Bypass surgery versus endovascular interventions in severe or critical limb ischemia.

OBJECTIVE: Critical limb ischemia is associated with a significant morbidity and mortality. We systematically reviewed the evidence to compare bypass surgery with endovascular revascularization in patients with critical limb ischemia. METHODS: We systematically searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, CINAHL, and Scopus through October 2014 for comparative studies (randomized and nonrandomized). Predefined outcomes of interest were mortality, major amputation, patency, and wound healing. We pooled odds ratios (ORs) of the outcomes of interest using the random-effects model. RESULTS: Nine studies that enrolled 3071 subjects were included. There was no significant difference in mortality (OR, 0.72; 95% confidence interval [CI], 0.44-1.16) or amputation (OR, 1.2; 95% CI, 0.87-1.65). Bypass surgery was associated with higher primary patency (OR, 2.50; 95% CI, 1.25-4.99) and assisted primary patency (OR, 3.39; 95% CI, 1.53-7.51). The quality of evidence was low for mortality and amputation outcomes and moderate for patency outcomes. CONCLUSIONS: Low quality of evidence due to imprecision and heterogeneity suggests that bypass surgery and endovascular approaches may have similar effect on mortality and major amputations. However, better primary and primary assisted patency can be expected with surgery.

Nonrevascularization-based treatments in patients with severe or critical limb ischemia.

OBJECTIVE: The aim of this systematic review was to synthesize the existing evidence about various nonrevascularization-based therapies used to treat patients with severe or critical limb ischemia (CLI) who are not candidates for surgical revascularization. METHODS: We systematically searched multiple databases through November 2014 for controlled randomized and nonrandomized studies comparing the effect of medical therapies (prostaglandin E1 and angiogenic growth factors) and devices (pumps and spinal cord stimulators). We report odds ratios (ORs) and 95% confidence intervals (CIs) of the outcomes of interest pooling data across studies using the random effects model. RESULTS: We included 19 studies that enrolled 2779 patients. None of the nonrevascularization-based treatments were associated with a significant effect on mortality. Intermittent pneumatic compression (OR, 0.14; 95% CI, 0.04-0.55) and spinal cord stimulators (OR, 0.53; 95% CI, 0.36-0.79) were associated with reduced risk of amputation. A priori established subgroup analyses (combined vs single therapy; randomized vs nonrandomized) were not statistically significant. CONCLUSIONS: Very low-quality evidence, mainly due to imprecision and increased risk of bias, suggests that intermittent pneumatic compression and spinal cord stimulators may reduce the risk of amputations. Evidence supporting other medical therapies is insufficient.

The natural history of untreated severe or critical limb ischemia.

OBJECTIVE: Critical limb ischemia (CLI) is associated with high morbidity and mortality. Because most patients with CLI will eventually undergo some type of revascularization, the natural history of CLI is not well defined, although it is important to know when patients decide to pursue treatment. METHODS: We systematically searched multiple databases for controlled and uncontrolled studies of patients with CLI who did not receive revascularization with a minimum follow-up of ≥1 year. Predefined outcomes of interest were mortality, major amputation, and wound healing. Random-effects meta-analysis was used to pool cumulative incidence across studies. RESULTS: We identified 13 studies enrolling 1527 patients. During a median follow-up of 12 months, all-cause mortality rate was 22% (confidence interval [CI], 12%-33%) and major amputation rate was 22% (CI, 2%-42%). Worsened wound or ulcer was found at 35% (CI, 10%-62%). There was a trend toward improvement in mortality and amputation rate in studies done after 1997. The quality of evidence was low because of increased risk of bias and inconsistency. CONCLUSIONS: Mortality and major amputations are common in patients who have untreated CLI during a median follow-up of 1 year, although these outcomes have improved in recent times.

Treatment of acute iliofemoral deep vein thrombosis.

OBJECTIVE: The objective of this systematic review and meta-analysis was to compare the efficacy of three available treatments for acute iliofemoral deep vein thrombosis (DVT): systemic anticoagulation, surgical thrombectomy, and catheter-directed thrombolysis. METHODS: We searched electronic databases (MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, and Scopus) and sought additional references from experts. Eligible studies enrolled participants with acute iliofemoral DVT and measured the outcomes of interest. Reviewers working independently in duplicate extracted study characteristics, quality, and outcome data (death, pulmonary embolism, local complications, hemorrhagic complications, postthrombotic syndrome, pain, quality of life, and surrogate markers of venous function such as valve competence and patency). We pooled relative risks (RRs) from each study using the random effects model and estimated the 95% confidence intervals (CIs). Bayesian indirect comparison techniques were used to compare thrombectomy to catheter-directed thrombolysis. RESULTS: We found 15 unique studies that fulfilled eligibility criteria. When compared to systemic anticoagulation, thrombectomy was associated with a statistically significant reduction in the risk of developing postthrombotic syndrome (RR, 0.67; 95% CI, 0.52-0.87), venous reflux (RR, 0.68; 95% CI, 0.46-0.99), and a trend for reduction in the risk of venous obstruction (RR, 0.84; 95% CI, 0.60-1.19). When compared to systemic anticoagulation, pharmacologic catheter-directed thrombolysis was associated with statistically significant reduction in the risk of postthrombotic syndrome (RR, 0.19; 95% CI, 0.07-0.48), venous obstruction (RR, 0.38; 95% CI, 0.18-0.37), and a trend for reduction in the risk of venous reflux (RR, 0.39; 95% CI, 0.16-1.00). Overall, the quality of evidence was low; downgraded due to the observational nature of the majority of studies, lack of comparability of study cohorts at baseline, loss to follow-up, imprecision, and indirectness of outcomes (surrogacy). There were insufficient data to compare the outcomes of thrombectomy to catheter-directed thrombolysis. CONCLUSIONS: Low-quality evidence suggests that surgical thrombectomy decreases the incidence of postthrombotic syndrome and venous reflux. Catheter-directed pharmacologic thrombolysis decreases the incidence of postthrombotic syndrome and venous obstruction.

A systematic review and meta-analysis of the treatments of varicose veins.

OBJECTIVES: Several treatment options exist for varicose veins. In this review we summarize the available evidence derived from comparative studies about the relative safety and efficacy of these treatments. METHODS: We searched MEDLINE, Embase, Current Contents, Cochrane Central Register of Controlled Trials (CENTRAL) expert files, and the reference section of included articles. Eligible studies compared two or more of the available treatments (surgery, liquid or foam sclerotherapy, laser, radiofrequency ablations, or conservative therapy with compression stockings). Two independent reviewers determined study eligibility and extracted descriptive, methodologic, and outcome data. We used random-effects meta-analysis to pool relative risks (RR) and 95% confidence intervals (CI) across studies. RESULTS: We found 39 eligible studies (30 were randomized trials) enrolling 8285 participants. Surgery was associated with a nonsignificant reduction in the risk of varicose vein recurrence compared with liquid sclerotherapy (RR, 0.56; 95% CI, 0.29-1.06) and all endoluminal interventions (RR, 0.63; 95% CI, 0.37-1.07). Studies of laser and radiofrequency ablation and foam sclerotherapy demonstrated short-term effectiveness and safety. The quality of evidence presented in this review was limited by imprecision (small number of events), short-term follow-up, and indirectness (use of surrogate outcomes). CONCLUSION: Low-quality evidence supports long-term safety and efficacy of surgery for the treatment of varicose veins. Short-term studies support the efficacy of less invasive treatments, which are associated with less periprocedural disability and pain.

Indexed left ventricular mass to QRS voltage ratio is associated with heart failure hospitalizations in patients with cardiac amyloidosis.

In cardiac amyloidosis (CA), amyloid infiltration results in increased left ventricular (LV) mass disproportionate to electrocardiographic (EKG) voltage. We assessed the relationship between LV mass-voltage ratio with subsequent heart failure hospitalization (HHF) and mortality in CA. Patients with confirmed CA and comprehensive cardiovascular magnetic resonance (CMR) and EKG exams were included. CMR-derived LV mass was indexed to body surface area. EKG voltage was assessed using Sokolow, Cornell, and Limb-voltage criteria. The optimal LV mass-voltage ratio for predicting outcomes was determined using receiver operating characteristic curve analysis. The relationship between LV mass-voltage ratio and HHF was assessed using Cox proportional hazards analysis adjusting for significant covariates. A total of 85 patients (mean 69 ± 11 years, 22% female) were included, 42 with transthyretin and 43 with light chain CA. At a median of 3.4-year follow-up, 49% of patients experienced HHF and 60% had died. In unadjusted analysis, Cornell LV mass-voltage ratio was significantly associated with HHF (HR, 1.05; 95% CI 1.02-1.09, p = 0.001) and mortality (HR, 1.05; 95% CI 1.02-1.07, p = 0.001). Using ROC curve analysis, the optimal cutoff value for Cornell LV mass-voltage ratio to predict HHF was 6.7 gm/m2/mV. After adjusting for age, NYHA class, BNP, ECV, and LVEF, a Cornell LV mass-voltage ratio > 6.7 gm/m2/mV was significantly associated with HHF (HR 2.25, 95% CI 1.09-4.61; p = 0.03) but not mortality. Indexed LV mass-voltage ratio is associated with subsequent HHF and may be a useful prognostic marker in cardiac amyloidosis.

Surgical modifications of the upper airway for obstructive sleep apnea in adults: a systematic review and meta-analysis.

A substantial portion of patients with obstructive sleep apnea (OSA) seek alternatives to positive airway pressure (PAP), the usual first-line treatment for the disorder. One option is upper airway surgery. As an adjunct to the American Academy of Sleep Medicine (AASM) Standards of Practice paper, we conducted a systematic review and meta-analysis of literature reporting outcomes following various upper airway surgeries for the treatment of OSA in adults, including maxillomandibular advancement (MMA), pharyngeal surgeries such as uvulopharyngopalatoplasty (UPPP), laser assisted uvulopalatoplasty (LAUP), and radiofrequency ablation (RFA), as well as multi-level and multi-phased procedures. We found that the published literature is comprised primarily of case series, with few controlled trials and varying approaches to pre-operative evaluation and post-operative follow-up. We include surgical morbidity and adverse events where reported but these were not systematically analyzed. Utilizing the ratio of means method, we used the change in the apnea-hypopnea index (AHI) as the primary measure of efficacy. Substantial and consistent reductions in the AHI were observed following MMA; adverse events were uncommonly reported. Outcomes following pharyngeal surgeries were less consistent; adverse events were reported more commonly. Papers describing positive outcomes associated with newer pharyngeal techniques and multi-level procedures performed in small samples of patients appear promising. Further research is needed to better clarify patient selection, as well as efficacy and safety of upper airway surgery in those with OSA.

Effect of sex steroid use on cardiovascular risk in transsexual individuals: a systematic review and meta-analyses.

OBJECTIVE: To summarize the available evidence on the cardiovascular effects of cross-sex steroid use in transsexuals. METHODS: We searched relevant electronic databases and sought additional references from experts. Eligible studies reported on cardiovascular events, venous thromboembolism, blood pressure and fasting serum lipids. Data were extracted in duplicate. We used the random-effects model to estimate the pooled weighted mean difference (WMD) and 95% confidence intervals (CIs). RESULTS: We found 16 eligible studies, mostly uncontrolled cohorts of varied follow-up durations (1471 male-to-female (MF) and 651 female-to-male (FM) individuals). In the MF individuals, cross-sex hormone use was associated with a statistically significant increase in fasting serum triglycerides without changes in the other parameters (WMD = 23.39 mg/dl; 95% CI = 4.82-41.95). In the FM individuals, there was a similar increase of triglycerides (WMD = 31.35 mg/dl; 95% CI = 7.53-55.17) and a reduction of high density lipoprotein (HDL)-cholesterol (WMD = -6.09 mg/dl; 95% CI = -11.44 to -0.73). There was a statistically significant but clinically trivial increase in systolic blood pressure (WMD = 1.74 mmHg; 95% CI = 0.21-3.27). Analyses were associated with significant heterogeneity across studies. There were very few reported cardiovascular events (deaths, strokes, myocardial infarctions or venous thromboembolism), more commonly among MF individuals. CONCLUSIONS: Very low quality evidence, downgraded due to methodological limitations of included studies, imprecision and heterogeneity, suggests that cross-sex hormone therapies increase serum triglycerides in MF and FM and have a trivial effect on HDL-cholesterol and systolic blood pressure in FM. Data about patient important outcomes are sparse and inconclusive.

Hormonal therapy and sex reassignment: a systematic review and meta-analysis of quality of life and psychosocial outcomes.

OBJECTIVE: To assess the prognosis of individuals with gender identity disorder (GID) receiving hormonal therapy as a part of sex reassignment in terms of quality of life and other self-reported psychosocial outcomes. METHODS: We searched electronic databases, bibliography of included studies and expert files. All study designs were included with no language restrictions. Reviewers working independently and in pairs selected studies using predetermined inclusion and exclusion criteria, extracted outcome and quality data. We used a random-effects meta-analysis to pool proportions and estimate the 95% confidence intervals (CIs). We estimated the proportion of between-study heterogeneity not attributable to chance using the I(2) statistic. RESULTS: We identified 28 eligible studies. These studies enrolled 1833 participants with GID (1093 male-to-female, 801 female-to-male) who underwent sex reassignment that included hormonal therapies. All the studies were observational and most lacked controls. Pooling across studies shows that after sex reassignment, 80% of individuals with GID reported significant improvement in gender dysphoria (95% CI = 68-89%; 8 studies; I(2) = 82%); 78% reported significant improvement in psychological symptoms (95% CI = 56-94%; 7 studies; I(2) = 86%); 80% reported significant improvement in quality of life (95% CI = 72-88%; 16 studies; I(2) = 78%); and 72% reported significant improvement in sexual function (95% CI = 60-81%; 15 studies; I(2) = 78%). CONCLUSIONS: Very low quality evidence suggests that sex reassignment that includes hormonal interventions in individuals with GID likely improves gender dysphoria, psychological functioning and comorbidities, sexual function and overall quality of life.

Prenatal dexamethasone use for the prevention of virilization in pregnancies at risk for classical congenital adrenal hyperplasia because of 21-hydroxylase (CYP21A2) deficiency: a systematic review and meta-analyses.

CONTEXT: Prenatal treatment with dexamethasone to prevent virilization in pregnancies at risk for classical congenital adrenal hyperplasia (CAH) remains controversial. OBJECTIVE: To conduct a systematic review and meta-analyses of studies that evaluated the effects of dexamethasone administration during pregnancies at risk for classical CAH because of 21-hydroxylase deficiency (CYP21A2). DATA SOURCES: We searched MEDLINE, EMBASE, and Cochrane CENTRAL from inception through August 2009. Review of reference lists and contact with CAH experts further identified candidate studies. STUDY SELECTION: Reviewers working independently and in duplicate determined trial eligibility. Eligible studies reported the effects on either foetal or maternal outcomes of dexamethasone administered during pregnancy compared to a control group that did not receive any treatment. DATA EXTRACTION: Reviewers working independently and in duplicate determined the methodological quality of studies and collected data on patient characteristics, interventions, and outcomes. DATA SYNTHESIS: We identified only four eligible observational studies (325 pregnancies treated with dexamethasone). The methodological quality of the included studies was overall low. Meta-analysis demonstrates a reduction in foetus virilization measured by Prader score in female foetuses treated with dexamethasone initiated early during pregnancy (weighted mean difference, -2.33, 95% CI, -3.38, -1.27). No deleterious effects of dexamethasone on stillbirths, spontaneous abortions, foetal malformations, neuropsychological or developmental outcomes were found although these data are quite sparse. There was increased oedema and striae in the mothers treated with dexamethasone. There were no data on long-term follow-up of physical and metabolic outcomes in children exposed to dexamethasone. CONCLUSIONS: The observational nature of the available evidence and the overall small sample size of the whole body of the literature significantly weaken inferences about the benefits and harms of dexamethasone in this setting. Dexamethasone seems to be associated with reduction in foetus virilization without significant maternal or foetal adverse effects. However, this review underscores the current uncertainty and further investigation is clearly needed. The decision about initiating treatment should be based on patients' values and preferences and requires fully informed and consenting parents.

Effect on bone health of estrogen preparations in premenopausal women with anorexia nervosa: a systematic review and meta-analyses.

OBJECTIVE: Because estrogen therapies are widely prescribed for amenorrhea associated with anorexia nervosa (AN), we conducted a systematic review and meta-analyses to estimate the influence of estrogen preparations (EP) on bone mineral density in women with AN. METHOD: Prospective cohort studies and randomized clinical trials (RCTs) comparing the effect of EP use to no treatment or placebo on bone mineral density and bone fractures were included. Independent reviewers selected studies for inclusion and extracted study characteristics, markers of methodologic quality, and outcomes for the intention-to-treat population. RESULTS: Using random-effects meta-analyses and inconsistency across trials using the I(2) statistic, data were combined across two eligible prospective cohort studies and four RCTs; none reported effects on bone fractures. Compared with placebo or no treatment, low quality evidence found EPs have a moderate effect on bone mineral density in the lumbar spine [ES (effect size) 0.33, 95% CI (confidence interval) 0.09, 0.56; I(2) = 0%)], but no significant effect on the femoral neck (ES 0.13, 95% CI -0.16, 0.43; I(2) = 0%). There were no significant treatment-subgroup interactions. DISCUSSION: In general, EPs have uncertain benefit and should be avoided by women with AN in whom the success of weight and nutritional rehabilitation is judged by menses resumption.

Stopping randomized trials early for benefit and estimation of treatment effects: systematic review and meta-regression analysis.

CONTEXT: Theory and simulation suggest that randomized controlled trials (RCTs) stopped early for benefit (truncated RCTs) systematically overestimate treatment effects for the outcome that precipitated early stopping. OBJECTIVE: To compare the treatment effect from truncated RCTs with that from meta-analyses of RCTs addressing the same question but not stopped early (nontruncated RCTs) and to explore factors associated with overestimates of effect. DATA SOURCES: Search of MEDLINE, EMBASE, Current Contents, and full-text journal content databases to identify truncated RCTs up to January 2007; search of MEDLINE, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects to identify systematic reviews from which individual RCTs were extracted up to January 2008. STUDY SELECTION: Selected studies were RCTs reported as having stopped early for benefit and matching nontruncated RCTs from systematic reviews. Independent reviewers with medical content expertise, working blinded to trial results, judged the eligibility of the nontruncated RCTs based on their similarity to the truncated RCTs. DATA EXTRACTION: Reviewers with methodological expertise conducted data extraction independently. RESULTS: The analysis included 91 truncated RCTs asking 63 different questions and 424 matching nontruncated RCTs. The pooled ratio of relative risks in truncated RCTs vs matching nontruncated RCTs was 0.71 (95% confidence interval, 0.65-0.77). This difference was independent of the presence of a statistical stopping rule and the methodological quality of the studies as assessed by allocation concealment and blinding. Large differences in treatment effect size between truncated and nontruncated RCTs (ratio of relative risks <0.75) occurred with truncated RCTs having fewer than 500 events. In 39 of the 63 questions (62%), the pooled effects of the nontruncated RCTs failed to demonstrate significant benefit. CONCLUSIONS: Truncated RCTs were associated with greater effect sizes than RCTs not stopped early. This difference was independent of the presence of statistical stopping rules and was greatest in smaller studies.

Sexual abuse and lifetime diagnosis of somatic disorders: a systematic review and meta-analysis.

CONTEXT: Many patients presenting for general medical care have a history of sexual abuse. The literature suggests an association between a history of sexual abuse and somatic sequelae. OBJECTIVE: To systematically assess the association between sexual abuse and a lifetime diagnosis of somatic disorders. Data Sources and Extraction A systematic literature search of electronic databases from January 1980 to December 2008. Pairs of reviewers extracted descriptive, quality, and outcome data from included studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled across studies by using the random-effects model. The I(2) statistic was used to assess heterogeneity. STUDY SELECTION: Eligible studies were longitudinal (case-control and cohort) and reported somatic outcomes in persons with and without history of sexual abuse. RESULTS: The search identified 23 eligible studies describing 4640 subjects. There was a significant association between a history of sexual abuse and lifetime diagnosis of functional gastrointestinal disorders (OR, 2.43; 95% CI, 1.36-4.31; I(2) = 82%; 5 studies), nonspecific chronic pain (OR, 2.20; 95% CI, 1.54-3.15; 1 study), psychogenic seizures (OR, 2.96; 95% CI, 1.12-4.69, I(2) = 0%; 3 studies), and chronic pelvic pain (OR, 2.73; 95% CI, 1.73-4.30, I(2) = 40%; 10 studies). There was no statistically significant association between sexual abuse and a lifetime diagnosis of fibromyalgia (OR, 1.61; 95% CI, 0.85-3.07, I(2) = 0%; 4 studies), obesity (OR, 1.47; 95% CI, 0.88-2.46; I(2) = 71%; 2 studies), or headache (OR, 1.49; 95% CI, 0.96-2.31; 1 study). We found no studies that assessed syncope. When analysis was restricted to studies in which sexual abuse was defined as rape, significant associations were observed between rape and a lifetime diagnosis of fibromyalgia (OR, 3.35; 95% CI, 1.51-7.46), chronic pelvic pain (OR, 3.27; 95% CI, 1.02-10.53), and functional gastrointestinal disorders (OR, 4.01; 95% CI, 1.88-8.57). CONCLUSION: Evidence suggests a history of sexual abuse is associated with lifetime diagnosis of multiple somatic disorders.

Clinical review: Insulin sensitizers for the treatment of hirsutism: a systematic review and metaanalyses of randomized controlled trials.

CONTEXT: Insulin sensitizers, including metformin and thiazolidinediones (TZDs), improve hyperinsulinemia and reproductive dysfunctions in some women with hyperandrogenism. The extent to which these agents improve hirsutism remains unclear. OBJECTIVE: Our objective was to conduct a systematic review and metaanalyses of randomized controlled trials of metformin or TZDs for the treatment of hirsutism. DATA SOURCES: We searched the following databases: MEDLINE, EMBASE, and Cochrane CENTRAL (up to May 2006). Review of reference lists and contact with hirsutism experts further identified candidate trials. STUDY SELECTION: Reviewers working independently and in duplicate, with acceptable chance-adjusted agreement (kappa = 0.72), determined trial eligibility. Eligible trials randomly assigned women with hirsutism to at least 6 months of insulin sensitizers or control and measured hirsutism outcomes. DATA EXTRACTION: Reviewers working independently and in duplicate determined the methodological quality of trials and collected data on patient characteristics, interventions, and outcomes. DATA SYNTHESIS: Of 348 candidate studies, 16 trials (22 comparisons) were eligible. The methodological quality of these trials was low. Random-effects metaanalyses showed a small decrease in Ferriman-Gallwey scores in women treated with insulin sensitizers compared with placebo [pooled weighted mean difference (WMD) of -1.5; 95% confidence interval (CI), -2.8 to -0.2; inconsistency (I(2)) = 75%]. There was no significant difference between insulin sensitizers and oral contraceptives (WMD of -0.5; CI, -5.0, 3.9; I(2) = 79%). Metformin was inferior to both spironolactone (WMD of 1.3; CI, 0.03, 2.6) and flutamide (WMD of 5.0; CI, 3.0, 7.0; I(2) = 0%). CONCLUSIONS: Imprecise and inconsistent evidence of low to very low quality suggests that insulin sensitizers provide limited or no important benefit for women with hirsutism.

Accuracy of diagnostic tests for Cushing's syndrome: a systematic review and metaanalyses.

CONTEXT: The diagnosis of Cushing's syndrome (CS) requires the use of tests of unregulated hypercortisolism that have unclear accuracy. OBJECTIVE: Our objective was to summarize evidence on the accuracy of common tests for diagnosing CS. DATA SOURCES: We searched electronic databases (MEDLINE, EMBASE, Web of Science, Scopus, and citation search for key articles) from 1975 through September 2007 and sought additional references from experts. STUDY SELECTION: Eligible studies reported on the accuracy of urinary free cortisol (UFC), dexamethasone suppression test (DST), and midnight cortisol assays vs. reference standard in patients suspected of CS. DATA EXTRACTION: Reviewers working in duplicate and independently extracted study characteristics and quality and data to estimate the likelihood ratio (LR) and the 95% confidence interval (CI) for each result. DATA SYNTHESIS: We found 27 eligible studies, with a high prevalence [794 (9.2%) of 8631 patients had CS] and severity of CS. The tests had similar accuracy: UFC (n = 14 studies; LR+ 10.6, CI 5.5-20.5; LR- 0.16, CI 0.08-0.33), salivary midnight cortisol (n = 4; LR+ 8.8, CI 3.5-21.8; LR- 0.07, CI 0-1.2), and the 1-mg overnight DST (n = 14; LR+ 16.4, CI 9.3-28.8; LR- 0.06, CI 0.03-0.14). Combined testing strategies (e.g. a positive result in both UFC and 1-mg overnight DST) had similar diagnostic accuracy (n = 3; LR+ 15.4, CI 0.7-358; LR- 0.11, CI 0.007-1.57). CONCLUSIONS: Commonly used tests to diagnose CS appear highly accurate in referral practices with samples enriched with patients with CS. Their performance in usual clinical practice remains unclear.

Immunotherapeutic agents in type 1 diabetes: a systematic review and meta-analysis of randomized trials.

OBJECTIVE: Although recent trial results of anti-CD3 therapy are promising, there have been conflicting results of various immunotherapeutic agents used in patients with type 1 diabetes. We conducted a systematic review and meta-analysis to determine the efficacy of nonantigen-based immunotherapeutic approaches for preservation of beta-cell function in patients with type 1 diabetes. METHODS: We searched MEDLINE, EMBASE, Cochrane CENTRAL, reference lists, and content expert files up to September 2006. Eligible studies were randomized controlled trials (RCTs) of antiproliferative agents (methotrexate, azathioprine), monoclonal antibodies (CD3, CD4), T-cell inhibitors (cyclosporin) and other immunotherapeutic agents (photopheresis, linomide, fusidin, buffy coat, intravenous immunoglobulin, BCG, nicotinamide) in patients with newly diagnosed type 1 diabetes followed for > or = 6 months. Pairs of reviewers working independently and with adequate reliability assessed the trials' methodological quality, collected data, and conducted random-effects meta-analyses on measures of preservation of beta-cell function (e.g. C-peptide secretion, insulin independence). RESULTS: Of the 299 potentially relevant articles identified after an initial search, 20 trials met selection criteria. Meta-analysis of 20 trials (n = 1187 patients) found a small to moderate improvement in beta-cell function with immunotherapy [vs. placebo, effect size 0.37, 95% confidence interval (CI) 0.14-0.6] but there was moderate inconsistency in results across trials (I(2) 65%, 95% CI 39-77%). Subgroup analysis suggested a greater effect of cyclosporin and antiproliferative agents on beta-cell function when used for > or = 6 months (pooled effect size 0.77 vs. -0.11, respectively; P(interaction) = 0.002). CONCLUSIONS: Long-term immunotherapy may preserve beta-cell function in newly diagnosed patients with type 1 diabetes. Patients and clinicians must await the conduct of rigorous trials reporting on diabetes resolution, adverse events, and other patient-important outcomes.

Endarterectomy vs stenting for carotid artery stenosis: a systematic review and meta-analysis.

OBJECTIVES: The relative efficacy and safety of endarterectomy and stenting in patients with carotid stenosis remain unclear. In this review we synthesize the available evidence derived from randomized controlled trials (RCTs) that compared the two procedures in terms of the risks of death, stroke (disabling and nondisabling), and nonfatal myocardial infarction. METHODS: We searched for RCTs in MEDLINE, EMBASE, Current Contents, and Cochrane CENTRAL; expert files, and bibliographies of included articles. Two reviewers, working independently, determined trial eligibility and extracted descriptive, methodologic, and outcome data from each eligible RCT. Random-effects meta-analysis was used to assess relative and absolute risks and the I(2) statistic was used to assess heterogeneity of treatment effect among trials. RESULTS: Ten RCTs with 3182 participants proved eligible. At 30 days and compared with endarterectomy, carotid stenting was associated with a nonsignificant reduction in the risk of death (relative risk [RR], 0.61; 95% confidence interval [CI], 0.27-1.37; I(2) = 0%), a nonsignificant reduction in the risk of nonfatal myocardial infarction (RR, 0.43; 95% CI 0.17-1.11; I(2) = 0%), and a nonsignificant increase in the risk of any stroke (RR, 1.29; 95% CI, 0.73-2.26; I(2) = 40%) and major/disabling stroke (RR, 1.06; 95% CI, 0.32-3.52; I(2) = 45%). If one considers the two procedures equivalent if the absolute difference in events is <2%, these results provide moderate-quality evidence for equivalence with respect to death (risk difference [RD] -0.40, 95% CI -1.02 to 0.40) and nonfatal myocardial infarction (RD, -0.70; 95% CI -1.90 to 0.50), but because of much wider CI, only low-quality evidence of equivalence in stroke (RD, 1.00; 95% CI, -1.00 to 3.10). CONCLUSION: In RCTs, carotid stenting and carotid endarterectomy seem equivalent in terms of death and nonfatal myocardial infarction. Although the impact on stroke remains unestablished, results are consistent with a clinically important increase in stroke risk with stenting, an intervention that aims at reducing the risk of stroke.

Timing of referral for vascular access placement: a systematic review.

OBJECTIVE: This review was conducted to determine the optimal timing for referring patients with end-stage renal disease to vascular surgery for access placement. METHODS: A systematic review of the electronic databases (MEDLINE, EMBASE, Current Contents, Cochrane CENTRAL and Web of Science) was conducted through March 2007. Randomized and observational studies were eligible if they compared an early referral cohort with a late referral cohort in terms of patient-important outcomes such as death, access-related sepsis, and hospitalization related to access complications. RESULTS: We found no studies that fulfilled eligibility criteria. CONCLUSION: At the present time, the optimal timing for referral to vascular surgery for vascular access placement is based on expert opinion and choices made by patients and physicians.

Autogenous versus prosthetic vascular access for hemodialysis: a systematic review and meta-analysis.

OBJECTIVES: The autogenous arteriovenous access for chronic hemodialysis is recommended over the prosthetic access because of its longer lifespan. However, more than half of the United States dialysis patients receive a prosthetic access. We conducted a systematic review to summarize the best available evidence comparing the two accesses types in terms of patient-important outcomes. METHODS: We searched electronic databases (MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science and SCOPUS) and included randomized controlled trials and controlled cohort studies. We pooled data for each outcome using a random effects model to estimate the relative risk (RR) and its associated 95% confidence interval (CI). We estimated inconsistency caused by true differences between studies using the I(2) statistic. RESULTS: Eighty-three studies, of which 80 were nonrandomized, met eligibility criteria. Compared with the prosthetic access, the autogenous access was associated with a significant reduction in the risk of death (RR, 0.76; 95% CI, 0.67-0.86; I(2) = 48%, 27 studies) and access infection (RR, 0.18; 95% CI, 0.11-0.31; I(2) = 93%, 43 studies), and a nonsignificant reduction in the risk of postoperative complications (hematoma, bleeding, pseudoaneurysm and steal syndrome, RR 0.73; 95% CI, 0.48-1.16; I(2) = 65%, 31 studies) and length of hospitalization (pooled weighted mean difference -3.8 days; 95% CI, -7.8 to 0.2; P = .06). The autogenous access also had better primary and secondary patency at 12 and 36 months. CONCLUSION: Low-quality evidence from inconsistent studies with limited protection against bias shows that autogenous access for chronic hemodialysis is superior to prosthetic access.

Surveillance of arteriovenous hemodialysis access: a systematic review and meta-analysis.

OBJECTIVES: Hemodialysis centers regularly survey arteriovenous (AV) accesses for signs of dysfunction. In this review, we synthesize the available evidence to determine to what extent proactive vascular access monitoring affects the incidence of AV access thrombosis and abandonment compared with clinical monitoring. METHODS: We searched electronic databases (MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, and SCOPUS) and sought references from experts, bibliographies of included trials, and articles that cited included studies. Two reviewers independently assessed trial quality and extracted data. We used random effects meta-analysis to estimate the pooled relative risk (RR) and 95% confidence interval (CI) across studies and conducted subgroup analyses to explain heterogeneity. The I(2) statistic was used to assess heterogeneity of treatment effect among trials. RESULTS: Nine studies (1363 patients) compared a strategy of surveillance vs clinical monitoring. A vascular intervention to maintain or restore patency was provided to both groups if needed. Surveillance followed by intervention led to a nonsignificant reduction of the risk of access thrombosis (RR, 0.82; 95% CI, 0.58-1.16; I(2) = 37%) and access abandonment (RR, 0.80; 95% CI, 0.51-1.25; I(2) = 60%). Three studies (207 patients) compared the effect of vascular interventions vs observation in patients with abnormal surveillance result. Vascular interventions after an abnormal AV access surveillance led to a significant reduction of the risk of access thrombosis (RR, 0.53; 95% CI, 0.36-0.76) and a nonsignificant reduction of the risk of access abandonment (RR, 0.76; 95% CI, 0.43-1.37). CONCLUSION: Very low quality evidence yielding imprecise results suggests a potentially beneficial effect of AV access surveillance followed by interventions to restore patency. This inference, however, is weak and will require randomized trials of AV access surveillance vs clinical monitoring for rejection or confirmation.