Randomised placebo-controlled trial of rhesus-human reassortant rotavirus vaccine for prevention of severe rotavirus gastroenteritis

BACKGROUND: Rotavirus is the most common cause of acute childhood gastroenteritis. Vaccination with live oral heterologous rotavirus vaccines may prevent rotavirus gastroenteritis. We assessed the efficacy of rhesus-human reassortant rotavirus tetravalent vaccine (RRV-TV) against severe rotavirus gastroenteritis in Finnish children in a randomised placebo-controlled double-blind trial. METHODS: Placebo or RRV-TV (titre 4x10(5) plaque-forming units) was given to infants at ages 2, 3, and 5 months. The children were followed up for one or two rotavirus epidemic seasons. The main outcome measure was protection against severe rotavirus gastroenteritis (score > or =11 on a 20-point severity scale). 2398 children were enrolled and received at least one dose of RRV-TV (n=1191) or placebo (n=1207). The primary efficacy analysis was based on children who received three doses of RRV-TV (n=1128) or placebo (n=1145). FINDINGS: 256 episodes of rotavirus gastroenteritis occurred at any time during the study; 65 were among 1191 RRV-TV recipients, and 191 among 1207 placebo recipients (vaccine efficacy 66% [95% CI 55-74]; intention-to-treat analysis). 226 episodes were included in the primary efficacy analysis of fully vaccinated children (54 among 1128 RRV-TV recipients, 172 among 1145 placebo recipients; vaccine efficacy 68% [57-76]). 100 episodes were severe, eight in RRV-TV recipients and 92 in placebo recipients (vaccine efficacy 91% [82-96]). INTERPRETATION: RRV-TV vaccine was highly effective against severe rotavirus gastroenteritis in young children. Incorporation of this vaccine into routine immunisation schedules of infants could reduce severe rotavirus gastroenteritis by 90% and severe gastroenteritis of all causes in young children by 60%.     

Randomised placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Austrian Immunoglobulin in Multiple Sclerosis Study Group

BACKGROUND: Multiple sclerosis is an autoimmune disorder characterised by the repeated occurrence of demyelinating lesions within the central nervous system. Uncontrolled studies and experimental evidence suggest beneficial effects of repeated administration of intravenous immunoglobulin (IVIg) by immunomodulating mechanisms and induction or remyelination. We aimed to investigate the efficacy of IVIg in a randomised double-blind multicentre study. METHODS: Patients with relapsing-remitting multiple sclerosis were randomly assigned a monthly dose of IVIg (0.15-0.2 g/kg bodyweight) or placebo. Duration of treatment was 2 years. The primary outcome measures were the effect of treatment on clinical disability-measured by the absolute change in Kurtzke's expanded disability status scale (EDSS) score- and the proportion of patients with improved, stable, or worse clinical disability (> or = 1.0 grade on EDSS score). FINDINGS: Of the 243 patients screened, 150 met our eligibility criteria and were randomly assigned to IVIg or placebo. Before the start of treatment two patients in the placebo group dropped out, so there were 75 patients in the IVIg group and 73 in the placebo group. Intention-to-treat analysis showed that IVIg treatment had a beneficial effect on the course of clinical disability. The EDSS score decreased in the IVIg-treated patients and increased in the placebo group (-0.23 [95% CI -0.43 to -0.03] vs 0.12 [-0.13 to 0.37], p = 0.008). In the IVIg group, the numbers of patients with improved, stable, or worse clinical disability were 23 (31%), 40 (53%), and 12 (16%) compared with ten (14%), 46 (63%), and 17 (23%) in the placebo group. Side-effects were reported in three (4%) IVIg-treated patients and in four (5%) placebo-group patients, but were not directly linked to study medication. INTERPRETATION: Monthly IVIg is an effective and well-tolerated treatment for patients with relapsing-remitting multiple sclerosis.     

Perception of others’ body size influences weight loss and regain for European American but not African American women.

Objective: The authors investigated whether European American (EA) and African American (AA) women took longer to lose weight, and were less likely to maintain weight loss if they perceived others to be overweight. Design: Overweight EA and AA women completed a Figure Rating Scale and the Three-Factor Eating Questionnaire prior to a weight loss intervention. Body composition was assessed by dual energy X-ray absorptiometry prior to and following weight loss. Main Outcome Measures: rate of weight loss, % body fat at follow-up. Results: For EA, but not AA women, perception of others’ body size was inversely associated with rate of weight loss and cognitive restraint, and positively associated with body fat gain following intervention. In linear regression modeling, EA, but not AA, women who perceived others as large, subsequently had greater percent body fat 1 year after weight loss than did those who perceived others as lean, independent of age, baseline body fat, and body size deemed “acceptable.” Inclusion of cognitive restraint in the model weakened this effect. Conclusion: Among EA but not AA women, perception of others’ body size influenced weight loss and maintenance. This effect may have been mediated by cognitive restraint. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Psychological effects of weight loss and regain: A prospective evaluation.

This study prospectively assessed the psychological effects of weight loss and regain (i.e., weight cycling) in obese women. Measures of mood, binge eating, restraint, disinhibition, and hunger were obtained from 55 participants at baseline, after 6 months of treatment, and 58 months posttreatment. Women lost 21.1 ± 8.4 kg after 6 months of treatment but were 3.6 ± 10.9 kg above baseline weight at the time of the follow-up. Contrary to expectations, after this 21-kg cycle of weight loss and regain, women reported significant improvements in mood and binge eating, as well as reductions in hunger and disinhibition. Restraint was unchanged from baseline to follow-up. These data suggest that weight loss and regain are not associated with long-term adverse psychological effects. The findings also confirm earlier reports of significant weight regain after treatment and underscore the need for research to improve the maintenance of weight loss. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Multicentre trial to introduce the Ottawa ankle rules for use of radiography in acute ankle injuries. Multicentre Ankle Rule Study Group

OBJECTIVE: To assess the feasibility and impact of introducing the Ottawa ankle rules to a large number of physicians in a wide variety of hospital and community settings over a prolonged period of time. DESIGN: Multicentre before and after controlled clinical trial. SETTING: Emergency departments of eight teaching and community hospitals in Canadian communities (population 10,000 to 3,000,000). SUBJECTS: All 12,777 adults (6288 control, 6489 intervention) seen with acute ankle injuries during two 12 month periods before and after the intervention. INTERVENTION: More than 200 physicians of varying experience were taught to order radiography according to the Ottawa ankle rules. MAIN OUTCOME MEASURES: Referral for ankle and foot radiography. RESULTS: There were significant reductions in use of ankle radiography at all eight hospitals and within a priori subgroups: for all hospitals combined 82.8% control v 60.9% intervention(P < 0.001); for community hospitals 86.7% v 61.7%; (P < 0.001); for teaching hospitals 77.9% v 59.9%; (P < 0.001); for emergency physicians 82.1% v 61.6%; (P < 0.001); for family physicians 84.3% v 60.1%; (P < 0.001); and for housestaff 82.3% v 60.1%; (P < 0.001). Compared with patients without fracture who had radiography during the intervention period those who had no radiography spent less time in the emergency department (54.0 v 86.9 minutes; P < 0.001) and had lower medical charges ($70.20 v $161.60; P < 0.001). There was no difference in the rate of fractures diagnosed after discharge from the emergency department (0.5 v 0.4%). CONCLUSIONS: Introduction of the Ottawa ankle rules proved to be feasible in a large variety of hospital and community settings. Use of the rules over a prolonged period of time by many physicians of varying experience led to a decrease in ankle radiography, waiting times, and costs without an increased rate of missed fractures. The multiphase methodological approach used to develop and implement these rules may be applied to other clinical problems.     

Effect of parent weight on weight loss in obese children.

Assessed the effect of parent weight (obese/nonobese parent) and parent control vs child self-control on the weight loss of 41 obese 8–12 yr olds over a 3-yr period. Children of nonobese parents had significantly greater decrease in relative weight after 1 yr, but not after 3 yrs, than children of obese parents. Locus of control was not related to treatment outcome over the 3 yrs. Results suggest that parent weight was related to weight loss, but not weight maintenance, in obese children. (9 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tumor necrosis factor-alpha in sera of obese patients: fall with weight loss

In view of the recent demonstration that obesity in animals and humans is associated with an increase in tumor necrosis factor-alpha (TNFalpha) expression, that this expression falls with weight loss, and that TNFalpha may specifically inhibit insulin action, the possibility that TNFalpha may be a mediator of insulin resistance has been raised. We have undertaken this study to investigate whether serum TNFalpha concentrations are elevated in obese subjects, whether they fall after weight loss, and whether this fall parallels the fall in insulin release after glucose challenge. Obese patients (age range: 25-54, weight mean +/- SD: 96.4 +/- 13.8 kg, body mass index: 35.7 +/- 5.6 kg/m2) were started on a diet program. The mean weight fell to 84.5 +/- 11.3 (P < 0.0001) and body mass index to 31.3 +/- 4.9 (P < 0.0001). Plasma TNFalpha concentrations were markedly elevated in the obese (3.45 +/- 0.16 pg/mL), when compared with controls (0.72 +/- 0.28 pg/mL), and fell significantly (2.63 +/- 1.40 pg/mL) after weight loss (P < 0.02). The magnitude of insulin release after glucose (75 g) challenge (area under the curve) also fell significantly (P < 0.01) after weight loss. The magnitude of weight loss and fall in TNFalpha were related to basal body weight (r = 0.57, P < 0.001) and basal TNFalpha (r = 0.55, P < 0.001) concentrations, respectively, but not to each other or to the glucose-induced insulin release (area under the curve). We conclude that obesity is associated with increased plasma TNFalpha concentrations, which fall with weight loss. Because circulating TNFalpha may mediate insulin resistance in the obese, a fall in TNFalpha concentrations may contribute to the restoration of insulin resistance after weight loss, Thus, TNFalpha may be an important circulating cytokine, which may provide a potentially reversible mechanism for mediating insulin resistance.     

Are smaller weight losses or more achievable weight loss goals better in the long term for obese patients?

Weight losses and psychological well-being were examined at 30 months in 69 men and 61 women initially treated with behavior therapy as a function of (a) initial weight loss and (b) weight-loss goals. Initial weight losses were positively, not negatively, related to weight loss at 30 months. Weight loss goals did not predict short-term or long-term weight loss. People who reached weight goals had better long-term weight losses than those who did not, but this finding was largely due to differences in initial weight loss. Psychological well-being at 30 months was not related to initial weight losses or goals. Although correlational rather than experimental, these results do not support the hypothesis that obese patients should be encouraged to set lower weight-loss goals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Randomised placebo controlled trial of effect on mood of lowering cholesterol concentration. Oxford Cholesterol Study Group

OBJECTIVE: To evaluate the effects on mood of a substantial and prolonged reduction in total cholesterol concentration. DESIGN: Randomised placebo controlled comparison of patients who had been allocated to receive simvastatin 20 mg or 40 mg daily versus those allocated matching placebo in a ratio of 2:1. Follow up at an average of 152 weeks after randomisation. SUBJECTS: Men and women aged between 40 and 75 years at entry with blood total cholesterol of 3.5 mmol/l or greater, who were considered to be at higher than average risk of coronary heart disease based on medical history. MAIN OUTCOME MEASURES: The shortened profile of mood states questionnaire, reported use of psychotropic medication, and symptoms possibly related to mood. RESULTS: Simvastatin reduced total cholesterol by 1.9 mmol/l (26.7%) at the time of follow up. Among all 621 patients randomised to simvastatin (414 patients) or placebo (207 patients) there were no significant differences in the use of psychotropic medication or in reports of symptoms possibly related to mood. Of these patients, 491 (334 simvastatin, 157 placebo) completed the mood questionnaire, and there were no significant differences between the treatment groups in total or subscale scores, even when patients with low baseline cholesterol concentrations or elderly subjects were considered separately. CONCLUSION: These results do not support the hypothesis that treatment to lower cholesterol concentration causes mood disturbance.     

Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. CHIB 201 International Study Group

BACKGROUND: Currently available immunosuppressive regimens for cadaver-kidney recipients are far from ideal because acute-rejection episodes occur in about 30% to 50% of these patients. In the phase III study described here we assessed the ability of basiliximab, a chimeric interleukin (IL)-2 receptor monoclonal antibody, to prevent acute-rejection episodes in renal allograft recipients. METHODS: 380 adult recipients of a primary cadaveric kidney transplant were randomly allocated, in this double-blind trial, to receive a 20 mg infusion of basiliximab on day 0 (day of surgery) and on day 4, to provide IL-2-receptor suppression for 4-6 weeks (n=193), or to receive placebo (n=187). Both groups received baseline dual immunosuppressive therapy with cyclosporin and steroids throughout the study. The primary outcome measure was incidence of acute-rejection episodes during the 6 months after transplantation. Safety and tolerability were monitored over the 12 months of the study. FINDINGS: 376 patients were eligible for intention-to-treat analysis (basiliximab, n=190; placebo, n=186). No significant differences in patient characteristics were apparent. The incidence of biopsy-confirmed acute rejection 6 months after transplantation was 51 (29.8%) of 171 in the basiliximab group compared with 73 (44.0%) of 166 in the placebo group (32% reduction; 14.2% difference [95% Kaplan-Meier CIs 3% to 24%], p=0.012). The incidence of steroid-resistant first rejection episodes that required antibody therapy was significantly lower in the basiliximab group (10% vs 23.1%, 13.1% difference [5.4% to 20.8%], p<0.001). At weeks 2 and 4 post-transplantation, the mean daily dose of steroids was significantly higher in the placebo group (p<0.001 with one-way analysis of variance). The incidence of graft loss at 12 months post-transplantation was 23 (12.1%) of 190 in the basiliximab group and 25 (13.4%) of 186 in the placebo group (1.3% difference [-5% to 9%], p=0.591). The incidence of infection and other adverse events was similar in the two treatment groups. The acute tolerability of basiliximab was excellent, with no evidence of cytokine-release syndrome. 14 deaths (basiliximab n=9; placebo n=5; -2.0% difference [-6% to 2%], p=0.293) occurred during the 12-month study and a further three deaths (basiliximab n=1; placebo n=2) occurred within the 380-day cut-off period. One post-transplantation lymphoproliferative disorder was recorded in each group. INTERPRETATION: Prophylaxis with 40 mg basiliximab reduces the incidence of acute rejection episodes significantly, with no clinically relevant safety or tolerability concerns.     

The effect of epoetin beta (recombinant human erythropoietin) on the need for transfusion in very-low-birth-weight infants. European Multicentre Erythropoietin Study Group

BACKGROUND: Anemia of prematurity is characterized by low reticulocyte counts and inadequate erythropoietin response, for which many very-low-birth-weight infants receive multiple blood transfusions. We investigated whether early treatment of such infants with recombinant human erythropoietin would reduce their need for transfusions. METHODS: We performed a controlled, blinded trial in 241 infants with very low birth weights at 12 centers in six European countries. When three days old, the infants were randomly assigned either to the epoetin group or to the control group. Those in the epoetin group received 250 IU of epoetin beta per kilogram of body weight subcutaneously three times a week from day 3 to day 42 (for a total of 17 doses); those in the control group did not receive this drug. Infants in both groups received oral iron (2 mg per day) from day 14 onward. RESULTS: The control infants needed a mean of 1.25 transfusions each, as compared with 0.87 transfusion for epoetin-treated infants (P = 0.013). The median cumulative volume of blood transfused per kilogram per day was 0.41 ml in the control group (first quartile, 0 ml; third quartile, 0.8 ml) and 0.09 ml in the epoetin group (first quartile, 0 ml; third quartile, 0.8 ml) (P = 0.044). The rate of success, defined as an absence of need for transfusions and a hematocrit that never fell below 32 percent, was 4.1 percent in the control group and 27.5 percent in the epoetin group (P = 0.008). Epoetin was most beneficial in boys with birth weights of 1200 g or more and a base-line hematocrit of 48 percent or more. No toxic effects were observed in the epoetin group; as compared with the control group, the epoetin group had an increased incidence of septicemia (14 vs. 7 episodes, P not significant) and reduced weight gain (520 vs. 571 g, P = 0.02). CONCLUSIONS: Infants with very low birth weights have less need of transfusions if given epoetin beta during the first six weeks of life (250 IU per kilogram three times a week). We recommend early epoetin treatment for all such infants, but further studies of nutrition and iron supplementation during treatment are needed.     

Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial

CONTEXT: Orlistat, a gastrointestinal lipase inhibitor that reduces dietary fat absorption by approximately 30%, may promote weight loss and reduce cardiovascular risk factors. OBJECTIVE: To test the hypothesis that orlistat combined with dietary intervention is more effective than placebo plus diet for weight loss and maintenance over 2 years. DESIGN: Randomized, double-blind, placebo-controlled study conducted from October 1992 to October 1995. SETTING AND PARTICIPANTS: Obese adults (body mass index [weight in kilograms divided by the square of height in meters], 30-43 kg/m2) evaluated at 18 US research centers. INTERVENTION: Subjects received placebo plus a controlled-energy diet during a 4-week lead-in. On study day 1, the diet was continued and subjects were randomized to receive placebo 3 times a day or orlistat, 120 mg 3 times a day, for 52 weeks. After 52 weeks, subjects began a weight-maintenance diet, and the placebo group (n = 133) continued to receive placebo and orlistat-treated subjects were rerandomized to receive placebo 3 times a day (n = 138), orlistat, 60 mg (n = 152) or 120 mg (n = 153) 3 times a day, for an additional 52 weeks. MAIN OUTCOME MEASURES: Body weight change and changes in blood pressure and serum lipid, glucose, and insulin levels. RESULTS: A total of 1187 subjects entered the protocol, and 892 were randomly assigned on day 1 to double-blind treatment. For intent-to-treat analysis, 223 placebo-treated subjects and 657 orlistat-treated subjects were evaluated. During the first year orlistat-treated subjects lost more weight (mean +/- SEM, 8.76+/-0.37 kg) than placebo-treated subjects (5.81+/-0.67 kg) (P<.001). Subjects treated with orlistat, 120 mg 3 times a day, during year 1 and year 2 regained less weight during year 2 (3.2+/-0.45 kg; 35.2% regain) than those who received orlistat, 60 mg (4.26+/-0.57 kg; 51.3% regain), or placebo (5.63+/-0.42 kg; 63.4% regain) in year 2 (P<.001). Treatment with orlistat, 120 mg 3 times a day, was associated with improvements in fasting low-density lipoprotein cholesterol and insulin levels. CONCLUSIONS: Two-year treatment with orlistat plus diet significantly promotes weight loss, lessens weight regain, and improves some obesity-related disease risk factors.     

High-versus low-dose erythropoietin in extremely low birth weight infants. The European Multicenter rhEPO Study Group

BACKGROUND: Road traffic accidents (RTA) are an important yet preventable cause of death and disability in developing countries like Pakistan. Yet accurate epidemiological data on injuries in developing country injuries is often difficult to obtain. We applied the capture-recapture method to estimate the death and injury rates due to RTA in Karachi. METHODS: We applied the two-sample capture-recapture method using traffic police records as one source of capture and the logs of a non-government ambulance service as the second capture source for the same 10 months and 20 days for which 1994 data were available. We generated a conservative adjusted estimate of injuries and deaths by considering entries in the two sources as matched if they reported the same date, time, and place, and at least one of the other matching variables, of name, vehicle registration number, vehicle types or patient outcome. We then compared the estimated rates with the police rates. RESULTS: In 1994 police reported 544 deaths and 793 injuries due to RTA while ambulance records noted 343 deaths and 2048 injuries. The capture-recapture analysis estimated at least 972 (95% CI: 912-1031) deaths and 18,936 (95% CI: 15,507-22,342) injuries attributable to RTA during the study period. Official sources counted only 56% of deaths and 4% of serious injuries. The estimated rates for the year 1994 were 185 injuries and 11.2 deaths per 100,000 population. CONCLUSION: Road traffic injuries and deaths in Karachi are a much more substantial health problem than is evident from official statistics.     

Body image in obese women before, during, and after weight loss treatment.

Body image, as measured by the Appearance Evaluation and Body Areas Satisfaction scales of the Multidimensional Body-Self Relations Questionnaire (T. F. Cash, 1994b), was assessed in 59 obese women before, during, and after 48 weeks of weight loss treatment. Before treatment, positive ratings of body image were associated with higher levels of self-esteem, lower levels of dysphoria, and fewer previous diets. After 24 weeks and a mean weight loss of 19.4 kg (SD?=?6.5), participants showed significant (p ?p ?     

Multinational randomised controlled trial of lubeluzole in acute ischaemic stroke. European and Australian Lubeluzole Ischaemic Stroke Study Group

The purpose of this investigation was to examine whether inhaled nitric oxide (NO) may alter oxidative stress parameters and induce lung inflammation in moderate hyaline membrane disease (HMD). Eighteen moderately premature lambs (130 days gestation, term = 147 days) were randomly assigned to treatment with 20 ppm inhaled NO (n = 8) from the onset of ventilation or used as control (n = 10). Except inhaled NO, treatments were intentionally similar to those applied in clinical situations. The main studied parameters were oxidative stress index measurements on lung parenchyma and in circulating blood, lung parenchyma microscopic examination and bronchoalveolar lavage cell count. We found that 20 ppm of inhaled NO for 5 h did not change significantly either malondialdehyde and total antioxidant status levels in circulating blood, or malondialdehyde, reduced glutathione, glutathione peroxidase and glutathione reductase in lung parenchyma. Amino-imino-propene bond generation, which are lipoperoxidation markers, was similar in both groups. Furthermore, no significant changes in the number of inflammatory cells in lung lavage products and in lung parenchyma microscopic examination could be found. Therefore, these data do not support the hypothesis that short-term NO inhalation increases oxidative stress and lung inflammation in an experimental model of moderate HMD.     

The impact of self-efficacy on behavior change and weight change among overweight participants in a weight loss trial.

Despite considerable clinical interest, attempts to link perceived self-efficacy with successful weight control have had mixed success. Definitive data on prospective associations between self-efficacy and weight loss are particularly sparse. This study examined relationships between self-efficacy beliefs, weight control behaviors, and weight change among individuals participating in a weight loss trial (N = 349, 87% women). Cross-sectionally, eating and exercise self-efficacy beliefs were strongly associated with corresponding weight loss behaviors. Self-efficacy beliefs prospectively predicted weight control behavior and weight change during active treatment but not during follow-up. Mediational models indicate that people's weight control behaviors mediate the impact of self-efficacy on weight change. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Moclobemide and imipramine in chronic depression (dysthymia): an international double-blind, placebo-controlled trial. International Collaborative Study Group

An international, multicenter, placebo-controlled study was undertaken to determine the safety and antidepressant efficacy of moclobemide, a new reversible inhibitor of monoamine oxidase A, and imipramine in the treatment of dysthymia (DSM-III-R). A total of 315 patients were enrolled and randomly assigned to an 8-week treatment in one of three groups (moclobemide, imipramine and placebo). Patients were male or female outpatients aged between 18 and 65 years meeting DSM-III-R criteria for dysthymia, primary type, with late or early onset. Of the patients in each group 85% completed the 8-week treatment period. The percentage of patients who no longer fulfilled DSM-III-R symptom criteria at treatment endpoint was significantly higher in the moclobemide (60%) and imipramine (49%) treatment groups than in the placebo group (22%). Differences to placebo were also statistically significant both for moclobemide and for imipramine on the other efficacy variables (i.e. Hamilton Rating Scale for Depression, final overall efficacy assessment, Clinical Global Impression and symptom check list self-rating). A significant superiority of moclobemide and imipramine over placebo was found in pure dysthymia and in double-depression, as well as in early and late onset subgroups. In early onset cases, moclobemide was significantly more effective than was imipramine on the Hamilton Rating Scale for Depression. Anticholinergic symptoms and sleepiness were significantly more frequent side effects on imipramine than on moclobemide or on placebo, and the investigators' final overall assessment of tolerability significantly favoured moclobemide over imipramine. This study demonstrates the efficacy of high dose moclobemide (mean dose 675 mg/day) and high dose imipramine (220 mg/day) against placebo in the treatment of dysthymia. Moclobemide was better tolerated than was imipramine.