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.

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.

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.

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.

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.

Body composition and quality of life in adults treated with GH therapy: a systematic review and meta-analysis.

OBJECTIVE: To summarise the evidence about the efficacy and safety of using GH in adults with GH deficiency focusing on quality of life and body composition. DATA SOURCES: We searched MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science and Scopus through April 2011. We also reviewed reference lists and contacted experts to identify candidate studies. STUDY SELECTION: Reviewers, working independently and in duplicate, selected randomised controlled trials (RCTs) that compared GH to placebo. DATA SYNTHESIS: We pooled the relative risk (RR) and weighted mean difference (WMD) by the random effects model and assessed heterogeneity using the I(2) statistic. RESULTS: Fifty-four RCTs were included enrolling over 3400 patients. The quality of the included trials was fair. GH use was associated with statistically significant reduction in weight (WMD, 95% confidence interval (95% CI): -2.31 kg, -2.66 and -1.96) and body fat content (WMD, 95% CI: -2.56 kg, -2.97 and -2.16); increase in lean body mass (WMD, 95% CI: 1.38, 1.10 and 1.65), the risk of oedema (RR, 95% CI: 6.07, 4.34 and 8.48) and joint stiffness (RR, 95% CI: 4.17, 1.4 and 12.38); without significant changes in body mass index, bone mineral density or other adverse effects. Quality of life measures improved in 11 of the 16 trials although meta-analysis was not feasible. RESULTS: GH therapy in adults with confirmed GH deficiency reduces weight and body fat, increases lean body mass and increases oedema and joint stiffness. Most trials demonstrated improvement in quality of life measures.

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.

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.

Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis.

CONTEXT: The risks of testosterone therapy in men remain poorly understood. OBJECTIVE: The aim of this study was to conduct a systematic review and meta-analyses of testosterone trials to evaluate the adverse effects of testosterone treatment in men. DATA SOURCES: We searched MEDLINE, EMBASE, and Cochrane CENTRAL from 2003 through August 2008. Review of reference lists and contact with experts further identified candidate studies. STUDY SELECTION: Eligible studies were comparative, randomized, and nonrandomized and reported the effects of testosterone on outcomes of interest (death, cardiovascular events and risk factors, prostate outcomes, and erythrocytosis). Reviewers, working independently and in duplicate, determined study eligibility. DATA EXTRACTION: Reviewers working independently and in duplicate determined the methodological quality of studies and collected descriptive, quality, and outcome data. DATA SYNTHESIS: The methodological quality of the 51 included studies varied from low to medium, and follow-up duration ranged from 3 months to 3 yr. Testosterone treatment was associated with a significant increase in hemoglobin [weighted mean difference (WMD), 0.80 g/dl; 95% confidence interval (CI), 0.45 to 1.14] and hematocrit (WMD, 3.18%; 95% CI, 1.35 to 5.01), and a decrease in high-density lipoprotein cholesterol (WMD, -0.49 mg/dl; 95% CI, -0.85 to -0.13). There was no significant effect on mortality, prostate, or cardiovascular outcomes. CONCLUSIONS: The adverse effects of testosterone therapy include an increase in hemoglobin and hematocrit and a small decrease in high-density lipoprotein cholesterol. These findings are of unknown clinical significance. Current evidence about the safety of testosterone treatment in men in terms of patient-important outcomes is of low quality and is hampered by the brief study follow-up.

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.

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.

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.