PLoS clinical trials最新文献

Objectives: Sulfadoxine-pyrimethamine (SP) is an antimalarial drug that acts on the folate metabolism of the malaria parasite. We investigated whether folate (FA) supplementation in a high or a low dose affects the efficacy of SP for the treatment of uncomplicated malaria in pregnant women.

Design: This was a randomized, placebo-controlled, double-blind trial.

Setting: The trial was carried out at three hospitals in western Kenya.

Participants: The participants were 488 pregnant women presenting at their first antenatal visit with uncomplicated malaria parasitaemia (density of >or= 500 parasites/microl), a haemoglobin level higher than 7 g/dl, a gestational age between 17 and 34 weeks, and no history of antimalarial or FA use, or sulfa allergy. A total of 415 women completed the study.

Interventions: All participants received SP and iron supplementation. They were randomized to the following arms: FA 5 mg, FA 0.4 mg, or FA placebo. After 14 days, all participants continued with FA 5 mg daily as per national guidelines. Participants were followed at days 2, 3, 7, 14, 21, and 28 or until treatment failure.

Outcome measures: The outcomes were SP failure rate and change in haemoglobin at day 14.

Results: The proportion of treatment failure at day 14 was 13.9% (19/137) in the placebo group, 14.5% (20/138) in the FA 0.4 mg arm (adjusted hazard ratio [AHR], 1.07; 98.7% confidence interval [CI], 0.48 to 2.37; p = 0.8), and 27.1% (38/140) in the FA 5 mg arm (AHR, 2.19; 98.7% CI, 1.09 to 4.40; p = 0.005). The haemoglobin levels at day 14 were not different relative to placebo (mean difference for FA 5 mg, 0.17 g/dl; 98.7% CI, -0.19 to 0.52; and for FA 0.4 mg, 0.14 g/dl; 98.7% CI, -0.21 to 0.49).

Conclusions: Concomitant use of 5 mg FA supplementation compromises the efficacy of SP for the treatment of uncomplicated malaria in pregnant women. Countries that use SP for treatment or prevention of malaria in pregnancy need to evaluate their antenatal policy on timing or dose of FA supplementation.

Objectives: Changes in the way dietary fat is metabolized can be considered causative in obesity. The role of sedentary behavior in this defect has not been determined. We hypothesized that physical inactivity partitions dietary fats toward storage and that a resistance exercise training program mitigates storage.

Design: We used bed rest, with randomization to resistance training, as a model of physical inactivity.

Setting: The trial took place at the Space Clinic (Toulouse, France).

Participants: A total of 18 healthy male volunteers, of mean age +/- standard deviation 32.6 +/- 4.0 y and body mass index 23.6 +/- 0.7 kg/m(2), were enrolled.

Interventions: An initial 15 d of baseline data collection were followed by 3 mo of strict bed-rest alone (control group, n = 9) or with the addition of supine resistance exercise training every 3 d (exercise group, n = 9).

Outcome measures: Oxidation of labeled [d(31)]palmitate (the main saturated fatty acid of human diet) and [1-(13)C]oleate (the main monounsaturated fatty acid), body composition, net substrate use, and plasma hormones and metabolites were measured.

Results: Between-group comparisons showed that exercise training did not affect oxidation of both oleate (mean difference 5.6%; 95% confidence interval [95% CI], -3.3% to 14.5%; p = 0.20) and palmitate (mean difference -0.2%; 95% CI, -4.1% to 3.6%; p = 0.89). Within-group comparisons, however, showed that inactivity changed oxidation of palmitate in the control group by -11.0% (95% CI, -19.0% to -2.9%; p = 0.01) and in the exercise group by -11.3% (95% CI, -18.4% to -4.2%; p = 0.008). In contrast, bed rest did not significantly affect oleate oxidation within groups. In the control group, the mean difference in oleate oxidation was 3.2% (95% CI, -4.2% to 10.5%; p = 0.34) and 6.8% (95% CI, -1.2% to 14.7%; p = 0.08) in the exercise group.

Conclusions: Independent of changes in energy balance (intake and/or output), physical inactivity decreased the oxidation of saturated but not monounsaturated dietary fat. The effect is apparently not compensated by resistance exercise training. These results suggest that Mediterranean diets should be recommended in sedentary subjects and recumbent patients.

Objectives: We evaluated the hypothesis that cyclooxygenase (COX) inhibitor use might have counteracted a beneficial effect of postmenopausal hormone therapy, and account for the absence of cardioprotection in the Women's Health Initiative hormone trials. Estrogen increases COX expression, and inhibitors of COX such as nonsteroidal anti-inflammatory agents appear to increase coronary risk, raising the possibility of a clinically important interaction in the trials.

Design: The hormone trials were randomized, double-blind, and placebo-controlled. Use of nonsteroidal anti-inflammatory drugs was assessed at baseline and at years 1, 3, and 6.

Setting: The Women's Health Initiative hormone trials were conducted at 40 clinical sites in the United States.

Participants: The trials enrolled 27,347 postmenopausal women, aged 50-79 y.

Interventions: We randomized 16,608 women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or to placebo, and 10,739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo.

Outcome measures: Myocardial infarction, coronary death, and coronary revascularization were ascertained during 5.6 y of follow-up in the estrogen plus progestin trial and 6.8 y of follow-up in the estrogen alone trial.

Results: Hazard ratios with 95% confidence intervals were calculated from Cox proportional hazard models stratified by COX inhibitor use. The hazard ratio for myocardial infarction/coronary death with estrogen plus progestin was 1.13 (95% confidence interval 0.68-1.89) among non-users of COX inhibitors, and 1.35 (95% confidence interval 0.86-2.10) among continuous users. The hazard ratio with estrogen alone was 0.92 (95% confidence interval 0.57-1.48) among non-users of COX inhibitors, and 1.08 (95% confidence interval 0.69-1.70) among continuous users. In a second analytic approach, hazard ratios were calculated from Cox models that included hormone trial assignment as well as a time-dependent covariate for medication use, and an interaction term. No significant interaction was identified.

Conclusions: Use of COX inhibitors did not significantly affect the Women's Health Initiative hormone trial results.

Objectives: The supermarket industry now services many customers through online food shopping over the Internet. The Internet shopping process offers a novel opportunity for the modification of dietary patterns. The aim of this study was to evaluate the effects on consumers' purchases of saturated fat of a fully automated computerised system that provided real-time advice tailored to the consumers' specific purchases recommending foods lower in saturated fat.

Design: This study was a blinded, randomised controlled trial.

Setting: The study was conducted in Sydney, New South Wales, Australia.

Participants: The participants were consumers using a commercial online Internet shopping site between February and June 2004.

Interventions: Individuals assigned to intervention received fully automated advice that recommended specific switches from selected products higher in saturated fat to alternate similar products lower in saturated fat. Participants assigned to control received general non-specific advice about how to eat a diet lower in saturated fat.

Outcome measures: The outcome measure was the difference in saturated fat (grams per 100 g of food) in shopping baskets between the intervention and control groups.

Results: There were 497 randomised participants, mean age 40 y, each shopping for an average of about three people. The amount of saturated fat in the foods purchased by the intervention group was 0.66% lower (95% confidence interval 0.48-0.84, p < 0.001) than in the control group. The effects of the intervention were sustained over consecutive shopping episodes, and there was no difference in the average cost of the food bought by each group.

Conclusions: Fully automated, purchase-specific dietary advice offered to customers during Internet shopping can bring about changes in food purchasing habits that are likely to have significant public health implications. Because implementation is simple to initiate and maintain, this strategy would likely be highly cost-effective.

Objectives: Previous studies have shown that in children with severe malaria, resuscitation with albumin infusion results in a lower mortality than resuscitation with saline infusion. Whether the apparent benefit of albumin is due solely to its colloidal properties, and thus might also be achieved with other synthetic colloids, or due to the many other unique physiological properties of albumin is unknown. As albumin is costly and not readily available in Africa, examination of more affordable colloids is warranted. In order to inform the design of definitive phase III trials we compared volume expansion with Gelofusine (succinylated modified fluid gelatin 4% intravenous infusion) with albumin.

Design: This study was a phase II safety and efficacy study.

Setting: The study was conducted at Kilifi District Hospital, Kenya.

Participants: The participants were children admitted with severe falciparum malaria (impaired consciousness or deep breathing), metabolic acidosis (base deficit > 8 mmol/l), and clinical features of shock.

Interventions: The interventions were volume resuscitation with either 4.5% human albumin solution or Gelofusine.

Outcome measures: Primary endpoints were the resolution of shock and acidosis; secondary endpoints were in-hospital mortality and adverse events including neurological sequelae.

Results: A total of 88 children were enrolled: 44 received Gelofusine and 44 received albumin. There was no significant difference in the resolution of shock or acidosis between the groups. Whilst no participant developed pulmonary oedema or fluid overload, fatal neurological events were more common in the group receiving gelatin-based intervention fluids. Mortality was lower in patients receiving albumin (1/44; 2.3%) than in those treated with Gelofusine (7/44; 16%) by intention to treat (Fisher's exact test, p = 0.06), or 1/40 (2.5%) and 4/40 (10%), respectively, for those treated per protocol (p = 0.36). Meta-analysis of published trials to provide a summary estimate of the effect of albumin on mortality showed a pooled relative risk of death with albumin administration of 0.19 (95% confidence interval 0.06-0.59; p = 0.004 compared to other fluid boluses).

Conclusions: In children with severe malaria, we have shown a consistent survival benefit of receiving albumin infusion compared to other resuscitation fluids, despite comparable effects on the resolution of acidosis and shock. The lack of similar mortality benefit from Gelofusine suggests that the mechanism may involve a specific neuroprotective effect of albumin, rather than solely the effect of the administered colloid. Further exploration of the benefits of albumin is warranted in larger clinical trials.

Objectives: Treatment of Plasmodium falciparum malaria with sulfadoxine-pyrimethamine (SP) is followed by a sharp rise in the prevalence and density of gametocytes. We did a randomized trial to determine the effect of treatment of asymptomatic infections with SP or SP plus one dose of artesunate (SP+AS) on gametocyte carriage.

Design: The study was a three-arm open-label randomized trial. We randomized asymptomatic carriers of P. falciparum to receive antimalarial treatment or placebo, and recorded the prevalence and density of gametocytes over the next 2 mo.

Setting: The trial was conducted during the dry (low malaria transmission) season in four rural villages in Gambia.

Participants: Participants were adults and children aged over 6 mo with asexual P. falciparum infection and confirmed free of clinical symptoms of malaria over a 2-d screening period.

Interventions: Participants were randomized to receive a single dose of SP or SP+AS or placebo.

Outcome measures: The outcome measures were the presence of gametocytes 7 and 56 d after treatment, and the duration and density of gametocytaemia over 2 mo.

Results: In total, 372 asymptomatic carriers were randomized. Gametocyte prevalence on day 7 was 10.5% in the placebo group, 11.2% in the SP group (risk difference to placebo 0.7%, 95% confidence interval -7.4% to 8.7%, p = 0.87), and 7.1% in the SP+AS group (risk difference to placebo 4.1%, 95% confidence interval -3.3% to 12%, p = 0.28). By day 56, gametocyte prevalence was 13% in the placebo group and 2% in both drug-treated groups. Gametocyte carriage (the area under the curve of gametocyte density versus time), was reduced by 71% in the SP group, and by 74% in the SP+AS group, compared to placebo. Gametocyte carriage varied with age and was greater among children under 15 than among adults.

Conclusions: Treatment of asymptomatic carriers of P. falciparum with SP does not increase gametocyte carriage or density. Effective treatment of asexual parasitaemia in the dry season reduces gametocyte carriage to very low levels after 4 wk.

Objectives: We investigated the long-term impact of early childhood malaria prophylaxis on cognitive and educational outcomes.

Design: This was a household-based cluster-controlled intervention trial.

Setting: The study was conducted in 15 villages situated between 32 km to the east and 22 km to the west of the town of Farafenni, the Gambia, on the north bank of the River Gambia.

Participants: A total of 1,190 children aged 3-59 mo took part in the trial. We traced 579 trial participants (291 in the prophylaxis group and 288 in the placebo group) in 2001, when their median age was 17 y 1 mo (range 14 y 9 mo to 19 y 6 mo).

Interventions: Participants received malaria chemoprophylaxis (dapsone/pyrimethamine) or placebo for between one and three malaria transmission seasons from 1985 to 1987 during the controlled trial. At the end of the trial, prophylaxis was provided for all children under 5 y of age living in the study villages.

Outcome measures: The outcome measures were cognitive abilities, school enrolment, and educational attainment (highest grade reached at school).

Results: There was no significant overall intervention effect on cognitive abilities, but there was a significant interaction between intervention group and the duration of post-trial prophylaxis (p = 0.034), with cognitive ability somewhat higher in the intervention group among children who received no post-trial prophylaxis (treatment effect = 0.2 standard deviations [SD], 95% confidence interval [CI] -0.03 to 0.5) and among children who received less than 1 y of post-trial prophylaxis (treatment effect = 0.4 SD, 95% CI 0.1 to 0.8). The intervention group had higher educational attainment by 0.52 grades (95% CI = -0.041 to 1.089; p = 0.069). School enrolment was similar in the two groups.

Conclusions: The results are suggestive of a long-term effect of malaria prophylaxis on cognitive function and educational attainment, but confirmatory studies are needed.