Gilbert Ramirez

St John's wort for depression—an overview and meta-analysis of randomised clinical trials

Abstract Objective: To investigate if extracts of Hypericum perforatum (St Johns wort) are more effective than placebo in the treatment of depression, are as effective as standard antidepressive treatment, and have fewer side effects than standard antidepressant drugs. Design: Systematic review and meta-analysis of trials revealed by searches. Trials: 23 randomised trials including a total of 1757 outpatients with mainly mild or moderately severe depressive disorders: 15 (14 testing single preparations and one a combination with other plant extracts) were placebo controlled, and eight (six testing single preparations and two combinations) compared hypericum with another drug treatment. Main outcome measures: A pooled estimate of the responder rate ratio (responder rate in treatment group/responder rate in control group), and numbers of patients reporting and dropping out for side effects. Results: Hypericum extracts were significantly superior to placebo (ratio = 2.67; 95% confidence interval 1.78 to 4.01) and similarly effective as standard antidepressants (single preparations 1.10; 0.93 to 1.31, combinations 1.52; 0.78 to 2.94). There were two (0.8%) drop outs for side effects with hypericum and seven (3.0%) with standard antidepressant drugs. Side effects occurred in 50 (19.8%) patients on hypericum and 84 (52.8%) patients on standard antidepressants. Conclusion: There is evidence that extracts of hypericum are more effective than placebo for the treatment of mild to moderately severe depressive disorders. Further studies comparing extracts with standard antidepressants in well defined groups of patients and comparing different extracts and doses are needed. Key messages There is evidence from randomised trials that such extracts are more effective than placebo for the treatment of depressive disorders, but it is not known whether they are more effective for certain disorders than others Current evidence is inadequate to establish whether hypericum is as effective as other antidepressants and if it has fewer side effects Additional trials should be conducted to compare hypericum with other antidepressants in well defined groups of patients; to investigate long term side effects; and to evaluate the relative efficacy of different preparations and doses

Case-Finding Instruments for Depression in Primary Care Settings

Depressive disorders are common, persistent, and recurring afflictions among primary care patients. They cause substantial suffering for patients and their families and are associated with a loss of personal productivity and a markedly increased risk for suicide. Further, the presence of depression puts persons with comorbid conditions, such as recent myocardial infarction, at increased risk for illness and death. Persons with depression spend more time with their physicians during office visits and use more health care than persons without depression [1]. The annual health care cost associated with depression in the United States is estimated to be

The Effectiveness of Worksite Nutrition and Physical Activity Interventions for Controlling Employee Overweight and Obesity. A Systematic Review

43.7 billion [2]. Underscoring the importance of identifying patients with depression is that the effectiveness of therapy, including antidepressants, psychotherapy, and counseling, has clearly been established [3]. Despite these issues, primary care providers fail to diagnose and treat as many as 35% to 50% of patients with depressive disorders [4, 5]. Obstacles to the appropriate recognition of depression include inadequate provider knowledge of diagnostic criteria; competing comorbid conditions and priorities among primary care patients; time limitations in busy office settings; concern about the implications of labeling; poor reimbursement mechanisms; and uncertainty about the value, accuracy, and efficiency of screening mechanisms for identifying patients with depression. We address the last of these obstacles and assess the feasibility and operating characteristics of several case-finding instruments that have been used to detect depressive disorders in primary care settings. Our ultimate goal is to familiarize providers with the advantages and disadvantages of these instruments so that they can make informed decisions about incorporating them into practice. Methods Data Acquisition We did a MEDLINE search of the English-language medical literature published from 1966 through February 1994. Search terms included depressive disorder or depression, diagnosis, and the specific names of each of 11 case-finding instruments cited in previous relevant reviews or bibliographies [6-9]. Other sources were references identified from pertinent articles and national experts in the field of depression. Experts included authors of papers that were selected for review and two members of the Agency for Health Care Policy and Research Guideline Panel on Depression. Of 906 articles identified through MEDLINE, 210 were deemed potentially relevant. These were reviewed to identify studies that met the following selection criteria. Study samples had to have been composed of primary care patients attending clinic. Patients were excluded if they had been selected because they had specific conditions (such as chronic pain or cancer) or because they had specific demographic characteristics (for example, they were immigrants in a particular ethnic group). Both a case-finding instrument and a diagnostic criterion standard had to have been administered. The criterion standard had to have had formal standardized diagnostic criteria for depression. Accepted criterion standards were the Diagnostic Schedule Manual-3 criteria (DSM-III or DSM-III-R) and the Research Diagnostic Criteria, or a close approximation of these. Standard interview procedures, such as the Diagnostic Interview Schedule or the Structured Clinical Interview for DSM-III, had to have been used to arrive at the diagnosis. Chart or physician diagnoses of depression that were made without specified formal interview procedures and diagnostic criteria were excluded. Nineteen studies involving nine case-finding instruments met the selection criteria: Fourteen were found during the MEDLINE search; 1 came from a relevant bibliography; and 4 were unpublished at the time of the search and came from experts [10-28]. Of the remaining articles screened, 92% were excluded because they did not involve primary care patients, 6% were excluded because they had used an inadequate criterion standard, and 2% were excluded because they involved selected populations [29, 30] or because they had tested modified and unvalidated versions of case-finding instruments [31]. Data Extraction Articles were abstracted by two independent reviewers. Determination of study quality was made on the basis of 1) whether the case-finding instrument was administered and interpreted independently of the criterion standard and 2) whether the proportion of persons receiving the criterion standard assessment was less than or more than 50% of those approached for criterion standard assessment. Quality assessment addressed methodologic issues relevant to the evaluation of diagnostic tests (such as independent assessment and selection bias) and did not necessarily reflect the ability of studies to address their original aims. There were no disagreements about quality assessments. Data Synthesis Established cut-points for case-finding instruments (Table 1) were used. Two-by-two tables were constructed that categorized numbers of screened-positive and screened-negative persons who did and did not meet criterion standard diagnosis for major depression and major depression or dysthymia. Kraemers method [32] was used to adjust for verification bias for studies that used two-stage assessment techniques; whereby the criterion standard was administered only to a random sample of persons who screened negative on case-finding instruments [33]. The authors of all but one study provided us with additional data and analyses when two-by-two tables could not be derived from abstraction of the published article. This one study [28] was dropped from further review because its authors could not be contacted and tables could not be derived from published information. Table 1. Characteristics of Case-Finding Instruments That Have Been Used to Detect Depression in Primary Care Settings* A scattergram (Figure 1) plotting true-positive against false-positive rates was constructed to visually evaluate variability among studies [34]. To provide a visual reference for the consistency of study results, we modeled a summary receiver-operating curve based on the logit transformations of the true-positive and false-positive rates. Figure 1. Plot of true-positive rate against false-positive rate for case-finding instruments to detect major depression. Average sensitivities and specificities, weighted by study size and corrected for two-stage assessment techniques when indicated, were computed both by case-finding instrument and by overall instruments [35]. The point estimates and 95% CIs were calculated using a linear random-effects model [36, 37]. Approximate 95% CIs were estimated using quadratic root formulae because most of the point estimates were near unity [37]. Differences in weighted average sensitivities and specificities between case-finding instruments were evaluated using the z statistic with the Scheffe multiple-comparison adjustment [37]. Stratified analyses were done to evaluate whether estimated sensitivities and specificities varied between high-quality studies and those with major selection bias or lack of independent assessment. Regression analysis was used to determine associations between reported study prevalences and sensitivity estimates [37]. Results Descriptions of Case-Finding Instruments Characteristics of the nine case-finding instruments that have been evaluated in primary care settings are presented in Table 1. All of the questionnaires are written either at the easy (3rd to 5th grade) or average (6th to 9th grade) reading level [38]. Almost all can be self-administered in less than 5 minutes. Except for the General Health Questionnaire, all include specific questions aimed at assessing depressed mood or whether a patient feels sad or blue. All include questions assessing anhedonia. Most are available in languages other than English, such as Spanish. The Beck Depression Inventory, the Center for Epidemiologic Studies Depression Screen, and the Zung Self-Assessment Depression Scale are three commonly used, traditional instruments that were developed specifically to identify depression. They include similar numbers of questions and use response formats that rely either on ranking symptom severity or on classifying frequency of symptoms. The time frames of questions are today for the Beck Depression Inventory, over the past week for the Center for Epidemiologic Studies Depression Screen, and recently for the Zung Self-Assessment Depression Scale. These three instruments have been used in numerous settings (including the community, the clinic, and the hospital) not only to identify depression but also to rate severity of depression and to monitor response to therapy. The General Health Questionnaire and the Hopkins Symptom Checklist are questionnaires that screen for general psychiatric illness; the Hopkins Checklist has a specific category for depression. Both of these instruments have several versions with different numbers of questions. The Medical Outcomes Study Depression Screen is a depression-specific screening instrument that was developed by combining two questions from the Diagnostic Interview Schedule [39] with six questions from the Center for Epidemiologic Studies Depression Screen. A logistic regression scoring method is used; this requires a calculator. The Primary Care Evaluation of Mental Disorders (PRIME-MD) and the Symptom Driven Diagnostic System-Primary Care instruments are recently developed, multidimensional questionnaires. Each has screening questions arranged in several categories (for example, mood or depression, anxiety, alcohol abuse, and somatization) that are used to trigger more extensive diagnostic interviewing sections for specific DSM-III-R diagnoses. The depression components of these two instruments include the fewest questions of all case-finding instruments that have been studied in primary care settings. Descriptions of Studies and Fi

Guide to community preventive servicesThe Effectiveness of Worksite Nutrition and Physical Activity Interventions for Controlling Employee Overweight and Obesity: A Systematic Review

This report presents the results of a systematic review of the effectiveness of worksite nutrition and physical activity programs to promote healthy weight among employees. These results form the basis for the recommendation by the Task Force on Community Preventive Services on the use of these interventions. Weight-related outcomes, including weight in pounds or kilograms, BMI, and percentage body fat were used to assess effectiveness of these programs. This review found that worksite nutrition and physical activity programs achieve modest improvements in employee weight status at the 6-12-month follow-up. A pooled effect estimate of -2.8 pounds (95% CI=-4.6, -1.0) was found based on nine RCTs, and a decrease in BMI of -0.5 (95% CI=-0.8, -0.2) was found based on six RCTs. The findings appear to be applicable to both male and female employees, across a range of worksite settings. Most of the studies combined informational and behavioral strategies to influence diet and physical activity; fewer studies modified the work environment (e.g., cafeteria, exercise facilities) to promote healthy choices. Information about other effects, barriers to implementation, cost and cost effectiveness of interventions, and research gaps are also presented in this article. The findings of this systematic review can help inform decisions of employers, planners, researchers, and other public health decision makers.

A meta-analysis of randomized trials of prenatal smoking cessation interventions+

This report presents the results of a systematic review of the effectiveness of worksite nutrition and physical activity programs to promote healthy weight among employees. These results form the basis for the recommendation by the Task Force on Community Preventive Services on the use of these interventions. Weight-related outcomes, including weight in pounds or kilograms, BMI, and percentage body fat were used to assess effectiveness of these programs. This review found that worksite nutrition and physical activity programs achieve modest improvements in employee weight status at the 6-12-month follow-up. A pooled effect estimate of -2.8 pounds (95% CI=-4.6, -1.0) was found based on nine RCTs, and a decrease in BMI of -0.5 (95% CI=-0.8, -0.2) was found based on six RCTs. The findings appear to be applicable to both male and female employees, across a range of worksite settings. Most of the studies combined informational and behavioral strategies to influence diet and physical activity; fewer studies modified the work environment (e.g., cafeteria, exercise facilities) to promote healthy choices. Information about other effects, barriers to implementation, cost and cost effectiveness of interventions, and research gaps are also presented in this article. The findings of this systematic review can help inform decisions of employers, planners, researchers, and other public health decision makers.

Acupuncture-point stimulation for chemotherapy- induced nausea and vomiting

OBJECTIVE Our purpose was to assess the effect of prenatal smoking interventions on rates of smoking cessation and low birth weight. STUDY DESIGN We used a meta-analysis model to compare and summarize smoking cessation and low birth weight outcomes with the risk ratio used as a common metric. We located 11 randomized, controlled trials with objective validation of smoking status; four of these studies also measured rates of low birth weight. RESULTS Risk ratios for smoking cessation ranged from 0.9 to 7.1. The combined risk ratio for the homogeneous group of 10 studies was 1.50 (95% confidence interval 1.22 to 1.86) after the outlier study with a risk ratio of 7.1 was excluded. This was a 50% increase in smoking cessation. Low birth weight risk ratios of 0.6 for two studies that achieved a 50% increase in cessation suggested that the incidence of low birth weight was decreased. CONCLUSION Prenatal smoking cessation interventions increase rates of smoking cessation during pregnancy, and there is evidence that they reduce the incidence of low birth weight.

Statin Therapy in the Prevention of Recurrent Cardiovascular Events: A Sex-Based Meta-analysis

PURPOSE Assess the effectiveness of acupuncture-point stimulation on acute and delayed chemotherapy-induced nausea and vomiting in cancer patients. MATERIALS AND METHODS Randomized trials of acupuncture-point stimulation by needles, electrical stimulation, magnets, or acupressure were retrieved. Data were provided by investigators of the original trials and pooled using a fixed-effects model. RESULTS Eleven trials (N = 1,247) were pooled. Overall, acupuncture-point stimulation reduced the proportion of acute vomiting (relative risks [RR] = 0.82; 95% CI, 0.69 to 0.99; P = .04), but not the mean number of acute emetic episodes or acute or delayed nausea severity compared with controls. By modality, stimulation with needles reduced the proportion of acute vomiting (RR = 0.74; 95% CI, 0.58 to 0.94; P = .01), but not acute nausea severity. Electroacupuncture reduced the proportion of acute vomiting (RR = 0.76; 95% CI, 0.60 to 0.97; P = .02), but manual acupuncture did not; delayed symptoms were not reported. Acupressure reduced mean acute nausea severity (standardized mean difference = -0.19; 95% CI, -0.38 to -0.01; P = .03) and most severe acute nausea, but not acute vomiting or delayed symptoms. Noninvasive electrostimulation showed no benefit for any outcome. All trials used concomitant pharmacologic antiemetics, and all, except electroacupuncture trials, used state-of-the-art antiemetics. CONCLUSION This review complements data on postoperative nausea and vomiting, suggesting a biologic effect of acupuncture-point stimulation. Electroacupuncture has demonstrated benefit for chemotherapy-induced acute vomiting, but studies with state-of-the-art antiemetics as well as studies for refractory symptoms are needed to determine clinical relevance. Acupressure seems to reduce chemotherapy-induced acute nausea severity, though studies did not involve a placebo control. Noninvasive electrostimulation seems unlikely to have a clinically relevant impact when patients are given state-of-the-art pharmacologic antiemetic therapy.

Clinical studyMilk thistle for the treatment of liver disease: A systematic review and meta-analysis☆

BACKGROUND The effect of statins on the prevention of cardiovascular events is well demonstrated. Whether this protective effect is equal for women and men remains less well established. Our objective was to evaluate if statin therapy is equally effective in decreasing recurrent cardiovascular events in women and men. DATA SOURCES Randomized clinical trials were searched in PubMed using as indexing terms (statins OR cholesterol lowering medications) AND (cardiovascular events OR stroke OR myocardial infarction OR cardiovascular death). STUDY SELECTION We included randomized, double-blinded, placebo-controlled trials evaluating statins for secondary prevention of cardiovascular events. Studies with an open-label design and observational studies were excluded. DATA EXTRACTION The earliest citation was used to determine the characteristic of the studied population and the methodology. All subsequent citations corresponding to the trial were evaluated for outcome rates by sex. DATA SYNTHESIS Eleven trials representing 43,193 patients were included in the analysis. Overall, statin therapy was associated with a reduced risk of cardiovascular events in all outcomes for women (relative risk [RR], 0.81 [95% CI, 0.74-0.89]) and men (RR, 0.82 [95% CI, 0.78-0.85]). However, they did not reduce all-cause mortality in women vs men (RR, 0.92 [95% CI, 0.76-1.13] vs RR, 0.79 [95% CI, 0.720.87]) or stroke (RR, 0.92 [95% CI, 0.76-1.10] vs RR, 0.81 [95% CI, 0.72-0.92]). CONCLUSIONS Statin therapy is an effective intervention in the secondary prevention of cardiovascular events in both sexes, but there is no benefit on stroke and all-cause mortality in women.

How well can the chest radiograph diagnose left ventricular dysfunction

PURPOSE Milk thistle, an herbal compound, is the dietary supplement taken most frequently by patients with chronic liver disease. We performed a systematic review of the literature to determine the efficacy and safety of this herb for the treatment of liver disease. METHODS We searched English and non-English reports through July 1999 using thirteen databases and reference lists, and contacting manufacturers and technical experts. Reviewers independently screened all reports to identify randomized placebo-controlled trials that evaluated milk thistle for the treatment of liver disease. Outcomes of primary interest included mortality, histological findings on liver biopsy specimens, serum aminotransferase and albumin levels, and prothrombin times. RESULTS Fourteen trials met inclusion criteria. Four trials reported outcomes for mortality among 433 participants. The overall summary odds ratio for mortality in the milk thistle group compared with placebo was 0.8 (95% confidence interval [CI]: 0.5 to 1.5; P = 0.6). Three trials assessed histology on liver biopsy; study quality was inversely associated with the likelihood of histological benefit for milk thistle compared with placebo. There were no differences in serum alanine aminotransferase, aspartate aminotransferase, or albumin levels, or prothrombin times, among participants assigned to milk thistle compared with those assigned to placebo. The only statistically significant difference was a greater reduction in alanine aminotransferase levels among patients with chronic liver disease assigned to milk thistle (-9 IU/L, 95% CI: -18 to -1 IU/L; P = 0.05), but this reduction was of negligible clinical importance and no longer statistically significant after limiting analyses to studies of longer duration or of higher quality. The frequency of adverse effects was low and, in clinical trials, indistinguishable from placebo. CONCLUSION Treatment with milk thistle appears to be safe and well tolerated. We found no reduction in mortality, in improvements in histology at liver biopsy, or in biochemical markers of liver function among patients with chronic liver disease. Data are too limited to exclude a substantial benefit or harm of milk thistle on mortality, and also to support recommending this herbal compound for the treatment of liver disease.

Endotoxin Exposure and Childhood Wheeze and Asthma: A Meta-Analysis of Observational Studies

OBJECTIVES: To review the diagnostic utility of the chest radiograph for left ventricular dysfunction.DATA SOURCES: Structured MEDLINE searches, citation reviews of relevant primary research, review articles, and textbooks, personal files, and data from experts.STUDY SELECTION: Studies of patients without valvular disease that allowed calculation of the sensitivity and specificity of selected radiographic signs compared with a criterion standard of increased left ventricular preload or reduced ejection fraction.DATA EXTRACTION: Two independent readers reviewed 29 studies. Studies were pooled after stratification by radiographic finding, criterion standard, and clinical setting.MAIN RESULTS: Redistribution best diagnosed increased preload with a sensitivity of 65% (95% confidence interval [CI] 55%, 75%) and specificity 67% (95% CI 53%, 79%). Cardiomegaly best diagnosed decreased ejection fraction with a sensitivity of 51% (95% CI 43%, 60%) and specificity of 79% (95% CI 71%, 85%). Interrater reliability was fair to moderate for redistribution and moderate for cardiomegaly. The clinical setting affected results by decreasing the specificity of cardiomegaly to 8% in detecting increased preload in patients with severe systolic dysfunction. The absence of redistribution could only exclude increased preload in situations in which the suspicion (pretest probability) of disease was less than 9%, whereas redistribution could confirm increased preload when the pretest probability was greater than 91%. The absence of cardiomegaly could only exclude a reduced ejection fraction if the pretest probability was less than 8%, whereas cardiomegaly could confirm a reduced ejection fraction if the pretest probability was greater than 87%.CONCLUSIONS: Redistribution and cardiomegaly are the best chest radiographic findings for diagnosing increased preload and reduced ejection fraction, respectively. Unfortunately, neither finding alone can adequately exclude or confirm left ventricular dysfunction in usual clinical settings. Redistribution is not always reliably interpreted.