Effects of policy options for human resources for health: an analysis of systematic reviews. The efficacy of psychological, educational, and behavioral treatment. Confirmation from meta-analysis. Design of the multicenter Australian study of epidural anesthesia and analgesia in major surgery: the MASTER trial. Vitamins and perinatal outcomes among HIV-negative women in Tanzania. Behaviour change in clients of health centre-based voluntary HIV counselling and testing services in Kenya. Increasing colorectal cancer screening among individuals in the carpentry trade: test of risk communication interventions. Palivizumab for immunoprophylaxis of respiratory syncytial virus (RSV) bronchiolitis in high-risk infants and young children: a systematic review and additional economic modelling of subgroup analyses. Prospective randomized study of surgical morbidity following primary systemic therapy for breast cancer. Reducing stillbirths: behavioural and nutritional interventions before and during pregnancy. A randomized trial to determine the optimal dosage of multivitamin supplements to reduce adverse pregnancy outcomes among HIV-infected women in Tanzania. A randomised comparison of strategies for reducing infective complications of induced abortion. Reducing stillbirths: prevention and management of medical disorders and infections during pregnancy. The effects of hospitalization for bed rest on duration of gestation, fetal growth and neonatal morbidity in triplet pregnancy. Efficacy of pneumococcal vaccine in severe chronic obstructive pulmonary disease. Evolution of the randomized controlled trial in oncology over three decades. Association of funding and conclusions in randomized drug trials: a reflection of treatment effect or adverse events? Reducing the risk of infection in the elderly by dietary intake of yoghurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1. Five percent albumin for adult burn shock resuscitation: lack of effect on daily multiple organ dysfunction score. Short-stay intensive care after coronary artery bypass surgery: randomized clinical trial on safety and cost-effectiveness. Effect of written feedback by editors on quality of reviews: two randomized trials. Multiple risk expert systems interventions: impact of simultaneous stage-matched expert system interventions for smoking, high-fat diet, and sun exposure in a population of parents. Results of a year-long incentives-based worksite smoking-cessation program. Randomized trial of intake of fat, fiber, and beta carotene to prevent colorectal adenomas. Blunt vascular injuries of the head and neck: is heparinization necessary? Improving services for disadvantaged childbearing women. Randomised trial of effects of vitamin supplements on pregnancy outcomes and T cell counts in HIV-1-infected women in Tanzania. Disease management for depression and at-risk drinking via telephone in an older population of veterans. Effect of attendance at a training session on peer reviewer quality and performance. Kangaroo mother method: randomised controlled trial of an alternative method of care for stabilised low-birthweight infants. Maternidad Isidro Ayora Study Team. Reducing social inequalities in smoking: can evidence inform policy? A pilot study. Effects on quality of life with comprehensive rehabilitation after acute myocardial infarction.
Policy makers face challenges to ensure an appropriate supply and distribution of trained health workers and to manage their performance in delivery of services, especially in countries with low and middle incomes. We aimed to identify all available policy options to address human resources for health in such countries, and to assess the effectiveness of these policy options.
                We searched Medline and Embase from 1979 to September, 2006, the Cochrane Library, and the Human Resources for Health Global Resource Center database. We also searched up to 10 years of archives from five relevant journals, and consulted experts. We included systematic reviews in English which assessed the effects of policy options that could affect the training, distribution, regulation, financing, management, organisation, or performance of health workers. Two reviewers independently assessed each review for eligibility and quality, and systematically extracted data about main effects. We also assessed whether the policy options were equitable in their effects; suitable for scaling up; and applicable to countries with low and middle incomes.
                28 of the 759 systematic reviews of effects that we identified were eligible according to our criteria. Of these, only a few included studies from countries with low and middle incomes, and some reviews were of low quality. Most evidence focused on organisational mechanisms for human resources, such as substitution or shifting tasks between different types of health workers, or extension of their roles; performance-enhancing strategies such as quality improvement or continuing education strategies; promotion of teamwork; and changes to workflow. Of all policy options, the use of lay health workers had the greatest proportion of reviews in countries with a range of incomes, from high to low.
                We have identified a need for more systematic reviews on the effects of policy options to improve human resources for health in countries with low and middle incomes, for assessments of any interventions that policy makers introduce to plan and manage human resources for health, and for other research to aid policy makers in these countries. Conventional reviews of research on the efficacy of psychological, educational, and behavioral treatments often find considerable variation in outcome among studies and, as a consequence, fail to reach firm conclusions about the overall effectiveness of the interventions in question. In contrast meta-analytic reviews show a strong, dramatic pattern of positive overall effects that cannot readily be explained as artifacts of meta-analytic technique or generalized placebo effects. Moreover, the effects are not so small that they can be dismissed as lacking practical or clinical significance. Although meta-analysis has limitations, there are good reasons to believe that its results are more credible than those of conventional reviews and to conclude that well-developed psychological, educational, and behavioral treatment is generally efficacious. The Multicenter Australian Study of Epidural Anesthesia and Analgesia in Major Surgery (The MASTER Trial) was designed to evaluate the possible benefit of epidural block in improving outcome in high-risk patients. The trial began in 1995 and is scheduled to reach the planned sample size of 900 during 2001. This paper describes the trial design and presents data comparing 455 patients randomized in 21 institutions in Australia, Hong Kong, and Malaysia, with 237 patients from the same hospitals who were eligible but not randomized. Nine categories of high-risk patients were defined as entry criteria for the trial. Protocols for ethical review, informed consent, randomization, clinical anesthesia and analgesia, and perioperative management were determined following extensive consultation with anesthesiologists throughout Australia. Clinical and research information was collected in participating hospitals by research staff who may not have been blind to allocation. Decisions about the presence or absence of endpoints were made primarily by a computer algorithm, supplemented by blinded clinical experts. Without unblinding the trial, comparison of eligibility criteria and incidence of endpoints between randomized and nonrandomized patients showed only small differences. We conclude that there is no strong evidence of important demographic or clinical differences between randomized and nonrandomized patients eligible for the MASTER Trial. Thus, the trial results are likely to be broadly generalizable. Prematurity and low birth weight are associated with high perinatal and infant mortality, especially in developing countries. Maternal micronutrient deficiencies may contribute to these adverse outcomes.
                In a double-blind trial in Dar es Salaam, Tanzania, we randomly assigned 8468 pregnant women (gestational age of fetus, 12 to 27 weeks) who were negative for human immunodeficiency virus infection to receive daily multivitamins (including multiples of the recommended dietary allowance) or placebo. All the women received prenatal supplemental iron and folic acid. The primary outcomes were low birth weight (<2500 g), prematurity, and fetal death.
                The incidence of low birth weight was 7.8% among the infants in the multivitamin group and 9.4% among those in the placebo group (relative risk, 0.82; 95% confidence interval [CI], 0.70 to 0.95; P=0.01). The mean difference in birth weight between the groups was modest (67 g, P<0.001). The rates of prematurity were 16.9% in the multivitamin group and 16.7% in the placebo group (relative risk, 1.01; 95% CI, 0.91 to 1.11; P=0.87), and the rates of fetal death were 4.3% and 5.0%, respectively (relative risk, 0.87; 95% CI, 0.72 to 1.05; P=0.15). Supplementation reduced both the risk of a birth size that was small for gestational age (<10th percentile; 10.7% in the multivitamin group vs. 13.6% in the placebo group; relative risk, 0.77; 95% CI, 0.68 to 0.87; P<0.001) and the risk of maternal anemia (hemoglobin level, <11 g per deciliter; relative risk, 0.88; 95% CI, 0.80 to 0.97; P=0.01), although the difference in the mean hemoglobin levels between the groups was small (0.2 g per deciliter, P<0.001).
                Multivitamin supplementation reduced the incidence of low birth weight and small-for-gestational-age births but had no significant effects on prematurity or fetal death. Multivitamins should be considered for all pregnant women in developing countries. (ClinicalTrials.gov number, NCT00197548 [ClinicalTrials.gov].).
                Copyright 2007 Massachusetts Medical Society. To explore behaviour change, baseline risk behaviour, perception of risk, HIV disclosure and life events in health centre-based voluntary counselling and testing (VCT) clients.
                Single-arm prospective cohort with before-after design at three (one urban and two rural) government health centres in Kenya; study duration 2 years, 1999-2001.
                Consecutive eligible adult clients.
                Numbers of sexual partners, partner type, condom use, reported symptoms of sexually transmitted infection, HIV disclosure and life events.
                High rates of enrollment and follow-up provided a demographically representative sample of 401 clients with mean time to follow-up of 7.5 months. Baseline indicators showed that clients were at higher risk than the general population, but reported a poor perception of risk. Clients with multiple partners showed a significant reduction of sexual partners at follow-up (16% to 6%; p<0.001), and numbers reporting symptoms of sexually transmitted infection decreased significantly also (from 40% to 15%; p<0.001). Condom use improved from a low baseline. Low rates of disclosure (55%) were reported by HIV-positive clients. Overall, no changes in rates of life events were seen.
                This study suggests that significant prevention gains can be recorded in clients receiving health centre-based VCT services in Africa. Prevention issues should be considered when refining counselling and testing policies for expanding treatment programmes. Individuals in the carpentry trade, due to lifestyle habits and occupational exposures, may be at above-average risk for colorectal cancer (CRC). Based on the literature which suggests that increasing perceived risk motivates behavior change, we report on the effectiveness of four risk-communication interventions targeted to increase initial, yearly and repeat fecal occult screening (FOBT) among carpenters (N = 860) over a 3-year period.
                Our 2 x 2 factorial design intervention study varied two dimensions of providing CRC risk factor information: (1) type of risk factor-one set of interventions emphasized three basic risk factors (age, family history and polyps); the other set emphasized a comprehensive set of risk factors including basic, lifestyle, and occupational factors, and (2) tailoring/not tailoring risk factor information. Participants were provided FOBTs. Outcomes were the proportion of returned FOBTs.
                Varying the amount and intensity of delivering CRC risk factors information affected neither risk perceptions nor initial, yearly, or repeat screening. However, yearly and repeat screening rates were greater among participants who received interventions addressing comprehensive set of risk factors, especially with increasing age.
                Tailoring on several CRC risk factors appears insufficient to increase and sustain elevated perceptions of CRC risks to promote screening. Respiratory syncytial virus (RSV) is a seasonal infectious disease, with epidemics occurring annually from October to March in the UK. It is a very common infection in infants and young children and can lead to hospitalisation, particularly in those who are premature or who have chronic lung disease (CLD) or congenital heart disease (CHD). Palivizumab (Synagis®, MedImmune) is a monoclonal antibody designed to provide passive immunity against RSV and thereby prevent or reduce the severity of RSV infection. It is licensed for the prevention of serious lower respiratory tract infection caused by RSV in children at high risk. While it is recognised that a policy of using palivizumab for all children who meet the licensed indication does not meet conventional UK standards of cost-effectiveness, most clinicians feel that its use is justified in some children.
                To use systematic review evidence to estimate the cost-effectiveness of immunoprophylaxis of RSV using palivizumab in different subgroups of children with or without CLD or CHD who are at high risk of serious morbidity from RSV infection.
                A systematic review of the literature and an economic evaluation was carried out. The bibliographic databases included the Cochrane Library [Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA)] and five other databases, from inception to 2009. Research registries of ongoing trials including Current Controlled Trials metaRegister, Clinical Trials.gov and the National Institute for Health Research Clinical Research Network Portfolio were also searched.
                Searches were conducted for prognostic and hospitalisation studies covering 1950-2009 (the original report searches conducted in 2007 covering the period 1950-2007 were rerun in August 2009 to cover the period 2007-9) and the database of all references from the original report was sifted to find any relevant studies that may have been missed. The risk factors identified from the systematic review of included studies were analysed and synthesised using stata. The base-case decision tree model developed in the original HTA journal publication [Health Technol Assess 2008;12(36)] was used to derive the cost-effectiveness of immunoprophylaxis of RSV using palivizumab in different subgroups of pre-term infants and young children who are at high risk of serious morbidity from RSV infection. Cost-effective spectra of prophylaxis with palivizumab compared with no prophylaxis for children without CLD/CHD, children with CLD, children with acyanotic CHD and children with cyanotic CHD were derived.
                Thirteen studies were included in this analysis. Analysis of 16,128 subgroups showed that prophylaxis with palivizumab may be cost-effective [at a willingness-to-pay threshold of £30,000/quality-adjusted life-year (QALY)] for some subgroups. For example, for children without CLD or CHD, the cost-effective subgroups included children under 6 weeks old at the start of the RSV season who had at least two other risk factors that were considered in this report and were born at 24 weeks gestational age (GA) or less, but did not include children who were > 9 months old at the start of the RSV season or had a GA of > 32 weeks. For children with CLD, the cost-effective subgroups included children < 6 months old at the start of the RSV season who were born at 28 weeks GA or less, but did not include children who were > 21 months old at the start of the RSV season. For children with acyanotic CHD, the cost-effective subgroups included children < 6 months old at the start of the RSV season who were born at 24 weeks GA or less, but did not include children who were > 21 months old at the start of the RSV season. For children with cyanotic CHD, the cost-effective subgroups included children < 6 weeks old at the start of the RSV season who were born at 24 weeks GA or less, but did not include children who were > 12 months old at the start of the RSV season.
                The poor quality of the studies feeding numerical results into this analysis means that the true cost-effectiveness may vary considerably from that estimated here. There is a risk that the relatively high mathematical precision of the point estimates of cost-effectiveness may be quite inaccurate because of poor-quality inputs.
                Prophylaxis with palivizumab does not represent good value for money based on the current UK incremental cost-effectiveness ratio threshold of £30,000/QALY when used unselectively in children without CLD/CHD or children with CLD or CHD. This subgroup analysis showed that prophylaxis with palivizumab may be cost-effective (at a willingness-to-pay threshold of £30,000/QALY) for some subgroups. In summary, the cost-effective subgroups for children who had no CLD or CHD must contain at least two other risk factors apart from GA and birth age. The cost-effective subgroups for children who had CLD or CHD do not necessarily need to have any other risk factors. Future research should be directed towards conducting much larger, better powered and better reported studies to derive better estimates of the risk factor effect sizes.
                This report was funded by the HTA programme of the National Institute for Health Research. The influence of primary systemic therapy in treating operable breast cancer on postmastectomy morbidity rates was investigated. The contribution of other risk factors was assessed by multiple logistic regression. Seventy-nine eligible patients were randomly allocated, 39 to undergo immediate modified radical mastectomy, and 40 to receive initial cytotoxic or endocrine treatment followed by mastectomy. Postoperative wound seroma, infection and necrosis were recorded prospectively. Fourteen minor and six major complications occurred in 17 patients treated conventionally, while 14 patients developed 11 minor and six major complications after systemic therapy (P > 0.4). Median hospital stay was 8 days for both groups. Age, smoking, immediate breast reconstruction and the type of primary systemic treatment given were not independent predictors of complication risk. Obesity emerged as a significant risk factor for postmastectomy complications (P = 0.015). Primary systemic therapy does not increase the rate of morbidity after mastectomy. The vast majority of global stillbirths occur in low- and middle-income countries, and in many settings, the majority of stillbirths occur antenatally, prior to the onset of labour. Poor nutritional status, lack of antenatal care and a number of behaviours increase women's risk of stillbirth in many resource-poor settings. Interventions to reduce these risks could reduce the resulting burden of stillbirths, but the evidence for the impact of such interventions has not yet been comprehensively evaluated.
                This second paper of a systematic review of interventions that could plausibly impact stillbirth rates covers 12 different interventions relating to behavioural and socially mediated risk factors, including exposures to harmful practices and substances, antenatal care utilisation and quality, and maternal nutrition before and during pregnancy. The search strategy reviewed indexed medical journals on PubMed and the Cochrane Library. If any eligible randomised controlled trials were identified that were published after the most recent Cochrane review, they were added to generate new meta-analyses. Interventions covered in this paper have a focus on low- and middle-income countries, both because of the large burden of stillbirths and because of the high prevalence of risk factors including maternal malnutrition and harmful environmental exposures. The reviews and studies belonging to these interventions were graded and conclusions derived about the evidence of benefit of these interventions.
                From a programmatic perspective, none of the interventions achieved clear evidence of benefit. Evidence for some socially mediated risk factors were identified, such as exposure to indoor air pollution and birth spacing, but still require the development of appropriate interventions. There is a need for additional studies on culturally appropriate behavioural interventions and clinical trials to increase smoking cessation and reduce exposure to smokeless tobacco. Balanced protein-energy supplementation was associated with reduced stillbirth rates, but larger well-designed trials are required to confirm findings. Peri-conceptional folic acid supplementation significantly reduces neural tube defects, yet no significant associated reductions in stillbirth rates have been documented. Evidence for other nutritional interventions including multiple micronutrient and Vitamin A supplementation is weak, suggesting the need for further research to assess potential of nutritional interventions to reduce stillbirths.
                Antenatal care is widely used in low- and middle-income countries, and provides a natural facility-based contact through which to provide or educate about many of the interventions we reviewed. The impact of broader socially mediated behaviors, such as fertility decision-making, access to antenatal care, and maternal diet and exposures like tobacco and indoor air pollution during pregnancy, are poorly understood, and further research and appropriate interventions are needed to test the association of these behaviours with stillbirth outcomes. For most nutritional interventions, larger randomised controlled trials are needed which report stillbirths disaggregated from composite perinatal mortality. Many antepartum stillbirths are potentially preventable in low- and middle-income countries, particularly through dietary and environmental improvement, and through improving the quality of antenatal care - particularly including diagnosis and management of high-risk pregnancies - that pregnant women receive. We previously reported that supplementation with multivitamins (vitamin B complex, vitamin C, and vitamin E) at multiples of the Recommended Dietary Allowance (RDA) significantly decreased the risk of adverse pregnancy outcomes among HIV-infected women. The minimum dosage of multivitamins necessary for optimal benefits is unknown.
                We investigated the efficacy of multivitamin supplements at single compared with multiple RDAs on decreasing the risk of adverse pregnancy outcomes among HIV-infected women.
                We conducted a double-blind, randomized controlled trial among 1129 HIV-infected pregnant women in Tanzania. Eligible women between 12 and 27 gestational weeks were randomly assigned to receive daily oral supplements of either single or multiple RDA multivitamins from enrollment until 6 wk after delivery.
                Multivitamins at multiple and single doses of the RDA had similar effects on the risk of low birth weight (11.6% and 10.2%, respectively; P = 0.75). We found no difference between the 2 groups in the risk of preterm birth (19.3% and 18.4%, respectively; P = 0.73) or small-for-gestational-age (14.8% and 12.0%, respectively; P = 0.18). The mean birth weights were similar in the multiple RDA (3045 + or - 549 g) and single RDA multivitamins group (3052 + or - 534 g; P = 0.83). There were no significant differences between the 2 groups in the risk of fetal death (P = 0.99) or early infant death (P = 0.19).
                Multivitamin supplements at a single dose of the RDA may be as efficacious as multiple doses of the RDA in decreasing the risk of adverse pregnancy outcomes among HIV-infected women. This trial was registered at clinicaltrials.gov as NCT00197678. To determine lower genital tract carriage rates of C. trachomatis, N. gonorrhoeae and bacterial vaginosis among women seeking termination of pregnancy. To compare two clinical management strategies for minimising the risks of infective morbidity after induced abortion.
                Prevalence of infections was assessed by screening women undergoing abortion. Clinical management strategies were compared by a randomised trial.
                The gynaecology departments of four hospitals in Scotland.
                1672 women undergoing induced abortion.
                Women randomised to prophylaxis received metronidazole 1 g rectally before abortion plus doxycycline 100 mg twice daily for seven days. Women randomised to screen-and-treat received appropriate antibiotics only if screening proved positive for one or more infection.
                Prevalences of infections; morbidity in the eight weeks following abortion as assessed by reported symptoms, general practitioner consultation and prescription rates and hospital re-attendances; costs to the NHS of alternative managements.
                Prevalence rates: C. trachomatis 5.6%; N gonorrhoeae 0.19%; bacterial vaginosis 17.5%. Overall, women allocated to receive prophylaxis had lower rates of measures of short term infective morbidity than those allocated to screen-and-treat. These differences only reached statistical significance for women who were reported negative on screening. The direct costs to the NHS of prophylaxis and screen-and-treat were calculated to be 8.17 and 18.34 per woman, respectively.
                Prevalences of lower genital tract infections which have been implicated in increased rates of infective morbidity after abortion are similar to those reported elsewhere. Universal antibiotic prophylaxis is at least as effective as a policy of screen-and-treat in minimising the risk of short term infective morbidity and is far more cost efficient. An estimated two-thirds of the world's 3.2 million stillbirths occur antenatally, prior to labour, and are often overlooked in policy and programs. Poorly recognised, untreated or inadequately treated maternal infections such as syphilis and malaria, and maternal conditions including hypertensive disorders, are known risk factors for stillbirth.
                We undertook a systematic review of the evidence for 16 antenatal interventions with the potential to prevent stillbirths. We searched a range of sources including PubMed and the Cochrane Library. For interventions with prior Cochrane reviews, we conducted additional meta-analyses including eligible newer randomised controlled trials following the Cochrane protocol. We focused on interventions deliverable at the community level in low-/middle-income countries, where the burden of stillbirths is greatest.
                Few of the studies we included reported stillbirth as an outcome; most that did were underpowered to assess this outcome. While Cochrane reviews or meta-analyses were available for many interventions, few focused on stillbirth or perinatal mortality as outcomes, and evidence was frequently conflicting. Several interventions showed clear evidence of impact on stillbirths, including heparin therapy for certain maternal indications; syphilis screening and treatment; and insecticide-treated bed nets for prevention of malaria. Other interventions, such as management of obstetric intrahepatic cholestasis, maternal anti-helminthic treatment, and intermittent preventive treatment of malaria, showed promising impact on stillbirth rates but require confirmatory studies. Several interventions reduced known risk factors for stillbirth (e.g., anti-hypertensive drugs for chronic hypertension), yet failed to show statistically significant impact on stillbirth or perinatal mortality rates. Periodontal disease emerged as a clear risk factor for stillbirth but no interventions have reduced stillbirth rates.
                Evidence for some newly recognised risk factors for stillbirth, including periodontal disease, suggests the need for large, appropriately designed randomised trials to test whether intervention can minimise these risks and prevent stillbirths. Existing evidence strongly supports infection control measures, including syphilis screening and treatment and malaria prophylaxis in endemic areas, for preventing antepartum stillbirths. These interventions should be incorporated into antenatal care programs based on attributable risks and burden of disease. Nineteen women attending a special multiple pregnancy antenatal clinic with a triplet pregnancy were randomly allocated to either bed rest in hospital from 24 weeks gestation onwards until delivery, or to continue conventional outpatient management. Conclusions are limited by the trial size, but the study suggests that routine hospitalization for bed rest decreases the incidence of preterm delivery and light-for-gestational age infants and reduces the need for intensive neonatal care. Although still compatible with change variation, the observations, if confirmed in a larger randomized study, would have considerable implications for clinical practice. The policy needs further evaluation in a large multicentered collaborative study. Although pneumococcal vaccine has been recommended for patients with chronic obstructive pulmonary disease (COPD), its efficacy in this population has not been shown. A double-blind randomized controlled trial of 14-valent pneumococcal vaccine was carried out in 189 men and women aged 40 to 89 years with a clinical diagnosis of COPD and a forced expiratory volume in 1 second of less than 1.5 L. Of the 189, 92 received the vaccine and 97 received saline placebo. In a randomly chosen subsample of those who received the vaccine the mean titres of specific IgG antibody to selected pneumococcal polysaccharide serotypes increased two- to threefold by 4 weeks after vaccination. Over a 2-year period the rates of death, hospital admissions and emergency visits and the mean length of hospital stay were not significantly different in the two groups. Although a protective effect of 14-valent pneumococcal vaccine could not be shown, the small size of the sample and the relatively low follow-up rates preclude firm conclusions about efficacy from these data alone. The elevated antibody levels before vaccination in some of the patients, suggesting prior infection with Diplococcus pneumoniae, may partly explain the findings. The randomized controlled trial (RCT) is the gold standard for establishing new therapies in clinical oncology. Here we document changes with time in design, sponsorship, and outcomes of oncology RCTs.
                Reports of RCTs evaluating systemic therapy for breast, colorectal (CRC), and non-small-cell lung cancer (NSCLC) published 1975 to 2004 in six major journals were reviewed. Two authors abstracted data regarding trial design, results, and conclusions. Conclusions of authors were graded using a 7-point Likert scale. For each study the effect size for the primary end point was converted to a summary measure.
                A total of 321 eligible RCTs were included (48% breast, 24% CRC, 28% NSCLC). Over time, the number and size of RCTs increased considerably. For-profit/mixed sponsorship increased substantially during the study period (4% to 57%; P < .001). There was increasing use of time-to-event measures (39% to 78%) and decreasing use of response rate (54% to 14%) as primary end point (P < .001). Effect size remained stable over the study period. Authors have become more likely to strongly endorse the experimental arm (P = .017). A significant P value for the primary end point and industry sponsorship were each independently associated with endorsement of the experimental agent (odds ratio [OR] = 19.6, 95% CI, 8.9 to 43.1, and OR = 3.5, 95% CI, 1.6 to 7.5, respectively).
                RCTs in oncology have become larger and are more likely to be sponsored by industry. Authors of modern RCTs are more likely to strongly endorse novel therapies. For-profit sponsorship and statistically significant results are independently associated with endorsement of the experimental arm. Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions.
                To explore whether the association between funding and conclusions in randomized drug trials reflects treatment effects or adverse events.
                Observational study of 370 randomized drug trials included in meta-analyses from Cochrane reviews selected from the Cochrane Library, May 2001. From a random sample of 167 Cochrane reviews, 25 contained eligible meta-analyses (assessed a binary outcome; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment). The primary binary outcome from each meta-analysis was considered the primary outcome for all trials included in each meta-analysis. The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect, adverse events, and additional confounding factors (methodological quality, control intervention, sample size, publication year, and place of publication).
                Conclusions in trials, classified into whether the experimental drug was recommended as the treatment of choice or not.
                The experimental drug was recommended as treatment of choice in 16% of trials funded by nonprofit organizations, 30% of trials not reporting funding, 35% of trials funded by both nonprofit and for-profit organizations, and 51% of trials funded by for-profit organizations (P<.001; chi2 test). Logistic regression analyses indicated that funding, treatment effect, and double blinding were the only significant predictors of conclusions. Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice (odds ratio, 5.3; 95% confidence interval, 2.0-14.4) compared with trials funded by nonprofit organizations. This association did not appear to reflect treatment effect or adverse events.
                Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results. Readers should carefully evaluate whether conclusions in randomized trials are supported by data. Immune senescence potentially leads to an increased risk of infections. It is desirable to augment the immune system and protect against infections by daily consumption of immunostimulatory food. The present study evaluated whether the intake of yoghurt fermented with Lactobacillus delbrueckii ssp. bulgaricus (L. bulgaricus) OLL1073R-1 has an effect on resistance to the common cold. We conducted two independent studies, in which fifty-seven (median age 74.5 years) and eighty-five healthy elderly individuals (median age 67.7 years) were participants. In each study, the subjects were divided into two groups based on age and sex and instructed to eat 90 g yoghurt or drink 100 ml milk once per d over an 8- or 12-week period. A meta-analysis of the results of these two independent studies showed the risk of catching the common cold was about 2.6 times lower (OR 0.39; P = 0.019) in the yoghurt group than in the milk group and the increase of natural killer cell activity was significantly higher in the yoghurt group than in the milk group (P = 0.028). In addition, the quality of life score for the 'eye/nose/throat' system after intake was significantly higher in the yoghurt group than in the milk group and the improvement of the score was correlated with the promotion of natural killer cell activity. In conclusion, consumption of yoghurt fermented with L. bulgaricus OLL1073R-1 augmented natural killer cell activity and reduced the risk of catching the common cold in elderly individuals. The effect of 5 percent human albumin on multiple organ dysfunction was investigated during the first 14 days of treatment to determine whether albumin resuscitation might benefit adult burn patients.
                Multicenter unblinded controlled trial with stratified block (two patients per block) randomization by center and mortality prediction at enrollment (high-risk stratum [predicted mortality, 50%-90%] and low-risk stratum [predicted mortality, <50%]). The primary outcome was the worst multiple organ dysfunction score (MODS), excluding the cardiovascular component, to Day 14. Eligible adults (>15 years) suffering from thermal injury not more than 12 hours before enrollment received fluid resuscitation with Ringer's lactate (n=23) or 5 percent human albumin plus Ringer's lactate (n=19) by protocol to achieve recommended (American Burn Association) resuscitation endpoints.
                Forty-two patients were randomly assigned. There were no significant differences (median [95% confidence intervals]) in age (36 [24-45] vs. 31 [25-39] years), burn size (39 [32-53] vs. 32 [26-34] total body surface area percentage), inhalation injury (n=12/19 vs. n=11/23), or baseline MODS (3 [1-5] vs. 1.5 [0-2]) between the treatment and control groups. In an intention-to-treat analysis, there was no significant difference between the treatment and control group in the lowest MODS from Day 0 to Day 14 (analysis of covariance, p=0.73).
                Treatment with 5 percent albumin from Day 0 to Day 14 does not decrease the burden of MODS in adult burn patients. To evaluate the safety and cost-effectiveness of short-stay intensive care (SSIC) treatment for low-risk coronary artery bypass patients.
                Randomized clinical equivalence trial.
                University Hospital Maastricht, the Netherlands.
                Low-risk coronary artery bypass patients.
                A total of 600 patients were randomly assigned to undergo either SSIC treatment (8 hrs of intensive care treatment) or control treatment (care as usual, overnight intensive care treatment).
                The primary outcome measures were intensive care readmissions and total hospital stay. The secondary outcome measures were total hospital costs, quality of life, postoperative morbidity, and mortality. Hospital costs consisted of the cost of hospital admission or admissions and outpatient costs.
                The difference in intensive care readmission between the two groups of 1.13% was very small and not significantly different (p = .241; 95% confidence interval, -0.9% to 2.9%). The total hospital stay (p = .807; 95% confidence interval, 1.2 to -0.4) and postoperative morbidity were comparable between the groups. The SSIC group's quality of life improved more compared with the control group's quality of life (p = .0238; 95% confidence interval, 0.0012 to 0.0464). The total hospital costs for SSIC were significantly lower (95% confidence interval, -1,581 to -174) compared with those for the control group (4,625 and 5,441, respectively). The estimated incremental cost-effectiveness ratio (cost/delta quality-adjusted life months) thus showed the dominance of SSIC. Bootstrap and sensitivity analyses confirm the robustness of the study findings.
                Compared with usual care, SSIC is a safe and cost-effective approach. SSIC can be considered as an alternative for conventional postoperative intensive care treatment for low-risk coronary artery bypass graft patients. Better peer review is needed, but proven methods to improve quality are unknown. Our objective was to determine whether written feedback to reviewers improves subsequent reviews.
                Eligible reviewers were randomized to intervention or control (receiving other reviewers' unscored reviews and the editor's decision letter). Study 1 (September 1998-September 2000) included reviewers with a median quality score of 3 or lower; study 2 (April 2000-January 2002), reviewers with median score of 4 or lower. Study 1 was designed with a power of 0.80 to detect a difference in score of 1; study 2, with a power of 0.80 to detect a difference of 0.5. All reviewers were at a peer-reviewed journal (Annals of Emergency Medicine). The main outcome measure was the editor's routine quality rating (1-5) of all reviews (blinded to study enrollment).
                For study 1, 51 reviewers were eligible and randomized and 35 had sufficient data (182 reviews) for analysis. The mean individual reviewer rating change was 0.16 (95% confidence interval [CI], -0.26 to 0.58) for control and -0.13 (-0.49 to 0.23) for intervention. For study 2, 127 reviewers were eligible and randomized, and 95 had sufficient data (324 reviews). Controls had a mean individual rating change of 0.12 (95% CI, -0.20 to 0.26) and intervention reviewers, 0.06 (-0.19 to 0.31).
                In study 1, minimal feedback from editors on review quality had no effect on subsequent performance of poor-quality reviewers, and the trend was toward a negative effect. In study 2, feedback to average reviewers was more extensive and supportive but produced no improvement in reviewer performance. Simple written feedback to reviewers seems to be an ineffective educational tool. Three stage-based expert system interventions for smoking, high-fat diet, and unsafe sun exposure were evaluated in a sample of 2,460 parents of teenagers. Eighty-four percent of the eligible parents were enrolled in a 2-arm randomized control trial, with the treatment group receiving individualized feedback reports for each of their relevant behaviors at 0, 6, and 12 months as well as a multiple behavior manual. At 24 months, the expert system outperformed the comparison condition across all 3 risk behaviors, resulting in 22% of the participants in action or maintenance for smoking (vs. 16% for the comparison condition), 34% for diet (vs. 26%), and 30% for sun exposure (vs. 22%). Proactive, home-based, and stage-matched expert systems can produce significant multiple behavior changes in at-risk populations where the majority of participants are not prepared to change.
                ((c) 2004 APA, all rights reserved) This study evaluated the impact of a year-long incentives-based worksite smoking-cessation program. Nineteen moderate-sized worksites, employing a total of approximately 1100 smokers, were randomized to Incentive or No Incentive conditions. All identified smokers in the worksite were considered as subjects, whether or not they participated in the intervention. Analyses were conducted at both the worksite and individual level, and using both self-reported and biochemically validated cessation as endpoints. The incentive program did not significantly improve cessation rates at either the 1-year or 2-year follow-up assessments. We conclude that more broadly focused interventions that also address worksite smoking policies, skills training, and cessation resources, or programs that target additional risk factors are needed to substantially enhance quit rates. Epidemiologic evidence of associations between the high intake of fat and low intake of dietary fiber, beta carotene, and other dietary constituents and the risk of colorectal neoplasia has been inconsistent and has not provided a sufficient basis for recommendations concerning the dietary prevention of large-bowel cancer in humans.
                We conducted a clinical trial to assess the effects on the incidence of adenomas of reducing dietary fat to 25% of total calories and supplementing the diet with 25 g of wheat bran daily and a capsule of beta carotene (20 mg daily).
                We performed a randomized, partially double-blinded, placebo-controlled factorial trial in which half the patients were assigned to each intervention, resulting in seven intervention groups and one control group. Eligibility criteria included histologic confirmation of at least one colorectal adenoma and confidence expressed by the colonoscopist that all polyps had been removed. Dietary changes were individually initiated and monitored by dietitians and research nurses. At surveillance colonoscopy, the size and location of all polyps were recorded, and their histology was later centrally reviewed. Among 424 patients who were randomly assigned in the trial, 13 were found to be ineligible upon histologic review. Among the remaining 411, complete outcome data were collected from 390 at 24 months and from 306 at 48 months. All P values are from two-sided tests of statistical significance.
                There was no statistically significant prevention of total new adenomas with any of the interventions. We found a statistically non-significant reduced risk of large adenomas (> or = 10 mm) with the low-fat intervention: At 24 months, the odds ratio (OR) adjusted for potential confounders = 0.4 and 95% confidence interval (CI) = 0.1-1.1; at 48 months, OR = 0.3 and 95% CI = 0.1-1.0. Less and statistically nonsignificant reductions in the risk of large adenomas were found with wheat bran: At 24 months, OR = 0.8 and 95% CI = 0.3-2.2; at 48 months, OR = 0.8 and 95% CI = 0.3-2.5. Patients on the combined intervention of low fat and added wheat bran had zero large adenomas at both 24 and 48 months, a statistically significant finding (P = .03).
                Because only small numbers of patients were studied, our finding that the combination of fat reduction and a supplement of wheat bran reduced the incidence of large adenomas in this randomized, controlled trial must be treated with caution. The results do suggest, however, that these interventions may reduce the transition from smaller to larger adenomas, a step that may critically define those adenomas most likely to progress to malignancy. Blunt vascular injuries to the head and neck (BHVI) represent some of the most devastating and morbid injuries seen by a trauma surgeon. This series reviewed the experience of a single institution to determine if diagnostic and therapeutic guidelines can be established for these uncommon injuries. In particular, the utility of anticoagulation in the treatment of these injuries is examined.
                The institutional trauma registry of a single state-designated Level I trauma center was examined for patients with BHVI. Patients were identified and their charts reviewed individually with regard to multiple data points including the type of injury, its presentation, the treatment of the injury, and the functional outcome of the patient.
                Twenty-nine BHVI in 23 patients were reviewed from 1989 to 1997. No mortalities were noted. Among the injuries noted were 14 internal carotid artery dissections and 8 carotid artery tears. Thirteen patients had accompanying closed head injuries. Ten patients were diagnosed after an abnormal neurologic examination, and eight others were diagnosed after having carotid canal fractures. Heparin was started within 48 hours of injury in 4 patients (17%) and was used in a total of 12 patients (52%). No patient worsened neurologically after diagnosis independent of the use of heparin. Thirteen patients (57%) had no or minimal deficits upon discharge.
                BHVI represent a serious cause of morbidity in the patient with multiple injuries. Patients with closed head injuries and carotid canal fractures appear most at risk. A multicenter, randomized trial involving antiplatelet therapy, full systemic anticoagulation, or observation with a long-term functional assessment is indicated to determine the optimal management of these injuries. Tackling health inequalities is high on the political agenda of the Labour government. The government wants to reduce inequalities through policies based on evidence, the health of childbearing women and their babies being priority areas for action. National Service Frameworks (NSFs) are being set up to ensure high quality services for all groups. The External Working Group looking into maternity services for the Children's NSF seeks evidence upon which to plan strategies for all women, while focusing attention on the most disadvantaged. Wide differentials are noted between high- and low-income groups in the outcomes of pregnancy and the health of babies. The worst outcomes appear to be concentrated in small subgroups of disadvantaged women.
                To report on a review of studies of interventions improving perinatal outcomes for disadvantaged women, to inform policy and practice around the organization and delivery of statutory services in the UK.
                We searched six relevant databases for reviews, intervention studies, audits and descriptions of services reporting outcomes for disadvantaged groups of women, published between 1990 and 2003. Synthesis was performed around what works and what does not work. Gaps in the evidence base were identified.
                We found limited evidence of effective and promising interventions for childbearing women from minority ethnic groups, women experiencing domestic violence, women with mental health illness and HIV infected women. Few studies were well-designed or powered to detect effectiveness. There were no studies of interventions for women prisoners, homeless women and travellers.
                Searching for intervention studies primarily by participant subgroup has brought in evidence from few well-designed studies on which to plan policy. Combining this approach with searching for intervention studies addressing behaviour like smoking, and needs like social support, may provide further evidence to tackle inequalities in the perinatal period. In HIV-1-infected women, poor micronutrient status has been associated with faster progression of HIV-1 disease and adverse birth outcomes. We assessed the effects of vitamin A and multivitamins on birth outcomes in such women.
                In Tanzania, 1075 HIV-1-infected pregnant women at between 12 and 27 weeks' gestation received placebo (n=267), vitamin A (n=269), multivitamins excluding vitamin A (n=269), or multivitamins including vitamin A (n=270) in a randomised, double-blind, placebo-controlled trial with a 2x2 factorial design. We measured the effects of multivitamins and vitamin A on birth outcomes and counts of T lymphocyte subsets. We did analyses by intention to treat.
                30 fetal deaths occurred among women assigned multivitamins compared with 49 among those not on multivitamins (relative risk 0.61 [95% CI 0.39-0.94] p=0.02). Multivitamin supplementation decreased the risk of low birthweight (<2500 g) by 44% (0.56 [0.38-0.82] p=0.003), severe preterm birth (<34 weeks of gestation) by 39% (0.61 [0.38-0.96] p=0.03), and small size for gestational age at birth by 43% (0.57 [0.39-0.82] p=0.002). Vitamin A supplementation had no significant effect on these variables. Multivitamins, but not vitamin A, resulted in a significant increase in CD4, CD8, and CD3 counts.
                Multivitamin supplementation is a low-cost way of substantially decreasing adverse pregnancy outcomes and increasing T-cell counts in HIV-1-infected women. The clinical relevance of our findings for vertical transmission and clinical progression of HIV-1 disease is yet to be ascertained. The purpose of this study was to explore the efficacy in a primary care setting of a telephone-based disease management program for the acute management of depression and/or at-risk drinking.
                Veterans (N= 97) with depression and/or at-risk drinking were identified by systematic screening and assessment. Eligible subjects received either telephone disease management (TDM) program or usual care based on random assignment of their clinician. The TDM program consisted of regular contacts with each subject by a behavioral health specialist (BHS) to assist in assessment, education, support, and treatment planning. Symptomatic outcomes were assessed at 4 months.
                Overall response rates favored those assigned to TDM compared with those assigned to usual care (39.1% responded vs. 17.6%, p= 0.022). Response rates within the separate diagnostic groups also favored TDM, but this was only significant for depressive disorders.
                Although the sample size was modest and the sample was limited to veterans, findings strongly suggest that a telephone-based disease management program can improve outcomes for patients with a behavioral health problem. Findings also suggest that a health specialist can focus and manage patients with different diagnoses, thus expanding the role beyond just depression care. TDM may be a viable, low-cost, model for primary care clinicians to deliver manual guideline-adherent behavioral health care, especially in a VA clinical setting. To determine whether attendance at a voluntary training workshop improves quality ratings of medical journal peer reviewers.
                Peer reviewers for Annals of Emergency Medicine who completed two or more reviews during the 20 months before or the 20 months after October 1995 were eligible. Reviews were routinely rated by editors on a subjective 5-point quality scale. Comparisons were made between reviewers who chose to attend a 4-hour workshop on peer review sponsored by the journal in 1995 (attendees) and 2 groups of reviewers who did not attend: controls matched for review quality and number of reviews completed before the workshop, and unmatched controls. Guest reviewers were excluded.
                A total of 298 reviewers completed 1906 reviews before the workshop and 2,194 after the workshop; 2,117 of these reviews were rated by editors. Forty-five attendees participated in the workshop, 39 of whom had sufficient ratings for analysis. Matched controls were almost identical in performance to attendees, but unmatched controls had performed fewer reviews and had lower average ratings before the workshop. There was no significant change in any performance measurement after the workshop, including average quality rating, percent change in quality rating, odds ratio for recommending acceptance, and odds ratio for congruence with editor's decision.
                In a self-selected group of experienced reviewers who attended a 4-hour workshop on peer review, no effect could be identified in subsequent performance as measured by editors' quality ratings or reviewer performance statistics. Because resources for care of low-birthweight (LBW) infants in developing countries are scarce, the Kangaroo mother method (KMM) was developed. The infant is kept upright in skin-to-skin contact with the mother's breast. Previous studies reported several benefits with the KMM but interpretation of their findings is limited by small size and design weaknesses. We have done a longitudinal, randomised, controlled trial at the Isidro Ayora Maternity Hospital in Quito, Ecuador. Infants with LBW (< 2000 g) who satisfied out-of-risk criteria of tolerance of food and weight stabilisation were randomly assigned to KMM and control (standard incubator care) groups (n = 128 and 147, respectively). During 6 months of follow-up the KMM group had a significantly lower rate than the control group of serious illness (lower-respiratory-tract disorders, apnoea, aspiration, pneumonia, septicaemia, general infections; 7 [5%] vs 27 [18%], p < 0.002), although differences between the groups in less severe morbidity were not significant. There was no significant difference in growth or in the proportion of women breastfeeding, perhaps because the proportion breastfeeding was high in both groups owing to strong promotion. Mortality was the same in both groups; most deaths occurred during the stabilisation period before randomisation. KMM mothers made more unscheduled clinic visits than control mothers but their infants had fewer re-admissions and so the cost of care was lower with the KMM. Since the eligibility criteria excluded nearly 50% of LBW infants from the study, the KMM is not universally applicable to these infants. The benefits might be greater in populations where breastfeeding is not so common. To assess the potential contribution of evidence from existing systematic reviews of effectiveness to answering the question: what works in reducing social inequalities in smoking?
                The Cochrane Library (2002/4).
                Systematic reviews of the effectiveness of community based tobacco control interventions, and all the primary studies included in one of these reviews.
                Reviews and primary studies were assessed for intent to assess the social distribution of intervention effects, information about the social inclusiveness or targeting of interventions, baseline sociodemographic data collected on participants, and estimates of effect size stratified by sociodemographic variables.
                Only one review aimed to examine outcomes stratified by sex, age or socioeconomic status, and these aims were only achieved with respect to sex. Sociodemographic data about participants were frequently collected in primary studies, but not used to compare intervention effects between social groups.
                There may be scope for using existing research more effectively to contribute to evidence based policy to reduce social inequalities in smoking-by explicitly seeking stratified outcome data in new systematic reviews, by re-analysing original datasets, and/or by meta-analysis of individual participant data. This investigation was designed to determine the impact of a brief period of cardiac rehabilitation, initiated within 6 weeks of acute myocardial infarction (AMI), on both disease-specific and generic health-related quality of life, exercise tolerance and return to work after AMI. With a stratified, parallel group design, 201 low-risk patients with evidence of depression or anxiety, or both, after AMI, were randomized to either an 8-week program of exercise conditioning and behavioral counseling or to conventional care. Although the differences were small, significantly greater improvement was seen in rehabilitation group patients at 8 weeks in the emotions dimension of a new disease-specific, health-related Quality of Life Questionnaire, in their state of anxiety and in exercise tolerance. All measures of health-related quality of life in both groups improved significantly over the 12-month follow-up period. However, the 95% confidence intervals around differences between groups at the 12-month follow-up effectively excluded sustained, clinically important benefits of rehabilitation in disease-specific (limitations, -2.70, 1.40; emotions, -4.86, 1.10, where negative values favor conventional care and positive values favor rehabilitation) and generic health-related quality of life (time trade-off, -0.062, 0.052; quality of well-being, -0.042, 0.035) or in exercise tolerance (-38.5, 52.1 kpm/min); also, return to work was similar in the 2 groups (relative risk, 0.93; confidence interval, 0.71, 1.64).(ABSTRACT TRUNCATED AT 250 WORDS)
Despite reviewing 39 eligible trials, few firm conclusions could be reached because of the multiple comparisons considered, the small size of individual trials, and their low quality. Whether or not to use a particular policy is usually a trade-off between the risks of morbidity (especially infection) and risks of recatheterisation.