and 36 (100%) patients receiving ciprofloxacin (difference, -6% [Cl, -14% to 2%]). Peak serum concentrations of azithromycin were equal to the minimum inhibitory concentration (MIC) of the infecting Shigella strains, whereas serum concentrations of ciprofloxacin were 28 times the MIC. Stool concentrations of both drugs were more than 200 times the MIC.\n Azithromycin is effective in the treatment of moderate to severe shigellosis caused by multidrug-resistant Shigella strains.", "The efficacy of oral pivmecillinam was compared with nalidixic acid in the treatment of acute shigellosis in children 1-8 years of age. In a double-blind trial we studied 80 comparable children with bloody diarrhoea of less than 3 days' duration. Shigella spp. was isolated in 71 children. Patients were randomly assigned to receive either pivmecillinam, 50 mg/kg.day, or nalidixic acid, 60 mg/kg.day, both given orally for 5 days. The stool frequency decreased progressively in both treatment groups. Nalidixic acid failed to eradicate Shigella species in 10 patients, compared with three in the pivmecillinam group (p = 0.04). Similarly, clinical failure was observed in 11 of 37 patients receiving nalidixic acid and in 2 of 26 patients infected with nalidixic acid-susceptible strains as against none in the group receiving pivmecillinam. The results suggest that pivmecillinam given orally was, in fact, more effective than nalidixic acid in the treatment of acute shigellosis in children, particularly when the resistant strains are taken into account.", "nan", "An outpatient study of 125 children with acute invasive diarrhea was conducted at the Hospital Infantil de Mexico Federico Gomez. Through a single-blind randomization, we compared the efficacy of furazolidone, 7.5 mg/kg/day (49 patients), with trimethoprim-sulfamethoxazole (TMP-SMX), 8 mg/40 mg/kg/day (52 patients), each given for 5 days. A control group of 24 patients received no antimicrobials. Stool samples were collected from all patients at the time of admission, and active drugs were administered before the stool culture results were available. At baseline, 48 of 125 patients (38.5%) had negative stool cultures. In the other patients, the most frequently isolated pathogens were Shigella sp and enteropathogenic Escherichia coli. Of the total population who completed the study 43 of 49 (87.8%) of the patients in the furazolidone group and 43 of 52 (82.7%) of the patients in the TMP-SMX group achieved clinical cure by day 3, compared with 10 of 22 (45.5%) of the patients in the control group. Day 3 cure rates were similar between groups, independent of baseline stool culture results. Of those patients who had positive stool cultures on day 1, 20 of 34 (58.8%) in the furazolidone group and 19 of 29 (65.5%) in the TMP-SMX group had negative culture results on day 6, compared with 4 of 12 (33.3%) in the control group. Overall, clinical and bacteriologic success was achieved in 31 of 49 (63%) patients treated with furazolidone and in 36 of 52 (69%) patients treated with TMP-SMX, compared with 5 of 22 (23%) patients in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)", "Acute invasive diarrhea is a potentially serious condition in children. Because of the increasing resistance of enteric pathogens to commonly used oral antibiotics, intramuscular ceftriaxone has become the routine drug in the treatment of acute invasive diarrhea requiring an emergency visit in southern Israel. The inconvenience of this parenteral regimen created an increased need for oral pediatric formulations for the treatment of invasive diarrhea.\n To evaluate the efficacy and safety of a suspension formulation of ciprofloxacin in the treatment of acute invasive diarrhea in infants and children.\n From July 1996 through December 1997, 201 evaluable children ages 6 months to 10 years (35% <1 year; 70% <3 years) presenting with acute invasive diarrhea at the Pediatric Emergency Room were randomized to receive either ciprofloxacin suspension (10 mg/kg twice a day + im placebo; n = 95) or im ceftriaxone (50 mg/kg/day + placebo suspension; n = 106) for 3 days in a double blind manner. Stool cultures for Shigella, Salmonella, Campylobacter spp. and diarrheagenic Escherichia coli were obtained on Days 1, 3, 4 to 5 and 21 +/- 5. Clinical response and safety were assessed on Days 1, 2, 3, 4 to 5 and 21 +/- 5.\n We isolated 127 pathogens from 121 (60%) patients: 73 (57%) Shigella; 23 (18%) Salmonella; 18 (14%) E. coli; and 13 (10%) Campylobacter. Overall bacteriologic eradication on Day 4 to 5 was 99% for Shigella, 77% for Salmonella and 77% for Campylobacter, with no difference between the 2 groups. Clinical cure or improvement was observed in 100 and 99% of the ciprofloxacin and ceftriaxone groups, respectively. Serum ciprofloxacin values determined on Day 3 of the treatment were higher in the majority of patients than were the MIC50 and MIC90 values for the Shigella and Salmonella spp. isolated. Possible drug-related adverse events occurred in 13 patients [ciprofloxacin, 8 (8%); ceftriaxone, 5 (4.7%)] and were mild and transient. Joint examination was normal during and after completion of therapy in all patients.\n Oral ciprofloxacin was as safe and effective as intramuscular ceftriaxone for the empiric treatment of acute invasive diarrhea in ambulatory pediatric patients requiring an emergency room visit.", "Ciprofloxacin, 500 mg every 12 h, was compared with ampicillin, 500 mg every 6 h, both given for 5 days, in the treatment of 121 adult males hospitalized with severe shigellosis. Treatment was randomized and double-blinded. At the completion of treatment, there was resolution or marked improvement in symptoms in 57 (95%) of 60 ciprofloxacin-treated patients, 23 (88%) of 26 ampicillin-treated patients infected with an ampicillin-susceptible strain of Shigella, and 15 (43%) of 35 ampicillin-treated patients infected with an ampicillin-resistant strain of Shigella (ampicillin-R group) (P less than .01, ciprofloxacin or ampicillin groups vs. ampicillin-R group). Bacteriologic failure was less common (P less than .025) in the ciprofloxacin group (0/60) than in the ampicillin (3/26, 12%) or ampicillin-R groups (5/35, 14%). Ciprofloxacin-treated patients had a mean of 29 stools during the study, compared with 46 for ampicillin-treated patients (P = .004). Thus ciprofloxacin seems to be an effective, and perhaps superior, alternative to ampicillin in treating patients with shigellosis." ]

[ "12870569", "6438683" ]

[ "Differential effect of quetiapine on depressive symptoms in patients with partially responsive schizophrenia.", "Effects of sulpiride and chlorpromazine on depressive symptoms in schizophrenic patients--relationship to drug concentrations." ]

[ "While atypical antipsychotics appear to be effective in reducing depressive symptoms in the acute phase of schizophrenia, little is known about their efficacy in patients with ongoing symptoms. The present study assessed whether quetiapine (Seroquel) is more effective than haloperidol in treating depressive symptoms in patients with persistent positive symptoms, and investigated whether this effect is independent, or secondary to, reductions in other symptoms such as positive, negative or extrapyramidal symptoms. Patients with schizophrenia and a history of partial refractoriness to conventional antipsychotics who had not responded to 4 weeks of fluphenazine treatment (20 mg/day) were randomized to receive either quetiapine (600 mg/day) or haloperidol (20 mg/day) for a further 8 weeks. Change in the Positive and Negative Syndrome Scale depression factor score from baseline to endpoint was calculated and path analyses were performed on data from 269 patients. Quetiapine produced a greater reduction in depressive scores than haloperidol (-1.60 versus -0.54; p = 0.006). The path analyses indicated that this was a direct effect on depressive symptoms. These findings extend the evidence for an antidepressant effect for the novel antipsychotics in schizophrenia, and suggest that this is not limited to acutely psychotic patients.", "Schizophrenic patients were treated with fixed doses of sulpiride (800 mg/day) or chlorpromazine (CPZ) (400 mg/day) over a period of 8 weeks using a double-blind design. There were 25 patients in each group and all the patients were in an acute phase of their disease. They all fulfilled the Research Diagnostic Criteria (RDC) for schizophrenia. Depressive symptoms as rated according to the Comprehensive Psychopathological Rating Scale (CPRS) were present in the patients before treatment was started. The depressive and psychotic symptoms in both groups decreased in parallel during the whole period of treatment. Patients in the sulpiride group recovered more quickly from depressive symptoms than patients in the CPZ group. It was also found that patients with low concentrations of sulpiride or CPZ in serum recovered more completely from depressive symptoms and had fewer extrapyramidal side effects than patients with high drug concentrations." ]

[ "1105489", "1678921", "7539854", "10226868", "2872804", "2669473", "2969740" ]

[ "Double-blind studies of the clinical effectiveness of prazosin.", "Antihypertensive dose-response relationships: studies with the selective alpha 1-blocking agent terazosin.", "Doxazosin for the treatment of benign prostatic hyperplasia in patients with mild to moderate essential hypertension: a double-blind, placebo-controlled, dose-response multicenter study.", "Effects of doxazosin in the gastrointestinal therapeutic system formulation versus doxazosin standard and placebo in mild-to-moderate hypertension. Doxazosin Investigators' Study Group.", "Terazosin: an effective once-daily monotherapy for the treatment of hypertension.", "Efficacy and safety of Minipress XL, a new once-a-day formulation of prazosin.", "Effect of doxazosin monotherapy on blood pressure and plasma lipids in patients with essential hypertension." ]

[ "In separate double-blind trials, prazosin was compared with placebo and with methyldopa and placebo. In both, prazosin was well tolerated and succeeded in lowering blood pressure in patients with mild to moderate hypertension. The mean reductions with methyldopa were greater, but the difference was not statistically significant and a higher percentage of the patients in the prazosin group became normotensive.", "Terazosin is a selective alpha 1-adrenergic-blocking agent indicated for the treatment of hypertension. The aim of this multicenter study, performed in 256 patients with mild to moderate essential hypertension, was to define the dosing characteristics of terazosin (in the range of 1 to 80 mg) administered once daily. Patients were randomly assigned to placebo or active treatment groups; each group received 3 months of treatment, which comprised three ascending doses of terazosin, each administered for a 1-month period. As determined by conventional office measurements of supine diastolic blood pressure and by automated ambulatory blood pressure monitoring, there was a clear antihypertensive dose-response relationship for terazosin in the range of 1 to 5 mg daily. Except for the 80 mg dose, none of the doses above 5 mg (10 to 40 mg) appeared to provide additional efficacy. Both the office measurements and the monitoring data indicated that the ratio of trough (effect at the end of the dosing interval) to peak (maximum effect during the dosing interval) was at least 50% or greater during treatment with the 5 mg dose. Thus the 5 mg dose appeared to provide meaningful clinical antihypertensive efficacy and to sustain its effects throughout the full 24-hour period.", "A total of 248 hypertensive patients 45 years old or older with benign prostatic hyperplasia (BPH) was included in this 16-week, multicenter, double-blind, placebo-controlled, parallel-group dose-response study. Doxazosin, a selective alpha 1-adrenoceptor antagonist, produced a significant increase in maximum urinary flow rate (2.3 to 3.6 ml. per second) at doses of 4 mg., 8 mg. and 12 mg., and in average flow rate (8 mg. and 12 mg.) compared with placebo. The increase in maximum flow rate was significant with doxazosin versus placebo within 1 week of initiating double-blind therapy. Doxazosin compared to placebo significantly decreased patient-assessed total, obstructive and irritative BPH symptoms. Blood pressure was significantly lower with all doxazosin doses compared with placebo. Adverse events, primarily mild to moderate in severity, were reported in 48% of patients on doxazosin and 35% on placebo. Our results strongly support the use of doxazosin as a nonoperative therapeutic alternative in the management of uncomplicated BPH. Doxazosin would also be particularly useful in the management of patients who have BPH and hypertension.", "The alpha 1-blocker doxazosin is a well-established therapy for hypertension and benign prostatic hyperplasia; however, in its standard form, a multiple-step titration regimen is usually required. The new gastrointestinal therapeutic system (GITS) formulation of doxazosin greatly minimizes the need for titration by changing drug-delivery rate and the pharmaco-kinetic profile. To demonstrate this in hypertensive patients, we assessed the effects of doxazosin GITS 4 or 8 mg once daily versus doxazosin standard 1-8 mg once daily, and placebo, in an integrated analysis of two multicenter, double-blind, randomized, parallel-group trials. Each trial included a 2-week washout period and 12 weeks of therapy. One study compared doxazosin GITS, doxazosin standard, and placebo in 392 patients with mild hypertension [blood pressure (BP) 95-105/ < or = 180 mm Hg]; the other study compared doxazosin GITS with doxazosin standard in 315 patients with mild-to-moderate hypertension (BP 95-115/ < or = 220 mm Hg). The primary outcome measure was the proportion of responders (sitting diastolic BP < 90 mm Hg or 10-mm Hg decrease from baseline 24 h after the dose) at the final visit for the per-protocol population. Mean baseline BP and heart rate were well matched in each group. Approximately 64% of patients with doxazosin GITS (198 of 309 patients) and 68% with doxazosin standard (207 of 304 patients) achieved goal BP response at the final visit versus 36% with placebo (25 of 70 patients; p < 0.05). The majority with doxazosin GITS (60%) remained at the initial 4-mg starting dose. Doxazosin GITS was as effective as doxazosin standard, and both were more effective than placebo in controlling BP in mild-to-moderate hypertension. Doxazosin GITS was well tolerated, and fewer patients with the GITS formulation discontinued therapy because of side effects compared with doxazosin standard or placebo. Syncope was not reported with doxazosin GITS. Whereas the efficacy of doxazosin GITS at 4 or 8 mg is equivalent to that of the standard regimen in this combined analysis, the GITS formulation appears to eliminate the need for titration in most patients.", "The safety and efficacy of once-daily terazosin as monotherapy were evaluated in five randomized, double-blind, placebo-controlled studies in which 351 patients with mild to moderate hypertension participated. The five studies included two dose-titration studies and three fixed-dose studies. In the dose-titration studies, terazosin doses were titrated at weekly intervals until supine diastolic blood pressure was below 90 mm Hg. In the fixed-dose studies, titration continued until a predetermined dosage level of terazosin or corresponding placebo was reached. The dose of terazosin ranged from 1 to 40 mg once daily, and responses were assessed after a four-week course of therapy at a constant dosage level. Terazosin administration resulted in significantly greater mean decreases in supine diastolic blood pressure in comparison with placebo in four of the five studies. Similar decreases were observed for supine systolic and standing blood pressures in selected studies. In all five studies, terazosin caused a significant decrease in supine and standing blood pressures from baseline to the final visit. Adverse experiences occurring with a significantly greater prevalence rate in terazosin-treated versus placebo-treated patients and 7 percent of placebo-treated patients), asthenia (17 percent of the terazosin group and 4 percent of the placebo group), and peripheral edema (10 percent of the terazosin group and 3 percent of the placebo group). On the basis of these studies, it appears that terazosin, when administered once daily as monotherapy, is both safe and effective for the treatment of mild to moderate hypertension.", "The efficacy and safety of prazosin GITS (gastro-intestinal therapeutic system), a new extended-release once-a-day formulation, were assessed both as monotherapy in mild essential hypertension and in combination with a diuretic in moderate essential hypertension in two multicenter, double-blind, placebo-controlled trials. Prazosin GITS (Minipress XL) given once daily in doses of either 10 or 20 mg significantly reduced sitting and standing systolic and diastolic blood pressure compared with placebo in both mild and moderate essential hypertension. There were minimal, clinically insignificant changes in heart rate following prazosin-GITS treatment (2.5, 10, and 20 mg) compared with placebo treatment. Prazosin GITS was well tolerated; the most common adverse experiences reported were headache, dizziness, and fatigue. All adverse experiences in the moderate hypertension group and the majority (91 percent) in the mild hypertension group were mild-to-moderate in severity. The results from these multicenter trials demonstrate the efficacy and safety of this new extended-release once-a-day formulation of prazosin in the treatment of patients with mild and moderate essential hypertension.", "The efficacy and safety of doxazosin (DOX) for the treatment of hypertension was investigated. A multicenter, double-blind, placebo-controlled, parallel design was employed. A 4-week placebo runin period was followed by a 9-week double-blind period during which patients were randomly assigned to placebo or 2, 4, or 8 mg doxazosin. Blood pressures (BP) and heart rates (HR) were measured 24 hours postdose. The mean changes in standing BP (mmHg) were -6.2/-6.9 (2-mg regimen), -5.7/-5.8 (4-mg regimen), -8.5/-7.7 (8-mg regimen) for DOX patients and 0.7/-2.9 for placebo patients. The mean changes in supine BP (mmHg) were -3.2/-4.7 (2-mg regimen), -4.0/-5.1 (4-mg regimen), -4.6/-5.6 (8-mg regimen) for DOX patients and -0.5/-3.3 for placebo patients. There was no evidence of a dose-response relationship for DOX; however, DOX serum levels were linearly related to the dose. Responder rate for the combined DOX patients was 38% (32/84) and for the placebo patients 27% (8/30). HR (24 hours postdose) was not modified by DOX. Patients in the 8-mg regimen had a significantly higher gain in mean body weight (+ 1.3 +/- 0.3 kg; P less than 0.05) compared to the 2-mg regimen, 4-mg regimen, and placebo groups. Plasma norepinephrine was not significantly modified by DOX. DOX had a favorable effect on plasma lipids. DOX lowered LDL cholesterol (P less than 0.05), total cholesterol, and apoprotein B and increased HDL/(LDL + VLDL) ratio (0.05 less than or equal to P less than 0.1) compared to placebo. Dropout rate and treatment-related side effects were equally distributed among the DOX and placebo groups. No patients had the dose of medication reduced because of side effects. Three DOX patients were withdrawn because of postural dizziness." ]

[ "14499023", "11600924", "9761803", "8456141", "6210835", "10730357", "12642755", "10626305", "10332798", "14734329", "12809196", "9527292", "15129059", "8976475", "11109471", "9883955", "1533941", "10457579", "14967569", "1835157", "2147702", "14699269", "15377573", "8434332", "14559046", "10394282", "2140432", "9196462", "7823996", "3157894", "9253097", "9231969", "12195058", "12443524", "10426734", "9854761", "14520029", "12381971", "2139241", "10534796", "8185727", "15055095", "12605431", "11389408", "8235809", "4257208", "12221343", "10906914", "6453571", "10763797", "11853276", "11013502", "7552649" ]

[ "The use of electro-acupuncture in conjunction with exercise for the treatment of chronic low-back pain.", "Evaluation of a program to reduce back pain in nursing personnel.", "A comparison of physical therapy, chiropractic manipulation, and provision of an educational booklet for the treatment of patients with low back pain.", "Evidence for use of an extension-mobilization category in acute low back syndrome: a prescriptive validation pilot study.", "Acute low back pain. Comparison of two conservative treatment approaches.", "[Effects of elastic lumbar belts on the effect of a muscle training program for patients with chronic back pain].", "Manual therapy and exercise therapy in patients with chronic low back pain: a randomized, controlled trial with 1-year follow-up.", "A randomized clinical trial of three active therapies for chronic low back pain.", "The efficacy of active rehabilitation in chronic low back pain. Effect on pain intensity, self-experienced disability, and lumbar fatigability.", "Graded activity for low back pain in occupational health care: a randomized, controlled trial.", "Intensive group training versus cognitive intervention in sub-acute low back pain: short-term results of a single-blind randomized controlled trial.", "The use of a back class teaching extension exercises in the treatment of acute low back pain in primary care.", "Effects of functional restoration versus 3 hours per week physical therapy: a randomized controlled study.", "Trunk exercise combined with spinal manipulative or NSAID therapy for chronic low back pain: a randomized, observer-blinded clinical trial.", "[Cesar therapy is temporarily more effective in patients with chronic low back pain than the standard treatment by family practitioner: randomized, controlled and blinded clinical trial with 1 year follow-up].", "Conservative treatment in patients sick-listed for acute low-back pain: a prospective randomised study with 12 months' follow-up.", "The effect of graded activity on patients with subacute low back pain: a randomized prospective clinical study with an operant-conditioning behavioral approach.", "The effect of a Mensendieck exercise program as secondary prophylaxis for recurrent low back pain. A randomized, controlled trial with 12-month follow-up.", "[Use of isokinetic techniques vs standard physiotherapy in patients with chronic low back pain. Preliminary results].", "Effects of spinal flexion and extension exercises on low-back pain and spinal mobility in chronic mechanical low-back pain patients.", "Effectiveness of behavioral therapy for chronic low back pain: a component analysis.", "Prolotherapy injections, saline injections, and exercises for chronic low-back pain: a randomized trial.", "Randomised controlled trial of physiotherapy compared with advice for low back pain.", "Intensive, dynamic back-muscle exercises, conventional physiotherapy, or placebo-control treatment of low-back pain. A randomized, observer-blind trial.", "Stabilizing training compared with manual treatment in sub-acute and chronic low-back pain.", "[Mobilizing or stabilizing exercise in degenerative disk disease in the lumbar region?].", "A controlled trial of transcutaneous electrical nerve stimulation (TENS) and exercise for chronic low back pain.", "Does folk medicine work? A randomized clinical trial on patients with prolonged back pain.", "The treatment of acute low back pain--bed rest, exercises, or ordinary activity?", "An open study of diflunisal, conservative and manipulative therapy in the management of acute mechanical low back pain.", "Effect of exercise on sick leave due to low back pain. A randomized, comparative, long-term study.", "The effect of dynamic strength back exercise and/or a home training program in 57-year-old women with chronic low back pain. Results of a prospective randomized study with a 3-year follow-up period.", "The effect of McKenzie therapy as compared with that of intensive strengthening training for the treatment of patients with subacute or chronic low back pain: A randomized controlled trial.", "Combined physiotherapy and education is efficacious for chronic low back pain.", "Randomised controlled trial of exercise for low back pain: clinical outcomes, costs, and preferences.", "Efficiency and costs of medical exercise therapy, conventional physiotherapy, and self-exercise in patients with chronic low back pain. A pragmatic, randomized, single-blinded, controlled trial with 1-year follow-up.", "A randomized trial of combined manipulation, stabilizing exercises, and physician consultation compared to physician consultation alone for chronic low back pain.", "Evaluation of a specific home exercise program for low back pain.", "Conservative treatment of acute low-back pain. A prospective randomized trial: McKenzie method of treatment versus patient education in \"mini back school\".", "Endurance training of the trunk extensor muscles in people with subacute low back pain.", "Lumbar strengthening in chronic low back pain patients. Physiologic and psychological benefits.", "The impact of modified Hatha yoga on chronic low back pain: a pilot study.", "Efficacy of low power laser therapy and exercise on pain and functions in chronic low back pain.", "Long-term effects of specific stabilizing exercises for first-episode low back pain.", "A randomized, placebo-controlled trial of exercise therapy in patients with acute low back pain.", "Physical therapy on low back pain and sciatica. An attempt at evaluation.", "Treatment of chronic lower back pain with lumbar extension and whole-body vibration exercise: a randomized controlled trial.", "Effectiveness of massage therapy for subacute low-back pain: a randomized controlled trial.", "Lumbar disc disease: comparative analysis of physical therapy treatments.", "An experimental controlled study on postural sway and therapeutic exercise in subjects with low back pain.", "The efficacy of an aerobic exercise and health education program for treatment of chronic low back pain.", "Functional restoration versus outpatient physical training in chronic low back pain: a randomized comparative study.", "Active treatment programs for patients with chronic low back pain: a prospective, randomized, observer-blinded study." ]

[ "To determine the effect of a series of electro-acupuncture (EA) treatment in conjunction with exercise on the pain, disability, and functional improvement scores of patients with chronic low-back pain (LBP).\n A blinded prospective randomized controlled study. Subjects and interventions: A total of 52 patients were randomly allocated to an exercise group (n = 26) or an exercise plus EA group (n = 26) and treated for 12 sessions.\n Numerical Rating Scale (NRS), Aberdeen LBP scale, lumbar spinal active range of movement (AROM), and the isokinetic strength were assessed by a blinded observer. Repeated measures analysis of variance (R-ANOVA) with factors of group and time was used to compare the outcomes between the two groups at baseline (before treatment), immediately after treatment, 1-month follow-up, and 3-month follow-up. The level of significance was set at p = 0.05.\n Significantly better scores in the NRS and Aberdeen LBP scale were found in the exercise plus EA group immediately after treatment and at 1-month follow-up. Higher scores were also seen at 3-month follow-up. No significant differences were observed in spinal AROM and isokinetic trunk concentric strength between the two groups at any stage of follow-up.\n This study provides additional data on the potential role of EA in the treatment of LBP, and indicates that the combination of EA and back exercise might be an effective option in the treatment of pain and disability associated with chronic LBP.", "To evaluate the effectiveness of a program designed to reduce back pain in nursing aides.\n Female nursing aides from a university hospital who had suffered episodes of back pain for at least six months were included in the study. Participants were randomly divided into a control group and an intervention group. The intervention program involved a set of exercises and an educational component stressing the ergonomic aspect, administered twice a week during working hours for four months. All subjects answered a structured questionnaire and the intensity of pain was assessed before and after the program using a visual analogue scale (VAS). Student's t-test or the Wilcoxon Rank Sum Test for independent samples, and Chi-square test or the Exact Fisher test for categorical analysis, were used. The McNemar test and the Wilcoxon matched pairs test were used to compare the periods before and after the program.\n There was a statistically significant decrease in the frequency of cervical pain in the last two months and in the last seven days in the intervention group. There was also a reduction in cervical pain intensity in the two periods (2 months, 7 days) and lumbar pain intensity in the last 7 days.\n The results suggest that a program of regular exercise with an emphasis on ergonomics can reduce musculoskeletal symptoms in nursing personnel.", "There are few data on the relative effectiveness and costs of treatments for low back pain. We randomly assigned 321 adults with low back pain that persisted for seven days after a primary care visit to the McKenzie method of physical therapy, chiropractic manipulation, or a minimal intervention (provision of an educational booklet). Patients with sciatica were excluded. Physical therapy or chiropractic manipulation was provided for one month (the number of visits was determined by the practitioner but was limited to a maximum of nine); patients were followed for a total of two years. The bothersomeness of symptoms was measured on an 11-point scale, and the level of dysfunction was measured on the 24-point Roland Disability Scale.\n After adjustment for base-line differences, the chiropractic group had less severe symptoms than the booklet group at four weeks (P=0.02), and there was a trend toward less severe symptoms in the physical therapy group (P=0.06). However, these differences were small and not significant after transformations of the data to adjust for their non-normal distribution. Differences in the extent of dysfunction among the groups were small and approached significance only at one year, with greater dysfunction in the booklet group than in the other two groups (P=0.05). For all outcomes, there were no significant differences between the physical-therapy and chiropractic groups and no significant differences among the groups in the numbers of days of reduced activity or missed work or in recurrences of back pain. About 75 percent of the subjects in the therapy groups rated their care as very good or excellent, as compared with about 30 percent of the subjects in the booklet group (P<0.001). Over a two-year period, the mean costs of care were $437 for the physical-therapy group, $429 for the chiropractic group, and $153 for the booklet group.\n For patients with low back pain, the McKenzie method of physical therapy and chiropractic manipulation had similar effects and costs, and patients receiving these treatments had only marginally better outcomes than those receiving the minimal intervention of an educational booklet. Whether the limited benefits of these treatments are worth the additional costs is open to question.", "The prescriptive validity of a treatment-oriented extension-mobilization category for patients with low back syndrome (LBS) was examined.\n Of a total of 39 patients with LBS referred for physical therapy, 24 patients (14 male, 10 female), aged 14 to 50 years (means = 31.3, SD = 11.6), were classified as having signs and symptoms indicating treatment with an extension-mobilization approach. The remaining subjects were dismissed from the study. Patients in the extension-mobilization category were randomly assigned to either an experimental (treatment) group (n = 14) or a comparison group (n = 10).\n The experimental and comparison group subjects were treated with either mobilization and extension (a treatment matched to the category) or a flexion exercise regimen (an unmatched treatment). Outcome was assessed with a modified Oswestry Low Back Pain Questionnaire administered initially and at 3 and 5 days after initiation of treatment. Data were analyzed with a 2 x 3 (treatment group x treatment period) analysis of variance.\n The subjects' rate of improvement, as indicated by the Oswestry questionnaire scores, was dependent on the treatment group to which they were assigned. Subjects treated with extension and mobilization positively responded at a faster rate than did those treated with a flexion-oriented program.\n This study illustrates that a priori classification of selected patients with LBS into a treatment category of extension and mobilization and subsequently treating the patients accordingly with specified interventions can be an effective approach to conservative management of selected patients.", "In a controlled clinical trial, we allocated 48 subjects with acute low back pain but without neurological signs, at random to two treatment groups. The conservative treatments compared were passive mobilisation and manipulation of the lumbar spine and a regimen of microwave diathermy, isometric abdominal exercises and ergonomic instructions. The duration of low back pain symptoms was significantly shorter for subjects receiving mobilisation and manipulation; they also achieved symptom-free status with fewer treatment sessions. While the duration of symptoms before first treatment, the treatment administered, and the pretest forward flexion movement indices accounted for 44% of the variance in the duration of symptoms, a stepwise multiple regression analysis showed that treatment is the most significant factor in predicting the length of time before a subject achieves symptom-free status.", "Aim of the study was to evaluate the influence of elastic lumbar belts on the effect of muscle training for patients with low back pain.\n 97 male subjects aged from 23 to 42 years with and without low back pain participated in the investigation. The low back pain patients (n = 63) were randomized into a training group without and a training group with elastic lumbar belts and a control group. The subjects with healthy backs (n = 34) were divided age-matched into a training group with elastic lumbar belts and a control group. The three training groups took part in a muscle strenghtening program over 8 weeks. The control groups did not receive any alternative physiotherapeutic treatment. All groups were tested at the beginning, after 8 weeks and further 6 months later.\n The data obtained for the control groups remained virtually unchanged over the period of investigation. However, a significant increase of the muscle flexibility of the lower limbs could be proved for the training groups. Furthermore the coordination between the lumbar spine and pelvis when flexing the trunk deeply forward was more leveled out for the training groups with patients suffered low back pain. The results confirmed a reduction for pain severity and for limitations in activities of daily living as well. The modifications for the criteria investigated were significant stronger for the training group with patients using the elastic lumbar belt.\n The effectiveness of the muscle strengthening program for patients with low back pain could be improved significantly by means of the elastic lumbar belt as an applicable therapy instrument in the functional rehabilitation of spinal injuries.", "A multicenter, randomized, controlled trial with 1-year follow-up.\n To compare the effect of manual therapy to exercise therapy in sick-listed patients with chronic low back pain (>8 wks).\n The effect of exercise therapy and manual therapy on chronic low back pain with respect to pain, function, and sick leave have been investigated in a number of studies. The results are, however, conflicting.\n Patients with chronic low back pain or radicular pain sick-listed for more than 8 weeks and less than 6 months were included. A total of 49 patients were randomized to either manual therapy (n = 27) or to exercise therapy (n = 22). Sixteen treatments were given over the course of 2 months. Pain intensity, functional disability (Oswestry disability index), general health (Dartmouth COOP function charts), and return to work were recorded before, immediately after, at 4 weeks, 6 months, and 12 months after the treatment period. Spinal range of motion (Schober test) was measured before and immediately after the treatment period only.\n Although significant improvements were observed in both groups, the manual therapy group showed significantly larger improvements than the exercise therapy group on all outcome variables throughout the entire experimental period. Immediately after the 2-month treatment period, 67% in the manual therapy and 27% in the exercise therapy group had returned to work (P < 0.01), a relative difference that was maintained throughout the follow-up period.\n Improvements were found in both intervention groups, but manual therapy showed significantly greater improvement than exercise therapy in patients with chronic low back pain. The effects were reflected on all outcome measures, both on short and long-term follow-up.", "A randomized clinical trial.\n To examine the relative efficacy of three active therapies for chronic low back pain.\n There is much evidence documenting the efficacy of exercise in the conservative management of chronic low back pain, but many questions remain regarding its exact prescription and method of application. The most successful method must be identified to enable refinement of future rehabilitation programs to target the specific needs of the patient with chronic low back pain and the budget of the healthcare provider.\n One hundred forty-eight patients with chronic low back pain were randomized to one of the following treatments, which they attended twice a week for 3 months: 1) modern active physiotherapy, 2) muscle reconditioning on training devices, or 3) low-impact aerobics. Pretherapy and posttherapy, objective measurements of lumbar mobility were performed, and questionnaires were administered inquiring about self-rated pain and disability, and psychosocial factors. Similar questionnaires were administered 6 months after therapy. The data were analyzed using the intention-to-treat principle.\n Of the 148 patients, 16 (10.8%) dropped out of the therapy. One hundred thirty-seven questionnaires (93%) were available for analysis at all three time points. After therapy, significant reductions were observed in pain intensity, frequency, and disability; Fear-Avoidance Beliefs about physical activity (FABQactivity); and \"praying/hoping,\" \"catastrophizing,\" and \"pain behavior\" coping strategies--each with no group differences in the extent of the response. These effects were maintained over the subsequent 6 months, with the exception of disability and FABQactivity for the physiotherapy group. There were small but significant posttherapy increases in lumbar mobility, with aerobics and devices showing a greater response than physiotherapy.\n The general lack of treatment specificity suggests that the main effects of the therapies were educed not through the reversal of physical weaknesses targeted by the corresponding exercise modality, but rather through some \"central\" effect, perhaps involving an adjustment of perception in relation to pain and disability. The direct costs associated with administering physiotherapy were three times as great, and devices four times as great, as those for aerobics. Administration of aerobics as an efficacious therapy for chronic low back pain has the potential to relieve some of the huge financial burden associated with the condition.", "A randomized study comparing the results of active rehabilitation and passive control treatment in patients with chronic low back pain with follow-up at 6 months and 1 year.\n To study the efficacy of active rehabilitation on pain, self-experienced disability, and lumbar fatigability.\n Exercises in an outpatient setting are widely used for the treatment of chronic low back pain. The efficacy of the active rehabilitation approach has been documented in randomized control studies, but these studies have seldom been focused on lumbar fatigability, which is now recognized as a frequent problem among patients with chronic low back pain.\n Fifty-nine middle-aged patients (37 men and 22 women) with nonspecific chronic low back pain were randomly assigned to 12 weeks' active rehabilitation or to a passive control treatment (massage, thermal therapy). Pain and disability index, low back pain intensity (visual analog scale, 100 mm), and the objectively assessed lumbar muscle fatigability (spectral electromyogram, mean power frequency slope [MPFSLOPE]) in a new 90-second submaximal isoinertial back endurance test were recorded before and after the interventions and at 6-month and 1-year follow-up visits.\n Results of repeated measures multivariate analysis of variance indicated that back pain intensity (visual analog scale) and functional disability (pain and disability index score) decreased, and lumbar endurance (MPFSLOPE) improved significantly more (P < 0.05) in the active rehabilitation group than in the passive control treatment group, when measured at a 1-year follow-up examination. The group difference in visual analog scale and pain and disability index changes became even more significant at the end of 1 year. The change in lumbar endurance was significantly greater in the active rehabilitation group than in the passive control treatment group at the 6-month follow-up, but not at the 1-year follow-up.\n The active progressive treatment program was more successful in reducing pain and self-experienced disability and also in improving lumbar endurance than was the passive control treatment. However, the group difference in lumbar endurance tended to diminish at the 1-year follow-up.", "Low back pain is a common medical and social problem frequently associated with disability and absence from work. However, data on effective return to work after interventions for low back pain are scarce.\n To determine the effectiveness of a behavior-oriented graded activity program compared with usual care.\n Randomized, controlled trial.\n Occupational health services department of an airline company in the Netherlands.\n 134 workers who were absent from work because of low back pain were randomly assigned to either graded activity (n = 67) or usual care (n = 67).\n Graded activity, a physical exercise program based on operant-conditioning behavioral principles, to stimulate a rapid return to work.\n Outcomes were the number of days of absence from work because of low back pain, functional status (Roland Disability Questionnaire), and severity of pain (11-point numerical scale).\n The median number of days of absence from work over 6 months of follow-up was 58 days in the graded activity group and 87 days in the usual care group. From randomization onward, graded activity was effective after 50 days of absence from work (hazard ratio, 1.9 [95% CI, 1.2 to 3.2]; P = 0.009). The graded activity group was more effective in improving functional status and pain than the usual care group. The effects, however, were small and not statistically significant.\n Graded activity was more effective than usual care in reducing the number of days of absence from work because of low back pain.", "To evaluate the short-term effect of physical exercise and a cognitive intervention in low back pain.\n Randomized controlled trial.\n Ninety-three patients sick-listed for 8-12 weeks for sub-acute low back pain were randomized to an exercise regime (n = 30), a cognitive intervention (n = 34) or a control group (n = 29).\n Primary outcome measures were pain, disability, sick-listing and satisfaction with care. Secondary outcome measures were self-efficacy for pain and for function, fear-avoidance beliefs, emotional distress, generic health status and life satisfaction.\n Eighteen percent of subjects dropped out. Drop-out was most frequent in the exercise group. At 18 weeks after inclusion fear-avoidance beliefs were reduced in both intervention groups. The cognitive group demonstrated significant improvement in disability, self-efficacy for pain, emotional distress, general health and life satisfaction. Patients in the exercise group were significantly more satisfied with the treatment, and patients following the exercise protocol reduced pain significantly. No effect on sick-listing was seen.\n Cognitive intervention improved disability and may be feasible for most patients sick-listed in the sub-acute phase. Physical exercise reduced patients' symptoms, but requires high motivation by patients. Despite positive effects in intervention groups on variables considered as negative prognostic factors for long-term disability and sickness absence, interventions had no effect on sick-listing.", "Back extension exercises are commonly recommended to treat acute low back pain. Evidence of their beneficial effect is, however, weak.\n We aimed to demonstrate a benefit of teaching back extension exercises in addition to usual GP care for acute low back pain.\n Patients with acute simple low back pain of less than 28 days duration, presenting to a GP, were randomized either to attend a back class or to receive conventional management. Outcome was measured using changes in the Oswestry disability score and visual analogue pain scale (VAS) on six occasions during 1 year and also a VAS and patient assessment of degree of disability during the previous 6 months at 1 year.\n Seventy-five patients were recruited. The principal outcome measures showed no difference between the two groups. The treatment group reported less chronic disability at 1 year (50% versus 14%, P < 0.007).\n A treatment effect has not been demonstrated, but some patients who would otherwise have reported mild pain were pain free after 1 year. This approach to treating back pain has not been shown to be effective. More much larger studies, with more intensive treatment, are required in order to decide whether physical therapy in primary care is beneficial as treatment for acute back pain.", "Randomized parallel-group comparative trial with a 6-month follow-up period.\n To compare, in chronic low back pain patients, the effectiveness of a functional restoration program, including intensive physical training, occupational therapy, and psychological support to an active individual therapy consisting of 3 hours physical therapy per week during 5 weeks.\n Controlled studies conducted in the United States showed a benefit of functional restoration in patients with low back pain, especially on return to work. Randomized Canadian and European trials had less favorable results. In France, there has been up to now no randomized study. Controlled studies suggested a positive effect of functional restoration programs.\n Eighty-six patients with low back pain were randomized to either the functional restoration (44 patients) or the active individual therapy (42 patients) program. One person in each group never started the program. Two patients did not complete the functional restoration program, and one was lost to follow-up at 6 months. The mean number of sick-leave days in the 2 previous years was 6 months.\n After adjustment on the variable \"workplace enrolled in an ergonomic program\", the mean number of sick-leave days was significantly lower in the functional restoration group. Physical criteria and treatment appreciation were also better. There was no significant difference in the intensity of pain, the quality of life and functional indexes, the psychological characteristics, the number of contacts with the medical system, and the drug intake.\n This study demonstrates the effectiveness of a functional restoration program on important outcome measures, such as sick leave, in a country that has a social system that protects people facing difficulties at work.", "To study the relative efficacy of three different treatment for chronic low back pain (CLBP). Two preplanned comparisons were made: (a) Spinal manipulative therapy (SMT) combined with trunk strengthening exercises (TSE) vs. SMT combined with trunk stretching exercises, and (b) SMT combined with TSE vs. nonsteroidal anti-inflammatory drug (NSAID) therapy combined with TSE.\n Interdisciplinary, prospective, observer-blinded, randomized clinical trial with a 1-yr follow-up period. The trial evaluated therapies in combination only and was not designed to test the individual treatment components.\n Primary contact, college out-patient clinic.\n In total, 174 patients aged 20-60 yr were admitted to the study.\n Patient-rated low back pain, disability, and functional health status at 5 and 11 wk.\n Five weeks of SMT or NSAID therapy in combination with supervised trunk exercise, followed by and additional 6 wk of supervised exercise alone.\n Individual group comparisons after 5 and 11 wk of intervention on all three main outcome measures did not reveal any clear clinically important or statistically significant differences. There seemed to be a sustained reduction in medication use at the 1-yr follow-up. in the SMT/TSE group. Continuance of exercise during the follow-up year, regardless of type, was associated with a better outcome.\n Each of the three therapeutic regimens was associated with similar and clinically important improvement over time that was considered superior to the expected natural history of long-standing CLBP. For the management of CLBP, trunk exercise in combination with SMT or NSAID therapy seemed to be beneficial and worthwhile. The magnitude of nonspecific therapeutic (placebo) effects, cost-effectiveness and relative risks of side effects associated with these types of therapy need to be addressed in future studies.", "To determine the effectiveness of a special form of exercise therapy ('Cesar therapy') on self reported recovery and improvement of posture amongst patients with chronic aspecific lower back pain.\n Prospective randomized controlled and blinded investigation.\n After informed consent had been obtained, patients with chronic aspecific lower back pain were given, on a randomized basis, either an exercise therapy (experimental group, n = 112) or a standard treatment by their general practitioner (control group, n = 110). Outcome measures were self reported recovery of back pain and improvement of posture (thoracic and lumbar spine, pelvis). Self reported recovery was determined by means of a dichotomized 7-point scale (questionnaire). Posture was measured qualitatively by a panel of 11 Cesar therapists (blinded) and quantitatively by an optical-electronic posture recording system (Vicon). Measurements were taken at baseline (pre-randomization) and at 3, 6 and 12 months after randomization.\n Three months after randomization, patients who were treated according to Cesar therapy, reported an improvement in their back symptoms (80%) significantly more often than the control group (47%). In both groups, however, only small improvements in posture were found. The judgement of the Cesar panel exhibited a significant difference between the two groups, with respect to the spine, in favour of Cesar therapy. Differences between the groups were still present 6 months after randomization, but could no longer be detected at 12 months after randomization.\n Cesar therapy was significantly more effective than standard treatment among patients with chronic lower back pain for a period of 6 months after randomization.", "We evaluated three different conservative treatment methods for acute low-back pain patients in groups following a manual therapy programme, an intensive training programme, or a general practitioner programme, the latter serving as the control group. Patients aged 19-64 years on sick leave for low-back pain with or without sciatica were included in a prospective randomised study evaluating outcomes such as impairment, pain, functional disability, socio-economic disability and satisfaction with the treatment or explanations. Evaluation by unbiased observers was performed at 1, 3 and 12 months. The three treatment groups were comparable at baseline. With regard to satisfaction, the patients in the manual therapy programme and those in the intensive training programme were more satisfied with the treatment than those in the general practitioner programme at all follow-ups. With regard to the explanations of current low-back pain episodes, the patients in the manual therapy programme were more satisfied than those in the general practitioner programme at all follow-ups. The manual therapy programme group were also more satisfied with the explanations than those in the intensive training programme at the 1-month follow-up. However, no differences were revealed between the groups with respect to outcomes on measures of impairment, pain, functional disability or socioeconomic disability. All three study groups showed rapid improvement. After 1 month a significant improvement was noted in all outcome values compared with the values on entry to the study. Within the limitations discussed in our study, it is concluded that (1) patients sick listed with acute low-back pain, with or without sciatica, will be significantly improved after 1 month regardless of conservative treatment programme; (2) they will be more satisfied with the treatment if they are referred to a manual treatment programme or a training treatment programme; (3) they will be more satisfied with the explanations of the acute low-back problem if they are referred to one of the above groups, especially the manual treatment group; (4) they will not show any other differences with respect to subjective and objective variables, either at short-term or at long-term follow-ups.", "The aim of this study was to determine whether graded activity restored occupational function in industrial blue-collar workers who were sick-listed for 8 weeks because of subacute, nonspecific, mechanical low back pain (LBP). Patients with LBP, who had been examined by an orthopedic surgeon and a social worker, were randomly assigned to either an activity group (n = 51) or a control group (n = 52). Patients with defined orthopedic, medical, or psychiatric diagnoses were excluded before randomization. The graded activity program consisted of four parts: (1) measurements of functional capacity; (2) a work-place visit; (3) back school education; and (4) an individual, submaximal, gradually increased exercise program, with an operant-conditioning behavioral approach, based on the results of the tests and the demands of the patient's work. Records of the amount of sick leave taken over a 3-year period (ie, the 1-year periods before, during, and after intervention) were obtained from each patient's Social Insurance Office. The patients in the activity group returned to work significantly earlier than did the patients in the control group. The median number of physical therapist appointments before return to work was 5, and the average number of appointments was 10.7 (SD = 12.3). The average duration of sick leave attributable to LBP during the second follow-up year was 12.1 weeks (SD = 18.4) in the activity group and 19.6 weeks (SD = 20.7) in the control group. Four patients in the control group and 1 patient in the activity group received permanent disability pensions. The graded activity program made the patients occupationally functional again, as measured by return to work and significantly reduced long-term sick leave.", "A prospective, randomized, controlled trial with a stratification block design in which a Mensendieck exercise program was compared with the experience of a control group.\n To evaluate the effect of a Mensendieck program on the incidence of recurrent episodes of low back pain in patients with a history of the condition who currently are working.\n One episode of low back pain increases the risk of further episodes of the condition. The Mensendieck approach combines education and exercise. This approach has been used for many years in Scandinavia and the Netherlands. However, the effects on low back pain have not been evaluated previously in a randomized, controlled trial.\n A total of 77 men and women, mean age 39.6 years (range, 21.2-49.8 years), who had finished treatment for a low back pain episode, were stratified according to incidence of low back pain episodes and symptoms of sciatica over the preceding 3 years. The patients were assigned at random to either the Mensendieck program or a control group. The Mensendieck group received 20 group sessions of exercises and ergonomic education in 13 weeks. At 5- and 12-month follow-up examinations, the patients were assessed for recurrence of low back pain, days of sick leave, low back pain, and functional scores.\n After 12 months, there was a significant reduction in recurrent low back pain episodes in the Mensendieck group compared with the control group (P < 0.05). There was a trend toward fewer days of sick leave because of low back pain in the Mensendieck group, but no significant differences between the groups. There was reduction in pain and improvement in function in both groups, with no significant differences between the groups.\n A secondary prophylaxis Mensendieck exercise program of 20 group sessions significantly reduced the incidence of low back pain recurrences in a population with history of the condition. However, there were no differences between the groups with regard to days of sick leave, low back pain, and function.", "To determine if the use of an isokinetic device for trunk exercise is more effective than standard physiotherapy in promoting motor disinhibition for patients with chronic low back pain.\n chronic low back pain outpatients who are treated in a Rheumatology or PM & R unit within an academic hospital.\n This is a prospective, controlled, randomized study, with two groups of treatment: one treated with isokinetic techniques and the other with standard physiotherapy, six sessions for each treatment during 2 weeks. Outcome measures include pain (VSA), trunk mobility (Schöber index, distance from fingers to floor), muscle extensibility and muscle strength (Biering-Sorensen and Shirado-Ito test), and functional capacity (Quebec scale).\n Seventeen subjects were enrolled. The results suggest that both isokinetic exercise and physiotherapy result in improved range of motion, extensibility, muscle strength, and pain, without any significant superiority of one technique over the other. However, each technique has specific advantage.\n Despite methodologic limitations, this study shows that isokinetic exercise is not better than physiotherapy in reversing motor inhibition in chronic low back pain. Our results are consistent with those of other studies in the literature, with regard to the absence of established overall superiority of one exercise technique or program over the other in this population, and with regard to partial benefits of specific exercise techniques.\n The non-specific benefit of one technique indicates that further studies are needed to evaluate the benefit of combining exercise techniques in chronic low back pain, in order to address the multiple factors involved in this pathology.", "It has been estimated that one fourth to one half of all patients treated in physical therapy clinics suffer from low-back pain. The purpose of this study was to compare the effects of spinal flexion (Group I) and extension (Group II) exercises on low-back pain severity and thoracolumbar spinal mobility in chronic mechanical low-back pain patients. Both groups had significantly less low-back pain after treatment (P less than .10). There was no significant difference, however, between the spinal flexion and extension exercises in reduction of low-back pain severity. The results indicated a significant difference between the groups in increasing the sagittal mobility (P less than .10). The results did not indicate any significant difference between and within groups in increasing the coronal and transverse mobility of the thoracolumbar spine. Either the spinal flexion or extension exercises could be used to reduce chronic mechanical low-back pain severity, but the flexion exercises had an advantage in increasing the sagittal mobility within a short period of time.", "The effects of outpatient group behavioral therapy including aerobic exercise (BE), behavioral therapy only (B), and aerobic exercise only (E) on pain and physical and psychosocial disability were evaluated and compared in a group of mildly disabled chronic low-back-pain patients. Ninety-six Ss were randomly assigned to the 3 treatments and a waiting-list control (WL) condition and assessed on a variety of patient self-report, spouse-rated, and direct observational measures at pretreatment, posttreatment, and 6- and 12-month follow-ups. Patients in the BE condition, but not the B or E conditions, improved significantly more pretreatment to posttreatment than did WL patients on the patient self-report and observer-rated measures. At both follow-ups, all 3 treatment groups remained significantly improved from pretreatment, with no significant differences among treatments.", "To assess the efficacy of a prolotherapy injection and exercise protocol in the treatment of chronic nonspecific low back pain.\n Randomized controlled trial with two-by-two factorial design, triple-blinded for injection status, and single-blinded for exercise status.\n General practice.\n One hundred ten participants with nonspecific low-back pain of average 14 years duration were randomized to have repeated prolotherapy (20% glucose/0.2% lignocaine) or normal saline injections into tender lumbo-pelvic ligaments and randomized to perform either flexion/extension exercises or normal activity over 6 months.\n Pain intensity (VAS) and disability scores (Roland-Morris) at 2.5, 4, 6, 12, and 24 months.\n Follow-up was achieved in 96% at 12 months and 80% at 2 years. Ligament injections, with exercises and with normal activity, resulted in significant and sustained reductions in pain and disability throughout the trial, but no attributable effect was found for prolotherapy injections over saline injections or for exercises over normal activity. At 12 months, the proportions achieving more than 50% reduction in pain from baseline by injection group were glucose-lignocaine: 0.46 versus saline: 0.36. By activity group these proportions were exercise: 0.41 versus normal activity: 0.39. Corresponding proportions for >50% reduction in disability were glucose-lignocaine: 0.42 versus saline 0.36 and exercise: 0.36 versus normal activity: 0.38. There were no between group differences in any of the above measures.\n In chronic nonspecific low-back pain, significant and sustained reductions in pain and disability occur with ligament injections, irrespective of the solution injected or the concurrent use of exercises.", "To measure the effectiveness of routine physiotherapy compared with an assessment session and advice from a physiotherapist for patients with low back pain.\n Pragmatic, multicentre, randomised controlled trial.\n Seven British NHS physiotherapy departments.\n 286 patients with low back pain of more than six weeks' duration.\n Routine physiotherapy or advice on remaining active from a physiotherapist. Both groups received an advice book.\n Primary outcome was scores on the Oswestry disability index at 12 months. Secondary outcomes were scores on the Oswestry disability index (two and six months), scores on the Roland and Morris disability questionnaire and SF-36 (2, 6 and 12 months), and patient perceived benefit from treatment (2, 6, and 12 months).\n 200 of 286 patients (70%) provided follow up information at 12 months. Patients in the therapy group reported enhanced perceptions of benefit, but there was no evidence of a long term effect of physiotherapy in either disease specific or generic outcome measures (mean difference in change in Oswestry disability index scores at 12 months -1.0%, 95% confidence interval -3.7% to 1.6%). The most common treatments were low velocity spinal joint mobilisation techniques (72%, 104 of 144 patients) and lumbar spine mobility and abdominal strengthening exercises (94%, 136 patients).\n Routine physiotherapy seemed to be no more effective than one session of assessment and advice from a physiotherapist.", "In a randomized, observer-blind trial, 150 men and women, aged 21-64 years, with chronic/subchronic low-back pain, followed one of these three treatment regimens: 1) intensive, dynamic back-muscle exercises; 2) conventional physiotherapy, including isometric exercises for the trunk and leg muscles; and 3) placebo-control treatment involving semihot packs and light traction. Eight treatment sessions were given during the course of 4 weeks, each session lasting 1 hour. The short-term effect was evaluated at the end of the treatment period and 1 month later, and the long-term effect at 6 and 12 months. The evaluations included recording of changes in pain level and assessment of overall treatment effect, which were indicated on visual interval scales. Subgroups of patients could be identified according to their treatment responses: physiotherapy was the superior treatment for the male participants, whereas the intensive back exercises appeared to be most efficient for the female participants. Patients with moderate or hard physical occupations tended toward a better response with physiotherapy, whereas intensive back exercises seemed most effective for those with sedentary/light job functions.", "The present aim was to compare the effects of stabilizing training with those of manual treatment in patients with sub-acute or chronic low-back pain (LBP). Forty-seven patients were randomized to a stabilizing training group (ST group) or a manual treatment group (MT group). The patients underwent a 6-week treatment programme on a weekly basis. Pain, health and functional disability level at the start of treatment, after treatment, and at 3- and 12-month follow-ups were assessed. In the ST group all assessed variables improved significantly (P<0.05) after the treatment period and were maintained long term. After the treatment period there was a significant difference between the groups in assessed function (P<0.05). More individuals in the ST group had improved than in the MT group. At the 3-month follow-up significantly more improved individuals were evident in the ST group regarding pain, general health and functional disability levels. In the long term, significantly more (P<0.05) patients in the MT group reported recurrent treatment periods. The study did not indicate any clear short-term differences between the groups in the accessed outcome measures. In the long term, however, stabilizing training seemed to be more effective than manual treatment in terms of improvement of individuals and the reduced need for recurrent treatment periods.", "Degenerative disc disease may affect younger and middle-aged people with a kind of premature disc degeneration. The majority of these low back pain patients are not candidates for a spinal fusion and are in need of a structured conservative treatment. In a controlled clinical trial, 27 low back pain patients (mean age 40 years, range 25-48) with a mean duration of symptoms of 7.4 years, were randomized to mobilizing (n = 12) or stabilizing (n = 15) daily half hour exercise for an eight weeks period. A clinical overall score (COS) based on pain intensity (VAS), physical signs, functional status (Oswestry) and analgetics was used as outcome criterion. The treatment results were best for the group undergoing stabilizing treatment. They achieved a 17% reduction in COS, compared to a 10% increase in the group undergoing mobilizing treatment (p = 0.02). These types of exercises are discussed in relation to the instability theory in disc degeneration.", "A number of treatments are widely prescribed for chronic back pain, but few have been rigorously evaluated. We examined the effectiveness of transcutaneous electrical nerve stimulation (TENS), a program of stretching exercises, or a combination of both for low back pain. Patients with chronic low back pain (median duration, 4.1 years) were randomly assigned to receive daily treatment with TENS (n = 36), sham TENS (n = 36), TENS plus a program of exercises (n = 37), or sham TENS plus exercises (n = 36). After one month no clinically or statistically significant treatment effect of TENS was found on any of 11 indicators of outcome measuring pain, function, and back flexion; there was no interactive effect of TENS with exercise. Overall improvement in pain indicators was 47 percent with TENS and 42 percent with sham TENS (P not significant). The 95 percent confidence intervals for group differences excluded a major clinical benefit of TENS for most outcomes. By contrast, after one month patients in the exercise groups had significant improvement in self-rated pain scores, reduction in the frequency of pain, and greater levels of activity as compared with patients in the groups that did not exercise. The mean reported improvement in pain scores was 52 percent in the exercise groups and 37 percent in the nonexercise groups (P = 0.02). Two months after the active intervention, however, most patients had discontinued the exercises, and the initial improvements were gone. We conclude that for patients with chronic low back pain, treatment with TENS is no more effective than treatment with a placebo, and TENS adds no apparent benefit to that of exercise alone.", "To determine whether traditional bone-setting or continuous light exercise therapy could case back pain and improve function better than ordinary physiotherapy.\n Observer-blinded, randomized clinical trial with a 6-month follow-up.\n An outpatient institution for folk medicine research.\n Of 147 back pain patients recruited from local health centers and by newspaper announcements, 132 were found eligible (non-retired-no contraindications to manipulation) and entered. A final 114 (one dropout) with back pain for longer than 7 weeks were included in this intent to treat analysis.\n Bone-setting, guidance for continuous light back movements or physiotherapy for up to ten 1-hour sessions during 6 weeks.\n Spinal mobility and muscular performance. Back pain assessed by visual analog scales (VAS).\n The physical measures changed only modestly, from one tenth to half of standard deviation, while the VAS was halved. The thoracolumbar side-bending, the modified Schober, and the VAS were significantly better improved by bone-setting than by exercise but not better than by physiotherapy.\n Neither bone-setting nor exercise differed significantly from physiotherapy, but bone-setting improved lateral and forward bending of the spine and back pain more than did exercise.", "Bed rest and back-extension exercises are often prescribed for patients with acute low back pain, but the effectiveness of these two competing treatments remains controversial.\n We conducted a controlled trial among employees of the city of Helsinki, Finland, who presented to an occupational health care center with acute, nonspecific low back pain. The patients were randomly assigned to one of three treatments: bed rest for two days (67 patients), back-mobilizing exercises (52 patients), or the continuation of ordinary activities as tolerated (the control group; 67 patients). Outcomes and costs were assessed after 3 and 12 weeks.\n After 3 and 12 weeks, the patients in the control group had better recovery than those prescribed either bed rest or exercises. There were statistically significant differences favoring the control group in the duration of pain, pain intensity, lumbar flexion, ability to work as measured subjectively, the Oswestry back-disability index, and number of days absent from work. Recovery was slowest among the patients assigned to bed rest. The overall costs of care did not differ significantly among the three groups.\n Among patients with acute low back pain, continuing ordinary activities within the limits permitted by the pain leads to more rapid recovery than either bed rest or back-mobilizing exercises.", "One hundred and twelve patients with acute mechanical low back pain were randomly divided into three treatment groups. All patients received ergonomic advice and then either a non-steroidal anti-inflammatory drug or conservative or manipulative types of physiotherapy. Serial assessments of pain and spinal mobility showed similar response rates in all three treatment groups and no significant difference between therapies. The overall improvement ratings, time off work, and economic cost favoured the group treated with the nonsteroidal anti-inflammatory drug, but this group had a better range of spinal flexion at the onset so firm conclusions regarding the preferred management of these patients in general practice cannot be drawn. Treatment failures occurred in all groups highlighting the need for a variety of therapeutic approaches in managing the patient with low back pain.", "The study was carried out as an open, randomized, multicenter, parallel-group study with an observation period of 12 months. Four norwegian physiotherapy institutes took part. Patients were subsequently followed for 12 months of home exercise on their own, without for 12 months of home exercise on their own, without the supervision of a physiotherapist.\n 1) To investigate and compare the effects of two different exercise programs on low back problems in patients after a 1-year training program under the supervision of a physiotherapist. 2) To investigate the effect supervision by, and motivation from, physiotherapists has on training compliance and efficacy.\n After ordinary physiotherapy treatment for low back problems, patients were randomly allocated either to a conventional training program designed by physiotherapists or to a training program using a new Norwegian-developed training apparatus called the TerapiMaster. The study included 153 patients with low back problems, all of whom had been referred to physiotherapy by their general practitioners. One hundred twenty-six patients were followed for an additional 12 months when performing home exercise programs on their own.\n Monitoring patient satisfaction with the training program, compliance with the program, and absenteeism from work during the training period.\n Patient satisfaction with both training programs was high, with about 83% of participating patients completing the study in accordance with the protocol. Mean absenteeism (SD) during the preceding year totaled 82.5 days (19.8) in the conventional training group and 61.6 days (14.7) in the TerapiMaster group. Significant reductions to 17.2 days (6.0) and 16.4 days (5.3) in the two groups, respectively, were recorded during the training period, corresponding to a 75% to 80% reduction compared with the preceding 1-year period. Mean absenteeism showed a further significant decline during the 12-month period without supervised training. The average values were 9.9 days (3.2) for conventional training and 9.3 days (3.1) for the TerapiMaster, respectively.\n Both exercise programs reduced absenteeism significantly (75-80%). No difference in the effects of the two different programs was discernible. Regular follow-up through encouragement and variation in the training programs appear to be important factors for motivating patients to adhere to regular exercise programs for low back problems. This thesis was corroborated by the 12-month study of unsupervised exercise.", "A prospective, randomized investigation.\n To compare the effect of dynamic strength back muscle training with that of a home training program and to evaluate the long-term effect of the home training program in patients with chronic low back pain.\n In a health survey of 57-year-old women, those with chronic low back pain were selected using the Nordic Questionnaire. Of 172 women with low back pain, 74 participated in the study.\n The participants were randomly assigned to either dynamic strength back exercises at a fitness center and a home training program or to the home training program for the first 3 months, after which both groups continued to pursue the home training program. Follow-up observation was by examination at 3 and 12 months and by mailed questionnaire after 3 years. The primary effect variables were disability, sick-leave, and use of health care services.\n Both training groups manifested significant improvement at the 3- and 12-month follow-up examinations, yet the adherence rate was much better in the group assigned to the fitness center. Those who adhered to the training program for the first year manifested significant improvement according to the 3-year follow-up questionnaire. There was a significant reduction in the number of women on sick-leave and in use of health care services after 1 year, but not after 3 years.\n The home training program was as effective as the supervised dynamic strength muscle training program and yielded lasting improvement after at least 1 year of adherence. The adherence rate was much better, however, when the training was supervised at the start.", "A randomized controlled comparative trial with an 8-month follow-up period was conducted.\n To compare the effect of the McKenzie treatment method with that of intensive dynamic strengthening training in patients with subacute or chronic low back pain.\n Randomized studies indicate that the efficacy of the McKenzie method in the treatment of patients with acute or subacute low back pain is debatable. Currently, no randomized studies examining the effects of this method for patients with chronic low back pain have been published.\n For this study, 260 consecutive patients with low back pain and at least 8 weeks duration of symptoms (85% of the patients had more than 3 months duration of symptoms) were randomized into two groups: Group A was treated with the McKenzie method (n = 132), and Group B was treated with intensive dynamic strengthening training (n = 128). The treatment period for both groups was 8 weeks at an outpatient clinic, followed by 2 months of self-training at home. Treatment results were recorded at the end of the treatment period at the clinic, then 2 and 8 months after. In both groups, 30% of the patients were lost to follow-up evaluation. An intention-to-treat analysis of the main effect variables, disability, and pain was performed for all the patients included in the study. A supplementary analysis of the 180 patients who completed the full treatment program also was undertaken.\n Intention-to-treat analysis showed a tendency toward a difference in reduction of disability in favor of the McKenzie group at the 2-month follow-up assessment (P = 0.04), but no differences at the end of treatment and at the 8-month follow-up evaluation. No differences in reduction of pain were observed at any time between the groups. The supplementary analysis of the patients who had completed the full intervention showed a tendency toward a difference in favor of the McKenzie method in reduction of pain at the end of treatment (P = 0.02). This difference reached statistical significance at the 2-month follow-up assessment (P = 0.01), but no difference was found after 8 months. The supplementary analysis showed no differences between the groups with regard to reduction of disability.\n The McKenzie method and intensive dynamic strengthening training seem to be equally effective in the treatment of patients with subacute or chronic low back pain.", "Manual therapy, exercise and education target distinct aspects of chronic low back pain and probably have distinct effects. This study aimed to determine the efficacy of a combined physiotherapy treatment that comprised all of these strategies. By concealed randomisation, 57 chronic low back pain patients were allocated to either the four-week physiotherapy program or management as directed by their general practitioners. The dependent variables of interest were pain and disability. Assessors were blind to treatment group. Outcome data from 49 subjects (86%) showed a significant treatment effect. The physiotherapy program reduced pain and disability by a mean of 1.5/10 points on a numerical rating scale (95% CI 0.7 to 2.3) and 3.9 points on the 18-point Roland Morris Disability Questionnaire (95% CI 2 to 5.8), respectively. The number needed to treat in order to gain a clinically meaningful change was 3 (95% CI 3 to 8) for pain, and 2 (95% CI 2 to 5) for disability. A treatment effect was maintained at one-year follow-up. The findings support the efficacy of combined physiotherapy treatment in producing symptomatic and functional change in moderately disabled chronic low back pain patients.", "To evaluate effectiveness of an exercise programme in a community setting for patients with low back pain to encourage a return to normal activities.\n Randomised controlled trial of progressive exercise programme compared with usual primary care management. Patients' preferences for type of management were elicited independently of randomisation.\n 187 patients aged 18-60 years with mechanical low back pain of 4 weeks to 6 months' duration.\n Exercise classes led by a physiotherapist that included strengthening exercises for all main muscle groups, stretching exercises, relaxation session, and brief education on back care. A cognitive-behavioural approach was used.\n Assessments of debilitating effects of back pain before and after intervention and at 6 months and 1 year later. Measures included Roland disability questionnaire, Aberdeen back pain scale, pain diaries, and use of healthcare services.\n At 6 weeks after randomisation, the intervention group improved marginally more than the control group on the disability questionnaire and reported less distressing pain. At 6 months and 1 year, the intervention group showed significantly greater improvement in the disability questionnaire score (mean difference in changes 1.35, 95% confidence interval 0.13 to 2.57). At 1 year, the intervention group also showed significantly greater improvement in the Aberdeen back pain scale (4.44, 1.01 to 7.87) and reported only 378 days off work compared with 607 in the control group. The intervention group used fewer healthcare resources. Outcome was not influenced by patients' preferences.\n The exercise class was more clinically effective than traditional general practitioner management, regardless of patient preference, and was cost effective.", "A multicenter, randomized, single-blinded controlled trial with 1-year follow-up.\n To evaluate the efficiency of progressively graded medical exercise therapy, conventional physiotherapy, and self-exercise by walking in patients with chronic low back pain.\n Varieties of medical exercise therapy and conventional physiotherapy are considered to reduce symptoms, improve function, and decrease sickness absence, but this opinion is controversial.\n Patients with chronic low back pain or radicular pain sick-listed for more than 8 weeks and less than 52 weeks (Sickness Certificate II) were included. The treatment lasted 3 months (36 treatments). Pain intensity, functional ability, patient satisfaction, return to work, number of days on sick leave, and costs were recorded.\n Of the 208 patients included in this study, 71 were randomly assigned to medical exercise therapy, 67 to conventional physiotherapy, and 70 to self-exercise. Thirty-three (15.8%) patients dropped out during the treatment period. No difference was observed between the medical exercise therapy and conventional physiotherapy groups, but both were significantly better than self-exercise group. Patient satisfaction was highest for medical exercise therapy. Return to work rates were equal for all 3 intervention groups at assessment 15 months after therapy was started, with 123 patients were back to work. In terms of costs for days on sick leave, the medical exercise therapy group saved 906,732 Norwegian Kroner (NOK) ($122,531.00), and the conventional physiotherapy group saved NOK 1,882,560 ($254,200.00), compared with the self-exercise group.\n The efficiency of medical exercise therapy and conventional physiotherapy is shown. Leaving patients with chronic low back pain untampered poses a risk of worsening the disability, resulting in longer periods of sick leave.", "A prospective randomized controlled trial.\n To examine the effectiveness of combined manipulative treatment, stabilizing exercises, and physician consultation compared with physician consultation alone for chronic low back pain.\n Strong evidence exists that manual therapy provides more effective short-term pain relief than does placebo treatment in the management of chronic low back pain. The evidence for long-term effect is lacking.\n Two hundred four chronic low back pain patients, whose Oswestry disability index was at least 16%, were randomly assigned to either a manipulative-treatment group or a consultation group. All were clinically examined, informed about their back pain, provided with an educational booklet, and were given specific instructions based on the clinical evaluation. The treatment included four sessions of manipulation and stabilizing exercises aiming to correct the lumbopelvic rhythm. Questionnaires inquired about pain intensity, self-rated disability, mental depression, health-related quality of life, health care costs, and production costs.\n At the baseline, the groups were comparable, except for the percentage of employees (P = 0.01). At the 5- and 12-month follow-ups, the manipulative-treatment group showed more significant reductions in pain intensity (P < 0.001) and in self-rated disability (P = 0.002) than the consultation group. However, we detected no significant difference between the groups in health-related quality of life or in costs.\n The manipulative treatment with stabilizing exercises was more effective in reducing pain intensity and disability than the physician consultation alone. The present study showed that short, specific treatment programs with proper patient information may alter the course of chronic low back pain.", "The prescription of exercise as a conservative treatment for lumbar pain is frequent and seems effective for the chronic cases of nonspecific low back pain. However, there is no evidence favoring one type of exercise over another. Often, exercise programs are prescribed without adequate evaluation of the individual characteristics like posture, muscular force, and extensibility. Patients with totally different causes of low back pain will often be given the same type of exercises.\n Our objective was to compare the effectiveness of 2 home exercise programs in decreasing disability and pain related to subacute and chronic nonspecific low back pain. To do so we compared a specific (individualized) exercise program with a program of commonly prescribed exercises for low back pain.\n In a control group study, 20 patients with chronic or subacute nonspecific low back pain participated after giving their informed consent. All subjects were evaluated (physical evaluation of lumbar and pelvic muscles [1] force and [2] extensibility, [3] trunk range of motion) and then divided in 2 groups: 10 patients received specific exercises (experimental group) based on their evaluation, and 10 patients received a commonly prescribed exercise program for low back pain (control group). Six weeks later a second physical evaluation was conducted. Pain (visual analog pain scale) and disability (modified Oswestry) questionnaires were also completed by each subject at both evaluations.\n This was a randomized experimental study.\n Both groups had similar age, weight, and sex characteristics. The experimental group showed significant improvements for some components targeted by the program. The control group significantly had improvement of some physical characteristics not related to their initial deficits. Even if both groups showed some improvements in muscular force and extensibility, only the members of the group who received specific exercises significantly reduced their level of pain and disability. Both groups showed a similar rate of participation in the program.\n The results of this study suggest that applying a specific physical evaluation and exercise prescription is an appropriate treatment for people having subacute or chronic nonspecific pain. Thus clinicians should prescribe exercise programs based on individual muscular deficits rather than most commonly prescribed exercise programs.", "The purpose of this study was to compare the effect of the McKenzie method of treatment with patient education in \"mini back school\" in patients with acute low-back pain. The study included 100 patients, 23 women and 77 men with the average age 34.4 +/- 9.7 (range 18-61) years. The study included only those who were employed. The patients were randomly allocated to two groups, one group receiving treatment according to the McKenzie technique and the other group receiving education in a \"mini back school.\" Assessments were made after 3 weeks by an independent observer and after 52 weeks they were seen by one of the authors. Patients were assessed on seven variables: return to work, sick-leave during the initial episode, sick-leave during recurrences, recurrences of pain during the year of observation, patients' ability to self-help, pain and movement. Although the effect of attention placebo cannot be ruled out, the results demonstrated that the McKenzie method of treatment for patients with acute low-back pain was superior for five out of seven variables studied. The only variables that did not show any statistically significant differences were sick-leave during recurring episodes of pain and patients' ability to self-help.", "Clinicians treating patients with low back pain often use exercise to reduce pain and improve function. The aim of this study was to evaluate the effectiveness of trunk extensor endurance training in reducing pain and decreasing disability in subjects with subacute low back pain (ie, onset of back pain within 7 days to 7 weeks).\n Patients were randomly assigned to either an experimental group or a control group. A visual analog scale and the pain rating index (PRI) of the McGill Pain Questionnaire (MPQ) were used to obtain baseline measurements of pain. The Roland Morris Disability Questionnaire (RMDQ) was used to measure disability, and the Sorensen Test was used to measure trunk extensor endurance. Subjects in the experimental group attended exercise sessions 3 times a week for 6 weeks. Subjects in the control group did not do exercises. Both groups were given back care advice and hot packs for 15 minutes, 3 to 5 times per week. Reassessments were carried out at 3 and 6 weeks.\n There were differences between the 2 groups at 3 weeks in regard to pain intensity during the evaluation session and pain experienced over the preceding 24 hours, the total MPQ PRI, the sensory component of the MPQ PRI, and the RMDQ. At 6 weeks, no differences were found for pain measurements, disability scores, and holding time on the Sorensen Test.\n Trunk extensor endurance training reduced pain and improved function at 3 weeks but resulted in no improvement at 6 weeks when compared with the control group. Endurance exercise is considered to expedite the recovery process for patients with an acute episode of low back pain.", "The effects of exercise for isolated lumbar extensor muscles were examined in 54 chronic low-back pain patients. Subjects were randomly assigned to a 10-week exercise program (N = 31) or a wait-list control group (N = 23). Results indicated a significant increase in isometric lumbar extension strength for the treatment group and a significant reduction in reported pain compared with the control group (P 0.05). Treated subjects reported less physical and psychosocial dysfunction whereas the control group increased in pain, and physical and psychosocial dysfunction. There were no concomitant changes in reported daily activity levels. These results show that lumbar extension exercise is beneficial for strengthening the lumbar extensors and results in decreased pain and improved perceptions of physical and psychosocial functioning in chronic back pain patients. However, these improvements were not related to changes in activities or psychological distress.", "The purpose of this randomized pilot study was to evaluate a possible design for a 6-week modified hatha yoga protocol to study the effects on participants with chronic low back pain.\n Twenty-two participants (M = 4; F = 17), between the ages of 30 and 65, with chronic low back pain (CLBP) were randomized to either an immediate yoga based intervention, or to a control group with no treatment during the observation period but received later yoga training.\n A specific CLBP yoga protocol designed and modified for this population by a certified yoga instructor was administered for one hour, twice a week for 6 weeks. Primary functional outcome measures included the forward reach (FR) and sit and reach (SR) tests. All participants completed Oswestry Disability Index (ODI) and Beck Depression Inventory (BDI) questionnaires. Guiding questions were used for qualitative data analysis to ascertain how yoga participants perceived the instructor, group dynamics, and the impact of yoga on their life.\n To account for drop outs, the data were divided into better or not categories, and analyzed using chi-square to examine differences between the groups. Qualitative data were analyzed through frequency of positive responses.\n Potentially important trends in the functional measurement scores showed improved balance and flexibility and decreased disability and depression for the yoga group but this pilot was not powered to reach statistical significance. Significant limitations included a high dropout rate in the control group and large baseline differences in the secondary measures. In addition, analysis of the qualitative data revealed the following frequency of responses (1) group intervention motivated the participants and (2) yoga fostered relaxation and new awareness/learning.\n A modified yoga-based intervention may benefit individuals with CLB, but a larger study is necessary to provide definitive evidence. Also, the impact on depression and disability could be considered as important outcomes for further study. Additional functional outcome measures should be explored. This pilot study supports the need for more research investigating the effect of yoga for this population.", "The aim of this study was to determine whether low power laser therapy (Gallium-Arsenide) is useful or not for the therapy of chronic low back pain (LBP).\n This study included 75 patients (laser + exercise-25, laser alone-25, and exercise alone-25) with LBP. Visual analogue scale (VAS), Schober test, flexion and lateral flexion measures, Roland Disability Questionnaire (RDQ) and Modified Oswestry Disability Questionnaire (MODQ) were used in the clinical and functional evaluations pre and post therapeutically. A physician, who was not aware of the therapy undertaken, evaluated the patients.\n Significant improvements were noted in all groups with respect to all outcome parameters, except lateral flexion (P < 0.05).\n Low power laser therapy seemed to be an effective method in reducing pain and functional disability in the therapy of chronic LBP.\n Copyright 2003 Wiley-Liss, Inc.", "A randomized clinical trial with 1-year and 3-year telephone questionnaire follow-ups.\n To report a specific exercise intervention's long-term effects on recurrence rates in acute, first-episode low back pain patients.\n The pain and disability associated with an initial episode of acute low back pain (LBP) is known to resolve spontaneously in the short-term in the majority of cases. However, the recurrence rate is high, and recurrent disabling episodes remain one of the most costly problems in LBP. A deficit in the multifidus muscle has been identified in acute LBP patients, and does not resolve spontaneously on resolution of painful symptoms and resumption of normal activity. Any relation between this deficit and recurrence rate was investigated in the long-term.\n Thirty-nine patients with acute, first-episode LBP were medically managed and randomly allocated to either a control group or specific exercise group. Medical management included advice and use of medications. Intervention consisted of exercises aimed at rehabilitating the multifidus in cocontraction with the transversus abdominis muscle. One year and three years after treatment, telephone questionnaires were conducted with patients.\n Questionnaire results revealed that patients from the specific exercise group experienced fewer recurrences of LBP than patients from the control group. One year after treatment, specific exercise group recurrence was 30%, and control group recurrence was 84% (P < 0.001). Two to three years after treatment, specific exercise group recurrence was 35%, and control group recurrence was 75% (P < 0.01).\n Long-term results suggest that specific exercise therapy in addition to medical management and resumption of normal activity may be more effective in reducing low back pain recurrences than medical management and normal activity alone.", "To assess the efficacy of exercise therapy for acute low back pain, a randomized, placebo-controlled trial was performed in 40 Dutch general practices. Patients received either exercise instruction with advice for daily life by a physiotherapist; placebo ultrasound therapy by a physiotherapist; or usual care by the general practitioner. All patients received analgesic agents and information on low back pain before randomization. Four hundred seventy-three patients were included. No differences in number of recurrences, functional health status, or medical care usage could be found among the three groups. In the exercise group, duration of recurrences was shorter and patients were less tired during the first 3 months than in the usual care group, but no differences were found between the exercise and placebo groups. It was concluded that exercise therapy for patients with acute low back pain has no advantage over usual care from the general practitioner.", "nan", "A randomized controlled trial with a 6-month follow-up period was conducted.\n To compare lumbar extension exercise and whole-body vibration exercise for chronic lower back pain.\n Chronic lower back pain involves muscular as well as connective and neural systems. Different types of physiotherapy are applied for its treatment. Industrial vibration is regarded as a risk factor. Recently, vibration exercise has been developed as a new type of physiotherapy. It is thought to activate muscles via reflexes.\n In this study, 60 patients with chronic lower back pain devoid of \"specific\" spine diseases, who had a mean age of 51.7 years and a pain history of 13.1 years, practiced either isodynamic lumbar extension or vibration exercise for 3 months. Outcome measures were lumbar extension torque, pain sensation (visual analog scale), and pain-related disability (pain disability index).\n A significant and comparable reduction in pain sensation and pain-related disability was observed in both groups. Lumbar extension torque increased significantly in the vibration exercise group (30.1 Nm/kg), but significantly more in the lumbar extension group (+59.2 Nm/kg; SEM 10.2; P < 0.05). No correlation was found between gain in lumbar torque and pain relief or pain-related disability (P > 0.2).\n The current data indicate that poor lumbar muscle force probably is not the exclusive cause of chronic lower back pain. Different types of exercise therapy tend to yield comparable results. Interestingly, well-controlled vibration may be the cure rather than the cause of lower back pain.", "The effectiveness of massage therapy for low-back pain has not been documented. This randomized controlled trial compared comprehensive massage therapy (soft-tissue manipulation, remedial exercise and posture education), 2 components of massage therapy and placebo in the treatment of subacute (between 1 week and 8 months) low-back pain.\n Subjects with subacute low-back pain were randomly assigned to 1 of 4 groups: comprehensive massage therapy (n = 25), soft-tissue manipulation only (n = 25), remedial exercise with posture education only (n = 22) or a placebo of sham laser therapy (n = 26). Each subject received 6 treatments within approximately 1 month. Outcome measures obtained at baseline, after treatment and at 1-month follow-up consisted of the Roland Disability Questionnaire (RDQ), the McGill Pain Questionnaire (PPI and PRI), the State Anxiety Index and the Modified Schober test (lumbar range of motion).\n Of the 107 subjects who passed screening, 98 (92%) completed post-treatment tests and 91 (85%) completed follow-up tests. Statistically significant differences were noted after treatment and at follow-up. The comprehensive massage therapy group had improved function (mean RDQ score 1.54 v. 2.86-6.5, p < 0.001), less intense pain (mean PPI score 0.42 v. 1.18-1.75, p < 0.001) and a decrease in the quality of pain (mean PRI score 2.29 v. 4.55-7.71, p = 0.006) compared with the other 3 groups. Clinical significance was evident for the comprehensive massage therapy group and the soft-tissue manipulation group on the measure of function. At 1-month follow-up 63% of subjects in the comprehensive massage therapy group reported no pain as compared with 27% of the soft-tissue manipulation group, 14% of the remedial exercise group and 0% of the sham laser therapy group.\n Patients with subacute low-back pain were shown to benefit from massage therapy, as regulated by the College of Massage Therapists of Ontario and delivered by experienced massage therapists.", "A randomized clinical trial was conducted to evaluate the efficacy of 3 physical therapy approaches--lumbar flexion exercise, manual therapy, and home care--in the treatment of lumbar disc disease. Twenty-eight patients were assigned to 1 of 3 treatment groups and were shown to be similar in age, sex, and prescores on 4 of the 5 outcome measures. With the exception of the home care patients, each patient received the appropriate treatment twice a week for a 1-month period. No statistically significant differences in measurements of pain, forward, right-side, and left-side flexion, or functional activity between the 3 groups were observed.", "To describe postural sway and its associations to background factors, low back pain and functional capacity. To evaluate the changes in postural sway after three months of therapeutic exercise in the gym or at home.\n A one-year randomized experimental trial evaluated postural sway in three study groups: intensive training, home exercise and control group.\n Subjects were recruited from seven local occupational health care centres in Central Finland and were examined at Central Finland Hospital by medical doctors. Measurements and therapeutic exercise programmes were carried out in the Research Laboratory of Sport and Health Sciences at Jyväskylä University.\n Initially, 49 male and 41 female subjects (aged 20-55 years) with nonspecific and subacute low back pain were examined.\n Postural sway using a force platform, the Oswestry Index, as well as a measure of low back pain intensity were measured at the initial stage of the study, directly after interventions, as well as at three and nine months after the interventions.\n The background variables were not strongly correlated with postural sway. No changes occurred in the amplitude of sway during the study, but the sway velocity of the home exercise group increased.\n Postural sway measurements with a force platform may be suitable for detecting impairments of balance performance among subjects with pronounced functional or activity limitations and severe low back pain problems. In order to enhance balance performance, specific and customized exercise programmes are required.", "Low back pain is one of the most common and important musculoskeletal disorders. In addition, chronic low back pain can deteriorate the patient's physical, psychosocial and socioeconomic status. The objective of this quasi-experimental research was to assess the efficacy of an aerobic exercise and health education program in the treatment of chronic low back pain. Seventy-two patients whose ages ranged from 30 to 50 years who had chronic low back pain were enrolled and randomly assigned into two groups. Eight men and 28 women in the experimental group participated in a series of 3 health education sessions and an aerobic exercise training program. Nine men and 27 women in the control group received regular health education and a lumbar flexion exercise program. After a 3-month period of treatment, the results revealed the experimental group had statistically significant improvement of pain score and resting pulse rates when compared to the values of the control group (p-value < 0.001 and < 0.01, respectively). The average serum High Density Lipoprotein-Cholesterol (HDL-C) in the experimental group was also significantly higher (p-value < 0.05) than that of the control group. This health education program is useful and may be applicable to patients with chronic low back pain as an alternative treatment.", "A randomized parallel-group comparative trial with a 1-year follow-up period was performed.\n To compare the effect of a comprehensive functional restoration program involving intensive physical training, ergonomic training, and behavioral support (39 hours per week for 3 weeks) with the effect of outpatient intensive physical training (1.5 hours three times per week for 8 weeks).\n Nonrandomized studies conducted in the United States favor functional restoration for patients with chronic low back pain. Two previously reported randomized studies from the authors' Back Center in Copenhagen concur with this recommendation, although the positive effects in one of the studies had faded out after 2 years. Randomized functional restoration studies in Canada and Finland have failed to demonstrate any substantive effect.\n Initially, 138 patients with chronic low back pain were included in the current study. They then were randomized to either functional restoration (n = 64) or outpatient intensive physical training (n = 74). Of the initial 138 patients, 11 never started (5 and 6, respectively); 21 dropped out during treatment (8 and 13); and 7 of the graduates did not take part in the 1-year follow-up evaluation (3 and 4). The conclusions were drawn from the 99 patients (48 and 51, respectively) who graduated and participated in a 1-year follow-up evaluation. The median age of the patients was 42 years (range, 21-55 years) The female-to-male ratio was 68 to 31, and the median sick leave days during the preceding 3 years was 180 (range, 0-1080 days). The average back pain was rated 5.5 on a scale of 0 (no pain) to 10 (maximal pain). For these variables, there were no important differences between the groups. However, the functional restoration group tended to be more capable of work at baseline (58% vs 42%; P = 0.09).\n At the 1-year follow-up evaluation, overall assessment favored functional restoration. Otherwise, no significant differences were observed regarding work capability, sick leave for those at work, health care contacts,back pain, leg pain, or self-reported activities of daily living.\n Only in terms of overall assessment, the functional restoration program was superior to a comparatively short time-consuming outpatient physical training program.\n It may be that lower economic benefits during sick leave in the United States lead to favorable results from functional restoration programs, whereas greater benefits in Canada, Finland, and Denmark result in different conclusions. Finally, it may be that the difference in results across studies points simply to whether the studies were randomized.", "Several new studies have indicated that an active approach to patients with chronic disabling low back pain (LBP) seems effective. Some of these studies emphasize the importance of dealing with the patient's total situation in comprehensive multidisciplinary programs--the bio-psycho-social model. However, these programs are expensive. The aim of this study was to evaluate the rehabilitation outcome from three different active programs in terms of: (1) return-to-work rate, (2) days of sick leave, (3) health-care contacts, (4) pain and disability scores, and (5) staying physically active. The subjects included 132 patients randomized to the study, of whom 123 started one of the treatment programs. They had all had at least 6 months of chronic LBP. The patients were randomized into one of three programs: group 1--a full-time, intensive 3-week multidisciplinary program, including active physical and ergonomic training and psychological pain management, followed by 1 day weekly for the subsequent 3 weeks; group 2--active physical training, twice a week for 6 weeks, for a total of 24h; group 3--psychological pain management combined with active physical training, twice a week for 6 weeks, also for a total of 24h. The results presented here are based on data collected 4 months following treatment, which shows an 86% response rate. The initial examination and the follow-up evaluation were performed by a blinded observer. The results show that 4 months after treatment, the intensive multidisciplinary program is superior to the less intensive programs in terms of return-to-work rate, health-care contacts, pain and disability scores, and staying physically active.(ABSTRACT TRUNCATED AT 250 WORDS)" ]

[ "9202087", "20484548", "8951265", "16087985", "16960174", "11522564", "11174621", "15447897", "15321815", "9537309", "15812454" ]

[ "Zinc supplementation affects the activity patterns of rural Guatemalan infants.", "Daily supplementation with iron plus folic acid, zinc, and their combination is not associated with younger age at first walking unassisted in malnourished preschool children from a deficient population in rural Nepal.", "Effect of zinc supplementation on observed activity in low socioeconomic Indian preschool children.", "Zinc supplementation and psychosocial stimulation: effects on the development of undernourished Jamaican children.", "Zinc supplementation does not affect growth, morbidity, or motor development of US term breastfed infants at 4-10 mo of age.", "Randomized controlled trial of the effect of zinc supplementation on the mental development of Bangladeshi infants.", "Effect of zinc supplementation on development and growth of Chilean infants.", "Iron and zinc supplementation promote motor development and exploratory behavior among Bangladeshi infants.", "A community-based randomized controlled trial of iron and zinc supplementation in Indonesian infants: effects on growth and development.", "Zinc supplementation, mental development and behaviour in low birth weight term infants in northeast Brazil.", "Impact of zinc supplementation on mental and psychomotor scores of children aged 12 to 18 months: a randomized, double-blind trial." ]

[ "Zinc deficiency has been associated with growth deficits, reduced dietary intake and appetite, and has been hypothesized to result in reduced activity. This randomized, double-blind, placebo-controlled study examined whether 10 mg of oral zinc as zinc sulfate, given daily for up to 7 mo, affected activity patterns of 85 Guatemalan infants recruited at 6-9 mo of age. Infant activity was assessed by time sampling-observation method at 10-min intervals during a 12-h data collection period, at base line, 3 and 7 mo follow-up. Motor development and the percentage of time infants were observed in various positions (being carried, lying down, sitting, crawling, standing or walking) and engaged in various activities (eating, sleeping, resting, crying/whining or playing) were compared by treatment group. No differences in motor development were observed by treatment group. However, at follow-up 2 (after 7 mo of supplementation), zinc-supplemented infants were significantly more frequently observed sitting up compared with lying down, and were playing during 4.18 +/- 1.95% (P < 0.05) more observations than unsupplemented infants. They were also somewhat less likely to be observed crying or whining (P < 0.10) compared with those receiving the placebo. These effects are independent of other factors including infant age, motor development, sex, maternal education, family socioeconomic status and nutritional status at base line. Further research must be conducted to determine the long-term developmental importance of these differences in activity patterns associated with zinc supplementation in this setting.", "A community-based, cluster-randomized, placebo-controlled trial of daily zinc and/or iron+folic acid supplementation was conducted in rural southern Nepal to examine motor milestone attainment among 3264 children 1-36 mo of age between 2001 and 2006. Treatment groups included placebo, zinc (10 mg), iron+folic acid (12.5 mg iron + 50 microg folic acid), and zinc+iron+folic acid (10 mg zinc + 12.5 mg iron + 50 microg folic acid). Infants received half of these doses. The iron arms were stopped November 2003 by recommendation of the Data Safety and Monitoring Board; zinc and placebo continued until January 2006. A total of 2457 children had not walked at the time of entry into the trial and 1775 were followed through 36 mo. Mean age at first walking unassisted did not differ among groups and was 444 +/- 81 d (mean +/- SD) in the placebo group, 444 +/- 81 d in the zinc group, 464 +/- 85 d in the iron+folic acid group, and 446 +/- 87 d in the iron+folic acid+zinc group. Results were similar after adjustment for age at enrollment, asset ownership, maternal literacy, and prior child deaths in the household and in children who consumed at least 60 tablets. Compared with placebo, iron+folic acid was associated with an adjusted mean delay of 28.0 d (95% CI: 11.3, 44.7) in time to walking among infants and the delay was more pronounced with mid-upper arm circumference (MUAC) < 9.5 cm [60.6 d, (95% CI: 28.5, 92.6)]. Risks and benefits of universal iron+folic acid supplementation of infants beyond improved hematologic status deserve further consideration.", "To investigate whether supplementation of zinc in preschool children is associated with improvement in observed activity levels.\n On 2 consecutive days, we performed 5-hour observations with momentary time sampling (instant activity every 10 minutes) in children selected from an ongoing double-blind, randomized trial of zinc supplementation. The study was conducted in Kalkaji, a low-socioeconomic urban population of New Delhi with high diarrheal incidence and rates of malnutrition. A total of 93 children (48 zinc and 45 control) 12 to 23 months of age from an ongoing community-based, randomized, controlled trial received supplements for at least 1 month before study; 71% had received supplementation for more than 120 days. Zinc gluconate (10 mg of elemental zinc) was given daily, with both zinc and control groups receiving vitamins A, B1, B2, B6, D3, and E and niacinamide in addition.\n Outcomes were percentages of time spent in each of five activity levels and two groups representing high and low movement and overall rating by two activity scores. Children in the zinc group spent 72% more time performing activities in the high-movement group. Among the zinc-supplemented children, the activity rating by the children's activity rating score was 12% higher and by the energy expenditure score was 8.3% higher than in the control group.\n In conclusion, zinc supplementation, given along with selected vitamins, was associated with significantly greater activity levels in children. The relationship between the activity increase and locomotor development needs to be investigated, as do the long-term implications of zinc supplementation in terms of developmental status and school performance.", "Undernourished children have poor levels of development that benefit from stimulation. Zinc deficiency is prevalent in undernourished children and may contribute to their poor development.\n We assessed the effects of zinc supplementation and psychosocial stimulation given together or separately on the psychomotor development of undernourished children.\n This was a randomized controlled trial with 4 groups: stimulation alone, zinc supplementation alone, both interventions, and control (routine care only). Subjects were 114 children aged 9-30 mo and below -1.5 z scores of the National Center for Health Statistics weight-for-age references who were recruited from 18 health clinics. Clinics were randomly assigned to receive stimulation or not; individual children were randomly assigned to receive zinc or placebo. The stimulation program comprised weekly home visits during which play was demonstrated and maternal-child interactions were encouraged. The supplementation was 10 mg Zn as sulfate daily or placebo. Development (assessed by use of the Griffiths Mental Development Scales), length, and weight were measured at baseline and 6 mo later. Weekly morbidity histories were taken.\n Significant interactions were found between zinc supplementation and stimulation. Zinc benefited the developmental quotient only in children who received stimulation, and benefits from zinc to hand and eye coordination were greater in stimulated children. Zinc supplementation alone improved hand and eye coordination, and stimulation alone benefited the developmental quotient, hearing and speech, and performance. Zinc supplementation also reduced diarrheal morbidity but did not significantly improve growth.\n Zinc supplementation benefits development in undernourished children, and the benefits are enhanced if stimulation is also provided.", "It has been documented that growth patterns differ between breastfed and formula-fed infants. Some investigators have suggested that these differences may be related to differences in zinc nutriture.\n The objective of this study was to examine the effect of zinc supplementation on growth, morbidity, and motor development in healthy, term, breastfed infants.\n We conducted a randomized double-blind intervention comparing zinc supplementation (5 mg/d as zinc sulfate) with placebo in breastfed infants aged 4-10 mo. Growth and indexes of body composition and gross motor development were measured monthly from 3 to 10 mo. Morbidity data were collected weekly.\n Eighty-five infants were enrolled, and 70 completed the study. The baseline characteristics, attained weight or length at 10 mo, growth velocity, gross motor development, and morbidity did not differ significantly between groups, even after control for potentially confounding variables.\n The dietary zinc intake of these breastfed infants appeared to be adequate, given that zinc supplementation did not affect growth, development, or risk of infection (although sample size for detection of differences in development or infection was limited). Previously described differences in growth between breastfed and formula-fed infants in such populations do not appear to be due to differences in zinc nutriture.", "Zinc deficiency is thought to be common in young children in developing countries and some data suggest that it may detrimentally affect children's development.\n Our goal was to assess the effect of zinc supplementation on the developmental levels and behavior of Bangladeshi infants.\n This was a randomized, double-blind, controlled trial conducted in Dhaka, Bangladesh. Three hundred one infants aged 1 mo were randomly assigned to receive either 5 mg elemental Zn or placebo daily for 5 mo, and subsequent growth and morbidity were observed. For the present study, developmental levels were assessed in a subsample of 212 infants at 7 and 13 mo of age with use of the Bayley Scales of Infant Development, and the infants' behavior during the tests was observed. The children's social backgrounds, weights, and lengths were also recorded.\n The children's nutritional status was generally poor. The zinc-treated group had slightly lower scores on the mental development index of the Bayley Scales than did the placebo group (beta = 3.7, SE = 1.3, P < 0.005). This effect remained significant when nutritional status and social background were controlled for. No other significant differences between groups were noted.\n The mental development index scores of the zinc-treated group were slightly but significantly lower than those of the placebo group. This finding may have been due to micronutrient imbalance. Caution should be exercised when supplementing undernourished infants with a single micronutrient.", "To evaluate the effect of zinc supplementation on growth and development during infancy.\n We randomized 150 term neonates of low socioeconomic status to receive supplemental zinc 5 mg/d (SG) or a lactose placebo (PG); 112 completed a 1-year follow-up. All were breast-fed and given cow milk formula after weaning; solid foods and iron were added at 5 months. Anthropometry measured monthly, psychomotor development (PDI), mental development (MDI), and behavior including motor quality factor were assessed by Bayley Scales at 6 and 12 months. The groups were comparable in maternal characteristics, birth weight, home environment, and mother-infant interaction.\n No effects of zinc on weight, length, and weight for length at 12 months were found controlling for sex and breast-feeding. The mean PDI (SG: 84.5 +/- 11.5 vs PG: 87.6 +/- 9.9) and MDI (90.9 +/- 10.5 vs 88.9 +/- 9.1) were similar; however, 46 of 52 infants in the PG scored <100 in MDI vs 42 of 57 in the SG (P <.05). A smaller proportion of the SG, 2 of 57, scored low in motor quality factor at 6 months compared with the PG, 8 of 52 (P =.02). The mean at 12 months for the SG was 31.9 +/- 2.8 and for the PG 30.8 +/- 2.9 (P <.05); zinc supplementation entered the multiple regression at 12 months (P =.037).\n Zinc supplementation may have a beneficial effect on mental development and motor quality behavior of healthy term infants.", "Iron and zinc deficiency are prevalent during infancy in low-income countries.\n The objectives were to examine whether a weekly supplement of iron, zinc, iron+zinc, or a micronutrient mix (MM) of 16 vitamins and minerals would alter infant development and behavior.\n The participants were 221 infants from rural Bangladesh at risk of micronutrient deficiencies. Development and behavior were evaluated at 6 and 12 mo of age by using the Bayley Scales of Infant Development II and the Home Observation Measurement of Environment (HOME) scale. In this double-blind trial, the infants were randomly assigned to 1 of 5 treatment conditions: iron (20 mg), zinc (20 mg), iron+zinc, MM (16 vitamins and minerals, including iron and zinc), or riboflavin weekly from 6 to 12 mo. Multivariate analyses were conducted to examine the change in development and behavior for each supplementation group, with control for maternal education, HOME score, months breastfed, anemia, growth at 6 mo, and change in growth from 6 to 12 mo.\n Iron and zinc administered together and with other micronutrients had a beneficial effect on infant motor development. Iron and zinc administered individually and in combination had a beneficial effect on orientation-engagement. Two-thirds of the infants were mildly anemic, no treatment effects on hemoglobin concentration were observed, and hemoglobin was not associated with measures of development or behavior.\n The beneficial effects of weekly iron and zinc supplementation on motor development and orientation-engagement suggest that infants benefit from these minerals when administered together.", "Deficiencies of iron and zinc are associated with delayed development, growth faltering, and increased infectious-disease morbidity during infancy and childhood. Combined iron and zinc supplementation may therefore be a logical preventive strategy.\n The objective of the study was to compare the effects of combined iron and zinc supplementation in infancy with the effects of iron and zinc as single micronutrients on growth, psychomotor development, and incidence of infectious disease.\n Indonesian infants (n = 680) were randomly assigned to daily supplementation with 10 mg Fe (Fe group), 10 mg Zn (Zn group), 10 mg Fe and 10 mg Zn (Fe+Zn group), or placebo from 6 to 12 mo of age. Anthropometric indexes, developmental indexes (Bayley Scales of Infant Development; BSID), and morbidity were recorded.\n At 12 mo, two-factor analysis of variance showed a significant interaction between iron and zinc for weight-for-age z score, knee-heel length, and BSID psychomotor development. Weight-for-age z score was higher in the Zn group than in the placebo and Fe+Zn groups, knee-heel length was higher in the Zn and Fe groups than in the placebo group, and the BSID psychomotor development index was higher in the Fe group than in the placebo group. No significant effect on morbidity was found.\n Single supplementation with zinc significantly improved growth, and single supplementation with iron significantly improved growth and psychomotor development, but combined supplementation with iron and zinc had no significant effect on growth or development. Combined, simultaneous supplementation with iron and zinc to infants cannot be routinely recommended at the iron-to-zinc ratio used in this study.", "To test whether zinc supplementation reduces the deficits in mental development and behaviour that are found in term infants of low birth weight in the study population.\n A prospective double-blind, part-randomised efficacy trial.\n A low-income population in Pernambuco, northeast Brazil, where the economy is largely dependent on sugar-cane production, and where over 90% of deliveries occur in health facilities.\n During a 20-month period, all singleton, term infants weighing 1500-2499 g born to families of low income ( < US $280/month) were enrolled at birth (n = 205). At 6 and 12-months, the numbers tested were 163 and 138 respectively.\n Infants born from January 1993-January 1994 were randomly assigned to receive daily, except Sundays, a placebo (n = 66) or 1 mg zinc (n = 68). Those born February-August 1994 were given 5 mg zinc (n = 71). Supplementation was for eight weeks, starting at birth. Field workers visited each infant at home to administer the supplement.\n At 6 and 12-months, mental and psychomotor development was assessed with the Bayley Scales of Infant Development and no significant differences in the scores of the three groups were found. At 12-months, behaviour was also assessed on 5 ratings. Ratings were highest in infants given 5 mg zinc (P = 0.042).\n Zinc supplementation (5 mg/d) for eight weeks may reverse some of the poor behaviours, particularly responsiveness, exhibited by low birth weight infants. No amelioration of their mental and psychomotor deficits was found.", "To evaluate the effect of zinc supplementation on mental and psychomotor scores in children aged 12 to 18 months.\n In this double-blind, randomized, placebo-controlled trial, children aged 6 to 30 months received daily elemental zinc (10 mg for infants and 20 mg for others) or placebo for 4 months. Bayley Scales of Infant Development II were used for development assessment in the 12- to 18-month subgroup at enrollment and the end of the study.\n At the end of the study, the adjusted mean mental ( P = .36) and psychomotor ( P = .28) index scores were similar in the intervention and control groups. In a multivariate model, the baseline mental development index score was positively associated with the mother's schooling, the child's height for age, packed cell volumes, hospital birth, and attendance at a day care center, and was negatively associated with the child's age. Breastfeeding, the child's weight for height, and packed cell volumes were positively associated with the baseline psychomotor index score.\n Zinc supplementation did not affect the mental or psychomotor development index scores in a setting in which zinc deficiency is common." ]

[ "8688396", "8442804", "6512783", "4006485", "4084103" ]

[ "A multicentre randomised controlled trial comparing elective and selective caesarean section for the delivery of the preterm breech infant.", "The Iowa premature breech trial.", "The delivery route for very-low-birth-weight infants. A preliminary report of a randomized, prospective study.", "A failed RCT to determine the best method of delivery for very low birth weight infants.", "Collaborative study on preterm breeches: vaginal delivery versus caesarean section." ]

[ "To determine the optimum mode of delivery for women in preterm breech labour at a gestational age of 26 to 32 weeks.\n A multicentre randomised controlled trial.\n Twenty-six hospitals in England, UK.\n Women with a singleton breech fetus in spontaneous preterm labour between 26 and 32 completed weeks of gestation, with no clear indication for a caesarean section or vaginal breech delivery.\n Random allocation to either \"intention to delivery vaginally' or \"intention to deliver by caesarean section'.\n Perinatal mortality, neonatal morbidity, maternal morbidity and gestation at delivery.\n The trial was closed after 17 months because of low recruitment, by which time substantial numbers of women had been in the eligible gestation period. Thirteen women from six hospitals were recruited. One infant, randomised to and delivered vaginally, was stillborn. Three fetal presentations were cephalic at delivery despite a diagnosis of breech presentation at trial entry. No formal statistical analysis was performed due to the small numbers.\n No conclusions about the optimum mode of delivery for women in preterm labour with a fetus presenting by the breech can be drawn from this trial. The low accrual rate was due to clinicians' reluctance to randomise eligible women, reflecting the circumstances and nature of the trial.", "A prospective, randomized clinical trial involving patients in premature labor (28 to 36 weeks' gestation) with breech presentation comparing 18 with immediate cesarean section with 20 with observed labor was undertaken at the University of Iowa from 1978 to 1983. The \"observed labor\" group had more deaths and lower Apgar scores (not statistically significant). Acidosis at delivery was not more common in the observed labor group, but 25% were delivered by cesarean section for fetal distress. The only neonatal deaths of nonanomalous babies, who were acidotic at delivery, occurred in patients who were managed outside of the trial, because delivery occurred soon after admission to the hospital. Congenital malformations accounted for one-third of the neonatal deaths; birth trauma did not occur in the 38 study patients.", "A major problem facing the perinatal team remains the care of the very-low-birth-weight infant (less than 1,500 gm), which includes not only the neonatal aspects but also the specific management aspects of labor and delivery. Numerous retrospective studies have suggested the potential benefits of cesarean delivery in the very-low-birth-weight group. In order to specifically address the question of the delivery route and its impact on neonatal outcome, a randomized, prospective study was designed. The study design specifically attempted to exclude the usual clinical estimation of fetal weight and sought to rely on other factors, which included the clinical availability of ultrasound as utilized by the physician staff. As the study proceeded, it became apparent on numerous occasions that the birth weights of infants who had been entered into this study were, in fact, in excess of the targeted weight range of 750-1,500 gm. In one instance an infant weighed in excess of 3,000 gm, and these observations led to a temporary discontinuation of the study. Data evaluation was undertaken from the first 40 patients entered into the study. This limited comparison failed to demonstrate significant differences regarding measures chosen to evaluate neonatal condition. It did define the limitations of correctly choosing infants for inclusion in this study. It is clear that more precise selection criteria must be available before the study of the effects of delivery route on outcome can be resumed appropriately.", "An RCT to determine the optimum method of delivery for very low birth weight (VLBW) infants was canceled after it had been in progress for only 5 months when it was discovered that more than 40% of eligible patients were being withdrawn from the trial before randomization. A review of hospital births before the trial began suggested that the trial was held too late: that a critical shift in obstetric practice towards abdominal delivery of VLBW infants had already occurred. Obtaining patient consent to participation, which had been the main predicted problem, was not difficult.", "nan" ]

[ "15636982" ]

[ "The elective use of oxytocin infusion during labour in nulliparous women using epidural analgesia: a randomised double-blind placebo-controlled trial." ]

[ "The obstetric outcome following the elective use of oxytocin infusion was determined in a randomised, double-blind placebo-controlled trial. 93 nulliparous women in a London hospital, who had requested epidural analgesia in labour (</= 6 cm.), were given an infusion of oxytocin (n = 46) or placebo (n = 47). The initial epidural dose was 15 ml of 0.125% bupivacaine, followed by an infusion at 10 ml per h, with 15 ml top-ups if required. When oxytocin was used electively there was a reduction in the length of the first stage of labour from 696 min to 578 min, (P < 0.05) even though more than half of the control group (53%) required oxytocin augmentation. There was no significant difference between the number of operative deliveries (34 [74%] vs 35 [74%]). The rotational delivery rate was less in the study group (2 [4%] vs 5 [11%]), though this did not reach significance. There were no adverse effects on the fetus, as judged by cord pH measurement, Apgar score, admission to the special care baby unit and neonatal jaundice. The prophylactic use of oxytocin in nulliparous women with epidurals reduces the length of the first stage of labour and appears to be safe. It does not reduce the operative delivery rate." ]

[ "15167393", "10728540", "12133129", "16818336", "8241919", "12751980", "16203467", "18190669", "11265828", "9231447", "10096306", "1990858", "3605473", "8110360" ]

[ "Effectiveness of crime prevention through environmental design in reducing criminal activity in liquor stores: a pilot study.", "Effectiveness of toughened glassware in terms of reducing injury in bars: a randomised controlled trial.", "Too drunk for a beer? A study of overserving in Stockholm.", "Promotion of responsible drinking in hotels.", "The role of alcohol providers in prevention: an evaluation of a server intervention programme.", "Education of key personnel in student pubs leads to a decrease in alcohol consumption among the patrons: a randomized controlled trial.", "Can training bar staff in responsible serving practices reduce alcohol-related harm?", "A randomized trial to evaluate a management training program to prevent illegal alcohol sales.", "Project ARM: alcohol risk management to prevent sales to underage and intoxicated patrons.", "A community-wide Responsible Beverage Service program in three communities: early findings.", "Long-term effects of a community-wide alcohol server training intervention.", "Responsible alcohol service: a study of server, manager, and environmental impact.", "Training bar personnel to prevent drunken driving: a field evaluation.", "Mandated server training and reduced alcohol-involved traffic crashes: a time series analysis of the Oregon experience." ]

[ "Liquor store employees experience disproportionately higher rates of workplace injury death than employees in any other retail setting. However, efforts to introduce workplace violence prevention programs into liquor stores have been minimal. This study examines the effectiveness of a Crime Prevention Through Environmental Design intervention in reducing criminal activity in Santa Monica, California liquor stores. Nine stores enrolling in the study received an individualized intervention safety plan; the remaining 13 served as a comparison group. Mixed-effects Poisson regression was used to examine intervention effectiveness. The largest reductions in criminal activity occurred for robbery and shoplifting outcomes. We conclude that the Crime Prevention Through Environmental Design program reduced crime and injury in liquor stores and educated small businesses about the risks associated with retail violence and the countermeasures that can be taken.", "To evaluate the effectiveness, in terms of injury prevention, of toughened pint glassware in bars.\n Randomised controlled trial.\n A random sample of 57 bars in South Wales, West Midlands, and West of England.\n A total of 1229 bar workers.\n Complete replacement of pint glasses with annealed (control) or toughened (intervention) glassware.\n Bar staff injuries recorded monthly: number, site, and severity (lifestyle impact; treatment need) of injuries.\n Ninety eight bar staff experienced 115 injuries: 43 in the control group, 72 in the intervention group. Adjusting for people at risk gave a relative risk (RR) of 1.48 (confidence interval (CI) 1.02 to 2.15). Similarly, adjusting for hours worked gave RR 1.57 (CI 1.08 to 2.29). Thus, injury rate was 60% higher in the intervention group (p<0.05), with no significant difference in severity. Most were hand injuries requiring first aid. Injuries tended to occur simultaneously in more than one body part in the intervention group, reportedly caused by spontaneous disintegration of toughened glassware. Impact resistance testing showed the energy required to break annealed glass (1.8 +/- 0.2 J) was greater than that for toughened glass (1.4 +/- 0.2 J), though the difference was not significant.\n Glass with lower impact resistance caused more injuries. \"Toughened\" glassware had lower impact resistance. Standards for toughening need to be developed.", "To evaluate the effects of a community alcohol prevention programme on the frequency of alcohol service to intoxicated patrons at licensed premises.\n Pretest (1996)-post-test (1999) design.\n Licensed premises in Stockholm, Sweden.\n The community alcohol prevention programme, including server training in responsible beverage service (RBS) and policy initiatives in the community, has been conducted since 1996.\n Actors were hired to enter licensed premises, enact a scene of severe intoxication and attempt to order a beer. At the baseline in 1996, actors visited 92 licensed premises, 47 from the central part of Stockholm and 45 from the southern part of Stockholm. At the follow-up in 1999, 103 licensed premises were visited, 61 from the central part of Stockholm and 42 from the southern part of Stockholm. Observers monitored each visit.\n At follow-up the actors were denied service of alcohol at 47% of the licensed premises, a statistically significant improvement compared to 5% in the baseline study.\n Licensed premises refused service of alcohol to intoxicated patrons to a much greater extent than in the baseline study. The improved results can probably be explained by a combination of policy initiatives in the community, changes in the overall enforcement environment and RBS training.", "This study reports on an intervention programme to promote responsible drinking in hotels. The licensees of eight hotels agreed to participate in a trial of measures designed to assist patrons to avoid drink-driving, and seven other hotels were used as controls. The interventions acceptable to licensees comprised commercial-quality promotional material with the theme \"0.05 Know Your Limits\", and a breath analysis machine and poster on its use. Patrons leaving the hotels on Thursday, Friday and Saturday nights were interviewed and breath-tested. Although the intervention material had been seen by one-third of patrons in the intervention hotels, there was no significant difference between them and control hotel patrons in either median BAC or the proportion who were going to drive with BAC over the legal limit. There was poor compliance by hotels with the intervention procedures, indicating that a major impediment to the implementation and evaluation of programmes to promote responsible drinking is a lack of motivation by many licensees, despite support by some licensees and the Australian Hotels Association.", "Server intervention is a relatively new approach in the attempt to reduce the incidence of drinking and driving. Although a number of evaluations have suggested that the approach may be effective, there have been few comprehensive evaluations of such programmes. The present study utilized process evaluation techniques to assess reactions to a programme developed by the Addiction Research Foundation, and a quasi-experimental design to determine the impact of the programme on the serving practices of servers. Actors portrayed behaviours often faced by servers, and observers rated the reactions of the servers, who were unaware of the simulations, to these situations. The programme appears to have been effective in changing behaviour, in that trained servers exhibited less inappropriate responses than did untrained servers. In addition the results suggested that the programme increased servers' knowledge about their obligations and potential strategies for dealing with these situations. The implications of these findings for future implementations of such programmes are discussed.", "To decrease alcohol consumption among patrons in student pubs by server-training programmes.\n Randomized controlled trial.\n University campus.\n A total of 1322 students visiting local student pubs during ordinary pub evenings.\n Educational programmes were given to bartenders (n = 40) in a randomized design in six of 12 pubs on a university campus. Bartenders in control pubs were not given the programme.\n Breath alcohol concentration (BAC), expressed in percentage, among the patrons and the reported social atmosphere in the pub ('high', 'cosy' and 'rowdy') measured on a visual analogue scale in the pub before and after the intervention programme was given.\n BACs of patrons in the intervention pubs were reduced by more than those of the patrons in the control pubs at a 1-month follow-up. The mean difference in BAC between intervention and control groups was -0.011% (95% confidence interval, 0.022-0.000). The intervention group also decreased more in reported level of 'rowdy' social atmosphere than did the control group. The mean difference was -6 points (95% confidence interval -11 to -1). No differences were found in reported 'cosy' and 'high' atmosphere.\n Alcohol levels among the patrons were decreased and the 'rowdy' social atmosphere reduced in the intervention group. Server-training programmes for personnel in student pubs could be a component in the prevention of alcohol problems in university student populations.", "A responsible service training programme aimed at reducing alcohol-related harm was implemented in a popular entertainment area over several months in 1992-93. Another popular entertainment area provided a control site. A number of evaluation measures were used: breath tests on 872 patrons from selected venues; drink driving data; risk assessments; the use of 'pseudo patrons'; and knowledge and attitude changes among trained bar staff (n = 88). Compared to control sites the intervention sites showed an immediate pre- to post-test reduction in patrons rated by researchers as extremely drunk and an eventual reduction from pre-test to follow-up in patrons with blood alcohol levels > = 0.08. There was also a small but significant increase in knowledge among bar staff. There was no significant reduction in patrons with blood alcohol levels > = 0.15 or in the number of drink driving offences from intervention sites during the study period. Pseudo drunk patrons were rarely refused service, identification was rarely checked and non-photographic identification was accepted on most occasions. The less than satisfactory outcome is attributed to poor implementation of the training and a lack of support among managers. The positive results from one venue, whose manager embraced the programme, served to highlight the importance of management support. It is suggested that mandatory training and routine enforcement of licensing laws are essential if the goals of responsible serving are to be met.", "To evaluate effects of a training program for owners/managers of alcohol establishments-Alcohol Risk Management (ARM)-on: (i) propensity to sell alcohol to obviously intoxicated patrons; and (ii) changing establishment-level policies/practices.\n We assigned alcohol establishments randomly to intervention (full-ARM) and delayed-intervention/control (ARM Express) conditions.\n One large metropolitan area in Midwestern United States.\n Owners and managers at 231 on-premise alcohol establishments (i.e. bars, restaurants).\n Training programs consisted of one-to-one sessions with the owner/manager at each establishment. The goal of training was to help owners/managers to select and implement alcohol control policies in their establishments. The full-ARM training consisted of four one-to-one sessions and the ARM Express was a single session.\n We measured intervention effects through baseline and follow-up pseudo-intoxicated alcohol purchase attempts (i.e. feigning intoxication while attempting to purchase alcohol) and telephone surveys of owners/managers at alcohol establishments.\n Sales rates to pseudo-intoxicated patrons reduced 23% (relative to delayed-intervention/control condition) at the first follow-up purchase attempt (P = 0.06) but returned to baseline levels 3 months later. On average, establishments selected 13 of 18 recommended policies, but in multivariate models we observed no significant differences at follow-up in reported policies/practices across establishments.\n Reliance on manager training to promote responsible establishment alcohol policies is not sufficient to prevent illegal alcohol sales to obviously intoxicated patrons and to reduce alcohol-related problems.", "Clear policies and expectations are key to increasing responsible service of alcohol in licensed establishments. Few training programs focus exclusively on owners and managers of alcohol establishments to reduce the risk of alcohol service. Project ARM: Alcohol Risk Management is a one-on-one consultation program for owners and managers. Participants received information on risk level, policies to prevent illegal sales, legal issues, and staff communication. This nonrandomized demonstration project was implemented in five diverse bars. Two waves of underage and pseudo-intoxicated purchase attempts were conducted pre- and postintervention in the five intervention bars and nine matched control bars. Underage sales decreased by 11.5%, and sales to pseudo-intoxicated buyers decreased by 46%. Results were in the hypothesized direction but not statistically significant. A one-on-one, outlet-specific training program for owners and managers is a promising way to reduce illegal alcohol sales, particularly to obviously intoxicated individuals.", "Evidence accumulating over the past 10 years or so suggests that commercial servers of alcoholic beverages will intervene to reduce levels of impairment among their patrons and will refuse service to intoxicated customers. While some Responsible Beverage Service (RBS) programs have had significant effects on server and patron behavior, others have not. This leads us to consider issues of implementation and program effectiveness. In the current paper, a community-wide RBS program is described in some detail. The program was comprised by a larger comprehensive community intervention project in three sites across California and South Carolina. Process evaluation data, to track program implementation and proximal effects, provide early findings. Expressed support for RBS principles was high for both the public and the hospitality industry in all sites. A telephone survey of managers also suggests that prevention policies at bars and restaurants are beginning to show up, but a direct measure of server intervention with heavy drinkers does not yet demonstrate a program effect.", "The Rhode Island Community Alcohol Abuse and Injury Prevention Project (CAAIPP), implemented from 1984 through 1989, employed the \"community gatekeeper\" approach to reduce alcohol-related injuries and deaths. Targeting alcohol servers rather than drinkers, community-wide interventions were designed and implemented to encourage responsible serving behaviors through the adoption of techniques of responsible service. The primary goal of the CAAIPP server intervention evaluation was to assess both short-term and long-term changes in behavior of alcohol beverage servers who were recipients of CAAIPP training.\n A 5-hour training curriculum on \"Responsible Alcohol Service\" was offered to all alcohol servers in a randomly selected study community. A prospective study design was used to evaluate long-term changes in the self-reported behavior of 321 trainees using three time-points over 5 years. A cross-sectional survey was conducted 4 years posttraining to compare rates of self-reported server behaviors in the intervention community (n = 106) with two comparison communities (nA = 56, nB = 49).\n Fifteen months after training, trainees reported significantly higher levels of desired serving behavior than nontrained servers. Though positive effects of server training diminished with time, responsible serving behavior 4 years posttraining remained higher than pretraining levels. The impact appeared greatest for servers with fewer years serving experience, wait-persons, younger servers and servers who worked in establishments without written policies regarding serving practices.\n The results with regard to modifying server behavior are positive and indicate that server interventions shown to be efficacious should be implemented. Training programs that target specific serving skills in repeat sessions may be most promising for improving server behavior, particularly among both young and new servers working in establishments without written policies regarding serving practices.", "A responsible alcohol-service training program was evaluated for its impact on changing beliefs, knowledge, and behavior in 97 servers and 43 managers and on changing establishment policies that encourage safer drinking environments. The training program had a significant impact on changing the beliefs and knowledge of both servers and managers. Observation 4 to 6 weeks after training showed no effects on server behavior, but there was a tendency toward more establishment policies compared with controls.", "The potential of a server intervention program to decrease the likelihood that a bar patron will leave a bar intoxicated was evaluated. Research assistants posing as regular patrons (\"pseudopatrons\") visited two bars where about half of the servers had received server intervention training. Pseudopatrons set the occasion for server intervention to occur by drinking six alcoholic beverages in two hours. The blood-alcohol concentration (BAC) of the pseudopatrons was measured after they left the bar. Results revealed that trained servers initiated more server interventions than did untrained personnel. Moreover, pseudopatrons served by trained personnel reached substantially lower BACs than those served by untrained servers. These results suggest that, if implemented on a large scale, server intervention programs have the potential of reducing drunken driving by helping to decrease the exit BACs of bar patrons.", "This paper reports the results from an evaluation of the first statewide mandated training for alcohol servers. The state of Oregon introduced training for all alcohol servers (and for one year all owners/managers) beginning in December 1986. Servers must complete training once over a five-year cycle; by December 1989, over 50% of servers and managers had been trained. We found statistically significant reductions in single-vehicle nighttime traffic crashes (those with high percentage of alcohol involvement) by the end of 1989 following the implementation of the compulsory server-training policy." ]

[ "9406488", "8978232", "9308382", "7496289", "11338918", "9351143", "9138212", "8646099", "8251847" ]

[ "Fundholding in the south Thames Region.", "Fundholders' prescribing costs: the first five years.", "GP fundholding and prescribing in UK general practice: evidence from two rural, English Family Health Services Authorities.", "Alterations in prescribing by general practitioner fundholders: an observational study.", "Effects of a monetary incentive on primary care prescribing in Ireland: changes in prescribing patterns in one health board 1990-1995.", "Unintended effects of a cost-containment policy: results of a natural experiment in Germany.", "GP fundholding and the costs of prescribing: further results.", "The extent of the two tier service for fundholders.", "Effect of fundholding and indicative prescribing schemes on general practitioners' prescribing costs." ]

[ "The general practice fundholding scheme is now at the forefront of the National Health Service (NHS) reforms and should lead to the more efficient use of services by making general practitioners more aware of the financial consequences of their clinical decisions. However, there is a concern that adverse effects may also occur.\n To monitor the changes occurring in a sample of fundholding and non-fundholding practices between 1992 and 1995, including providing care nearer to patients, the mixed economy of care, the efficiency and costs of fundholding, and the commitment of fundholders.\n Fifteen first-wave practices, four second-wave practices, and four non-fundholding practices in the former South East Thames Region took part in the study. Information was collected using interviews, questionnaires, prescribing data, and annual fundholders' income and expenditure accounts.\n Consultant clinics were set up in 10 different practices in 15 different specialties, and paramedical clinics in 12 different practices. Physiotherapy and mental health clinics constituted over 90% of the paramedical hours. Fundholders had private arrangements with an individual consultant or practitioner for approximately half of the contracted hours in both types of clinics. Fundholders had lower overall prescribing costs than non-fundholders, but the overall costs for prescribing for all groups had risen by about one third over three years.\n While outreach clinics may help to provide for the needs of patients with common conditions, they may lead to the fragmentation of services. The provision of primary care by those who are not NHS employees needs careful consideration. Recent policies for general practice have emphasized its role in disease prevention and in coordination of care for chronic illness. Fundholding also promotes two additional roles, the purchasing of care and the development of in-house facilities. Combining these different functions presents a considerable challenge.", "To determine whether the first five waves of English fundholding practices have reduced their prescribing costs relative to non-fundholding practices, and the duration of any reduction achieved.\n Analysis of item and cost data for all general practices in England in the six years from April 1990 to March 1996. The practices of each of the first five waves were identified at the Prescription Pricing Authority.\n All general practices in England.\n Changes and rates of change in net ingredient cost per prescribing unit, and changes in number of items per prescribing unit in fundholding practices, before and after fundholding, relative to continuing non-fundholders.\n Absolute prescribing costs increased over the six years, by 66% in the continuing non-fundholders and by 56-59% for fundholders. Successive waves of fundholders showed a similar pattern of change: a small relative reduction in the pre-fundholding year, maximum relative reduction in the first year, and a declining relative reduction in the second and third years. After this, their increases in costs were largely similar to those of non-fundholders. The number of items dispensed remained stable over the six years in all groups.\n The real budgets operated by fundholders were associated with a reduction in costs of about 6% relative to continuing non-fundholders, and this saving seemed to be retained during the study. The relative reduction was small compared with the absolute increase seen in all groups and disappeared after the third year of fundholding. It was brought about by lowering the average cost per item rather than by giving fewer items.", "Two separate prescribing budget regimes (part of GP fundholding and the indicative prescribing scheme) were introduced into UK general practice in April 1991 in an attempt to contain the growth in NHS expenditure on prescribed drugs.\n The aims of this study are (i) to examine whether the fundholding scheme has been more effective at containing prescribing cost growth than the indicative prescribing scheme and (ii) to ascertain whether its implementation, at a practice level, has been affected by local circumstances and conditions.\n Prescribing cost data were collected from two rural, English Family Health Services Authorities for the financial years 1990/1991 to 1993/1994. Exploratory analysis was performed using regression analysis and nonparametric statistical techniques.\n Initially, the fundholding scheme has been the more effective at containing expenditure on prescribed drugs. However, the implementation of the schemes in rural areas has probably been affected by the existence of practices with permission to dispense drugs to their own patients, due to a lack of pharmacies in such areas.", "To compare prescribing in general practices before and after they become fundholders to assess whether this affected prescribing patterns.\n Analysis of prescribing data (PACT) for one year before and one year after practices become first, second, or third wave fundholders and comparison with practices that were not fundholders during any part of the study.\n Prescribing costs (net ingredient cost per prescribing unit), prescribing volume (items per 1000 prescribing units), net ingredient cost per item, and percentage of generic prescribing.\n Former Mersey Regional Health Authority.\n 100 fundholders (20 first wave, 31 second wave, 49 third wave) and 312 nonfundholders.\n Prescribing costs and volume rose throughout the study in all groups. In all three fundholding waves the rate of increase of prescribing costs was significantly lower than for nonfundholders. Both cost per item and prescribing volume tended to decrease, the former probably because of a significant increase in generic prescribing. Fundholding and non-fundholding practices differed in several respects.\n Fundholding has altered practice prescribing patterns compared with those of nonfundholders, increasing generic prescribing and reducing the rate of increase of prescribing costs.", "In an attempt to curb the rapidly rising costs of primary care prescribing in Ireland, the government introduced a financial incentive scheme in 1993, to encourage general practitioners to restrain their prescribing.\n To investigate the effects of a financial incentive scheme on GP prescribing in Ireland on prescribing costs and volume, and on some specific therapeutic areas.\n Prescribing for 3 years before (1990-1992) and 3 years (1993-1995) after the introduction of incentives, based on a defined cohort of 233 general practitioners in the area of one health board. GPs were divided into tertiles based on their performance against their prescribing budgets into 'savers' (generally underspent and received incentive payments), modest overspenders and large overspenders.\n Savers were always lower cost prescribers than the other groups. They contained their rate and costs of prescribing in contrast to the other groups, e.g. percentage rise in prescribing costs in the year after the introduction of the scheme -7.9%, +1.2% and +7.3% respectively, (P < 0.05) for savers, modest overspenders and large overspenders respectively. This effect was short lived however and was gone by the third year of the study.\n The financial incentives had a marked effect on prescribing volume and cost on some practices who could achieve targets and hence incentive payments. The incentives had little effect on high spending practices. Such incentive schemes need careful evaluation if they are not to become perverse to the good health of patients.", "In this paper empirical evidence for substitution processes caused by the budget for drugs prescribed by office-based physicians is provided. Due to substitution processes in a natural experiment the number of referrals and hospital admissions increased significantly after the introduction of a drug budget in Germany. This leads to additional direct and indirect cost for the health care system.", "An earlier paper published in this journal suggested that fundholding practices in Lincolnshire had managed to constrain the growth in their prescribing costs more successfully than had non-fundholders, largely on the basis of restricting the number of items prescribed per patient. At that time, insufficient data were available to explore the impact of a change in status from non-fundholding to fundholding on prescribing behaviour.\n Time-series prescribing data for the fourth-wave of Lincolnshire fundholders are analysed, and comparisons are made between this group, non-fundholders and the fundholders of the earlier waves.\n In their first year of fundholding, fourth-wave practices adopted the prescribing strategies employed previously by existing fundholders, namely, reductions in the number of items prescribed per patient and substantial increases in generic prescribing. The hypothesis that prospective fundholders inflate their prescribing budget before attaining fundholding status is not generally supported by the Lincolnshire data. Evidence is presented which suggests that the prescribing cost economies accruing to fundholding status may be short term.\n With the acquisition of fundholding status, the structure of incentives facing practices changes. Our results suggest that, with respect to prescribing, practices adjust rapidly to the new incentive structure.", "To examine possible differential changes in outpatient referrals to orthopaedic clinics, attendances, and waiting times between fundholding and non-fundholding general practitioners.\n Observational controlled study of referrals by general practitioners to orthopaedic outpatients between April 1991 and March 1995.\n District health authority in south-west England.\n 10 fundholding practices with 108,300 registered patients; 22 control practices with 159,900 registered patients.\n Changes in age standardised referral and outpatient attendance ratios for the year before and the two years after achieving fundholder status; changes in outpatient waiting times.\n In the year before achieving fundholding status both groups were referring more patients than were being seen. Two years later, referral and attendance ratios had increased by 13% and 36% respectively for fundholders and 32% and 59% for controls, and both groups were referring fewer patients than were being seen. Attendances represented 112% of referrals for fundholders and 104% for controls. In 1991-2, a similar proportion of patients in the two groups was seen within three months of referral. The two hospitals that set up specific clinics exclusively for fundholders showed faster access for patients of fundholders by 1993-4, as did a third hospital without such clinics by 1994-5.\n Fundholders increased their orthopaedic referrals less than did controls and achieved a better balance between outpatient appointments and referrals. Their patients were likely to be seen more quickly, particularly if the hospital provided special clinics exclusively for fundholders. Lack of case mix information makes it impossible to judge whether these differences benefit or disadvantage patients.", "To compare general practitioners' prescribing costs in fundholding and non-fundholding practices before and after implementation of the NHS reforms in April 1991.\n Analysis of prescribing and cost information (PACT data; levels 2 and 3) over two six month periods in 1991 and 1992.\n Oxford region.\n Three dispensing fundholding practices; five non-dispensing fundholding practices; and seven non-dispensing, non-fundholding practices.\n Percentage change in net cost of ingredients, number of items prescribed, average cost per item, and proportion of generic drugs prescribed after NHS reforms.\n Prescribing costs increased in all practices in the six months after the reforms. The net costs of ingredients increased among dispensing fundholders by 10.2%, among non-dispensing fundholders by 13.2%, and among non-fundholders by 18.7%. The number of items prescribed also increased in all three groups (by 5.2%, 7.5%, and 6.1% respectively). The increase in average cost per item was 4.8% for dispensing fundholders, 5.3% for non-dispensing fundholders, and 11.9% for non-fundholders. Dispensing fundholders increased the proportion of generic drugs prescribed from 26.9% to 34.5% and non-dispensing fundholders from 44.5% to 48.7%; non-fundholders showed no change (47%). Five of the eight fundholding practices made savings in their drugs budgets at the end of the first year of fundholding (range 2.9-10.7%; the three other practices overspent by up to 3.6%). All non-fundholding practices exceeded their indicative prescribing amounts (range 3.2-20.0%).\n Fundholding has helped to curb increases in prescribing costs, even among dispensing general practitioners, for whom the incentives are different. Indicative prescribing amounts for non-fundholding practices do not seem to have had the same effect." ]

[ "11106204", "11316215", "17439600", "9525303", "17881928", "12921449", "15467597", "16968502", "11802014", "12795454", "19054529", "8148045", "10566703", "18201449", "1447654", "16467715" ]

[ "Chronic cough and gastro-oesophageal reflux: a double-blind placebo-controlled study with omeprazole.", "Lansoprazole treatment of patients with chronic idiopathic laryngitis: a placebo-controlled trial.", "Comparison of the effect of a cornstarch thickened formula and strengthened regular formula on regurgitation, gastric emptying and weight gain in infantile regurgitation.", "Chronic cough.", "Effects of a prethickened formula on esophageal pH and gastric emptying of infants with GER.", "Efficacy of a pre-thickened infant formula: a multicenter, double-blind, randomized, placebo-controlled parallel group trial in 104 infants with symptomatic gastroesophageal reflux.", "Proton pump inhibitor therapy for chronic laryngo-pharyngitis: a randomized placebo-control trial.", "Double-blind, placebo-controlled trial with single-dose pantoprazole for laryngopharyngeal reflux.", "Evaluation of omeprazole in the treatment of reflux laryngitis: a prospective, placebo-controlled, randomized, double-blind study.", "Effect of pantoprazole on the course of reflux-associated laryngitis: a placebo-controlled double-blind crossover study.", "Multicenter, double-blind, randomized, placebo-controlled trial assessing the efficacy and safety of proton pump inhibitor lansoprazole in infants with symptoms of gastroesophageal reflux disease.", "[Nocturnal spasmodic cough in the infant. Evolution after antireflux treatment].", "A prospective evaluation of esophageal testing and a double-blind, randomized study of omeprazole in a diagnostic and therapeutic algorithm for chronic cough.", "Treatment of postnasal drip with proton pump inhibitors: a prospective, randomized, placebo-controlled study.", "Thickened feedings as a cause of increased coughing when used as therapy for gastroesophageal reflux in infants.", "Treatment of chronic posterior laryngitis with esomeprazole." ]

[ "Gastro-oesophageal reflux (GOR) is an important cause of chronic cough. There has been a lack of placebo-controlled trials treating GOR related chronic cough with antireflux therapy. The aim of this study was to determine the efficacy of omeprazole on GOR related chronic cough. After excluding other common causes of cough, oesophageal pH monitoring was performed on 48 patients with chronic cough. Twenty-nine patients found to have GOR were randomized in a double-blind fashion to receive omeprazole 40 mg o.d. or placebo for 8 weeks. After a 2-week washout period, patients were crossed over to the other treatment. Symptoms were recorded daily in a diary. Twenty-one patients completed both treatment periods. Cough (p=0.02) and gastric symptoms (p=0.003) improved significantly during the omeprazole treatment in twelve patients who received placebo during the first and omeprazole during the second 8-week period. In nine patients who received omeprazole during the first 8-week period, amelioration in cough reached statistical significance only after cessation of omeprazole. Gastric symptoms also remained minor during placebo in these nine patients. Omeprazole 40 mg o.d. seems to improve chronic cough in patients with gastrooesophageal reflux and the effect of omeprazole in ameliorating both cough and reflux symptoms continues after treatment ceases.", "Previous uncontrolled studies suggested a therapeutic benefit for treating gastroesophageal reflux disease (GERD) among patients with laryngitis. The present study is the first randomized, placebo-controlled, double-blind study of gastric acid suppression among patients with laryngitis in the United States.\n Patients diagnosed with idiopathic chronic laryngitis were randomized to receive either lansoprazole 30 mg p.o. b.i.d. or a matching placebo for 3 months. Before randomization, all patients underwent upper endoscopy, dual probe ambulatory 24-h esophageal pH-metry, and laryngoscopy, as well as completing a symptom questionnaire for GERD and laryngitis. The primary outcome of treatment was the complete resolution of laryngeal symptoms.\n A total of 22 patients with symptoms and signs of chronic laryngitis were enrolled, 20 of whom completed the study. At baseline, there were no significant differences between the two groups with regards to GERD symptoms, erosive esophagitis, proximal and distal esophageal pH-metry, or laryngeal signs and symptoms. In an intention-to-treat analysis, six patients in the lansoprazole group (50%) and only one patient (10%) in the placebo group achieved a complete symptomatic response, p = 0.04. Apart from receiving lansoprazole, there were no significant differences between responders and nonresponders in any of baseline esophageal or laryngeal signs and symptoms.\n Empirical treatment with lansoprazole is efficacious in relieving symptoms of laryngitis compared to placebo. Such treatment can be considered as a first-line option in managing patients with idiopathic chronic laryngitis.", "The purpose of this study was to evaluate the efficacy of a specially selected cornstarch-supplemented formula on clinical symptoms, gastric emptying and weight gain in infants with regurgitation. We performed a prospective randomised trial evaluating the therapeutic efficacy of two different formula feedings (cornstarch-thickened formula, group A; 25% strengthened formula, group B) in 81 young infants with regurgitation/vomiting > or = 3 times/day. A Tc-99 m milk scintigraphy was performed at inclusion and after 2 months to quantify gastric emptying time; all studied infants underwent a 2-month period of clinical follow-up evaluating regurgitation and body weight gain. At inclusion, group A and B had a similar age and weight. After the 2-month period of intervention, regurgitation and vomiting had both greater decrease (both P < 0.001 at 1 and 2 months) in group A (from a score of 4.19 +/- 1.71 to 0.93 +/- 0.42) than in group B (from a score of 4.15 +/- 1.68 to 2.89 +/- 1.16). Non-regurgitation symptoms (irritability, cough, choking, night-waking) decreased (P = 0.045 at 1 month and 0.017 at 2 months) in group A (from a score of 18 at baseline to 3 after 8 weeks) as compared to group B (from a score of 18 at baseline to 11 after 8 weeks). Weight increased more in group A (29.1 +/- 3.9 g/day over 8 weeks) versus group B (23.6 +/- 3.5 g/day over 8 weeks) (P < 0.01 at 1 and 2 months) Gastric emptying improved significantly in group A as compared with group B (all P < 0.001 for T1/2, and residual volume at 60 and 90 min). Ingested feeding volume was significantly larger in the group receiving cornstarch-thickened formula, both at 4 weeks (109.4 +/- 24.5 vs. 98.5 +/- 23.6 mL/meal) (P: 0.042) and at 8 weeks (137.6 +/- 27.9 vs. 115.7 +/- 26.5 mL/meal) (P < 0.001). Cornstarch-thickened formula feeding decreases the frequency of regurgitation/vomiting, provides better body weight gain and has an accelerated gastric emptying in comparison to a 25% strengthened regular formula in infants with regurgitation.", "nan", "Advantages of prethickened formulas (AR) with regards to esophageal pH and gastric emptying were investigated in this study as compared with a regular formula (R).\n Seventy-four healthy infants, <6 months old, with gastroesophageal reflux were enrolled into the study. All infants underwent 24-hour esophageal pH monitoring while receiving R and AR, alternately. Electrogastrography was measured before and after feeding each study formula. Thereafter, the infants were randomly assigned to receive either R or AR for 1 month. Episodes of regurgitation, vomiting, coughing, crying, and bowel movements were recorded on a weekly interval.\n Reflux index (RI) of AR-fed infants were lower (5.64%) than the R-fed infants (7.77%) showing a significant difference (P<0.01) between the 2 groups, favoring AR. Eighty-seven percent of infants improved their RI while receiving the AR formula. Electrogastrography variables were not significantly different between the 2 study groups. A significant decrease (P<0.01) in the daily episodes of regurgitation and vomiting was observed in the AR-fed infants. No adverse events were reported during the study.\n Prethickened infant formula was effective in reducing clinical symptoms of uncomplicated gastroesophageal reflux and reducing RI. Prethickened formulas do not alter gastric emptying time and was very well tolerated.", "To evaluate a pre-thickened formula (Enfamil AR) for regurgitant gastroesophageal reflux, 104 infants were enrolled in a 5-week, multicenter, double-blind, randomized, placebo-controlled parallel group trial. The Enfamil AR group showed greater symptom reduction by the end of the first week: percent feedings with any regurgitation (p = 0.045), total regurgitation volume score (p = 0.035), and percent feedings with choke-gag-cough (p = 0.004). The most symptomatic infants at baseline had a reduction in trouble sleeping significantly with Enfamil AR by the end of the study (p = 0.030). This formula flows through a standard nipple, reduces regurgitation and choking-gagging-coughing within a week, and improves sleep in the most symptomatic babies by 5 weeks, without causing constipation.", "To determine the efficacy of proton-pump inhibitor (PPI) therapy for chronic laryngo-pharyngitis treated with lifestyle modification.\n Double-blind, randomized trial comparing two-month Rabeprazole (20 mg b.i.d.) to placebo control.\n Compared to baseline, both PPI and control patients had significant improvement in total reflux symptoms (P = 0.002 and P = 0.03 respectively), with significant improvement in \"laryngo-pharyngeal\" but not \"typical\" reflux symptoms. No significant difference was noted for change in reflux symptoms between PPI-treated and control patients (P = 0.44). Significant global improvement was noted by 50% of control and 53% of PPI-treated patients (P = 1.0). No significant differences were noted within or between treatment groups for change in health status or videostrobolaryngoscopy grade. Lifestyle modification compliance correlated significantly with global improvement.\n Compared to baseline, lifestyle modification for 2 months significantly improved chronic laryngo-pharyngitis symptoms. When compared to control, treatment with a PPI failed to demonstrate significantly greater improvement in reflux symptoms, health status, or laryngeal appearance.", "Results of randomized treatment trials for laryngopharyngeal reflux (LPR) are mixed. The cause and effect between gastroesophageal reflux and laryngeal symptoms remain elusive.\n To determine the efficacy of single-dose pantoprazole in newly diagnosed LPR and to correlate hypopharyngeal reflux with symptom improvement.\n Randomized, double-blind, placebo-controlled trial was performed with a 2-wk run-in, 12-wk treatment period (pantoprazole 40 mg q.a.m. or placebo), and 4-wk follow-up. Study criteria were laryngeal complaints >3 days/wk and a positive triple-sensor pH test. Laryngeal exam was graded using a reflux finding score before and after treatment. Repeat pH test was performed on study drug at week 12. Weekly diaries were kept on symptom severity and global assessment. Total laryngeal symptom score was defined as the sum of six laryngeal symptoms. Mann-Whitney U, Wilcoxon, and Pearson tests were used.\n Thirty-nine subjects (13 M/26 F, median age 39 yr) were randomized; 35 completed the study. During the treatment period, total laryngeal symptom scores significantly improved compared with pretreatment scores in both study groups, but there were no significant differences between them. Forty percent of pantoprazole group reported adequate relief at week 12, compared with 42% of placebo group (p= 0.89). No significant improvement in hypopharyngeal reflux was found in either study group. There were no significant correlations between laryngeal reflux finding scores and hypopharyngeal reflux episodes with symptom improvement.\n Response was similar between single-dose pantoprazole and placebo in newly diagnosed LPR. Our results suggested that laryngeal exam was not useful in following treatment response. Hypopharyngeal reflux may represent acid reflux or artifacts, but is not likely the underlying cause.", "Proton-pump inhibitors are often recommended in the treatment of laryngitis secondary to gastric reflux. Despite prospective treatment studies reporting high efficacy, only one previous report has been placebo-controlled and blinded. The objective of this study was to determine the efficacy of omeprazole in treating proven reflux laryngitis.\n Prospective, placebo-controlled, randomized, double-blind clinical trial.\n Fifty-three patients with one or more reflux laryngitis symptoms were recruited to undergo 24-hour dual-channel pH probe testing. Thirty patients with more than four episodes of laryngopharyngeal reflux were enrolled. By random assignment, 15 patients received 40 mg omeprazole twice a day and the other 15 received placebo for a period of 2 months. Symptoms (hoarseness, throat pain, lump in throat sensation, throat clearing, cough, excessive phlegm, dysphagia, odynophagia, and heartburn) and endoscopic laryngeal signs (erythema, edema, and mucus accumulation) were recorded initially, at 1 month, and 2 months.\n In general, most symptom scores improved over time for both the omeprazole and placebo groups. Hoarseness, when patients begin with low hoarseness symptom scores, and throat clearing improved significantly more in patients on omeprazole than in those on placebo during the 2-month study. Throat pain, lump in throat sensation, excessive phlegm, difficulty swallowing, pain with swallowing, and heartburn showed improvement in both treatment arms, signifying the possibility of a placebo effect. Endoscopic laryngeal signs did not change significantly over the course of the study for either treatment group.\n A placebo effect appears to exist in the treatment of reflux laryngitis. However, hoarseness, when initially scored low, and throat clearing resulting from reflux laryngitis are effectively treated by omeprazole.", "The optimal management of patients with reflux-associated laryngitis is unclear. We performed a placebo-controlled crossover trial in patients with proven reflux disease and associated laryngitis to determine the effect of pantoprazole and to gain information on the natural course of the disease.\n Sixty-two consecutive non-smoking patients with hoarseness and proven laryngitis were examined. Scores with respect to the larynx and for subjective complaints were determined and 24-h pH-metry to assess acid reflux in the lower oesophagus and pharynx was performed. Patients with pathologic reflux were given the chance to enter a double-blinded randomized crossover trial with pantoprazole 40 mg b.i.d. and placebo for a duration of 3 months each, separated by a 2-week washout period.\n Twenty-four of 62 patients showed pathological reflux; 21 patients were included in the study and 14 concluded all parts of the study. Both pantoprazole and placebo resulted in a marked improvement in laryngitis scores (decrease of 8.0 +/- 1.4 versus 5.6 +/- 2.6; no significant difference between the 2 treatments) and symptoms after the first 3 months (decrease of oesophageal symptom score of 2.2 +/- 1.4 versus 5.4 +/- 2.8; decrease of laryngeal scores of 8.3 +/- 3.6 versus 10.3 +/- 3.9; also no significant difference between the 2 treatments). A second pH-metry 2 weeks thereafter proved the persistence of reflux in most of these patients. Switching to pantoprazole led to a further improvement of scores. In the group switched to placebo there was recurrence only in a minority of patients. CONCLUSIONs: The self-limited nature of reflux-associated laryngitis in non-smokers is largely underestimated. Laryngitis improves despite the persistence of reflux. Pantoprazole may be helpful especially in relieving acute symptoms, but the advantage of long-term treatment over placebo has been greatly overestimated.", "To assess the efficacy and safety of lansoprazole in treating infants with symptoms attributed to gastroesophageal reflux disease (GERD) that have persisted despite a >or= 1-week course of nonpharmacologic management.\n This multicenter, double-blind, parallel-group study randomized infants with persisting symptoms attributed to GERD to treatment with lansoprazole or placebo for 4 weeks. Symptoms were tracked through daily diaries and weekly visits. Efficacy was defined primarily by a >or= 50% reduction in measures of feeding-related crying and secondarily by changes in other symptoms and global assessments. Safety was assessed based on the occurrence of adverse events (AEs) and clinical/laboratory data.\n Of the 216 infants screened, 162 met the inclusion/exclusion criteria and were randomized. Of those, 44/81 infants (54%) in each group were responders--identical for lansoprazole and placebo. No significant lansoprazole-placebo differences were detected in any secondary measures or analyses of efficacy. During double-blind treatment, 62% of lansoprazole-treated subjects experienced 1 or more treatment-emergent AEs, versus 46% of placebo recipients (P= .058). Serious AEs (SAEs), particularly lower respiratory tract infections, occurred in 12 infants, significantly more frequently in the lansoprazole group compared with the placebo group (10 vs 2; P= .032).\n This study detected no difference in efficacy between lansoprazole and placebo for symptoms attributed to GERD in infants age 1 to 12 months. SAEs, particularly lower respiratory tract infections, occurred more frequently with lansoprazole than with placebo.", "Several studies have shown the relationship between gastro-oesophageal reflux, bronchial asthma and chronic nocturnal cough and this should not be neglected, particularly in patients who present an unfavourable development in spite of conventional treatment. For diagnosis of gastroesophageal reflux, amongst other investigations, esophageal gammagraphy of swallowing, that detects alterations in the mobility of the oesophagus, secondary to a possible oesophagitis. The objective of this study was to evaluate the clinical progress and gammagraphy of a group of children with chronic predominantly nocturnal cough (with or without bronchial asthma) with initially pathological esophageal gammagraphy, after three months of treatment with gastrokinetic drugs (cisapride against domperidone) and postural dietetic limits, in comparison with a reference group who, although having followed the limits in question had not received the pharmacological treatment. From the clinical viewpoint, cough disappeared in 64.5% of cases without significant statistical differences between the two groups. Gammagraphy became normal in 20/55 cases, improved in 10/55 cases and was unchanged in 25/55. Although there was no significant difference, gammagraphy development was better in children who received domperidone. The agreement between clinical progress and gammagraphy was 60% with a large number of false positives in the gammagraphy. We believe that the simple introduction of the postural-dietetic measures may improve the clinical control in the type of patients who present with a chronic nocturnally predominant cough that does not yield to conventional treatment.", "Recent studies suggest an association between chronic cough and gastroesophageal reflux. Our study aims were 1) to define the prevalence of acid reflux induced cough in the general community, 2) to examine the ability of esophageal testing to identify gastroesophageal reflux related cough, and 3) to assess the utility of omeprazole in a chronic cough algorithm.\n Patients with chronic cough of unknown etiology, who were mostly from the community, were evaluated. Subjects underwent a chest x-ray, methacholine challenge test, and empiric trial of postnasal drip therapy, and completed daily cough symptom diaries subjectively evaluating cough frequency and severity on a graded scale of 0-4 (combined maximum 8). After excluding other causes of cough, the remaining patients underwent esophageal and pH testing. Those testing positive were randomized to omeprazole 40 mg b.i.d. or placebo for 12 weeks. Follow-up was 1 yr.\n A total of 71 patients were screened; 48 were excluded. Twenty-three patients were evaluated for gastroesophageal reflux disease; six (26%) were eventually determined to have an acid-related cough. Of these patients, 17 had a positive pH test, six (35%) of whom showed a striking improvement or resolution of their cough during omeprazole treatment which was sustained for up to 1 yr. Six had a negative pH test, none of whom responded to omeprazole therapy. No significant differences were seen between responders (n = 6) and nonresponders (n = 11) for demographic factors, baseline symptom frequency and duration, or physiological parameters (motility/pH).\n Acid-related chronic cough was present in 26% (six of 23) of patients evaluated for gastroesophageal reflux disease. Esophageal testing does not reliably identify patients with acid induced chronic cough responsive to proton pump inhibitor therapy. We suggest that the best diagnostic and therapeutic approach, after excluding asthma and postnasal drip syndrome, is empiric treatment for 2 wk with a high dose proton pump inhibitor.", "Patients commonly present with complaints of postnasal drainage (PND) without objective evidence to support a sinonasal or infectious etiology. PND has been attributed to extra-esophageal reflux (EER), and an empiric trial of antireflux medication often is used to treat PND and associated symptoms. This study was performed to (1) evaluate the relationship between symptoms of EER and PND and (2) assess the efficacy of proton pump inhibitors (PPIs) in the management of PND.\n Patients with a chief complaint of PND without objective evidence of sinonasal inflammatory disease were enrolled in a prospective, double-blinded, randomized placebo-controlled trial using rabeprazole, 20 mg, orally twice daily or placebo for 90 days. Subjects completed two-site 24-hour pharyngeal pH probe monitoring before treatment. Outcome measures included pre- and posttreatment visual analog scales for PND symptoms, reflux symptom index, and reflux finding score (RFS).\n Forty-seven patients were enrolled (mean age, 55 years)-21 patients in the PPI group and 26 in the placebo group. Fifty-six percent of subjects had pH probe confirmed EER using a cutoff of pH < 5.0. Baseline symptom measures between subjects with and without EER were not different. Compared with placebo, subjects receiving rabeprazole reported significant reduction in PND frequency (p = 0.0180), hoarseness (p = 0.0164), and chronic cough (p = 0.0204). The RFS decreased slightly in the placebo group (p = 0.1490) whereas it increased slightly in the PPI group (p = 0.5235). This difference between groups was significant (p = 0.0272).\n Although 50% of subjects had evidence of EER, there was no difference in baseline symptoms between subjects with and without. Our findings support the potential benefit of PPI therapy for reducing PND frequency, hoarseness, and chronic cough, and confirm a placebo effect for other laryngopharyngeal reflux symptoms. The effect on laryngeal findings is mixed and patients may experience symptomatic improvement before changes in laryngoscopic appearance.", "To determine whether thickening of infant formula feedings with rice cereal increases coughing, we studied 25 infants from birth to 6 months of age, referred for evaluation of gastroesophageal reflux. Coughing was blindly quantified after each of a pair of isocaloric meals (one thickened and one unthickened). Coughing was more frequent after thickened feedings than after unthickened feedings.", "To evaluate the efficacy of acid-suppressive therapy with the proton pump inhibitor esomeprazole on the signs and symptoms of chronic posterior laryngitis (CPL) in patients with suspected reflux laryngitis.\n Prospective, multicenter, randomized, parallel-group trial that compared twice-daily esomeprazole 40 mg with placebo for 16 weeks.\n Eligible patients had a history of one or more CPL symptoms (throat clearing, cough, globus, sore throat, or hoarseness) and laryngoscopic signs indicating reflux laryngitis based on CPL index (CPLI) scores measured during a screening laryngoscopy. Patients were randomized to treatment if their 7-day screening diary-card recordings showed a cumulative primary symptom score of 9 or higher and they had 3 or more days with moderately severe symptoms based on a 7-point scale. Efficacy was assessed by changes in symptoms as recorded by patients and investigators and by changes in CPLI scores based on laryngoscopic examinations.\n The patients' primary CPL symptom at final visit (primary efficacy end point) was resolved in 14.7% (14/95) and 16.0% (8/50) of patients in the esomeprazole and placebo groups, respectively (P=.799). Esomeprazole and placebo were not significantly different for change from baseline to the final visit in mean total CPLI (-1.66+/-2.13 vs. -2.0+/-2.55, respectively; P=.446) or any other secondary efficacy end points based on patient diary card or investigator assessments.\n This study provides no evidence of a therapeutic benefit of treatment with esomeprazole 40 mg twice daily for 16 weeks compared with placebo for signs and symptoms associated with CPL." ]

[ "11451296", "7968073", "3782631", "2060433", "10438259", "12433762", "1630666", "4578364", "9822092", "8339551", "8801446", "9613910", "3313041", "12479764", "10880410", "7566020" ]

[ "Long-term risk stratification for survivors of acute coronary syndromes. Results from the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) Study. LIPID Study Investigators.", "Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)", "Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin.", "Diabetes Intervention Study. Multi-intervention trial in newly diagnosed NIDDM.", "Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group.", "Bezafibrate in men with lower extremity arterial disease: randomised controlled trial.", "[Progression of lesions of the arterial wall evaluated by ultrasonic biopsy in asymptomatic subjects and in diabetic and hyperlipidemic patients treated with bezafibrate. A 4-year follow-up].", "A cooperative trial on the primary prevention of ischaemic heart disease using clofibrate: design, methods, and progress.", "Treatment effects on serum lipoprotein lipids, apolipoproteins and low density lipoprotein particle size and relationships of lipoprotein variables to progression of coronary artery disease in the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT).", "Effect of cholesterol reduction by simvastatin on progression of coronary atherosclerosis: Design, baseline characteristics, and progress of the Multicenter Anti-Atheroma Study (MAAS).", "The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators.", "Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study.", "Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease.", "Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT).", "Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease.", "Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group." ]

[ "We developed a prognostic strategy for quantifying the long-term risk of coronary heart disease (CHD) events in survivors of acute coronary syndromes (ACS).\n Strategies for quantifying long-term risk of CHD events have generally been confined to primary prevention settings. The Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study, which demonstrated that pravastatin reduces CHD events in ACS survivors with a broad range of cholesterol levels, enabled assessment of long-term prognosis in a secondary prevention setting.\n Based on outcomes in 8,557 patients in the LIPID study, a multivariate risk factor model was developed for prediction of CHD death or nonfatal myocardial infarction. Prognostic indexes were developed based on the model, and low-, medium-, high- and very high-risk groups were defined by categorizing the prognostic indexes.\n In addition to pravastatin treatment, the independently significant risk factors included: total and high density lipoprotein cholesterol, age, gender, smoking status, qualifying ACS, prior coronary revascularization, diabetes mellitus, hypertension and prior stroke. Pravastatin reduced coronary event rates in each risk level, and the relative risk reduction did not vary significantly between risk levels. The predicted five-year coronary event rates ranged from 5% to 19% for those assigned pravastatin and from 6.4% to 23.6% for those assigned placebo.\n Long-term prognosis of ACS survivors varied substantially according to conventional risk factor profile. Pravastatin reduced coronary risk within all risk levels; however, absolute risk remained high in treated patients with unfavorable profiles. Our risk stratification strategy enables identification of ACS survivors who remain at very high risk despite statin therapy.", "Drug therapy for hypercholesterolaemia has remained controversial mainly because of insufficient clinical trial evidence for improved survival. The present trial was designed to evaluate the effect of cholesterol lowering with simvastatin on mortality and morbidity in patients with coronary heart disease (CHD). 4444 patients with angina pectoris or previous myocardial infarction and serum cholesterol 5.5-8.0 mmol/L on a lipid-lowering diet were randomised to double-blind treatment with simvastatin or placebo. Over the 5.4 years median follow-up period, simvastatin produced mean changes in total cholesterol, low-density-lipoprotein cholesterol, and high-density-lipoprotein cholesterol of -25%, -35%, and +8%, respectively, with few adverse effects. 256 patients (12%) in the placebo group died, compared with 182 (8%) in the simvastatin group. The relative risk of death in the simvastatin group was 0.70 (95% CI 0.58-0.85, p = 0.0003). The 6-year probabilities of survival in the placebo and simvastatin groups were 87.6% and 91.3%, respectively. There were 189 coronary deaths in the placebo group and 111 in the simvastatin group (relative risk 0.58, 95% CI 0.46-0.73), while noncardiovascular causes accounted for 49 and 46 deaths, respectively. 622 patients (28%) in the placebo group and 431 (19%) in the simvastatin group had one or more major coronary events. The relative risk was 0.66 (95% CI 0.59-0.75, p < 0.00001), and the respective probabilities of escaping such events were 70.5% and 79.6%. This risk was also significantly reduced in subgroups consisting of women and patients of both sexes aged 60 or more. Other benefits of treatment included a 37% reduction (p < 0.00001) in the risk of undergoing myocardial revascularisation procedures. This study shows that long-term treatment with simvastatin is safe and improves survival in CHD patients.", "The Coronary Drug Project was conducted between 1966 and 1975 to assess the long-term efficacy and safety of five lipid-influencing drugs in 8,341 men aged 30 to 64 years with electrocardiogram-documented previous myocardial infarction. The two estrogen regimens and dextrothyroxine were discontinued early because of adverse effects. No evidence of efficacy was found for the clofibrate treatment. Niacin treatment showed modest benefit in decreasing definite nonfatal recurrent myocardial infarction but did not decrease total mortality. With a mean follow-up of 15 years, nearly 9 years after termination of the trial, mortality from all causes in each of the drug groups, except for niacin, was similar to that in the placebo group. Mortality in the niacin group was 11% lower than in the placebo group (52.0 versus 58.2%; p = 0.0004). This late benefit of niacin, occurring after discontinuation of the drug, may be a result of a translation into a mortality benefit over subsequent years of the early favorable effect of niacin in decreasing nonfatal reinfarction or a result of the cholesterol-lowering effect of niacin, or both.", "In a randomized 5-yr multi-intervention trial, we tested the efficacy of intensified health education (IHE) in improving metabolic control and reducing the level of coronary risk factors and incidence of ischemic heart disease (IHD).\n Within the intervention group, the benefit of clofibric acid was evaluated in a double-blind study. One thousand one hundred thirty-nine newly diagnosed middle-aged (30- to 55-yr-old) patients with non-insulin-dependent diabetes mellitus (NIDDM) entered the study. They were classified as diet controlled after a 6-wk screening phase with conventional dietary treatment. During the follow-up, the control group (n = 378) was cared for at different diabetes outpatient clinics with a standardized surveillance. The intervention group (n = 761) had a structured IHE that included dietary advice, antismoking and antialcohol education, and ways to enhance physical activity.\n Randomly, 379 of the IHE patients received 1.6 g clofibric acid/day, and the others received placebo. IHE resulted in improved glucose control (adjusted fasting blood glucose) levels after 5 yr (control subjects 9.27 mM, IHE group 8.71 mM, and IHE plus clofibric acid group 8.60 mM, P less than 0.01). The better glycemic control was achieved with fewer antidiabetic drugs. After 5 yr, antidiabetic drugs were prescribed to 47% of the control subjects, 28% of the IHE group, and 34% of the IHE plus clofibric acid group (cutoff limit for drug application was postprandial blood glucose of greater than or equal to 13.87 mM). The ratio of polyunsaturated to saturated fatty acids (0.26 vs. 0.40, P less than 0.01) and physical activity (174 vs. 327 scores, P less than 0.01) were increased, and blood pressure, tobacco, and alcohol consumption were significantly reduced by IHE. However, IHE had no effect on calorie intake, percentage of fat in the diet (45%), and body weight. The most important finding was the significant increase of blood cholesterol in all three groups (+0.47, +0.36, and +0.34 mM, respectively). Clofibric acid only prevented the increase of triglyceride levels (+0.56, +0.24, and +0.05 mM, respectively). The incidence rate per 1000 for myocardial infarction was 30.3 for control subjects, 53.6 for the IHE group, and 55.6 for the IHE plus clofibric acid group. The corresponding rates for IHD incidence were 90.9, 97.8, and 98.8, respectively. Men suffered more frequently from myocardial infarction, whereas women developed ECG criteria for IHD more frequently. Among the 35 cases of death, besides cardiovascular diseases, liver cirrhosis and neoplasia were the predominant causes. The death rate per 1000 in control subjects was 46.2, 30.6 in the IHE group, and 27 among patients with IHE plus clofibric acid.\n IHE was of substantial benefit for the control of glycemia, significantly diminished the need for antidiabetic drugs, and reduced a cluster of risk factors but had no effect on the control of blood lipids. This could be one major reason for the failure of IHE, effective lowering of blood pressure, and clofibric acid to prevent cardiovascular complications. Clofibric acid was only effective in reducing triglycerides.", "Although it is generally accepted that lowering elevated serum levels of low-density lipoprotein (LDL) cholesterol in patients with coronary heart disease is beneficial, there are few data to guide decisions about therapy for patients whose primary lipid abnormality is a low level of high-density lipoprotein (HDL) cholesterol.\n We conducted a double-blind trial comparing gemfibrozil (1200 mg per day) with placebo in 2531 men with coronary heart disease, an HDL cholesterol level of 40 mg per deciliter (1.0 mmol per liter) or less, and an LDL cholesterol level of 140 mg per deciliter (3.6 mmol per liter) or less. The primary study outcome was nonfatal myocardial infarction or death from coronary causes.\n The median follow-up was 5.1 years. At one year, the mean HDL cholesterol level was 6 percent higher, the mean triglyceride level was 31 percent lower, and the mean total cholesterol level was 4 percent lower in the gemfibrozil group than in the placebo group. LDL cholesterol levels did not differ significantly between the groups. A primary event occurred in 275 of the 1267 patients assigned to placebo (21.7 percent) and in 219 of the 1264 patients assigned to gemfibrozil (17.3 percent). The overall reduction in the risk of an event was 4.4 percentage points, and the reduction in relative risk was 22 percent (95 percent confidence interval, 7 to 35 percent; P=0.006). We observed a 24 percent reduction in the combined outcome of death from coronary heart disease, nonfatal myocardial infarction, and stroke (P< 0.001). There were no significant differences in the rates of coronary revascularization, hospitalization for unstable angina, death from any cause, and cancer.\n Gemfibrozil therapy resulted in a significant reduction in the risk of major cardiovascular events in patients with coronary disease whose primary lipid abnormality was a low HDL cholesterol level. The findings suggest that the rate of coronary events is reduced by raising HDL cholesterol levels and lowering levels of triglycerides without lowering LDL cholesterol levels.", "To assess the effect of bezafibrate on the risk of coronary heart disease and stroke in men with lower extremity arterial disease.\n Double blind placebo controlled randomised trial.\n 85 general practices and nine hospital vascular clinics.\n 1568 men, mean age 68.2 years (range 35 to 92) at recruitment.\n Bezafibrate 400 mg daily (783 men) or placebo (785 men). Main outcome measures: Combination of coronary heart disease and of stroke. All coronary events, fatal and non-fatal coronary events separately, and strokes alone (secondary end points).\n Bezafibrate did not reduce the incidence of coronary heart disease and stroke. There were 150 and 160 events in the active and placebo groups respectively (relative risk 0.96, 95% confidence interval 0.76 to 1.21). There were 90 and 111 major coronary events in the active and placebo groups respectively (0.81, 0.60 to 1.08), of which 64 and 65 were fatal (0.95, 0.66 to 1.37) and 26 and 46 non-fatal (0.60, 0.36 to 0.99). Beneficial effects on non-fatal events were greatest in men aged <65 years at entry, in whom benefit was also seen for all coronary events (0.38, 0.20 to 0.72). There were no significant effects in older men. There were 60 strokes in those on active treatment and 49 in those on placebo (1.34, 0.80 to 2.01). There were 204 and 195 deaths from all causes in the two groups respectively (1.03, 0.83 to 1.26). Bezafibrate reduced the severity of intermittent claudication for up to three years.\n Bezafibrate has no effect on the incidence of coronary heart disease and of stroke combined but may reduce the incidence of non-fatal coronary events, particularly in those aged <65 years at entry, in whom all coronary events may also be reduced.", "Non-invasive arterial ultrasonic biopsy (UB) has been used to evaluate and follow-up arterial wall changes in four years in asymptomatic subjects, hyperlipidemics and diabetics. Both groups of patients were randomised in a treatment group (bezafibrate 400 mg daily) and in a control group. The rate of progression (ROP) into the next higher UB class was recorded by UB scans repeated every six months. In diabetics and hyperlipidemics the rate of progression (ROP, namely the percent of patients progressing to the next class) was significantly higher than the ROP in the asymptomatic subjects. However in the bezafibrate group the ROP was significantly lower than that observed in the controls. As each UB class corresponds to different levels of risks of occult coronary ischemia and cardiovascular events in the following four years, the reduction of ROP with bezafibrate was an important and positive achievement.", "The paper describes the design of, and the procedures used in a double blind randomized trial to determine whether the incidence of ischaemic heart disease can be lowered by the reduction of high and moderately high lipid levels in healthy men aged 30-59 years. The trial started in Edinburgh in 1965 and was extended to Prague and Budapest in 1966 and 1967. It is coordinated and controlled by a committee of investigators convened by the World Health Organization. The subjects were selected on the basis of a preliminary determination of serum cholesterol level. Half of the men in the upper third of the distribution of cholesterol values have been assigned at random to a treated group and take 1.6 g of clofibrate daily; the other half make up a control group and take identical capsules containing 300-350 mg of olive oil. A second control group, chosen at random from the lowest third of the cholesterol distribution, also receives the olive oil capsules. The study is designed to have a 90% chance of detecting, in the treated group, a reduction of one-third in the incidence of ischaemic heart disease if this should occur. The subjects are examined at the beginning of the trial, then at 6-month intervals for 2 years, and thereafter annually for at least 3 further years. The criteria of ischaemic heart disease are defined and the different control procedures are described. The required 15 000 subjects have now been admitted to the trial and their characteristics are described, but it is too early to report any results.", "To investigate the mechanisms by which bezafibrate retarded the progression of coronary lesions in the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT), we examined the relationships of on-trial lipoproteins and lipoprotein subfractions to the angiographic outcome measurements.\n BECAIT, the first double-blind, placebo-controlled, randomized serial angiographic trial of a fibrate compound, showed that progression of focal coronary atherosclerosis in young survivors of myocardial infarction could be retarded by bezafibrate treatment.\n A total of 92 dyslipoproteinemic men who had survived a first myocardial infarction before the age of 45 years were randomly assigned to treatment for 5 years with bezafibrate (200 mg three times daily) or placebo; 81 patients underwent baseline and at least one post-treatment coronary angiography.\n In addition to the decrease in very low density lipoprotein (VLDL) cholesterol (-53%) and triglyceride (-46%) and plasma apolipoprotein (apo) B (-9%) levels, bezafibrate treatment resulted in a significant increase in high density lipoprotein-3 (HDL3) cholesterol (+9%) level and a shift in the low density lipoprotein (LDL) subclass distribution toward larger particle species (peak particle diameter +032 nm). The on-trial HDL3 cholesterol and plasma apo B concentrations were found to be independent predictors of the changes in mean minimum lumen diameter (r=-0.23, p < 0.05), and percent (%) stenosis (r = 0.30, p < 0.01), respectively. Decreases in small dense LDL and/or VLDL lipid concentrations were unrelated to disease progression.\n Our results suggest that the effect of bezafibrate on progression of focal coronary atherosclerosis could be at least partly attributed to a rise in HDL3 cholesterol and a decrease in the total number of apo B-containing lipoproteins.", "The Multicenter Anti-Atheroma Study (MAAS) is a 2 + 2-year, placebo-controlled trial to evaluate the effect of simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme a (HMG-CoA) reductase inhibitor, on progression and regression of coronary atherosclerosis in patients with established coronary artery disease. This paper describes the aims, methodology, and baseline data. Patients with at least two coronary segments visibly involved with atherosclerosis, in whom an angiogram was carried out according to the standards required for quantitative analysis, were selected provided that the serum total cholesterol was between 5.5 and 8.0 mmol/L and fasting triglycerides were lower than 4 mmol/L. Between march 1988 and October 1989, 383 eligible patients of both sexes aged 30-67 years were randomized in 11 European clinics. Patients received either 20 mg oral simvastatin or placebo daily for 2 years in addition to dietary counseling. The primary outcome measures are the change in the mean absolute width and in the mean of the minimal width of segments analyzed quantitatively by coronary angiography performed before and after 2 and 4 years of trial medication. To this end, at least 5 coronary artery segments are analyzed in each angiogram using matched view. The 2-year analysis was completed on 89% of eligible patients in February 1992. The trial was initially designed with a 2-year treatment period. To allow for the possibility to extend this, the decision was taken to keep all patients on the original medication allocation until all 2-year angiograms had been analyzed. Based on a predefined decision rule, an independent committee then recommended extension of treatment with another 2 years, to be concluded by a third angiogram. Of the patients enrolled initially, 81% continued. Four-year follow-up will be completed late 1993 and final results are expected mid 1994.", "In patients with high cholesterol levels, lowering the cholesterol level reduces the risk of coronary events, but the effect of lowering cholesterol levels in the majority of patients with coronary disease, who have average levels, is less clear.\n In a double-blind trial lasting five years we administered either 40 mg of pravastatin per day or placebo to 4159 patients (3583 men and 576 women) with myocardial infarction who had plasma total cholesterol levels below 240 mg per deciliter (mean, 209) and low-density lipoprotein (LDL) cholesterol levels of 115 to 174 mg per deciliter (mean, 139). The primary end point was a fatal coronary event or a nonfatal myocardial infarction.\n The frequency of the primary end point was 10.2 percent in the pravastatin group and 13.2 percent in the placebo group, an absolute difference of 3 percentage points and a 24 percent reduction in risk (95 percent confidence interval, 9 to 36 percent; P = 0.003). Coronary bypass surgery was needed in 7.5 percent of the patients in the pravastatin group and 10 percent of those in the placebo group, a 26 percent reduction (P=0.005), and coronary angioplasty was needed in 8.3 percent of the pravastatin group and 10.5 percent of the placebo group, a 23 percent reduction (P=0.01). The frequency of stroke was reduced by 31 percent (P=0.03). There were no significant differences in overall mortality or mortality from noncardiovascular causes. Pravastatin lowered the rate of coronary events more among women than among men. The reduction in coronary events was also greater in patients with higher pretreatment levels of LDL cholesterol.\n These results demonstrate that the benefit of cholesterol-lowering therapy extends to the majority of patients with coronary disease who have average cholesterol levels.", "Although cholesterol-reducing treatment has been shown to reduce fatal and nonfatal coronary disease in patients with coronary heart disease (CHD), it is unknown whether benefit from the reduction of low-density lipoprotein cholesterol (LDL-C) in patients without CHD extends to individuals with average serum cholesterol levels, women, and older persons.\n To compare lovastatin with placebo for prevention of the first acute major coronary event in men and women without clinically evident atherosclerotic cardiovascular disease with average total cholesterol (TC) and LDL-C levels and below-average high-density lipoprotein cholesterol (HDL-C) levels.\n A randomized, double-blind, placebo-controlled trial.\n Outpatient clinics in Texas.\n A total of 5608 men and 997 women with average TC and LDL-C and below-average HDL-C (as characterized by lipid percentiles for an age- and sex-matched cohort without cardiovascular disease from the National Health and Nutrition Examination Survey [NHANES] III). Mean (SD) TC level was 5.71 (0.54) mmol/L (221 [21] mg/dL) (51 st percentile), mean (SD) LDL-C level was 3.89 (0.43) mmol/L (150 [17] mg/dL) (60th percentile), mean (SD) HDL-C level was 0.94 (0.14) mmol/L (36 [5] mg/dL) for men and 1.03 (0.14) mmol/L (40 [5] mg/dL) for women (25th and 16th percentiles, respectively), and median (SD) triglyceride levels were 1.78 (0.86) mmol/L (158 [76] mg/dL) (63rd percentile).\n Lovastatin (20-40 mg daily) or placebo in addition to a low-saturated fat, low-cholesterol diet.\n First acute major coronary event defined as fatal or nonfatal myocardial infarction, unstable angina, or sudden cardiac death.\n After an average follow-up of 5.2 years, lovastatin reduced the incidence of first acute major coronary events (1 83 vs 116 first events; relative risk [RR], 0.63; 95% confidence interval [CI], 0.50-0.79; P<.001), myocardial infarction (95 vs 57 myocardial infarctions; RR, 0.60; 95% CI, 0.43-0.83; P=.002), unstable angina (87 vs 60 first unstable angina events; RR, 0.68; 95% CI, 0.49-0.95; P=.02), coronary revascularization procedures (157 vs 106 procedures; RR, 0.67; 95% CI, 0.52-0.85; P=.001), coronary events (215 vs 163 coronary events; RR, 0.75; 95% CI, 0.61-0.92; P =.006), and cardiovascular events (255 vs 194 cardiovascular events; RR, 0.75; 95% CI, 0.62-0.91; P = .003). Lovastatin (20-40 mg daily) reduced LDL-C by 25% to 2.96 mmol/L (115 mg/dL) and increased HDL-C by 6% to 1.02 mmol/L (39 mg/dL). There were no clinically relevant differences in safety parameters between treatment groups.\n Lovastatin reduces the risk for the first acute major coronary event in men and women with average TC and LDL-C levels and below-average HDL-C levels. These findings support the inclusion of HDL-C in risk-factor assessment, confirm the benefit of LDL-C reduction to a target goal, and suggest the need for reassessment of the National Cholesterol Education Program guidelines regarding pharmacological intervention.", "In a randomized, double-blind five-year trial, we tested the efficacy of simultaneously elevating serum levels of high-density lipoprotein (HDL) cholesterol and lowering levels of non-HDL cholesterol with gemfibrozil in reducing the risk of coronary heart disease in 4081 asymptomatic middle-aged men (40 to 55 years of age) with primary dyslipidemia (non-HDL cholesterol greater than or equal to 200 mg per deciliter [5.2 mmol per liter] in two consecutive pretreatment measurements). One group (2051 men) received 600 mg of gemfibrozil twice daily, and the other (2030 men) received placebo. Gemfibrozil caused a marked increase in HDL cholesterol and persistent reductions in serum levels of total, low-density lipoprotein (LDL), and non-HDL cholesterol and triglycerides. There were minimal changes in serum lipid levels in the placebo group. The cumulative rate of cardiac end points at five years was 27.3 per 1,000 in the gemfibrozil group and 41.4 per 1,000 in the placebo group--a reduction of 34.0 percent in the incidence of coronary heart disease (95 percent confidence interval, 8.2 to 52.6; P less than 0.02; two-tailed test). The decline in incidence in the gemfibrozil group became evident in the second year and continued throughout the study. There was no difference between the groups in the total death rate, nor did the treatment influence the cancer rates. The results are in accord with two previous trials with different pharmacologic agents and indicate that modification of lipoprotein levels with gemfibrozil reduces the incidence of coronary heart disease in men with dyslipidemia.", "Studies have demonstrated that statins administered to individuals with risk factors for coronary heart disease (CHD) reduce CHD events. However, many of these studies were too small to assess all-cause mortality or outcomes in important subgroups.\n To determine whether pravastatin compared with usual care reduces all-cause mortality in older, moderately hypercholesterolemic, hypertensive participants with at least 1 additional CHD risk factor.\n Multicenter (513 primarily community-based North American clinical centers), randomized, nonblinded trial conducted from 1994 through March 2002 in a subset of participants from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).\n Ambulatory persons (n = 10 355), aged 55 years or older, with low-density lipoprotein cholesterol (LDL-C) of 120 to 189 mg/dL (100 to 129 mg/dL if known CHD) and triglycerides lower than 350 mg/dL, were randomized to pravastatin (n = 5170) or to usual care (n = 5185). Baseline mean total cholesterol was 224 mg/dL; LDL-C, 146 mg/dL; high-density lipoprotein cholesterol, 48 mg/dL; and triglycerides, 152 mg/dL. Mean age was 66 years, 49% were women, 38% black and 23% Hispanic, 14% had a history of CHD, and 35% had type 2 diabetes.\n Pravastatin, 40 mg/d, vs usual care.\n The primary outcome was all-cause mortality, with follow-up for up to 8 years. Secondary outcomes included nonfatal myocardial infarction or fatal CHD (CHD events) combined, cause-specific mortality, and cancer.\n Mean follow-up was 4.8 years. During the trial, 32% of usual care participants with and 29% without CHD started taking lipid-lowering drugs. At year 4, total cholesterol levels were reduced by 17% with pravastatin vs 8% with usual care; among the random sample who had LDL-C levels assessed, levels were reduced by 28% with pravastatin vs 11% with usual care. All-cause mortality was similar for the 2 groups (relative risk [RR], 0.99; 95% confidence interval [CI], 0.89-1.11; P =.88), with 6-year mortality rates of 14.9% for pravastatin vs 15.3% with usual care. CHD event rates were not significantly different between the groups (RR, 0.91; 95% CI, 0.79-1.04; P =.16), with 6-year CHD event rates of 9.3% for pravastatin and 10.4% for usual care.\n Pravastatin did not reduce either all-cause mortality or CHD significantly when compared with usual care in older participants with well-controlled hypertension and moderately elevated LDL-C. The results may be due to the modest differential in total cholesterol (9.6%) and LDL-C (16.7%) between pravastatin and usual care compared with prior statin trials supporting cardiovascular disease prevention.", "Coronary heart disease patients with low high-density lipoprotein cholesterol (HDL-C) levels, high triglyceride levels, or both are at an increased risk of cardiovascular events, but the clinical impact of raising HDL-C or decreasing triglycerides remains to be confirmed.\n In a double-blind trial, 3090 patients with a previous myocardial infarction or stable angina, total cholesterol of 180 to 250 mg/dL, HDL-C < or =45 mg/dL, triglycerides < or =300 mg/dL, and low-density lipoprotein cholesterol < or =180 mg/dL were randomized to receive either 400 mg of bezafibrate per day or a placebo; they were followed for a mean of 6.2 years. The primary end point was fatal or nonfatal myocardial infarction or sudden death. Bezafibrate increased HDL-C by 18% and reduced triglycerides by 21%. The frequency of the primary end point was 13. 6% on bezafibrate versus 15.0% on placebo (P=0.26). After 6.2 years, the reduction in the cumulative probability of the primary end point was 7.3%, (P=0.24). In a post hoc analysis in the subgroup with high baseline triglycerides (> or =200 mg/dL), the reduction in the cumulative probability of the primary end point by bezafibrate was 39.5% (P=0.02). Total and noncardiac mortality rates were similar, and adverse events and cancer were equally distributed.\n Bezafibrate was safe and effective in elevating HDL-C levels and lowering triglycerides. An overall trend in a reduction of the incidence of primary end points was observed. The reduction in the primary end point in patients with high baseline triglycerides (> or =200 mg/dL) requires further confirmation.", "Lowering the blood cholesterol level may reduce the risk of coronary heart disease. This double-blind study was designed to determine whether the administration of pravastatin to men with hypercholesterolemia and no history of myocardial infarction reduced the combined incidence of nonfatal myocardial infarction and death from coronary heart disease.\n We randomly assigned 6595 men, 45 to 64 years of age, with a mean (+/- SD) plasma cholesterol level of 272 +/- 23 mg per deciliter (7.0 +/- 0.6 mmol per liter) to receive pravastatin (40 mg each evening) or placebo. The average follow-up period was 4.9 years. Medical records, electrocardiographic recordings, and the national death registry were used to determine the clinical end points.\n Pravastatin lowered plasma cholesterol levels by 20 percent and low-density-lipoprotein cholesterol levels by 26 percent, whereas there was no change with placebo. There were 248 definite coronary events (specified as nonfatal myocardial infarction or death from coronary heart disease) in the placebo group, and 174 in the pravastatin group (relative reduction in risk with pravastatin, 31 percent; 95 percent confidence interval, 17 to 43 percent; P < 0.001). There were similar reductions in the risk of definite nonfatal myocardial infarctions (31 percent reduction, P < 0.001), death from coronary heart disease (definite cases alone: 28 percent reduction, P = 0.13; definite plus suspected cases: 33 percent reduction, P = 0.042), and death from all cardiovascular causes (32 percent reduction, P = 0.033). There was no excess of deaths from noncardiovascular causes in the pravastatin group. We observed a 22 percent reduction in the risk of death from any cause in the pravastatin group (95 percent confidence interval, 0 to 40 percent; P = 0.051).\n Treatment with pravastatin significantly reduced the incidence of myocardial infarction and death from cardiovascular causes without adversely affecting the risk of death from noncardiovascular causes in men with moderate hypercholesterolemia and no history of myocardial infarction." ]

[ "16946694", "16953381", "12860772" ]

[ "The efficacy and safety of lower doses of aripiprazole for the treatment of patients with acute exacerbation of schizophrenia.", "Intramuscular aripiprazole for the treatment of acute agitation in patients with schizophrenia or schizoaffective disorder: a double-blind, placebo-controlled comparison with intramuscular haloperidol.", "Aripiprazole, an antipsychotic with a novel mechanism of action, and risperidone vs placebo in patients with schizophrenia and schizoaffective disorder." ]

[ "Efficacy and safety of aripiprazole administered at doses lower than those previously studied systematically were investigated in patients with acute exacerbation of schizophrenia.\n In this double-blind, multicenter study, 367 patients requiring inpatient hospitalization for acute relapse of schizophrenia were randomized to one of three fixed doses of aripiprazole (2, 5, or 10 mg/day) or placebo for 6 weeks. Efficacy and safety parameters were assessed weekly. Primary outcome measure was mean change from baseline in Positive and Negative Syndrome Scale (PANSS) Total score at endpoint.\n Aripiprazole 10 mg/day produced statistically significantly greater improvements from baseline compared with placebo for PANSS Total at endpoint (-11.3 vs -5.3; P=.03) and at weeks 2-5. Aripiprazole 5 mg/day did not produce significantly greater improvement in PANSS Total compared with placebo at endpoint, although significant differences were seen at weeks 3-5. No statistically significant improvements compared with placebo were achieved with aripiprazole 2 mg/day at any time points. All aripiprazole doses were well tolerated. Aripiprazole was not associated with significant extrapyramidal symptoms.\n While aripiprazole 5 mg/day warrants further study, the 10 mg/day dose provides effective and well-tolerated therapy for management of acute psychosis in patients with schizophrenia.", "This double-blind, placebo-controlled study investigated the efficacy and safety of intramuscular (IM) aripiprazole and IM haloperidol for the treatment of acute agitation in patients with schizophrenia or schizoaffective disorder.\n Four-hundred and forty-eight patients were randomized (2:2:1 ratio) to IM aripiprazole 9.75 mg, IM haloperidol 6.5 mg, or IM placebo. Patients could receive up to three injections over the first 24 h, with second and third injections administered > or =2 and > or =4 h, respectively, after the first if deemed clinically necessary. Primary efficacy measure was mean change in Positive and Negative Syndrome Scale Excited Component (PEC) score from baseline to 2 h.\n Mean improvement in PEC at 2 h was significantly greater for IM aripiprazole (-7.27) vs placebo (-4.78; p<0.001); IM aripiprazole was noninferior to IM haloperidol (-7.75) on PEC. All secondary efficacy measures showed significantly greater improvements at 2 h for IM aripiprazole and IM haloperidol over placebo. Mean number of injections/patient and percentage of patients requiring benzodiazepines were significantly lower for IM aripiprazole vs placebo (p<0.01). IM aripiprazole was well tolerated. Extrapyramidal symptom-related adverse events were similar for aripiprazole (1.7%) and placebo (2.3%) and lower than with haloperidol (12.6%).\n These results show that IM aripiprazole is an effective treatment, comparable to IM haloperidol, and well-tolerated for acute agitation in patients with schizophrenia.", "Aripiprazole is a dopamine D2 receptor partial agonist with partial agonist activity at serotonin 5HT1A receptors and antagonist activity at 5HT2A receptors. This multicenter trial examined the efficacy, safety, and tolerability of aripiprazole in patients with acute exacerbation of schizophrenia or schizoaffective disorder.\n In this 4-week double-blind study, 404 patients were randomized to 20 mg/d (n = 101) or 30 mg/d (n = 101) of aripiprazole, placebo (n = 103), or 6 mg/d of risperidone (n = 99). Efficacy assessments included Positive and Negative Syndrome Scale (PANSS) scores and Clinical Global Impression scores. Safety and tolerability evaluations included extrapyramidal symptoms and effects on weight, prolactin, and corrected QT (QTc) interval.\n Aripiprazole (20 and 30 mg/d) and risperidone (6 mg/d) were significantly better than placebo on all efficacy measures. Separation from placebo occurred at week 1 for PANSS total and positive scores with aripiprazole and risperidone and for PANSS negative scores with aripiprazole. There were no significant differences between aripiprazole and placebo in mean change from baseline in the extrapyramidal symptom rating scales. Mean prolactin levels decreased with aripiprazole but significantly increased 5-fold with risperidone. Mean change in QTc interval did not differ significantly from placebo with any active treatment group. Aripiprazole and risperidone groups showed a similar low incidence of clinically significant weight gain.\n Aripiprazole is effective, safe, and well tolerated for the positive and negative symptoms in schizophrenia and schizoaffective disorder. It is the first non-D2 receptor antagonist with clear antipsychotic effects and represents a novel treatment development for psychotic disorders." ]

[ "21783053", "16539572" ]

[ "A clinic-based motivational intervention improves condom use among subgroups of youth living with HIV.", "Healthy choices: motivational enhancement therapy for health risk behaviors in HIV-positive youth." ]

[ "More than 50% of youth living with HIV (YLH) have unprotected sex. In previous studies, we reported effects of a motivational interviewing-based multirisk reduction intervention, \"Healthy Choices\" in improving motivation, depression, and viral load in YLH. In this study, we report the effect of the intervention on increasing condom use.\n Six waves of longitudinal data (n = 142) across a period from baseline through 15 months postintervention were analyzed. The developmental trajectory modeling method was used for program effect evaluation.\n The three groups detected with distinct sexual risks were: Persistent low sexual risk (PLSR), delayed high sexual risk, and high and growing sexual risk with regard to levels and time trajectories of condom use throughout the trial. Receiving Healthy Choices increased the likelihood to be in the PLSR group (63% vs. 32%, p < .01) and reduced the likelihood to be in the delayed high sexual risk group (16% vs. 50%, p < .05). Receiving the intervention was also associated with progressive reductions in no-condom sex for PLSR youth (adjusted β = -.325, p < .01) and high and growing sexual risk youth (adjusted β = -.364, p < .01).\n The motivational interviewing-based program Healthy Choices, when delivered in clinic settings, can prevent unprotected sex in subgroups of YLH, although more intensive interventions may be needed to change risk trajectories among those at highest risk of transmitting the AIDS virus. Developmental trajectory analysis provides an alternative approach to evaluate program effects for study samples that contain distinct subgroups.\n Copyright © 2011 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.", "This study piloted a brief individual motivational intervention targeting multiple health risk behaviors in HIV-positive youth aged 16-25. Interviews about sexual behavior and substance use and viral load testing were obtained from 51 HIV-positive youth at baseline and post intervention. Youth were randomized to receive a four-session motivational enhancement intervention (N = 25) or to a wait-list control (N = 26). Of the eligible youth approached, 88% agreed to participate, and 80% percent of participants completed at least three of four sessions. The treatment group showed significantly greater reductions in unprotected sex acts and in viral load compared with controls. Although change scores for substance use were not significantly different between the two groups, paired t tests demonstrated that reductions in alcohol use and marijuana use were significant for the treatment group at the trend level. There were no significant differences in substance use from baseline to posttest for the control group. Findings demonstrate the potential of a brief motivational enhancement intervention to improve health risk behaviors in HIV-positive youth. Larger randomized clinical trials are warranted. Resources required for retention should not be underestimated." ]

[ "12454841", "15349901", "12612902", "8878773", "10841872" ]

[ "Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis.", "Randomized controlled study of TIPS versus paracentesis plus albumin in cirrhosis with severe ascites.", "The North American Study for the Treatment of Refractory Ascites.", "Transjugular intrahepatic portosystemic shunts: comparison with paracentesis in patients with cirrhosis and refractory ascites: a randomized trial. French Group of Clinicians and a Group of Biologists.", "A comparison of paracentesis and transjugular intrahepatic portosystemic shunting in patients with ascites." ]

[ "The transjugular intrahepatic portosystemic shunt (TIPS) has been shown to be more effective than repeated paracentesis plus albumin in the control of refractory ascites. However, its effect on survival and healthcare costs is still uncertain.\n Seventy patients with cirrhosis and refractory ascites were randomly assigned to TIPS (35 patients) or repeated paracentesis plus intravenous albumin (35 patients). The primary endpoint was survival without liver transplantation. Secondary endpoints were complications of cirrhosis and costs.\n Twenty patients treated with TIPS and 18 treated with paracentesis died during the study period, whereas 7 patients in each group underwent liver transplantation (mean follow-up 282 +/- 43 vs. 325 +/- 61 days, respectively). The probability of survival without liver transplantation was 41% at 1 year and 26% at 2 years in the TIPS group, as compared with 35% and 30% in the paracentesis group (P = 0.51). In a multivariate analysis, only baseline blood urea nitrogen levels and Child-Pugh score were independently associated with survival. Recurrence of ascites and development of hepatorenal syndrome were lower in the TIPS group compared with the paracentesis group, whereas the frequency of severe hepatic encephalopathy was greater in the TIPS group. The calculated costs were higher in the TIPS group than in the paracentesis group.\n In patients with refractory ascites, TIPS lowers the rate of ascites recurrence and the risk of developing hepatorenal syndrome. However, TIPS does not improve survival and is associated with an increased frequency of severe encephalopathy and higher costs compared with repeated paracentesis plus albumin.", "The transjugular intrahepatic portosystemic shunt (TIPS) has been shown to be effective in the control of refractory or recidivant ascites. However, the effect of TIPS on survival as compared with that of large-volume paracentesis plus albumin is uncertain. A multicenter, prospective, clinical trial was performed in 66 patients with cirrhosis and refractory or recidivant ascites (16 Child-Turcotte-Pugh class B and 50 Child-Turcotte-Pugh class C) randomly assigned to treatment with TIPS (n = 33) or with large-volume paracentesis plus human albumin (n = 33). The primary endpoint was survival without liver transplantation. Secondary endpoints were treatment failure, rehospitalization, and occurrence of complications. Thirteen patients treated with TIPS and 20 patients treated with paracentesis died during the study period, 4 patients in each group underwent liver transplantation. The probability of survival without transplantation was 77% at 1 year and 59% at 2 years in the TIPS group as compared with 52% and 29% in the paracentesis group (P = .021). In a multivariate analysis, treatment with paracentesis and higher MELD score showed to independently predict death. Treatment failure was more frequent in patients assigned to paracentesis, whereas severe episodes of hepatic encephalopathy occurred more frequently in patients assigned to TIPS. The number and duration of rehospitalizations were similar in the two groups. In conclusion, compared to large-volume paracentesis plus albumin, TIPS improves survival without liver transplantation in patients with refractory or recidivant ascites.\n Copyright 2004 American Association for the Study of Liver Diseases", "The clinical utility of transjugular intrahepatic portosystemic shunts (TIPS) vis-à-vis total paracentesis in the management of refractory ascites is unclear.\n A multicenter, prospective, randomized clinical trial was performed in which 109 subjects with refractory ascites were randomized to either medical therapy (sodium restriction, diuretics, and total paracentesis) (n = 57) or medical therapy plus TIPS (n = 52). The principal end points were recurrence of tense symptomatic ascites and mortality.\n A technically adequate shunt was created in 49 of 52 subjects. TIPS plus medical therapy was significantly superior to medical therapy alone in preventing recurrence of ascites (P < 0.001). The total number of deaths in the 2 groups was identical (TIPS vs. medical therapy alone: 21 vs. 21). There were no significant differences in the 2 arms with respect to overall and transplant-free survival. There was a higher incidence of moderate to severe encephalopathy in the TIPS group (20 of 52 vs. 12 of 57; P = 0.058). There were no significant differences in the number of subjects who developed liver failure (7 vs. 3), variceal hemorrhage (5 vs. 8), or acute renal failure (3 vs. 2). There were also no significant differences between the 2 groups in the frequency of emergency-department visits, medically indicated hospitalizations, or quality of life.\n Although TIPS plus medical therapy is superior to medical therapy alone for the control of ascites, it does not improve survival, affect hospitalization rates, or improve quality of life.", "Transjugular intrahepatic portosystemic shunts reduce portal pressure and can control ascites in patients with cirrhosis. We carried out a controlled study to evaluate this procedure for the management of refractory ascites in patients with cirrhosis and to clarify its mechanism of action.\n Twenty-five patients with refractory ascites were included in the trial; 13 were randomly assigned to shunts and 12 to paracentesis. Four patients in each group were Child-Pugh class C and the others were class B. Follow-up ranged from 9 to 34 months. Hemodynamic values, liver and renal tests and neurohumoral factors were measured before and at 4 months after inclusion.\n Shunts were successfully placed in 10 out of 13 patients. At 4 months, ascites had improved in all class B patients in the shunt group and in none of the patients in the paracentesis group (p < 0.05); ascites did not improve in any of the class C patients in either of the groups. At 2 years, the overall survival rate was 29 +/- 13% (mean +/- SE) in the shunt group and 56 +/- 17% in the paracentesis group (p < 0.05). In class B patients, there was no significant difference in mortality. At 4 months, portal pressure was significantly lower than before the shunt, while plasma levels of atrial natriuretic peptide were significantly higher and plasma levels of renin and norepinephrine significantly lower.\n In this trial, intrahepatic shunts were effective on refractory ascites in patients with cirrhosis. However, the overall survival rate was lower in shunted patients than in those treated with paracentesis. The efficacy of intrahepatic shunts on ascites was only observed in class B patients. Survival did not improve in class B patients, and decreased in class C patients compared to paracentesis. The efficacy of shunts on ascites might be due to neurohumoral factors which control natriuresis and depend on hepatic sinusoidal pressure.", "In patients with cirrhosis and ascites, creation of a transjugular intrahepatic portosystemic shunt may reduce the ascites and improve renal function. However, the benefit of this procedure as compared with that of large-volume paracentesis is uncertain.\n We randomly assigned 60 patients with cirrhosis and refractory or recurrent ascites (Child-Pugh class B in 42 patients and class C in 18 patients) to treatment with a transjugular shunt (29 patients) or large-volume paracentesis (31 patients). The mean (+/-SD) duration of follow-up was 45+/-16 months among those assigned to shunting and 44+/-18 months among those assigned to paracentesis. The primary outcome was survival without liver transplantation.\n Among the patients in the shunt group, 15 died and 1 underwent liver transplantation during the study period, as compared with 23 patients and 2 patients, respectively, in the paracentesis group. The probability of survival without liver transplantation was 69 percent at one year and 58 percent at two years in the shunt group, as compared with 52 percent and 32 percent in the paracentesis group (P=0.11 for the overall comparison, by the log-rank test). In a multivariate analysis, treatment with transjugular shunting was independently associated with survival without the need for transplantation (P=0.02). At three months, 61 percent of the patients in the shunt group and 18 percent of those in the paracentesis group had no ascites (P=0.006). The frequency of hepatic encephalopathy was similar in the two groups. Of the patients assigned to paracentesis in whom this procedure was unsuccessful, 10 received a transjugular shunt a mean of 5.5+/-4 months after randomization; 4 had a response to this rescue treatment.\n In comparison with large-volume paracentesis, the creation of a transjugular intrahepatic portosystemic shunt can improve the chance of survival without liver transplantation in patients with refractory or recurrent ascites." ]

[ "18434929", "16788419" ]

[ "Lateral attic reconstruction technique: preventive surgery for epitympanic retraction pockets.", "Cartilage tympanoplasty for management of tympanic membrane atelectasis: is ventilatory tube necessary?" ]

[ "To provide an estimate of the reliability of a preventive surgical approach named lateral attic reconstruction (LAR) technique for the treatment of Type II epitympanic retraction pockets.\n From a cohort of 25 adult patients presenting with a Type II epitympanic retraction pocket, 2 groups were randomly formed: a first one, with 15 patients who underwent LAR technique, and a second one, in whom (10 patients) only observation was planned and was therefore used as control.\n University hospital as tertiary referral center.\n Selection criteria for composing the 2 groups of study were the presence of a Type II epitympanic retraction pocket and a normal audiogram.\n The surgical procedure (LAR) consisted of a retroauricular approach, removal of a small piece of tragal cartilage, cleansing of the epitympanic pocket until denudation of the ossicular components, and placement of the cartilage graft to reconstruct the lateral epitympanic wall.\n All the patients were controlled at different postoperative or postobservation times (1, 3, 6, and 12 mo) via otomicroscopic examination, pure-tone audiometry, and tympanometry.\n All operated patients showed a normal anatomic pattern starting from the first postoperative control (1 mo) with a normal or near-normal hearing threshold and a Type A or As tympanogram in most cases.\n Lateral attic reconstruction technique has proved to be a reliable preventive technique for impeding a Type II epitympanic retraction pocket to worsen because it was observed in a percentage, although small (33.3%), of patients in whom a wait-and-scope policy was applied.", "Cartilage/perichondrium composite graft with concomitant placement of a ventilation tube is a common practice among otologists to reverse atelectasis and to repneumatize the middle ear. We conducted this study to investigate the necessity of a ventilation tube primarily incorporated into the perichondrium/cartilage graft for reconstruction of the atelectatic tympanic membrane (TM).\n Prospective clinical trial.\n Forty-six patients with TM atelectasis and intact ossicular chain were randomized to 2 groups. In Group I, 23 patients underwent reconstruction of the TM with perichondrium/cartilage graft and intraoperative T-tube insertion and in Group II, 23 patients underwent reconstruction of the TM with perichondrium/cartilage graft without ventilation tube insertion. Outcome measures were as follows: graft success, improvement of hearing, and postoperative complications. Analysis of the results was performed by Student's paired t test. The level of significance was set at 5%.\n Significant postoperative improvement of pure-tone air-conduction threshold averages and air-bone gap averages were reported in the 2 studied groups (p < 0.001). The postoperative air-bone gap averages showed no statistically significant difference between Groups I and II (p > 0.05). Conductive hearing loss requiring revision developed in 2 patients (8.69%) in Group I and in 3 patients (13%) in Group II.\n In the atelectatic ear, cartilage allowed reconstruction of the TM with good anatomical and functional results. Primary insertion of a ventilation tube into the graft is not necessary." ]

[ "11874395", "9148024", "9365428", "669832", "16317692", "7469632", "7779462", "8344093", "10719014", "14747807", "3280388", "15795719", "10425820", "9537445", "15362593", "11145772", "6492228", "12424720", "54634", "12811710", "6134626", "22454960", "12601369", "61500", "6165632", "1983801", "7469629", "10584587", "8135427", "3998201", "10783405", "2888073", "10736123", "12619021", "8733517", "1972496", "59181", "1102398", "16248859", "623980", "2076744", "8666322", "3345017", "2569851", "8020810", "11762668", "1928874", "10606832" ]

[ "Activated charcoal alone or after gastric lavage: a simulated large paracetamol intoxication.", "Early indicators of prognosis in fulminant hepatic failure: an assessment of the King's criteria.", "Efficacy of ipecac during the first hour after drug ingestion in human volunteers.", "Experiences in the treatment of fulminant hepatic failure by conservative therapy, charcoal haemoperfusion, and polyacrylonitrile haemodialysis.", "Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study.", "Treatment of acetaminophen poisoning. The use of oral methionine.", "Cimetidine as adjunctive treatment for acetaminophen overdose.", "Effects of PEG-electrolyte (Colyte) lavage on serum acetaminophen concentrations. A model for treatment of acetaminophen overdose.", "Acute liver failure: clinical features, outcome analysis, and applicability of prognostic criteria.", "Effect of whole bowel irrigation on the pharmacokinetics of an acetaminophen formulation and progression of radiopaque markers through the gastrointestinal tract.", "Controlled trials of charcoal hemoperfusion and prognostic factors in fulminant hepatic failure.", "The Australasian Clinical Toxicology Investigators Collaboration randomized trial of different loading infusion rates of N-acetylcysteine.", "[Evaluation of the efficacy of N-acetylcysteine administered alone or in combination with activated charcoal in the treatment of acetaminophen overdoses].", "Use and outcome of liver transplantation in acetaminophen-induced acute liver failure.", "Effect of anticholinergic drugs on the efficacy of activated charcoal.", "Treatment of acetaminophen ingestion with a superactivated charcoal-cola mixture.", "Evaluation of activated charcoal-sodium sulfate combination for inhibition of acetaminophen absorption and repletion of inorganic sulfate.", "Fulminant hepatic failure: outcome after listing for highly urgent liver transplantation-12 years experience in the nordic countries.", "Controlled trial of cysteamine in treatment of acute paracetamol (acetaminophen) poisoning.", "Efficacy of superactivated charcoal administered late (3 hours) after acetaminophen overdose.", "Comparison of activated charcoal and ipecac syrup in prevention of drug absorption.", "Charcoal haemoperfusion for paracetamol overdose.", "Serum phosphate as a predictor of outcome in acetaminophen-induced fulminant hepatic failure.", "Oral methionine in the treatment of severe paracetamol (Acetaminophen) overdose.", "Methionine and cysteamine in paracetamol (acetaminophen) overdose, prospective controlled trial of early therapy.", "A comparison of the efficacy of gastric lavage, ipecacuanha and activated charcoal in the emergency management of paracetamol overdose.", "Acetaminophen overdose. 662 cases with evaluation of oral acetylcysteine treatment.", "Activated charcoal reduces the need for N-acetylcysteine treatment after acetaminophen (paracetamol) overdose.", "A prospective evaluation of the effect of activated charcoal before oral N-acetylcysteine in acetaminophen overdose.", "Cimetidine--acetaminophen interaction in humans.", "Gastric lavage for liquid poisons.", "Ipecac-induced emesis and reduction of plasma concentrations of drugs following accidental overdose in children.", "Shorter duration of oral N-acetylcysteine therapy for acute acetaminophen overdose.", "Serum phosphorus levels predict clinical outcome in fulminant hepatic failure.", "Treating paracetamol overdose by charcoal haemoperfusion and long-hours high-flux dialysis.", "Improved outcome of paracetamol-induced fulminant hepatic failure by late administration of acetylcysteine.", "Cysteamine, methionine, and penicillamine in the treatment of paracetamol poisoning.", "Early changes in coagulation following a paracetamol overdose and a controlled trial of fresh frozen plasma therapy.", "Paracetamol overdose and hepatotoxicity at a regional Australian hospital: a 4-year experience.", "Late treatment of paracetamol poisoning with mercaptamine.", "Comparative antidotal efficacy of activated charcoal tablets, capsules and suspension in healthy volunteers.", "Admission levels of serum Gc-globulin: predictive value in fulminant hepatic failure.", "Sorbitol catharsis does not enhance efficacy of charcoal in a simulated acetaminophen overdose.", "Efficacy of charcoal cathartic versus ipecac in reducing serum acetaminophen in a simulated overdose.", "Serious paracetamol poisoning and the results of liver transplantation.", "How long after drug ingestion is activated charcoal still effective?", "Acetaminophen overdose: a 48-hour intravenous N-acetylcysteine treatment protocol.", "Effectiveness of delayed activated charcoal administration in simulated paracetamol (acetaminophen) overdose." ]

[ "Activated charcoal is now being recommended for patients who have ingested potentially toxic amounts of a poison, where the ingested substance adsorbs to charcoal. Combination therapy with gastric lavage and activated charcoal is widely used, although clinical studies to date have not provided evidence of additional efficacy compared with the use of activated charcoal alone. There are also doubts regarding the efficacy of activated charcoal, when administered more than 1 h after the overdose. The aim of this study was to examine if there was a difference in the effect of the two interventions 1 h post ingestion, and to determine if activated charcoal was effective in reducing the systemic absorption of a drug, when administered 2 h post ingestion.\n We performed a four-limbed randomized cross-over study in 12 volunteers, who 1 h after a standard meal ingested paracetamol 50 mg kg(-1) in 125 mg tablets to mimic real-life, where several factors, such as food, interfere with gastric emptying and thus treatment. The interventions were activated charcoal after 1 h, combination therapy of gastric lavage followed by activated charcoal after 1 h, or activated charcoal after 2 h. Serum paracetamol concentrations were determined by h.p.l.c. Percentage reductions in the area under the curve (AUC) were used to estimate the efficacy of each intervention (paired observations).\n There was a significant (P<0.005) reduction in the paracetamol AUC with activated charcoal at 1 h (median reduction 66%, 95% confidence intervals 49, 76) compared with controls, and a significant (P<0.01) reduction for gastric lavage followed by activated charcoal at 1 h (median reduction 48.2%, 95% confidence interval 32.4, 63.7) compared with controls. There was no significant difference between the two interventions (95% confidence interval for the difference -3.8, 34.0). Furthermore, we found a significant (P<0.01) reduction in the paracetamol AUC when activated charcoal was administered 2 h after tablet ingestion when compared with controls (median 22.7%, 95% confidence intervals 13.6--34.4).\n These results suggest that combination treatment may be no better than activated charcoal alone in patients presenting early after large overdoses. The effect of activated charcoal given 2 h post ingestion is substantially less than at 1 h, emphasizing the importance of early intervention.", "An accurate and early assessment of the individual patient is critical in deciding whether liver transplantation is indicated in the treatment of fulminant hepatic failure. Based on analysis of patients treated between 1973 and 1985, the Liver Unit at King's College Hospital, London, developed a prognostic model to identify patients with a poor prognosis. The present study was done to determine the applicability of this model in fulminant hepatic failure patients seen at our center in the 1990s.\n The records of 145 patients with fulminant hepatic failure, treated conservatively at Queen Elizabeth Hospital, Birmingham between 1990 and 1994, were analyzed. An additional 81 patients, who were transplanted for fulminant hepatic failure during the same period were excluded from the study.\n Application of King's College Hospital criteria at the time of admission to this hospital in the acetaminophen group, had a positive predictive value of 88%, negative predictive value of 65% and predictive accuracy of 71%. The positive predictive value, negative predictive value and predictive accuracy of these criteria for non-acetaminophen-induced fulminant hepatic failure, were 79%, 50% and 68%. Multivariate analysis identified prothrombin time, serum creatinine, white cell count and abnormal potassium levels as independent predictors of mortality in acetaminophen-induced fulminant hepatic failure; and prothrombin time alone in fulminant hepatic failure induced by other etiologies.\n The King's College Hospital criteria for predicting outcome of fulminant hepatic failure were found to have a slightly lower predictive accuracy than shown in the original study.", "To determine the decrease of drug absorption when syrup of ipecac is administered at various times within one hour of drug ingestion.\n Ten healthy human volunteers were recruited for a four-limbed randomized crossover study. The three experimental limbs consisted of administration of 30 mL syrup of ipecac, at 5, 30, or 60 minutes after ingestion of 3900 mg acetaminophen as 12 x 325 mg tablets with 250 mL room temperature water. The fourth limb served as control. Blood samples were drawn at 0, 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, and 8.0 hours after analgesic ingestion for serum acetaminophen concentration determination by high-performance liquid chromatography. Repeated measures ANOVA and Tukey's HSD tests were used for group comparisons.\n The area under the serum concentration vs time curve was (mean +/- SD) 206 +/- 48, 67 +/- 37, 183 +/- 78, and 162 +/- 47 mg/L for control, 5, 30, and 60 minutes, respectively. This corresponds to decreases in bioavailability of 67, 11, and 21%. Only the 5-minute group differed significantly from control (p < 0.05). Sedation was observed as a significant adverse effect of ipecac administration.\n Our data do not support benefit from ipecac administration at 30 minutes and beyond. Our data suggest that benefit is lost at some point between 5 and 30 minutes. The sedative effect of ipecac may confound the observation of patients who have ingested sedative hypnotic agents.", "nan", "Severe acetaminophen hepatotoxicity frequently leads to acute liver failure (ALF). We determined the incidence, risk factors, and outcomes of acetaminophen-induced ALF at 22 tertiary care centers in the United States. Detailed prospective data were gathered on 662 consecutive patients over a 6-year period fulfilling standard criteria for ALF (coagulopathy and encephalopathy), from which 275 (42%) were determined to result from acetaminophen liver injury. The annual percentage of acetaminophen-related ALF rose during the study from 28% in 1998 to 51% in 2003. Median dose ingested was 24 g (equivalent to 48 extra-strength tablets). Unintentional overdoses accounted for 131 (48%) cases, intentional (suicide attempts) 122 (44%), and 22 (8%) were of unknown intent. In the unintentional group, 38% took two or more acetaminophen preparations simultaneously, and 63% used narcotic-containing compounds. Eighty-one percent of unintentional patients reported taking acetaminophen and/or other analgesics for acute or chronic pain syndromes. Overall, 178 subjects (65%) survived, 74 (27%) died without transplantation, and 23 subjects (8%) underwent liver transplantation; 71% were alive at 3 weeks. Transplant-free survival rate and rate of liver transplantation were similar between intentional and unintentional groups. In conclusion, acetaminophen hepatotoxicity far exceeds other causes of acute liver failure in the United States. Susceptible patients have concomitant depression, chronic pain, alcohol or narcotic use, and/or take several preparations simultaneously. Education of patients, physicians, and pharmacies to limit high-risk use settings is recommended.", "One hundred thirty-two cases of severe acetaminophen (paracetamol) poisoning were treated with oral methionine. Seven of 96 patients who received the antidote within ten hours of ingestion of the overdose had severe liver damage (aspartate transaminase level, greater than 1,000 IU/L), but none of these patients died. Thirty-six patients received methionine between ten and 24 hours of ingestion; severe liver damage occurred in 47%, and two patients died. The treatment protocol for oral methionine is simple, and therapy is complete within 12 hours as compared with three days for oral acetylcysteine and 20 hours for intravenous acetylcysteine. Side effects from methionine were unimportant. Oral methionine is as effective as acetylcysteine in preventing severe liver damage and death after acetaminophen overdose. However, as with acetylcysteine, it must be given within ten hours of ingestion to be effective.", "The aim of this study was to determine if cimetidine in addition to N-acetylcysteine and standard supportive care provide additional hepatoprotection following acute acetaminophen poisoning. It was designed as a prospective study with alternate month treatment protocol, and the work was carried out at a regional certified poison information centre. For a 2-year period, consultations received by the Rocky Mountain Poison Center involving acute acetaminophen overdose patients with a serum level above the nomogram line, but who would not receive N-acetylcystine therapy until at least 8 h postingestion, were prospectively evaluated for adjunctive treatment with cimetidine. All patients received standard supportive therapy and N-acetylcysteine treatment. During odd numbered months, cimetidine 300 mg was administered intravenously every 6 h for the duration of N-acetylcysteine therapy. Forty-one cimetidine treated patients were compared to 66 patients in the control group. The peak measured AST levels (+/- s.e.) were 1259+/-330 and 1301+/-451 for the control and cimetidine treatment groups, respectively (P = 0.94). Fourteen of 64 patients (21%) in the control group and 8/41 patients (20%) in the cimetidine group developed an AST > 1000 IUL-1. There were no statistical differences between the cimetidine-treated and control groups when classified by AST < 100 IUL-1, 100-1000 IUL-1, or > 1000 IUL-1. The addition of cimetidine therapy to standard N-acetylcysteine treatment did not provide additional hepatoprotection in acutely acetaminophen poisoned patients when treatment was started later than 8 h post overdose.(ABSTRACT TRUNCATED AT 250 WORDS)", "The purpose of this study was to evaluate whole gut lavage with polyethylene glycol electrolyte solution (Colyte), as a potentially adjunctive measure in lowering serum acetaminophen levels. The effect of bowel lavage was evaluated on serial serum acetaminophen concentrations after 2-g and 4-g doses in 7 and 12 male patients, respectively. Mean peak level of serum acetaminophen after 2 g (60 min after intake) was not significantly lowered by bowel lavage. After 4 g, peak acetaminophen serum levels were significantly lower after bowel lavage (65.4% of controls, P < 0.001). Urinary concentrations of the mercapturic acid conjugate of the toxic metabolite were also significantly reduced by lavage (55% after 2 g and 45% after 4 g, P < 0.01). Activated charcoal given orally after administration of 4 g of acetaminophen had no significant effect on peak serum levels and had no additive effect on lavage. These studies suggest that rapid, complete bowel lavage with a polyethylene glycol electrolyte solution may be beneficial as an adjunct to the treatment of the acetaminophen intoxication.", "Acute liver failure (ALF) is an uncommon condition associated with high morbidity and mortality. We performed a retrospective analysis of patients evaluated for ALF. The aim of our study is to determine the clinical features and outcome of such patients and to assess the validity of King's College Hospital (KCH) prognostic criteria. One hundred seventy-seven patients were evaluated for ALF during a period of 13 years. Mean age was 39 years, and 63% were women. The causes included viral hepatitis (31%), acetaminophen toxicity (19%), idiosyncratic drug reactions (12%), miscellaneous causes (11%), and an indeterminate group (28%). Twenty-five patients (14%) recovered with medical therapy (group I), 65 patients (37%) died without orthotopic liver transplantation (OLT; group II), and 87 patients (49%) underwent OLT (group III). Patients in group II were older and often had advanced encephalopathy, whereas those in group I had less hyperbilirubinemia and often had hyperacute failure. KCH criteria had high specificity and positive predictive value but low negative predictive value for a poor outcome. We conclude that early prognostication is needed in patients with ALF to assist decision making regarding OLT. The fulfillment of KCH criteria usually predicts a poor outcome, but a lack of fulfillment does not predict survival.", "We describe the effects of whole bowel irrigation on a delayed-release acetaminophen preparation. We compare the mechanical effect of whole bowel irrigation on the progression of radiopaque markers through the gastrointestinal tract between an experimental and a control group.\n We performed a 2-armed, prospective, randomized, crossover volunteer study. In the experimental phase, subjects were administered a delayed-release acetaminophen preparation (75 mg/kg) along with a capsule containing radiopaque markers. We initiated whole bowel irrigation at 30 minutes after ingestion and continued until the rectal effluent was clear. Serum acetaminophen concentrations were measured at baseline and from 0.5 to 8 hours. Abdominal radiographs were obtained at the completion of whole bowel irrigation. In the control phase, whole bowel irrigation was not performed. The primary outcome measure was the effect on the area under the acetaminophen concentration versus time curve (AUC) between the 2 groups.\n Ten subjects participated in the study. We found an 11.5% reduction in the AUC, with the majority of the effect occurring in the delayed-release portion of the curve after the 2-hour mark. This reduction, however, was not statistically significant. Radiographs obtained at the end of whole bowel irrigation revealed radiopaque markers sequestered in the right hemicolon in 8 of 10 subjects. No discernible pattern was noted in the control arm.\n The effect of whole bowel irrigation on reduction of AUC for delayed-release acetaminophen preparation was not statistically significant. Whole bowel irrigation did appear to have a mechanical effect on the progression of radiopaque markers through the gastrointestinal tract, but the clinical significance of this finding is not clear.", "One hundred thirty-seven patients with fulminant hepatic failure were entered into two controlled trials of charcoal hemoperfusion carried out concurrently. In trial A, 75 patients with grade 3 encephalopathy were randomized to receive 5 or 10 h of hemoperfusion daily. Overall survival rates for the two groups were similar (51.3% vs. 50.0%) as was the frequency of major complications including cerebral edema and renal failure. In trial B, in which 62 patients with established grade 4 encephalopathy on admission were randomized to a no-perfusion group or to have 10 h of hemoperfusion daily, overall survival rates for the two groups were again similar (39.3% and 34.5%, respectively). There was in both trials a significant relationship between survival and etiology quite independent of the use or duration of hemoperfusion. Thus, percentage survival for the acetaminophen-overdose cases was 52.9%, for hepatitis A 66.7%, for hepatitis B 38.9%, for presumed non-A, non-B hepatitis 20%, and for halothane or drug reaction 12.5%. Within the etiologic subgroups survival was also influenced by the three major complications that developed, being inversely related to their frequency and combination, except in the non-A, non-B hepatitis and halothane or drug reaction subgroups, which had a high mortality throughout. In the latter cases particularly, orthotopic liver transplantation merits early consideration and in the group with better \"intrinsic\" survival (acetaminophen, hepatitis A and B) intensive management of complications (rather than charcoal hemoperfusion) would appear to be of major importance.", "We determine whether the incidence of adverse events caused by intravenous N -acetylcysteine is significantly less when the initial dose is infused over a 60-minute period compared with the standard infusion period of 15 minutes. A secondary objective is to assess the efficacy of the 2 treatment arms.\n This was a multicenter, randomized, prospective trial of patients who presented with acetaminophen poisoning and who were treated with N -acetylcysteine and had no history of hypersensitivity to N-acetylcysteine. Patients were randomly assigned to receive the initial dose of N-acetylcysteine over a 15-minute or 60-minute period. Baseline signs and symptoms and adverse events were serially evaluated before and during administration of N -acetylcysteine. Tests of liver injury and coagulation were collected at baseline and then at 12-hour intervals.\n The study was designed with an 80% power to detect a halving of the incidence of adverse events. Of 180 evaluable patients, 109 patients were randomized to the 15-minute group and 71 patients were randomized to the 60-minute group. The incidence of drug-related adverse events was 45% in the 15-minute group and 38% in the 60-minute group (95% confidence interval -8% to 22%). The study did not demonstrate a reduction of drug-related adverse outcomes with the 60-minute infusion. Incidence of maximum alanine aminotransferase levels indicating hepatotoxicity (serum level >1,000 IU/L) was 6.8% (5.6% for 15-minute, 8.7% for 60-minute). The difference did not attain statistical significance.\n This study did not demonstrate a reduction of drug-related adverse outcomes with the 60-minute infusion. The study also confirmed that early treatment with N -acetylcysteine (within 8 hours of ingestion) is more effective than later treatment.", "To evaluate the efficacy of N-acetylcysteine (N-AC) alone or combined with multiple-dose activated charcoal (AC) in the treatment of acetaminophen (ACT) overdose.\n Prospective observational case series of 14 consecutive pediatric patients. Group A (n = 7) were treated only with N-AC and group B (n = 7) with N-AC combined with AC. Plasma ACT concentrations were measured at 0.0, 24 and 48 h. As a measure of ACT disappearance, half-life of elimination (t1/2 beta) and exogenous body clearance (ClB) were calculated.\n Group A, Initial and final mean ACT plasmatic levels were 27 micrograms/mL and 4 micrograms/mL; t1/2 beta of 17 h and ClB 0.640 mL.kg.min. Group B, 27 micrograms/mL and 0.66 microgram/mL; t1/2 beta of 10 h and ClB 1.092 mL.kg.min. For both t1/2 beta and ClB differences, p < 0.05 (SS).\n N-AC significantly decreased the plasma ACT levels in both treatments; however, there were several advantages with the combined therapy: AC enhanced the efficacy of N-AC according with the higher eliminatión of the overdosed drug (97.6% vs. 85.2%), the t1/2 beta decreased 42%, and the ClB increased 70% in relation to the group A. Data of this study suggested that N-AC plus AC is more effective than N-AC alone in enhancing ACT elimination in overdosed patients and that it provided additional hepatoprotective benefit.", "Once defined clinical criteria are fulfilled in acetaminophen-induced hepatotoxicity, prognosis without orthotopic liver transplantation (OLT) may be very poor. In the present study, we examined the application and outcome of OLT in 548 patients admitted to a single center between 1990 and 1996. Four hundred twenty-four (77%) of the patients studied did not fulfill transplantation criteria, and 396 of these (93%) survived. The majority of the 28 nonsurvivors (7%) in this group fulfilled two of three combined criteria, and the finding of a high APACHE III score could be used as an indicator for the need for OLT. Of the 56 patients (45%) not listed, in only a small proportion was this caused by psychiatric reasons, and in the majority, it was a consequence of the rapid development of multiple organ failure and cerebral edema. This also applied to 24 (35%) of the 68 listed patients in whom the rapidity of clinical deterioration, reflected in increasing APACHE III scores, was such that even with the prompt availability of donor organs, OLT was not possible. In the final event, only 44 (35%) of those who fulfilled criteria underwent OLT, of whom 33 (75%) survived to leave the hospital. Survival was greatest in those receiving unreduced grafts, and markers of early graft function differed significantly between survivors and nonsurvivors. Liver transplantation is an effective treatment in a relatively small number of patients with acetaminophen-induced hepatotoxicity, and for a substantial proportion, transplantation was never an option because of the rapidity of clinical deterioration. APACHE III scoring may be of value in decision making and in better defining patients in clinical trials.", "Although it is a commonly held belief that the ingestion of drugs with an anticholinergic action would prolong the duration of time after drug ingestion for effective gastrointestinal decontamination, data are lacking to support this belief. The purpose of this study is to determine whether activated charcoal is more effective in the presence of concurrent anticholinergic activity.\n A three-limbed randomized crossover study in 10 healthy volunteers was completed to determine the ability of a 50 g dose of activated charcoal to reduce the bioavailability of a simulated overdose of acetaminophen (12 x 325 mg tablets) in the presence and absence of a concurrently present anticholinergic drug, atropine (0.01 mg/kg I. M. administered 15 min prior to the acetaminophen ingestion).\n After the acetaminophen ingestion, median Cmax occurred at 1 h for all three exposures but was lower in the atropine-treated study arm (31+/-19 mg/L) than in the control or charcoal alone intervention arms (49+/-13 and 51+/-16 mg/L, respectively) (P<0.05). Compared to the control area under the serum concentration vs. time curve, a single dose of activated charcoal 1 h after drug ingestion reduced acetaminophen bioavailability by 20% (95% CI 4-36%) and by 47% (95% CI 35-59%) in the presence of atropine (P<0.05 atropine plus charcoal vs. charcoal alone).\n Our data support the belief that activated charcoal is more effective in the presence of anticholinergic activity. Additional study is required to determine whether in patients with anticholinergic drug overdose, activated charcoal is effective at times beyond the recommendation for overdoses of drugs without this pharmacodynamic effect.", "We evaluate the adsorptive capacity of a superactivated charcoal-cola mixture to acetaminophen compared with superactivated charcoal alone.\n This was a triple-arm, prospective, unblinded study of 8 healthy adult human volunteers who ingested 80 mg/kg of acetaminophen. In the control arm of the study, participants ingested acetaminophen alone. In the next arm, acetaminophen was followed by 1 g/kg of superactivated charcoal mixed with water. In the final arm, acetaminophen was followed by 1 g/kg of superactivated charcoal mixed with caffeine-free diet cola. Serum acetaminophen concentrations over 6 hours for each arm were analyzed for area under the time-concentration curve (AUC), peak concentrations, and time to peak concentrations.\n AUCs were 298.5+/-82.5 mg-h/L (control), 77.1+/-85.2 mg-h/L (superactivated charcoal), and 81.3 +/- 71.8 mg-h/L (superactivated charcoal-cola). Comparison of AUCs by analysis of variance revealed mean square of 128,315.1 between treatments, and residual mean square of 6,405.0, yielding an F ratio of 20.03 (P <.0001). Student-Newman-Keuls pairwise multiple comparison procedure revealed a statistically significant difference in AUC for control versus superactivated charcoal (P <.05) and for control versus superactivated charcoal-cola (P <.05), but not for superactivated charcoal versus superactivated charcoal-cola (P >.05). Time-concentration curves for the 3 study arms were illustrated graphically.\n Combining superactivated charcoal with cola does not limit the adsorptive capacity of superactivated charcoal.", "Activated charcoal is an effective inhibitor of acetaminophen absorption while sodium sulfate can prevent the depletion of endogenous inorganic sulfate associated with the formation of acetaminophen sulfate. Administration of activated charcoal plus sodium sulfate soon after acetaminophen overdose may reduce acetaminophen absorption and facilitate the elimination of absorbed acetaminophen by providing sufficient sulfate ion for rapid sulfation of the drug. This investigation was designed to determine if sodium sulfate modifies the inhibitory effect of activated charcoal on acetaminophen absorption or if activated charcoal affects the absorption of sodium sulfate. Eight normal adults received, on separate occasions, 1 g acetaminophen, 1 g acetaminophen and 18 g sodium sulfate (decahydrate), 1 g acetaminophen with 10 g activated charcoal and 1 g acetaminophen, with 10 g activated charcoal and 18 g sodium sulfate, in random order. Urine was collected for 48 hours and assayed for acetaminophen and its major metabolites and for inorganic sulfate. The results confirm that activated charcoal can reduce acetaminophen absorption and show that oral administration of activated charcoal with sodium sulfate does not alter the inhibitory effect of activated charcoal on acetaminophen absorption or the bioavailability of the sulfate. A combination of activated charcoal and sodium sulfate may therefore be useful for the initial management of acetaminophen overdose.", "Fulminant hepatic failure is a common indication for liver transplantation. Outcomes of patients listed for a highly urgent liver transplantation have been studied, with special emphasis on etiology of the liver disease, clinical condition, and ABO blood type. Data have been collected from the Nordic Liver Transplantation Registry. All Nordic patients listed for a highly urgent primary liver transplantation during a 12-year period have been included. Of the 315 patients listed for a highly urgent liver transplantation, 229 (73%) received a first liver allograft, 50 patients (16%) died without transplantation, and 36 patients (11%) were permanently withdrawn and survived. In 43% of the patients, no definite etiology of the liver failure could be established. Paracetamol intoxication was the most frequent specific indication for listing. Patients with blood type A had no significant shorter waiting time (3.8 v 6.6 days; P =.1) but a higher rate of transplantation (82% v 66%, P =.006) as compared with blood type O patients. In a multivariate analysis, paracetamol intoxication remained the single independent predictor of an outcome without transplantation. In conclusion, a high transplantation rate was observed among patients listed for a highly urgent liver transplantation because of fulminant hepatic failure. Blood type O patients had a lower chance of receiving a liver allograft. Patients with paracetamol intoxication had both a higher mortality without transplantation and a higher withdrawal rate attributable to improved condition.", "A randomised controlled trial of the use of intravenous cysteamine in the treatment of severe paracetamol poisoning has been performed. Thirty-eight patients presenting 3-17 h after ingestion were admitted to the trial; of these eighteen received cysteamine. Two patients died from hepatic failure, one in each treatment group. Analysis of the series as a whole showed no advantage of cysteamine in preventing biochemical abnormalities of liver function except for aspartate aminotranferase and serum ferritin levels, which were significantly less after cysteamine therapy. Separate analysis of the patients treated within 9 h of paractamol ingestion and of those treated 9-17 h after paracetamol ingesion similarly showed no definite advantage of cysteamine. Histological evidence of liver damage showed a possible beneficial effect of cysteamine. Cysteamine therapy did not prevent renal or pancreatic damage.", "The purpose of this study was to investigate the effect of superactivated charcoal (SAC) given late after a drug overdose. Acetaminophen was chosen as our overdose drug because it has relatively few side effects, serum levels are easily attainable and measurable, and it is generally a common drug overdose. Forty-six healthy adult volunteers participated in this randomized, controlled study. Acetaminophen was administered the morning after an overnight fast. Thirteen participants received 2000 mg acetaminophen and the remaining 33 received 3000 mg. After 3 hours, half of the participants (22 of 46) received 75 g of SAC (Requa, Greenwich, CT) orally as a slurry in 8 oz of apple juice. Serum acetaminophen levels were measured at 4 and 7 hours after the initial acetaminophen administration. There were significantly lower uncorrected and corrected acetaminophen levels in the SAC group compared with the control group at both 4 and 7 hours after ingesting acetaminophen. This randomized human experimental design trial demonstrates some detoxification benefit in administering superactivated charcoal 3 hours after an overdose.", "The efficacy of activated charcoal and ipecac syrup in the prevention of drug absorption was studied in 6 healthy adult volunteers, using a randomized, cross-over design. Paracetamol 1000 mg, tetracycline 500 mg and aminophylline 350 mg were ingested on an empty stomach with 100 ml water. Then, after 5 or 30 min, the subjects ingested, either activated charcoal suspension (50 g charcoal), syrup of ipecac, or, only after 5 min, water 300 ml. Activated charcoal, given either after 5 or 30 min, significantly (p less than 0.01 or less 0.05) reduced the absorption of these 3 drugs measured, for example as AUC0-24 h. Syrup of ipecac caused emesis on each occasion, with a mean delay of 15 min. When ipecac was given 5 min after the drugs, its effect on absorption was significant, but when it was given after 30 min only the absorption of tetracycline was reduced. Activated charcoal was significantly (p less than 0.05) more effective than ipecac in reducing drug absorption when given at the same time points. In cases of acute intoxication, depending on the quality and quantity of the drugs ingested, the relative efficacy of charcoal and ipecac may be somewhat different from that observed in the present study. Despite its emetic action, however, ipecac syrup is not very effective in preventing drug absorption and, in general, activated charcoal should also be given after induced emesis or gastric lavage.", "1 A controlled trial of charcoal haemoperfusion as an early treatment for paracetamol overdose showed no benefit. 2 The plasma clearances of paracetamol by the charcoal column were variable and disappointingly small (range 4-119 ml/minute). The cumulative amounts removed were also low, mean 1.4 g (range 0.2-5.2 g). 3 No clinical problems were encountered with the technique of haemoperfusion and in particular the drop in blood platelet counts was small (mean fall 16%).", "nan", "30 patients at risk of hepatic damage from paracetamol (acetaminophen) ingestion were given 2-5 g oral methionine every four hours up to a total dose of 10 g. The first dose was given within ten hours of the overdose. There were no deaths and no reports of hepatic encephalopathy or other complications. In 21 patients plasma aspartate-aminotransferase remained within normal limits. These results suggest that methionine may be effective in reducing the frequency and severity of paracetamol-induced liver damage and may provide an effective non-toxic alternative to cysteamine.", "nan", "The aim of this prospective trial was to compare the efficacy of gastric lavage, activated charcoal and ipecacuanha at limiting the absorption of paracetamol in overdose and to assess the significance of the continued absorption of paracetamol following treatment. Patients aged 16 and over who had ingested 5 gms or more of paracetamol within 4h of admission were entered into the trial. The percentage fall in plasma paracetamol level was used as the measure of the success of a treatment at limiting absorption. The mean percentage fall was 39.3 for gastric lavage, 52.2 for activated charcoal and 40.7 for ipecacuanha, with a significant difference between the treatment methods (p = 0.03). Activated charcoal was more effective at limiting the absorption of paracetamol following overdose than either gastric lavage or ipecacuanha induced emesis. In treated patients continuing paracetamol absorption is not significant if more than 2h have elapsed since ingestion.", "Six hundred sixty-two consecutive patients with acetaminophen overdoses were evaluated. Those at risk on the basis of their acetaminophen blood levels, as plotted on the study nomogram, were treated with oral acetylcysteine. Statistically significant differences in severity of hepatic toxicity were observed between patients treated within 16 hours after ingestion and those treated between 16 and 24 hours after ingestion. No deaths occurred among patients treated within 24 hours of ingestion, except for one patient who was an alleged gunshot homicide. Seven percent of patients with plasma acetaminophen levels in the potentially toxic range and treated with acetylcysteine within ten hours of ingestion showed transient SGOT level elevations, whereas 29% of those treated between ten and 16 hours after ingestion and 62% of those treated between 16 and 24 hours after ingestion showed such transient toxicity. No consistent difference in hepatotoxicity could be demonstrated between those patients with a history of chronic alcohol use and those patients with no history of chronic alcohol use. Acute alcohol use resulted in less severe toxic reactions than in those patients without acute alcohol use.", "The evidence for efficacy of gastric lavage and activated charcoal for gastrointestinal decontamination in poisoning has relied entirely on volunteer studies and/or pharmacokinetic studies and evidence for any clinical benefits or resource savings is lacking.\n To investigate the value of gastrointestinal decontamination using gastric lavage and/or activated charcoal in acetaminophen (paracetamol) poisoning.\n We analyzed a series of 981 consecutive acetaminophen poisonings. These patients were treated with gastric lavage and activated charcoal, activated charcoal alone, or no gastrointestinal decontamination. The decision as to which treatment was received was determined by patient cooperation, the treating physician, coingested drugs, and time to presentation after the overdose.\n Of 981 patients admitted over 10 years, 10% (100) had serum concentrations of acetaminophen that indicated a probable or high risk of hepatotoxicity. The risk of toxic concentrations for patients ingesting less than 10 g of acetaminophen was very low. In patients presenting within 24 hours, who had ingested 10 g or more, those who had been given activated charcoal were significantly less likely to have probable or high risk concentrations (Odds ratio 0.36, 95% CI 0.23-0.58, p < 0.0001). Gastric lavage, in addition to activated charcoal, did not further decrease the risk (Odds ratio 1.12, 95% CI 0.57-2.20, p = 0.86).\n Toxic concentrations of serum acetaminophen (paracetamol) are uncommon in patients ingesting less than 10 g. In those ingesting more, activated charcoal appears to reduce the number of patients who achieve toxic acetaminophen concentrations and thus may reduce the need for treatment and hospital stay.", "To evaluate whether activated charcoal (AC) reduces the efficacy of subsequent oral N-acetylcysteine therapy during acute acetaminophen overdose.\n Prospective observational case series of all acute acetaminophen overdoses reported to three certified regional poison centers. TYPES OF PATIENTS: All patients with acute acetaminophen overdose in whom N-acetylcysteine therapy was initiated within 16 hours after ingestion.\n All patients were treated with oral N-acetylcysteine therapy for 72 hours. The decision to use AC was left to the treating physician without input from the investigator.\n One hundred twenty-two patients were evaluated. Maximum recorded SGOT levels of more than 125 U/mL were defined as evidence of hepatotoxicity. AC was used in addition to N-acetylcysteine in 82 of 122 patients. Hepatotoxicity developed in four of 82 patients who received AC versus ten of 40 patients who did not receive AC (P < .005). An increasing dose of N-acetylcysteine provided no additional benefit (P > .05). Spacing the administration of AC and oral N-acetylcysteine less than or more than two hours apart did not affect outcome (P > .05).\n Administration of AC before the administration of oral N-acetylcysteine in acetaminophen overdose does not reduce the efficacy of N-acetylcysteine therapy and may provide some additional hepatoprotective benefit. The practice of increasing the dose of oral N-acetylcysteine therapy after the administration of AC appears unwarranted.", "The effect of single-dose and multiple-dose cimetidine administration on acetaminophen pharmacokinetics was investigated in a three-phase, randomized, crossover study using four normal subjects. In each phase of the study, subjects ingested 750 mg of acetaminophen as a single dose alone (A), or in combination with 200 mg of cimetidine (A + C), or following a one-week pretreatment with daily cimetidine, 200 mg every six hours and 400 mg before retiring (A + C*). Statistical analysis using two-way analysis of variance indicated no significant difference in peak concentration and peak time of acetaminophen between treatments. Cimetidine did not significantly affect acetaminophen half-life, 2.38 hours (A), 2.65 hours (A + C), and 2.50 hours (A + C*). Acetaminophen clearance was minimally affected by cimetidine; the mean clearance of acetaminophen ranged from 4.16 (A + C*) to 5.57 mL/min/kg (A). Area under the acetaminophen plasma concentration-time curve was slightly increased by cimetidine, 35.4 (A), 41.6 (A + C), and 47.6 micrograms/mL/h (A + C*). Since cimetidine did not affect acetaminophen pharmacokinetics to any significant extent, clinical combination of both medications at therapeutic dosage presumably would not produce adverse interactions.", "This study was conducted to determine whether gastric lavage reduces the absorption of ingested liquids.\n The study design was a randomized controlled human volunteer crossover study in 10 subjects. On 2 separate occasions 2 weeks apart, the volunteers ingested a solution of 4.0 g of acetaminophen in 60 mL of water. Eight blood specimens were obtained over the initial 8 hours for determination of serum acetaminophen concentrations, which were used to calculate routine pharmacokinetic parameters. One hour after 1 drug ingestion, gastric lavage was performed through a 34-F orogastric tube. Serum acetaminophen concentrations were measured by high-performance liquid chromatography and a 2-tailed t test was used for statistical analysis.\n The mean values for area under the concentration curve (+/-SD) for the control and gastric lavage groups were 195+/-31 and 154+/-52 mg/L.hour, respectively (P <.05). The mean reduction in acetaminophen bioavailability because of gastric lavage was 20%+/-28% (95% confidence interval 3 to 37).\n In this experimental model for the ingestion of liquids, gastric lavage at 1 hour resulted in a significant decrease in the mean serum bioavailability of acetaminophen. Nonetheless, this treatment effect is unlikely to be of clinical value because of its modest extent, unreliable performance, and the availability of a more effective, less risky alternative, activated charcoal.", "Syrup of ipecac is widely used following accidental drug overdosage in children. Proof of its efficacy, however, in reducing the risk of poisoning is limited. We prospectively studied the effect of early v late induction of emesis by ipecac in 50 children younger than 5 years of age with accidental acetaminophen poisoning. The mean estimated ingested dose was 165 mg/kg, and all patients vomited within 15 to 255 (mean 78) minutes postingestion. Although the predicted four-hour plasma acetaminophen concentration was 97 +/- 4 micrograms/mL (mean +/- SEM, calculated on the basis of the estimated ingested dose), the measured four-hour plasma acetaminophen concentration was 34 +/- 5 micrograms/mL (P less than .01). To assess the efficacy of early v late ipecac-induced emesis, we used the ratio of measured to predicted four-hour acetaminophen plasma concentration. The ratio of the measured to predicted four-hour level increased as the delay in time to vomiting increased (r = .60, P less than .001). Ipecac syrup was administered more promptly when available in the home than when obtained from a pharmacy or a medical facility (26 +/- 8 v 83 +/- 13 minutes postingestion, respectively; P less than .001) and vomiting occurred earlier (49 +/- 9 v 103 +/- 12 minutes postingestion; P less than .01). Although the mean estimated doses ingested were greater in patients who received ipecac syrup at home, their four-hour plasma acetaminophen concentrations were lower. These data suggest that prompt administration of ipecac syrup results in a greater reduction in plasma acetaminophen concentrations in potentially toxic overdosages in children.(ABSTRACT TRUNCATED AT 250 WORDS)", "We sought to evaluate the safety and efficacy of a shorter N-acetylcysteine (NAC) regimen in the treatment of acute acetaminophen overdose.\n We performed a retrospective case series in a large urban county hospital. Of 305 patients identified through the emergency department, 75 patients met the criteria inclusion: an acute overdose ingestion, serum acetaminophen concentration in toxic range according to the Rumack-Matthew nomogram, and oral NAC treatment initiated within 24 hours of the ingestion. The regional poison control center recommended oral treatment with NAC 140 mg/kg, followed by maintenance doses of 70 mg/kg every 4 hours until the serum acetaminophen level was no longer detectable, rather than the standard 72-hour treatment regimen.\n The primary outcome measure was the development of hepatotoxicity. Twenty-five (33.3%) patients were treated for a period of less than 24 hours, 25 (33.3%) were treated for 24 to 36 hours, and 25 (33.3%) were treated for 37 to 64 hours; the mean and median duration of treatment was 31 hours. None of the patients treated for less than 24 hours had evidence of hepatotoxicity (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] level >1,000 IU/L); hepatotoxicity developed in 2 (8%) patients treated for 24 to 36 hours and 4 (16%) patients treated for 37 to 64 hours. There were no deaths or patients who received liver transplantation. The overall incidence of hepatotoxicity in our patients was similar to that found in other protocols with administration of oral NAC for 72 hours or intravenous NAC for 20 or 48 hours.\n This observational study suggests that a shorter course of oral NAC therapy in patients who do not show evidence of hepatotoxicity within 36 hours of an acute acetaminophen overdose is safe and effective.", "The aim of this pilot study was to evaluate the incidence of hypophosphatemia and its association with clinical outcome in fulminant hepatic failure (FHF). Patients with FHF referred for orthotopic liver transplantation (OLT) between January, 1991 and May, 2002 were identified. FHF was defined as the development of coagulopathy and encephalopathy within 8 weeks of onset of jaundice. Demographic and laboratory data, including serum phosphate, calcium, magnesium, creatinine, and PT/INR were obtained from medical records. Clinical outcomes (death, OLT, or hepatic recovery) and associated morbidities (renal failure, bleeding, and sepsis) also were noted. Thirty-eight patients, 8 men and 30 women, aged 34 +/- 4 years, were included in the study. Hypophosphatemia (< 2.5 mg/dL) developed in 33 of 38 (87%) patients within 10 days of referral. Twelve patients (32%) died, 14 patients (37%) underwent OLT, and 12 patients (32%) recovered. The mean nadir serum phosphorus level was significantly lower in those who recovered compared with those who either died or required OLT (1.18 +/- 0.54 versus 1.79 +/- 1.00 mg/dL; P =.02). A trend toward lower mean serum phosphorus level also was noted in those who recovered compared with those who died (1.18 +/- 0.54 versus 1.96 +/- 1.35 mg/dL; P =.09). Serum phosphorus levels > 2.5 mg/dL was a predictor of mortality, and when used alone, was equivalent to the King's College Criteria. In conclusion, hypophosphatemia occurred frequently in patients with FHF. Lower serum phosphorus levels were observed in patients who recovered as compared with those who died or required OLT, and may be associated with recovery of hepatic function. The greater decline in serum phosphorus level in those who recover hepatic function may represent cellular use of phosphorus during hepatocyte regeneration.", "After serious paracetamol overdose, charcoal haemoperfusion was used to remove paracetamol from the circulation, aiming to reduce the severity of subsequent hepatic damage. Daily long-hours high-flux dialysis was given to patients with grade III-IV hepatic encephalopathy, and also to those at risk of developing encephalopathy. We reviewed patients treated in this manner who had not received N-acetylcysteine within the first 15 h after overdose. From January 1983 to January 1993, 73 patients with serious paracetamol overdose were seen, of whom 51 received charcoal haemoperfusion and/or high-flux dialysis. Patients who were admitted within the first 42 h after overdose and who received haemoperfusion and/or dialysis had significantly lower peak levels of prothrombin time, bilirubin and creatinine than those who were admitted after 42 h. Mortality was also lower amongst patients admitted before 42 h, at 2/18 (11%) vs. 15/33 (45%), p < 0.05.", "The influence of acetylcysteine, administered at presentation to hospital, on the subsequent clinical course of 100 patients who developed paracetamol-induced fulminant hepatic failure was analysed retrospectively. Mortality was 37% in patients who received acetylcysteine 10-36 h after the overdose, compared with 58% in patients not given the antidote. In patients given acetylcysteine, progression to grade III/IV coma was significantly less common than in those who did not receive the antidote (51% vs 75%), although the median peak prothrombin time was similar for both groups. Whether the beneficial effect is related to replenishment of glutathione stores or a consequence of another hepatic protective mechanism of acetylcysteine requires further study.", "60 patients with paracetamol poisoning have been treated with intravenous cysteamine, L-methionine, or D-penicillamine and the incidence and severity of hepatic necrosis compared with those observed in 70 patients receiving supportive therapy only. Of 31 patients with 4-hour plasma-paracetamol concentrations greater than 250 mug/ml given supportive therapy 22 sustained severe liver damage, 3 died in hepatic failure, and 4 developed acute renal failure. None of 23 similarly poisoned patients given cysteamine within 10 hours of ingestion suffered severe liver damage or renal failure and none died. Cysteamine was partially effective at 10-12 hours, but ineffective 12 hours or more after ingestion. Liver damage was absent or mild in 17 patients given L-methionine within 10-12 hours of ingestion but severe in 3 treated within 10 hours. Of 5 patients treated with D-penicillamine, 1 developed severe liver damage with acute renal failure. It is concluded that cysteamine prevents severe liver damage after paracetamol poisoning if given within 10 hours in adequate dosage.", "Early changes in coagulation were found in patients following a paracetamol overdose. Low levels of clotting factors II, V and VII were present within 24 hours of the overdose. As the levels of factor II correlated with plasma fibrinogen values at this time, it is possible that they were consumed in the process of intravascular coagulation, although this was not supported by the presence of raised titres of fibrin degradation products. The prothrombin time ratio was greater than 2-2 within 30 hours of ingestion of the overdose in all patients who eventually died, whereas it was less than this in those developing only moderate liver damage. The administration of fresh frozen plasma to patients did appear to reduce the maximum abnormality of the prothrombin time ratio, which was significantly less three days after the overdose in the group receiving fresh frozen plasma. However, the coagulation disturbance was of short duration, and the prothrombin time ratio had also returned to normal within one week of the overdose in the control patients, and the administration of fresh frozen plasma did not appear to reduce the morbidity or mortality in the treated patients.", "Paracetamol is a component of a number of drugs taken in overdose (OD). The influence of alcohol use (acute or chronic) on the presentation and clinical course of paracetamol OD is contentious. This study explores the relationship between paracetamol OD, alcohol consumption and clinical outcomes at a regional Australian hospital.\n To determine the frequency, circumstances and outcomes of paracetamol OD presentations to a regional Australian general hospital over a 4-year period.\n Medical records of patients admitted to the Ballarat Health Services (BHS) as a result of paracetamol OD between January 2000 and December 2003 were reviewed. Patient demographics, amount of paracetamol ingested, other drug coingestions, alcohol history, previous medication OD, clinical course and outcomes were recorded.\n Annual admissions resulting from paracetamol OD almost doubled during the 4 years studied. The risk of a repeat paracetamol OD was highest within 4 weeks of the initial OD. Alcohol, benzodiazepines and antidepressants were commonly coingested. The strongest predictor of severe hepatotoxicity was delayed or no N-acetyl cysteine treatment in patients consuming greater than 10 g of paracetamol or with toxic serum paracetamol levels. A history of alcohol consumption did not appear to worsen outcomes.", "Forty patients who had taken overdoses of paracetamol were treated with mercaptamine. Twenty-three patients given mercaptamine within 10 hours of poisoning had normal liver function tests at follow-up, and one could not be traced. In 16 patients mecraptamine was begun more than 10 hours after ingestion of paracetamol (\"late\" mercaptamine). Eight of these patients developed severe liver damage, which in six was moderate or severe before mercaptamine administration. Acute renal failure occurred in two patients; in one other renal function was temporarily severely impaired. At follow-up two patients were not available, and one admitted moribund had died soon after admission. The remaining 13 all had normal liver function tests. It is concluded that late mercaptamine is not dangerous and may prevent further liver damage.", "The efficacy of several formulations of activated charcoal (AC) was compared by measuring the intestinal absorption of a solution of 1 g paracetamol administered 2 min before administration of 5 g AC as suspension (200 ml), tablets (40 of 125 mg) or capsules (25 of 200 mg). The suspension medium without AC was used as the control treatment. Based on the results of a pilot experiment, an 8 subject panel was used in a two 4 x 4 Latin square design. All treatments with AC resulted in a statistically significant decrease in paracetamol absorption compared to the control treatment. The suspension was considerably and significantly more effective than the tablets or capsules. Treatment with tablets was slightly but significantly more effective than capsules. The intake of large numbers of tablets and capsules was difficult. In the hospital AC suspensions are available. For first aid elsewhere, at home, at the working place or in the general practitioner's surgery a preservable and easily redispersible AC formulation would be preferable to the present solid forms.", "Gc-globulin scavenges actin released from necrotic hepatocytes to the extracellular space. In 77 patients with fulminant hepatic failure (FHF) (excluding patients treated with liver transplantation), admission levels of serum Gc-globulin and degree of complexing with monomeric actin (complex ratio) were determined to evaluate their predictive values in relation to survival/nonsurvival. Gc-globulin levels were significantly reduced in 47 nonsurvivors, compared with 30 survivors (96 +/- 71 mg/L vs. 169 +/- 101 mg/L, P < .001), whereas the complex ratio in nonsurvivors did not differ significantly from that of survivors. Gc-globulin levels were significantly lower in 59 patients with non-acetaminophen-induced FHF, compared with 18 patients with acetaminophen-induced FHF (P < .01). Using a cutoff level of serum Gc-globulin of 100 mg/L, a lesser value correctly predicted nonsurvival in 79 percent of patients with non-acetaminophen-induced FHF, whereas a higher value predicted survival in 60 percent. In patients with acetaminophen-induced FHF, nonsurvival was correctly predicted in 100 percent of patients and survival in 53 percent. In comparison, the King's College Hospital (KCH) criteria correctly predicted nonsurvival and survival in 69 percent and 57 percent, respectively, of the same non-acetaminophen-induced FHF patients and in 60 percent and 38 percent, respectively, of the acetaminophen-induced FHF patients. Thus, in our study population, the predictive properties of Gc-globulin were in the same range as the KCH criteria. An advantage of Gc-globulin is that it gives an estimate of the outcome already on admission. Acute liver transplantation should be considered in FHF patients with Gc-globulin less than 100 mg/L.", "The use of a 70% sorbitol solution has recently been advocated as an adjunct to activated charcoal. This results in rapid and profuse catharsis that could possibly cause fluid and electrolyte imbalance. An investigation was undertaken to determine if sorbitol catharsis enhanced the antidotal efficacy of activated charcoal. Eight healthy volunteers participated in a randomized, crossover trial. Subjects ingested 3 g of acetaminophen followed by either no intervention, 50 g of plain activated charcoal at one hour, or 50 g activated charcoal-sorbitol solution at one hour. Serial acetaminophen levels were determined at intervals over eight hours and side effects noted. Both interventions significantly reduced the area under the curve versus control (P less than .05). The addition of sorbitol did not enhance the efficacy of activated charcoal but did increase the side effects noted. Sorbitol has not been proven effective in enhancing drug removal and has side effects that can be significant in a poisoned patient. Current data do not warrant its use, and further investigations should be carried out with other ingested drugs.", "The traditional role of gastric emptying as the initial step in the management of the poisoned patient has recently been questioned; immediate activated charcoal administration has been recommended by some. In the setting of acetaminophen overdose, ipecac-induced emesis may interfere with subsequent oral antidotal therapy. Therefore, we conducted a study to compare the efficacy of initial therapy with ipecac with therapy with activated charcoal-cathartic in a simulated acetaminophen overdosage. Ten healthy volunteers participated in a randomized, crossover trial. Subjects ingested 3.0 g acetaminophen, followed by either no intervention, 30 mL syrup of ipecac, or 50 g activated charcoal-sorbitol solution at one hour. Serial acetaminophen levels were determined at intervals over eight hours. Both interventions significantly reduced the area under the curve compared with control (P less than .05). When comparing ipecac with activated charcoal-cathartic, no significant difference was noted among these groups.", "Paracetamol poisoning is the most common cause of fulminant liver failure in the United Kingdom. An accurate assessment of prognosis at the time of referral will allow the appropriate application of liver transplantation in this setting. The outcome of 92 patients consecutively admitted to a specialist liver unit with severe poisoning has been examined. In patients who did not have a transplant, a fatal outcome was seen for 26/82 (32%), and was associated with late presentation, coma grade, prothrombin time prolongation, metabolic acidosis, and renal dysfunction. Cerebral oedema, and sepsis were responsible for most deaths. Prognostic criteria defined at King's College Hospital seemed to predict the outcome of patients who did not have a transplant managed on the Birmingham liver unit. Seventeen patients were listed for transplantation, 10 had liver transplantation, and seven of 10 survived. Seven were listed but not transplanted, and one of seven survived. Psychological rehabilitation of patients who had a transplant has not proved difficult. These results suggest a role for liver transplantation in the management of selected patients with paracetamol poisoning.", "The recent American Academy of Clinical Toxicology/European Association of Poisons Centres and Clinical Toxicologists position statement on activated charcoal stated \"there are insufficient data to support or exclude its use after 1 hour of ingestion.'' The purpose of this study was to determine the effectiveness of activated charcoal administered 1, 2, and 3 hours after drug ingestion.\n This was a human volunteer, randomized crossover study. Ten volunteers ingested 4 g of acetaminophen on four occasions at least 1 week apart. One ingestion served as a control and the other three as experimental ingestions with charcoal being administered at 1, 2, and 3 hours after acetaminophen dosing. Eight blood specimens were obtained over the initial 8 hours for serum acetaminophen concentrations that were used for calculation of routine pharmacokinetic parameters. Repeated measures of ANOVA and Tukey's HSD test were used for statistical analysis.\n Pharmacokinetic parameters for acetaminophen in our volunteers were consistent with literature values. The mean area under the curve (AUC+/-SD) for the control and the 1-, 2-, and 3-hour groups were 221 +/- 54, 154 +/- 71, 206 +/- 67 and 204 +/- 58 mg/L/h, respectively. The 1-hour group was the only one differing from control (p < 0.01). The decrease of bioavailability at 1 hour was 30.3%, which is similar to previous studies.\n Our data do not support the administration of activated charcoal as a gastrointestinal decontamination strategy beyond 1 hour after drug overdose.", "To determine the safety and efficacy of a 48-hour IV N-acetylcysteine (IV NAC) treatment protocol for acute acetaminophen overdose.\n Nonrandomized trial open to all eligible patients.\n Multicenter; hospitals included moderate- and high-volume private, university, and municipal hospitals in urban and suburban settings.\n Two hundred twenty-three patients were entered. Of these, 179 met inclusion criteria: acute acetaminophen overdose, plasma acetaminophen concentration above the treatment nomogram line, treatment with IV NAC according to the protocol, and sufficient data to determine outcome.\n IV NAC treatment consisted of a loading dose of 140 mg/kg followed by 12 doses of 70 mg/kg every four hours.\n Patients were grouped for analysis according to risk group based on the initial plasma acetaminophen concentration. Hepatotoxicity (aspartate aminotransferase or alanine aminotransferase of more than 1,000 IU/L) developed in 10% (five of 50) of patients at \"probable risk\" when IV NAC was started within ten hours of acetaminophen ingestion and in 27.1% (23 of 85) when therapy was begun after ten to 24 hours. Among \"high-risk\" patients first treated 16 to 24 hours after overdose, hepatotoxicity occurred in 57.9% (11 of 19). There were two deaths (two of 179, 1.1%). Adverse reactions resulting from NAC occurred in 32 of 223 cases (14.3%), consisting in 29 of 32 patients (91% of reactions) of transient, patchy, skin erythema or mild urticaria during the loading dose that did not require discontinuation of therapy.\n This 48-hour IV NAC protocol is safe and effective antidotal therapy for acetaminophen overdose. Based on available data, it is equal to 72-hour oral and 20-hour IV treatment protocols when started early and superior to the 20-hour IV regimen when treatment is delayed. Further study will be required to determine its relative efficacy in the high-risk patient treated very late.", "Oral activated charcoal is used to treat drug overdose and is effective at reducing drug absorption when administered within 1 h of drug ingestion. There are fewer data on efficacy when the delay is longer, as is the case in most drug overdoses. This study investigated the efficacy of activated charcoal at preventing paracetamol (acetaminophen) absorption after simulated overdose when administration was delayed between 1 and 4 h.\n An open randomized-order four-way crossover study was performed in healthy volunteers comparing the effect of activated charcoal 50 g on the absorption of 3 g paracetamol tablets when administered after an interval of 1, 2 or 4 h or not at all. Plasma paracetamol concentrations were measured over 9 h after paracetamol ingestion using h.p.l.c. and areas under the curve between 4 and 9 h (AUC(4,9 h)) calculated as a measure of paracetamol absorption.\n Activated charcoal significantly reduced paracetamol AUC(4,9 h) when administered after 1 h (mean reduction 56%; 95% Confidence intervals 34, 78; P<0.002) or 2 h (22%; 6, 39; P<0.03) but not after 4 h (8%; -8, 24). When administered after 1 h activated charcoal reduced individual plasma paracetamol concentrations significantly at all times between 4 and 9 h after paracetamol administration. Administration at 2 or 4 h had no significant effect.\n These results in healthy volunteers cannot be extrapolated directly to poisoned patients. However, they provide no evidence of efficacy for activated charcoal when administered after an interval of more than 2 h." ]