Athina Tatsioni

Meta-analysis: The Effect of Dietary Counseling for Weight Loss

Key Summary Points This systematic review suggests that, on average, dietary counseling interventions for weight loss have resulted in a net loss of approximately 2 BMI units (6%) at 12 months compared with usual care. This weight difference narrows considerably over the subsequent 4 years. Long-term trials that evaluate the time course of weight changes are needed to confirm these conclusions. Factors that may alter the effectiveness of dietary counseling interventions require additional investigation. Future studies must improve their analyses, reporting of study design and findings, and follow-up of study participants. Obesity-related medical problems are among the most serious health problems facing U.S. adults. Approximately 65% of U.S. adults are overweight (body mass index [BMI] >25 kg/m2), and approximately half of overweight adults are obese (BMI >30 kg/m2) (1). Coronary heart disease is twice as common in obese people as in normal-weight people, and obesity substantially exacerbates all metabolic cardiac risk factors (2, 3). Obesity is associated with decreased longevity (47) and quality of life (8). Dietary and lifestyle modification efforts are the primary methods for treating and preventing obesity. Several important systematic reviews show that dietary-based lifestyle modification efforts can statistically significantly improve body weight and decrease related medical problems (917). The average weight change due to dietary counseling compared with usual care is unclear, particularly over the long term. We systematically reviewed and quantitatively synthesized published data on the net effect of dietary-based counseling compared with usual care over time. We also evaluated various sources of heterogeneity on the effectiveness of weight loss strategies. Methods Data Sources and Searches The starting point for the literature search was an extensive systematic review published in 1998, on which current clinical guidelines regarding identification, evaluation, and treatment of overweight and obesity in adults are based (9). For that report, a 24-member panel of experts methodically and critically examined all relevant scientific literature published between January 1980 and September 1997. After identifying all relevant studies from that report, we conducted a systematic literature search in all languages in MEDLINE and in the Cochrane Central Register of Controlled Trials databases from January 1997 through July 2006 to identify the effect on BMI of dietary-based weight-loss counseling interventions. We found additional studies from reference lists of other systematic reviews and included studies. Terms used in the searches of recent studies were weight loss, body mass index, obesity, diet, behavior therapy, and lifestyle. The search was limited to randomized, controlled trials. Study Selection We included randomized trials that reported original data on the effect of dietary counseling (advice to change dietary patterns) on body weight or BMI compared with the effect of control interventions (usual care or a minimal intervention, such as general verbal or written advice given at baseline, which was designed to approximate usual care). We excluded studies in which patients were younger than 18 years, the goal of the intervention was not weight loss, exercise was the only intervention, mean baseline BMI was less than 25 kg/m2, or SEs could not be determined. In keeping with the eligibility criteria of the 1998 evidence report (9), we also excluded studies with interventions that lasted fewer than 12 weeks and those that did not report effects at a minimum of 16 weeks. Figure 1 shows the number of studies that did not meet the eligibility criteria and the reasons for their exclusion. Figure 1. Study flow diagram. Cochrane = Cochrane Central Register of Controlled Trials; NHLBI/NIDDK = National Heart, Lung, and Blood Institute/National Institute of Diabetes and Digestive and Kidney Diseases. *Not randomized or quasi-randomized; no usual care control; weight loss not goal of intervention; exercise-only intervention; intervention duration less than 12 weeks or follow-up duration less than 16 weeks; baseline body mass index less than 25 kg/m2; no weight change data; insufficient data to calculate standard error; duplicate publication of study; abstract or letter. Data Extraction and Quality Assessment One of 3 reviewers used standardized forms to extract all studies that met the eligibility criteria. A second reviewer reviewed all extracted data. When necessary, disagreements were resolved by consensus of 2 or more authors. For all included studies, we extracted or estimated the net change in BMI and the SE of the net change from the reported data. Net change was defined as the change from baseline in the treatment group minus the change from baseline in the control group. We did not analyze change from baseline in the treatment groups alone (without subtracting changes in the control groups). When necessary, we calculated the change in BMI by using the ratio of baseline BMI to kilograms as the conversion factor. For the 9 studies that did not report such data, we assumed a ratio of 2.7 (equal to a height of 1.64 m), which corresponded well to ratios from other studies. Within studies, we preferentially chose data from intention-to-treat analyses; however, we retained data from all studies regardless of whether their analyses omitted missing data, used last observations carried forward, or replaced missing data with baseline data. For each study that reported change in BMI at multiple time points, we calculated the slopes of the net change in BMI across the different time points. When necessary, the SE of the net change was estimated from the SEs of the changes in BMI in the intervention and control groups, assuming that these values were independent of each other. Similarly, when necessary, the SEs of the intervention and control group changes in BMI were calculated from the SEs of the baseline and final values by using the following equation: where SE1, SE2 and SE12 are the SEs for baseline values, final values, and change in values, respectively, and is the correlation between SE1 and SE2 (18). We arbitrarily chose to be 0.50, the midpoint value. In secondary analyses, we used correlations of 0.25 and 0.75 (18). For the meta-analysis, we calculated the SE of the net BMI slopes by using the same methods. We also extracted data that described the counseling and usual care interventions, participants, study design, and adverse events. Active and maintenance phases of weight loss were defined according to the designations provided by the authors of each study. All studies were assessed for methodological quality according to the design, conduct, and reporting of the clinical study. We used a 3-level classification of study quality (19). Studies rated as good mostly adhered to the commonly held concepts of good quality, including clear description of the sample, setting, intervention, and comparison groups; blinding of outcome assessors; appropriate statistical and analytic methods and reporting of these methods, including randomization technique and intention-to-treat analysis; no obvious reporting errors; participant withdrawal less than 20%; clear reporting of those who withdrew; and no obvious bias. Fair-quality studies had some deficiencies (but none that were likely to cause major bias) or may have had missing information that made it difficult to assess limitations and potential problems. Poor-quality studies had serious errors in design, analysis, or reporting or may have had a large amount of missing information, discrepancies in reporting, or high rates of withdrawal. Data Synthesis and Analysis To summarize the net changes in BMI over time, we used different methods to analyze the data. All analyses were performed separately for data from the active and the maintenance phases of the behavioral weight loss programs. We graphed the net change in BMI for each study against time from the start of the intervention. Separate random-effects model meta-analyses assign a weight to each study on the basis of individual study variance and between-study heterogeneity (20) at each time point for which data were available from at least 3 cohorts of patients. For studies that reported data at multiple time points, not including baseline, we calculated slopes for each available period (for example, if data were reported at 3, 6, and 12 months, we calculated slopes for 3 to 6, 3 to 12, and 6 to 12 months). For periods where we had data from at least 3 cohorts of patients, we meta-analyzed the slopes by using a random-effects model. The calculated SEs of the slopes were used only for weighting the studies in the meta-analysis, not for estimating the statistical significance of the slopes. These SEs capture the relative variances of the net weight changes from baseline at the multiple time points but do not accurately estimate the SEs of the slopes themselves. For each period, we compared the effect of diabetes (inclusion vs. exclusion of patients with diabetes) and intervention (diet and exercise vs. diet alone) by using 2-sample t tests. In addition, all data were analyzed in a random-effects model meta-regressiona meta-analytic technique of multivariable linear regression across studiesaccording to the method of Morris (21) as described by Berkey and colleagues (22). This model is similar to the DerSimonian and Laird (20) random-effects model meta-analysis. We regressed net change BMI against time in months. We also conducted analyses with study-level variables that were potentially associated with the magnitude of the treatment effect, based on known associations within individual studies or on what we considered to be clinically or methodologically relevant from previous studies. These variables included intervention type (diet vs. diet and exercise) (23), frequency of support meetings (prorated for the first

Percutaneous coronary interventions for non-acute coronary artery disease: a quantitative 20-year synopsis and a network meta-analysis

BACKGROUND Over the past 20 years, percutaneous transluminal balloon coronary angioplasty (PTCA), bare-metal stents (BMS), and drug-eluting stents (DES) succeeded each other as catheter-based treatments for coronary artery disease. We undertook a systematic overview of randomised trials comparing these interventions with each other and with medical therapy in patients with non-acute coronary artery disease. METHODS We searched Medline for trials contrasting at least two of the four interventions (PTCA, BMS, DES, and medical therapy). Eligible outcomes were death, myocardial infarction, coronary artery bypass grafting, target lesion or vessel revascularisation, and any revascularisation. Random effects meta-analyses summarised head-to-head (direct) comparisons, and network meta-analyses integrated direct and indirect evidence. FINDINGS 61 eligible trials (25 388 patients) investigated four of six possible comparisons between the four interventions; no trials directly compared DES with medical therapy or PTCA. In all direct or indirect comparisons, succeeding advancements in percutaneous coronary intervention did not produce detectable improvements in deaths or myocardial infarction. The risk ratio (RR) for indirect comparisons between DES and medical therapy was 0.96 (95% CI 0.60-1.52) for death and 1.15 (0.73-1.82) for myocardial infarction. By contrast, we recorded sequential significant reductions in target lesion or vessel revascularisation with BMS compared with PTCA (RR 0.68 [0-60.0.77]) and with DES compared with BMS (0.44 [0.35-0.56]). The RR for the indirect comparison between DES and PTCA for target lesion or vessel revascularisation was 0.30 (0.17-0.51). INTERPRETATION Sequential innovations in the catheter-based treatment of non-acute coronary artery disease showed no evidence of an effect on death or myocardial infarction when compared with medical therapy. These results lend support to present recommendations to optimise medical therapy as an initial management strategy in patients with this disease.

Effect of Chromium Supplementation on Glucose Metabolism and Lipids

OBJECTIVE—A systematic review of the effect of chromium supplementation on glucose metabolism and lipid levels. RESEARCH DESIGN AND METHODS—A literature search was conducted in MEDLINE and the Commonwealth Agricultural Bureau. Eligible studies were English language randomized controlled trials of chromium supplement intake ≥3 weeks, with ≥10 participants receiving chromium. All trials with glucose metabolism outcomes and trials of individuals with diabetes or glucose intolerance for lipid outcomes were included. Meta-analyses were performed as appropriate. RESULTS—Forty-one studies met criteria, almost half of which were of poor quality. Among participants with type 2 diabetes, chromium supplementation improved glycosylated hemoglobin levels by −0.6% (95% CI −0.9 to −0.2) and fasting glucose by −1.0 mmol/l (−1.4 to −0.5) but not lipids. There was no benefit in individuals without diabetes. There were some indications of dose effect and differences among chromium formulations. Larger effects were more commonly observed in poor-quality studies. The evidence was limited by poor study quality, heterogeneity in methodology and results, and a lack of consensus on assessment of chromium status. CONCLUSIONS—No significant effect of chromium on lipid or glucose metabolism was found in people without diabetes. Chromium supplementation significantly improved glycemia among patients with diabetes. However, future studies that address the limitations in the current evidence are needed before definitive claims can be made about the effect of chromium supplementation.

Challenges in systematic reviews of diagnostic technologies.

Diagnostic tests, broadly construed, consist of any method of gathering information that may change a clinicians belief about the probability that a patient has a particular condition. Diagnosis is not an end in itself; rather, the purpose of a diagnostic test is to guide patient management decisions and thus improve patient outcomes. Because they are pivotal to health care decision making, diagnostic tests should be evaluated as rigorously as therapeutic interventions. A cursory search of the literature for a diagnostic technology may reveal many articles dealing with various aspects of the test. But rarely do these include reports of trials to assess the outcomes of using the test to guide patient management. In the mid-1970s, several groups (1-4) developed a now widely adopted framework to evaluate diagnostic technologies by categorizing studies into 6 levels (5). This framework is hierarchal: Level 1 consists of studies that address technical feasibility, and level 6 consists of those that address societal impact. Table 1 summarizes the framework and the key questions addressed by studies in each level. Table 1. Hierarchy of Diagnostic Evaluation and the Number of Studies Available for Different Levels of Diagnostic Test in a Technology Assessment of Magnetic Resonance Spectroscopy for Brain Tumors Evidence-based Practice Centers (EPCs) have produced several evidence reports and technology assessments of diagnostic technologies (www.ahrq.gov/clinic/techix.htm). This article uses 3 reports produced by the EPCs to illustrate the challenges involved in evaluating diagnostic technologies. The first assessed the use of magnetic resonance spectroscopy (MRS) to evaluate and manage brain mass. It exemplifies the challenges of identifying relevant studies and assessing the methodologic quality of diagnostic accuracy studies (6). The second, a report on technologies to diagnose acute cardiac ischemia, illustrates the problem of synthesizing studies that assess tests in different patient populations and report different outcomes (7). In particular, this report highlights the challenges in quantitatively combining data on test accuracy. The third report, on positron emission tomography (PET) for diagnosing and managing Alzheimer disease and dementia, exemplifies the challenges of assessing the societal impact of a diagnostic test (8). Finally, we discuss the problem of publication bias, which may slant the conclusions of a systematic review and meta-analysis in a biased direction. Challenge: Identifying Relevant Published and Unpublished Studies A report that assessed the value of MRS to diagnose and manage patients with space-occupying brain tumors demonstrates that there are few higher-level diagnostic test studies (8). Table 1 shows the number of studies and patients available for systematic review at each of the 6 levels of evaluation. Among the 97 studies that met the inclusion criteria, 85 were level 1 studies that addressed technical feasibility and optimization. In contrast, only 8 level 2 studies evaluated the ability of MRS to differentiate tumors from nontumors, assign tumor grades, and detect intracranial cystic lesions or assessed the incremental value of MRS added to magnetic resonance imaging (MRI). These indications were sufficiently different that the studies could not be combined or compared. Three studies provided evidence that assessed impact on diagnostic thinking (level 3) or therapeutic choice (level 4). No studies assessed patient outcomes or societal impact (levels 5 and 6). The case of MRS for use in diagnosis and management of brain tumors illustrates a threshold problem in systematic review of diagnostic technologies: the availability of studies providing at least level 2 evidence (since diagnostic accuracy studies are the minimum level relevant to assessing the outcomes of using the test to guide patient management). Although direct evidence is preferred, robust diagnostic accuracy studies can be used to create a causal chain for linking these studies with evidence on treatment effectiveness, thereby allowing an estimate of the effect on outcomes. The example of PET for Alzheimer disease, described later in this article, shows how decision analysis models can quantify outcomes to be expected from use of a diagnostic technology to manage treatment. The reliability of a systematic review hinges on the completeness of information used in the assessment. Identifying all relevant data poses another challenge. The Hedges Team at McMaster University developed and tested special MEDLINE search strategies that retrieved up to 99% of scientifically strong studies of diagnostic tests (9). Although these search strategies are useful, they do not identify grey literature publications, which by their nature are not easily accessible. The Grey Literature Report is the first step in the initiative of New York Academy of Medicine (www.nyam.org/library/grey.shtml) to collect grey literature items, which may include theses, conference proceedings, technical specifications and standards, noncommercial translations, bibliographies, technical and commercial documentation, and official documents not published commercially (10). Diagnostic studies with poor test performance results that are not published may lead to exaggerated estimates of a tests true sensitivity and specificity in a systematic review. Because there are typically few studies in the categories of clinical impact, unpublished studies showing no benefit by the use of a diagnostic test have even greater potential to cause bias during a review of evidence. Of note, the problem of publication bias in randomized, controlled trials has been extensively studied, and several visual and statistical methods have been proposed to detect and correct for unpublished studies (11). Funnel plots, which assume symmetrical scattering of studies around a common estimate, are popular for assessing publication bias in randomized, controlled trials. However, the appearance of the shape of the funnel plot has been shown to depend on the choices of weight and metric (12). Without adequate empirical assessments, funnel plots are being used in systematic reviews of diagnostic tests. However, their use and interpretation should be viewed with caution. The validity of using a funnel plot to detect publication bias remains uncertain. Statistical models to detect and correct for publication bias of randomized trials also have limitations (13). One solution to the problem of publication bias is the mandatory registration of all clinical trials before patient enrollment; for therapeutic trials, considerable progress has already been made in this area. Such a clinical trials registry could readily apply to studies of the clinical outcomes of diagnostic tests (14). Challenge: Assessing Methodologic Quality Diagnostic test evaluations often have methodologic weaknesses (15-17). Of the 8 diagnostic accuracy studies of MRS, half had small sample sizes. Of the larger studies, all had limitations related to patient selection or potential for observer bias. Methodologic quality of a study has been defined as the extent to which all aspects of a studys design and conduct can be shown to protect against systematic bias, nonsystematic bias that may arise in poorly performed studies, and inferential error (18). Test accuracy studies often have important biases, which may result in unreliable estimates of the accuracy of a diagnostic test (19-22). Several proposals have been advanced to assess the quality of a study evaluating diagnostic accuracy (23-25). Partly because of the lack of a true reference standard, there is no consensus for a single approach to assessing study quality (26). The lack of consistent relationships between specific quality elements and the magnitude of outcomes complicates the task of assessing quality (27, 28). In addition, quality is assessed on the basis of reported information that does not necessarily reflect how the study was actually performed and analyzed. The Standards for Reporting of Diagnostic Accuracy (STARD) group recently published a 25-item checklist as a guide to improve the quality of reporting all aspects of a diagnostic study (29). The STARD checklist was not developed as a tool to assess the quality of diagnostic studies. However, many items in the checklist are included in a recently developed tool for quality assessment of diagnostic accuracy studies (the QUADAS tool). The QUADAS tool consists of 14 items that cover patient spectrum, reference standard, disease progression bias, verification and review bias, clinical review bias, incorporation bias, test execution, study withdrawals, and intermediate results (28, 30). Challenge: Assessing Applicability of Study Populations Studies beyond the level of technical feasibility must include both diseased and nondiseased individuals who reflect the use of the diagnostic technologies in actual clinical settings. Because of the need to understand the relationship between test sensitivity and specificity, a study that reports only sensitivity (that is, evaluation of the test only in a diseased population) or only specificity (that is, evaluation of the test only in a healthy population) results cannot be used for this evaluation. In this section, we base our discussion on the evidence report on evaluating diagnostic technologies for acute cardiac ischemia in the emergency department (7). When the spectrum of disease ranges widely within a diseased population, the interpretation of results in a diagnostic accuracy study may be affected if study participants possess only certain characteristics of the diseased population (15, 21). For example, patients in cardiac care units are more likely to have acute cardiac ischemia than patients in the emergency department. When patients with more severe illness are analyzed, the false-positive rate is reduced and sensitivity is overestimated. For example, biomar

Effectiveness of Management Strategies for Renal Artery Stenosis: A Systematic Review

Context Is medical therapy as effective as revascularization for atherosclerotic renal artery stenosis? Contribution This systematic review found no trials that compared aggressive medical therapy and angioplasty with stent in adults with atherosclerotic renal artery stenosis. Some evidence suggested similar kidney outcomes but better blood pressure outcomes with angioplasty, particularly in patients with bilateral renal disease. Weak evidence suggested no large differences in mortality or cardiovascular events between medical and revascularization treatments. No evidence directly compared adverse event rates between treatments. Implications Available evidence comparing benefits and harms of modern treatments for atherosclerotic renal artery stenosis is sparse and inconclusive. The Editors Renal artery stenosis is defined as narrowing of the renal artery lumen. Atherosclerosis, which usually involves the ostium and proximal third of the main renal artery and the perirenal aorta, accounts for 90% of cases of renal artery stenosis (1). Atherosclerotic renal artery stenosis is increasingly common in aging populations, particularly elderly people with diabetes, hyperlipidemia, aortoiliac occlusive disease, coronary artery disease, or hypertension. Atherosclerotic renal artery stenosis is a progressive disease that may occur alone or in combination with hypertension and ischemic kidney disease (1). Although the prevalence of atherosclerotic renal artery stenosis is poorly defined, it may vary from 30% among patients with coronary artery disease identified by angiography (2) to 50% among elderly people or those with diffuse atherosclerotic vascular diseases (3). In the United States, 12% to 14% of patients in whom dialysis is initiated have been found to have atherosclerotic renal artery stenosis (4). Most authorities consider blood pressure control, preservation or salvage of kidney function, and prevention of flash pulmonary edema to be important treatment goals for patients with atherosclerotic renal stenosis. Treatment options include medication alone or revascularization of the stenosed artery or arteries. Combination therapy with multiple antihypertensive agents, often including angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, calcium-channel blockers, and -blockers, is frequently prescribed. Some clinicians also use statins to decrease low-density lipoprotein cholesterol levels and antiplatelet agents, such as aspirin or clopidogrel, to reduce the risk for thrombosis. The current standard for revascularization in most patients is percutaneous transluminal angioplasty with stent placement across the stenosis. Angioplasty without stent placement is less commonly used. Revascularization by surgical reconstruction is generally done only in patients with complicated renal artery anatomy or in those who require pararenal aortic reconstructions for aortic aneurysms or severe aortoiliac occlusive disease. The American College of Cardiology and the American Heart Association recently published guidelines for management of patients with peripheral arterial disease, including renal artery stenosis (5, 6). Although these guidelines provide recommendations about which patients should be considered for revascularization, considerable uncertainty remains about which intervention provides the best clinical outcomes. Among patients treated with medical therapy alone, experts are concerned about the risk for deterioration of kidney function and worsening cardiovascular morbidity and mortality. Revascularization procedures may provide immediate improvement in kidney function and blood pressure, but they are invasive interventions that could result in substantial morbidity or death, and because of the risk for restenosis the durability of their benefits is questioned. Although evidence regarding the optimal management of atherosclerotic renal artery stenosis appears uncertain, a Medicare claims analysis found that the rate of percutaneous renal artery revascularization has rapidly increased between 1996 and 2000, with the number of interventions increasing from 7660 to 18520 (7). To determine which patients, if any, with atherosclerotic renal artery stenosis would most benefit from angioplasty with stent placement, as opposed to continued aggressive medical treatment, the National Institutes of Health has sponsored the large, multicenter Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial. Participants are currently being enrolled in the trial, and results should be reported in 2010. Meanwhile, the Agency for Healthcare Research and Quality, under Section 1013 of the Medicare Modernization Act, commissioned a review asking key questions related to the effectiveness of aggressive medical therapy compared with renal artery angioplasty with stent placement. However, because no published evidence directly compared angioplasty with stent placement and aggressive medical treatment with currently available drugs, the review covered direct comparisons of revascularization, including angioplasty with or without stent placement and surgery, and various medical regimens and indirect comparisons of angioplasty (with stent placement) and surgical interventions, various medical therapies, and natural history (8). Methods Data Sources and Selection To identify articles relevant to several key questions, we searched the MEDLINE database from inception to 6 September 2005 for studies involving adults with atherosclerotic renal artery stenosis. The Figure shows the search and selection process. The full technical report (available at www.effectivehealthcare.ahrq.gov/reports/final.cfm) provides a more detailed description of the study methods. We also reviewed reference lists of related systematic reviews, selected narrative reviews, and primary articles, and we invited domain experts to provide additional citations. We combined search terms for renal artery stenosis, renal hypertension, and renal vascular disease, and we limited the search to English-language articles of studies in adult humans that had relevant research designs. We included peer-reviewed primary studies of adult patients treated for atherosclerotic renal artery stenosis and excluded studies that evaluated patients with renal artery stenosis in the setting of a transplanted kidney, renal artery aneurysm requiring repair, aortic disease requiring invasive intervention, or concurrent cancer or patients who had had previous surgical or angioplasty interventions for renal artery stenosis. We included only studies that reported outcomes of interest (mortality rate, kidney function, blood pressure, and cardiovascular events) at 6 months or more after the initial intervention. We excluded studies in which more than 20% of patients had renal artery stenosis due to other causes. We categorized studies according to whether they evaluated medical treatment, angioplasty, or surgical revascularization or were natural history studies, and by whether they directly compared interventions. Figure. Search and selection of studies for review. *Prospective study; enrolled 10 or more patients; study duration at least 6 months. Prospective study; angioplasty included stent placement; enrolled 30 or more patients; study duration at least 6 months; patients recruited in 1993 or later; patients did not have previous angioplasty. One study has data both for direct comparison of medical treatment to angioplasty and for natural history. Any study design; enrolled 10 or more patients; study duration at least 6 months. Studies with surgical intervention must have recruited patients in 1993 or later. Any study design; enrolled 10 or more patients; study duration at least 6 months; patients recruited in 1993 or later. Any study design; enrolled 100 or more patients (10 or more if the study was prospective); study duration at least 6 months; patients recruited in 1993 or later. We used different eligibility criteria for studies of different interventions, based on the varying number of studies available for each intervention and the relevance of the intervention to current practice. We included all direct comparisons of medical treatment with angioplasty and all uncontrolled (cohort) studies of medical treatment that had at least 10 patients in each group, regardless of study design. For angioplasty, surgical, or natural history studies, we included only those in which at least some patients were recruited in 1993 or later, after the publication of the Fifth Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. These guidelines marked a substantial change from previous guidelines in treatment recommendations for hypertension, including more aggressive blood pressure targets (9). In addition, at this time point, angiotensin-converting enzyme inhibitors began to be used more routinely in the treatment of patients with severe hypertension. We included only angioplasty studies that used stent placement, were prospective, and had at least 30 patients and retrospective surgery studies that included at least 100 patients. Any prospective surgery study that otherwise met criteria was eligible. Data Extraction and Quality and Applicability Assessments Data from each study were extracted by one of the authors and confirmed by another. The extracted data included information about patient samples, interventions, outcomes, adverse events, study design, quality, and applicability. We used predefined criteria to grade study quality as good, fair, or poor; study applicability as high, moderate, or low; and the strength of the overall body of evidence as robust, acceptable, or weak (Appendix Table). Each included study was graded by at least 2 of the authors. Appendix Table. Study Quality, Applicability, and Strength of Evidence Ratings Data Synthesis Because the study designs, participants, interventions, and reported outcome measures varied marke

Association of C677T polymorphism in the methylenetetrahydrofolate reductase gene with hypertension in pregnancy and pre-eclampsia: a meta-analysis.

Objective To evaluate whether the C677T polymorphism of the methylenetetrahydofolate reductase (MTHFR) gene is consistently associated with hypertension in pregnancy. Design Meta-analysis of studies comparing women with and without hypertension in pregnancy for the C677T MTHFR polymorphism. Methods Studies were identified with MEDLINE and EMBASE searches complemented with perusal of bibliographies of retrieved articles and communication with investigators. Between-study heterogeneity was estimated and data were combined with random effects models. Sensitivity analyses examined the effect of population and disease characteristics. Bias diagnostics evaluated the evolution of the postulated genetic effect over time and the potential for publication bias. Results Across 23 comparisons (3169 hypertensive women, 3044 controls), having the T allele (TT or CT) increased the odds of hypertensive disease of pregnancy by 1.21-fold (95% confidence interval, 1.01–1.44), but there was large between-study heterogeneity (P = 0.003). The results were similar and heterogeneity persisted when sensitivity analyses were limited to studies of Caucasian populations, or those of patients with significant proteinuria. While patients with diastolic hypertension ⩾ 110 mmHg showed an odds ratio of 1.41 (95% confidence interval, 1.03–1.73), no association was seen in patients with less severe diastolic hypertension (odds ratio, 1.00; 95% confidence interval, 0.61–1.65). Early published studies tended to show stronger associations than the subsequent studies. Conclusions While bias cannot be excluded, the meta-analysis suggests that the T allele may increase the risk of severe diastolic hypertension during pregnancy.

Maternal viral load and rate of disease progression among vertically HIV-1-infected children: an international meta-analysis.

Objective: To evaluate whether maternal human immunodeficiency virus type 1 (HIV-1) RNA levels in the serum/plasma of mothers at or close to the time of delivery affects the rate of disease progression among vertically HIV-1-infected children and whether it correlates with other parameters affecting infant disease progression. Methods: International meta-analysis of eight studies with 574 HIV-1 infected infants with available maternal HIV-1 RNA measurements at or close to delivery and clinical follow-up. The primary outcome was disease progression (stage C disease or death, n = 178). Cohort-stratified Cox models were used. Results: Higher maternal HIV-1 RNA level at or close to delivery significantly increased disease progression risk [hazard ratio (HR), 1.25; 95% confidence interval (CI), 1.04–1.52 per 1 log10 increase; P = 0.02) with a borderline effect on mortality (HR, 1.26; 95% CI, 0.96–1.65; P = 0.10]. The association with disease progression risk was strong in the first 6 months of life (HR, 1.77; 95% CI, 1.28–2.45; P = 0.001), but not subsequently (HR, 1.03; 95% CI, 0.81–1.30). Maternal HIV-1 RNA, early infant HIV-1 RNA (at 30–200 days after birth) and infant CD4 were independent predictors of disease progression in the first 6 months. Maternal HIV-1 RNA at or close to delivery correlated with early infant HIV-1 RNA (r = 0.26, P < 0.001). Effects were independent of maternal and infant treatment. Conclusions: Higher maternal HIV-1 RNA at or close to delivery strongly predicts disease progression for HIV-1-infected infants, especially in their first 6 months of life and correlates with the early peak of viremia in the infected child.

Allergens responsible for allergic contact dermatitis among children: a systematic review and meta-analysis

Background. Multiple studies have evaluated diverse allergens in paediatric populations. Consensus is still lacking on which allergens are most commonly implicated in allergic contact dermatitis.

Cancer in inflammatory bowel disease 15 years after diagnosis in a population-based European Collaborative follow-up study ☆

AIM OF THE STUDY To determine the occurrence of intestinal and extraintestinal cancers in the 1993-2009 prospective European Collaborative Inflammatory Bowel Disease (EC-IBD) Study Group cohort. PATIENTS-METHODS A physician per patient form was completed for 681 inflammatory bowel disease patients (445UC/236CD) from 9 centers (7 countries) derived from the original EC-IBD cohort. For the 15-year follow up period, rates of detection of intestinal and extraintestinal cancers were computed. RESULTS Patient follow-up time was fifteen years. In total 62/681 patients (9.1%) [41 with ulcerative colitis/21 with Crohns disease, 36 males/26 females] were diagnosed with sixty-six cancers (four patients with double cancers). Colorectal cancer was diagnosed in 9/681 patients [1.3%] (1 Crohns disease and 8 ulcerative colitis). The remaining 53 cancers were extraintestinal. There was a higher prevalence of intestinal cancer in the Northern centers compared to Southern centers [p=NS]. Southern centers had more cases of extraintestinal cancer compared to Northern centers [p=NS]. The frequency of all observed types of cancers in Northern and in Southern centers did not differ compared to the expected one in the background population. CONCLUSIONS In the fifteen-year follow up of the EC-IBD Study Group cohort the prevalence of cancer was 9.1% with most patients having a single neoplasm and an extraintestinal neoplasm. In Northern centers there were more intestinal cancers while in Southern centers there were more extraintestinal cancers compared to Northern centers. In this IBD cohort the frequency of observed cancers was not different from that expected in the background population.

Double versus single intrauterine insemination for unexplained infertility: a meta-analysis of randomized trials

OBJECTIVE To investigate the effect of double versus single intrauterine insemination (IUI) per treatment cycle in women with unexplained infertility. DESIGN Meta-analysis of randomized controlled trials. MAIN OUTCOME MEASURE(S) Clinical pregnancy rates per couple. INTERVENTION(S) Electronic searches of the Cochrane Central Trials Registry and Medline without year and language restriction through March 2009; hand searching of the abstract books of the European Society of Human Reproduction and Embryology and American Society for Reproductive Medicine annual meetings (2001-2008). RESULT(S) Six randomized trials, involving 829 women, were included in the analysis. Fifty-four (13.6%) clinical pregnancies were recorded for treatment with double IUI and 62 (14.4%) for treatment with single IUI. There was no significant difference between the single and double IUI groups in the probability for clinical pregnancy (odds ratio, 0.92; 95% confidence interval, 0.58-1.45; P=0.715). CONCLUSION(S) Double IUI offers no clear benefit in the overall clinical pregnancy rate in couples with unexplained infertility.