Helen G. Mayo

Long-term follow-up after bariatric surgery: a systematic review

IMPORTANCE Bariatric surgery is an accepted treatment for obesity. Despite extensive literature, few studies report long-term follow-up in cohorts with adequate retention rates. OBJECTIVE To assess the quality of evidence and treatment effectiveness 2 years after bariatric procedures for weight loss, type 2 diabetes, hypertension, and hyperlipidemia in severely obese adults. EVIDENCE REVIEW MEDLINE and Cochrane databases were searched from 1946 through May 15, 2014. Search terms included bariatric surgery, individual bariatric procedures, and obesity. Studies were included if they described outcomes for gastric bypass, gastric band, or sleeve gastrectomy performed on patients with a body mass index of 35 or greater, had more than 2 years of outcome information, and had follow-up measures for at least 80% of the initial cohort. Two investigators reviewed each study and a third resolved study inclusion disagreements. FINDINGS Of 7371 clinical studies reviewed, 29 studies (0.4%, 7971 patients) met inclusion criteria. All gastric bypass studies (6 prospective cohorts, 5 retrospective cohorts) and sleeve gastrectomy studies (2 retrospective cohorts) had 95% confidence intervals for the reported mean, median, or both exceeding 50% excess weight loss. This amount of excess weight loss occurred in 31% of gastric band studies (9 prospective cohorts, 5 retrospective cohorts). The mean sample-size-weighted percentage of excess weight loss for gastric bypass was 65.7% (n = 3544) vs 45.0% (n = 4109) for gastric band. Nine studies measured comorbidity improvement. For type 2 diabetes (glycated hemoglobin <6.5% without medication), sample-size-weighted remission rates were 66.7% for gastric bypass (n = 428) and 28.6% for gastric band (n = 96). For hypertension (blood pressure <140/90 mm Hg without medication), remission rates were 38.2% for gastric bypass ( n = 808) and 17.4% for gastric band (n = 247). For hyperlipidemia (cholesterol <200 mg/dL, high-density lipoprotein >40 mg/dL, low-density lipoprotein <160 mg/dL, and triglycerides <200 mg/dL), remission rates were 60.4% for gastric bypass (n = 477) and 22.7% for gastric band (n = 97). CONCLUSIONS AND RELEVANCE Very few bariatric surgery studies report long-term results with sufficient patient follow-up to minimize biased results. Gastric bypass has better outcomes than gastric band procedures for long-term weight loss, type 2 diabetes control and remission, hypertension, and hyperlipidemia. Insufficient evidence exists regarding long-term outcomes for gastric sleeve resections.

Metformin in Patients With Type 2 Diabetes and Kidney Disease: A Systematic Review

IMPORTANCE Metformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is contraindicated in many individuals with impaired kidney function because of concerns of lactic acidosis. OBJECTIVE To assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function. EVIDENCE ACQUISITION In July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining to metformin, kidney disease, and lactic acidosis in humans between 1950 and June 2014. We excluded reviews, letters, editorials, case reports, small case series, and manuscripts that did not directly pertain to the topic area or that met other exclusion criteria. Of an original 818 articles, 65 were included in this review, including pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-analyses, and a clinical trial. RESULTS Although metformin is renally cleared, drug levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rates, 30-60 mL/min per 1.73 m2). The overall incidence of lactic acidosis in metformin users varies across studies from approximately 3 per 100,000 person-years to 10 per 100,000 person-years and is generally indistinguishable from the background rate in the overall population with diabetes. Data suggesting an increased risk of lactic acidosis in metformin-treated patients with chronic kidney disease are limited, and no randomized controlled trials have been conducted to test the safety of metformin in patients with significantly impaired kidney function. Population-based studies demonstrate that metformin may be prescribed counter to prevailing guidelines suggesting a renal risk in up to 1 in 4 patients with type 2 diabetes mellitus--use which, in most reports, has not been associated with increased rates of lactic acidosis. Observational studies suggest a potential benefit from metformin on macrovascular outcomes, even in patients with prevalent renal contraindications for its use. CONCLUSIONS AND RELEVANCE Available evidence supports cautious expansion of metformin use in patients with mild to moderate chronic kidney disease, as defined by estimated glomerular filtration rate, with appropriate dosage reductions and careful follow-up of kidney function.

Axillary Node Interventions in Breast Cancer: A Systematic Review

IMPORTANCE Recent data from clinical trials have challenged traditional thinking about axillary surgery in patients with breast cancer. OBJECTIVES To summarize evidence regarding the role of axillary interventions (surgical and nonsurgical) in breast cancer treatment and to review the association of these axillary interventions with recurrence of axillary node metastases, mortality, and morbidity outcomes in patients with breast cancer. EVIDENCE REVIEW Ovid MEDLINE (1946-July 2013), Cochrane Database of Systematic Reviews (2005-July 2013), Cochrane Database of Abstracts of Reviews of Effects (1994-July 2013), and Cochrane Central Register of Controlled Trials (1989-July 2013) were searched for publications on axillary interventions in breast cancer. Clinical trials, observational studies, and meta-analyses with at least 2-year follow-up were included. A total of 1070 publications were reviewed, 17 of which met final inclusion criteria. FINDINGS Partial mastectomy followed by whole breast radiation is breast-conserving therapy. For women with no suspicious, palpable axillary nodes who undergo breast-conserving therapy, there is little evidence of benefit from surgical complete axillary node dissection compared with sentinel node biopsy alone. Complete axillary node dissection in patients with no palpable lymph nodes, compared with sentinel node biopsy, provides no survival benefit and is associated with a 1% to 3% reduction in recurrence of axillary lymph node metastases, but is associated with a 14% risk of lymphedema. Surgical axillary staging via sentinel node biopsy in patients with benign axillary nodes on radiological and clinical examination helps to inform decisions regarding adjuvant systemic and radiation therapy. Patients and physicians should tailor axillary lymph node interventions to maximize regional disease control and minimize morbidity. Complete axillary lymph node dissection is indicated in patients who present with palpable or needle biopsy-proven axillary metastases, patients with positive sentinel nodes undergoing mastectomy (who do not, as a standard, receive adjuvant radiation), patients with more than 3 positive sentinel nodes undergoing breast-conserving therapy, and patients not meeting eligibility criteria for recent trials establishing the safety of sentinel node biopsy alone in patients with breast cancer and metastases in their sentinel nodes. CONCLUSION AND RELEVANCE Available evidence suggests that axillary node dissection is associated with more harm than benefit in women undergoing breast-conserving therapy who do not have palpable, suspicious lymph nodes, who have tumors 3.0 cm or smaller, and who have 3 or fewer positive nodes on sentinel node biopsy.

Dose Response Relationship Between Physical Activity and Risk of Heart Failure: A Meta-Analysis

Background— Prior studies have reported an inverse association between physical activity (PA) and risk of heart failure (HF). However, a comprehensive assessment of the quantitative dose–response association between PA and HF risk has not been reported previously. Methods and Results— Prospective cohort studies with participants >18 years of age that reported association of baseline PA levels and incident HF were included. Categorical dose–response relationships between PA and HF risk were assessed with random-effects models. Generalized least-squares regression models were used to assess the quantitative relationship between PA (metabolic equivalent [MET]–min/wk) and HF risk across studies reporting quantitative PA estimates. Twelve prospective cohort studies with 20 203 HF events among 370 460 participants (53.5% women; median follow-up, 13 years) were included. The highest levels of PA were associated with significantly reduced risk of HF (pooled hazard ratio for highest versus lowest PA, 0.70; 95% confidence interval, 0.67–0.73). Compared with participants reporting no leisure-time PA, those who engaged in guideline-recommended minimum levels of PA (500 MET-min/wk; 2008 US federal guidelines) had modest reductions in HF risk (pooled hazard ratio, 0.90; 95% confidence interval, 0.87–0.92). In contrast, a substantial risk reduction was observed among individuals who engaged in PA at twice (hazard ratio for 1000 MET-min/wk, 0.81; 95% confidence interval, 0.77–0.86) and 4 times (hazard ratio for 2000 MET-min/wk, 0.65; 95% confidence interval, 0.58–0.73) the minimum guideline-recommended levels. Conclusions— There is an inverse dose–response relationship between PA and HF risk. Doses of PA in excess of the guideline-recommended minimum PA levels may be required for more substantial reductions in HF risk.

The HIV care cascade before, during, and after incarceration: A systematic review and data synthesis

We conducted a systematic literature review of the data on HIV testing, engagement in care, and treatment in incarcerated persons, and estimated the care cascade in this group. We identified 2706 titles in MEDLINE, EBSCO, and Cochrane Library databases for studies indexed to January 13, 2015, and included 92 for analysis. We summarized HIV testing results by type (blinded, opt-out, voluntary); reviewed studies on HIV care engagement, treatment, and virological suppression; and synthesized these results into an HIV care cascade before, during, and after incarceration. The HIV care cascade following diagnosis increased during incarceration and declined substantially after release, often to levels lower than before incarceration. Incarceration provides an opportunity to address HIV care in hard-to-reach individuals, though new interventions are needed to improve postrelease care continuity.

Continuous Dose-Response Association Between Sedentary Time and Risk for Cardiovascular Disease: A Meta-analysis

IMPORTANCE Prior studies suggest that higher sedentary time is associated with a greater risk for cardiovascular disease (CVD). However, the quantitative, dose-response association between sedentary time and CVD risk is not known. OBJECTIVE To determine the categorical and quantitative dose-response association between sedentary time and CVD risk. DATA SOURCES Two independent investigators searched the MEDLINE and EMBASE databases for all studies published before July 6, 2015, that evaluated the association between sedentary time and incident CVD. STUDY SELECTION Prospective cohort studies with participants 18 years or older that reported the association between sedentary time and incident CVD were included. DATA EXTRACTION AND SYNTHESIS Two independent investigators performed the data extraction and collection using a standardized form. The study quality was assessed using the Newcastle-Ottawa Scale. The categorical dose-response association was evaluated by comparing the pooled hazard ratio (HR) for incident CVD associated with different levels of sedentary time (vs lowest sedentary time) across studies. The continuous dose-response association was assessed using random-effects generalized least squares spline models. Data were collected from April 5 to July 6, 2015. MAIN OUTCOMES AND MEASURES Incident CVD (coronary heart disease, including nonfatal myocardial infarction, stroke, and cardiovascular mortality). RESULTS Nine prospective cohort studies with 720 425 unique participants (57.1% women; 42.9% men; mean age, 54.5 years) and 25 769 unique cardiovascular events and a median follow-up of 11 years were included. In categorical analyses, compared with the lowest sedentary time category (median, 2.5 h/d), participants in the highest sedentary time category (median, 12.5 h/d) had an increased risk for CVD (HR, 1.14; 95% CI, 1.09-1.19). However, no apparent risk associated with intermediate levels of sedentary time (HR for 7.5 h/d, 1.02; 95% CI, 0.96-1.08) was found. In continuous analyses, a nonlinear association between sedentary time and incident CVD was found (P for nonlinearity < .001), with an increased risk observed for more than 10 hours of sedentary time per day (pooled HR, 1.08; 95% CI, 1.00-1.14). CONCLUSIONS AND RELEVANCE The association between sedentary time and the risk for CVD is nonlinear with an increased risk only at very high levels. These findings could have implications for guideline recommendations regarding the risks related to sedentary behavior.

Biological mesh implants for abdominal hernia repair: US food and drug administration approval process and systematic review of its efficacy

IMPORTANCE Expensive biological mesh materials are increasingly used to reinforce abdominal wall hernia repairs. The clinical and cost benefit of these materials are unknown. OBJECTIVES To review the published evidence on the use of biological mesh materials and to examine the US Food and Drug Administration (FDA) approval history for these devices. EVIDENCE ACQUISITION Search of multiple electronic databases (Ovid, MEDLINE, EMBASE, Cochrane Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, and Cochrane National Health Service Economic Evaluation Database) to identify articles published between 1948 and June 30, 2015, on the use of biological mesh materials used to reinforce abdominal wall hernia repair. Keywords searched included surgical mesh, abdominal hernia, recurrence, infection, fistula, bioprosthesis, biocompatible materials, absorbable implants, dermis, and collagen. The FDA online database for 510(k) clearances was reviewed for all commercially available biological mesh materials. The median national price for mesh materials was established by a benchmarking query through several Integrated Delivery Network and Group Purchasing Organization tools. EVIDENCE SYNTHESIS Of 274 screened articles, 20 met the search criteria. Most were case series that reported results of convenience samples of patients at single institutions with a variety of clinical problems. Only 3 of the 20 were comparative studies. There were no randomized clinical trials. In total, outcomes for 1033 patients were described. Studies varied widely in follow-up time, operative technique, meshes used, and patient selection criteria. Reported outcomes and clinical outcomes, such as fistula formation and infection, were inconsistently reported across studies. Conflicts of interest were not reported in 16 of the 20 studies. Recurrence rates ranged from 0% to 80%. All biological mesh devices were approved by the FDA based on substantial equivalence to a group of nonbiological predicate devices that, on average, were one-third less costly. CONCLUSIONS AND RELEVANCE There is insufficient evidence to determine the extra costs associated with or the clinical efficacy of biological mesh materials for the repair of abdominal wall hernia.

Surrogate and clinical outcomes following ischemic postconditioning during primary percutaneous coronary intervention of ST‐Segment elevation myocardial infarction: A meta‐analysis of 15 randomized trials

To conduct a meta‐analysis on surrogate and clinical outcomes with myocardial ischemic postconditioning (IPoC) following revascularization with primary percutaneous intervention (PPCI) for ST‐segment myocardial infarction (STEMI) compared with PPCI alone.

Racial and Ethnic Disparities in Nonalcoholic Fatty Liver Disease Prevalence, Severity, and Outcomes in the United States: A Systematic Review and Meta-analysis

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States, affecting 75–100 million Americans. However, the disease burden may not be equally distributed among races or ethnicities. We conducted a systematic review and meta‐analysis to characterize racial and ethnic disparities in NAFLD prevalence, severity, and prognosis. METHODS: We searched MEDLINE, EMBASE, and Cochrane databases through August 2016 for studies that reported NAFLD prevalence in population‐based or high‐risk cohorts, NAFLD severity including presence of nonalcoholic steatohepatitis (NASH) and significant fibrosis, and NAFLD prognosis including development of cirrhosis complications and mortality. Pooled relative risks, according to race and ethnicity, were calculated for each outcome using the DerSimonian and Laird method for a random‐effects model. RESULTS: We identified 34 studies comprising 368,569 unique patients that characterized disparities in NAFLD prevalence, severity, or prognosis. NAFLD prevalence was highest in Hispanics, intermediate in Whites, and lowest in Blacks, although differences between groups were smaller in high‐risk cohorts (range 47.6%–55.5%) than population‐based cohorts (range, 13.0%–22.9%). Among patients with NAFLD, risk of NASH was higher in Hispanics (relative risk, 1.09; 95% CI, 0.98–1.21) and lower in Blacks (relative risk, 0.72; 95% CI, 0.60–0.87) than Whites. However, the proportion of patients with significant fibrosis did not significantly differ among racial or ethnic groups. Data were limited and discordant on racial or ethnic disparities in outcomes of patients with NAFLD. CONCLUSIONS: In a systematic review and meta‐analysis, we found significant racial and ethnic disparities in NAFLD prevalence and severity in the United States, with the highest burden in Hispanics and lowest burden in Blacks. However, data are discordant on racial or ethnic differences in outcomes of patients with NAFLD.

Premorbid body mass index and mortality in patients with lung cancer: A systematic review and meta-analysis

OBJECTIVES We aimed to assess the association between premorbid obesity, measured using body mass index (BMI) and lung cancer-related mortality, through a systematic review and meta-analysis. MATERIALS AND METHODS Observational studies reporting statistical measures of association between premorbid BMI categories and lung cancer-related mortality were included in our study. We estimated hazard ratios (aHR) with 95% confidence intervals (CI), comparing lung cancer-related mortality across BMI categories. The main outcome measure was lung cancer-related mortality in obese (BMI≥30kg/m2) and overweight participants (BMI 25.0-29.9kg/m2), compared with normal BMI participants. RESULTS We included 14 studies (including 2 pooled cohort studies) comprising 3,008,137 cancer-free participants at inception, reporting 28,592 lung cancer-related deaths. On meta-analysis, we observed a significantly lower lung cancer-related mortality in overweight (aHR, 0.76; 95% CI, 0.68-0.85) and obese (aHR, 0.68, 95% CI; 0.57-0.81) participants as compared to participants with normal BMI, with considerable heterogeneity; after excluding one study with large effect size, a more conservative and consistent association was observed between BMI and lung cancer-related mortality (overweight vs. normal BMI: aHR, 0.84; 95% CI, 0.79-0.90; obese vs. normal BMI: aHR, 0.81; 95% CI, 0.75-0.87), with moderate heterogeneity. Were similar in men vs. women, non-smokers vs. smokers, and Western vs Asia-Pacific populations. CONCLUSIONS Based on meta-analysis, we observed an independent protective association between premorbid obesity and lung cancer-related mortality. This association was observed across sex, smoking status and geographic region. Further studies are needed to prospectively study this association.