Christopher W Halladay

Comparative Effectiveness of Management Strategies for Renal Artery Stenosis: An Updated Systematic Review

As the population continues to age, the prevalence of atherosclerotic renal artery stenosis (ARAS) is increasing. Prevalence is particularly high among persons with risk factors for cardiovascular disease (CVD), with estimates ranging from 10.5% among patients undergoing coronary angiography to 54% among those with congestive heart failure (1). Among persons aged 66 years or older, 6.8% have been found to have ARAS (2). Hemodynamically significant ARAS, defined as at least 50% to 70% stenosis, is a leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) (3, 4). Options for ARAS treatment are medical therapyincluding aggressive blood pressure (BP) control, statins, and antiplateletsor renal artery revascularization with continued medical therapy. Percutaneous transluminal renal angioplasty with stent placement (PTRAS) is the current standard for revascularization (5). Use of PTRAS has decreased from its peak in 2006 but remains common at 6.7 procedures per 100000 adults (6). A 2007 systematic review of management strategies for ARAS concluded that the evidence did not support one treatment approach over another, and no defined set of clinical or intervention characteristics was convincingly associated with CVD, BP control, and kidney function (7, 8). Since then, 2 large trialsCORAL (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) (9) and ASTRAL (Angioplasty and Stenting for Renal Artery Lesions) (10)have been published, each calling into question the clinical value of invasive intervention for ARAS. Given the inconclusive prior review and new evidence, it is timely to reevaluate the comparative benefits and harms of strategies for management of patients with ARAS and to identify factors that may predict which patients are most likely to benefit from each intervention. Methods This review was based on a systematic review commissioned by the Agency for Healthcare Research and Quality (AHRQ). It followed a standard AHRQ protocol with input from a panel of nephrologists, invasive cardiologists, radiologists, and vascular surgeons. The protocol was published at www.effectivehealthcare.ahrq.gov on 20 January 2015. Data Sources We searched MEDLINE and EMBASE from January 2007 through 16 March 2016 and the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews through the fourth quarter of 2015. Eligible studies published between 1993 and 2007 from our previous systematic reviews (7, 8) were also included. We supplemented the search with studies in the U.S. Food and Drug Administration database, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform; recent systematic reviews; and proceedings of national renal, vascular surgery, and urology conferences from 2012 through 2014. We solicited additional citations from our expert panel and from manufacturers. The electronic search strategy combined terms for renal artery stenosis, renal hypertension, and renal vascular disease and was limited to adult humans, relevant research designs, and the English language (Supplement Table 1). Supplement. Supplemental Information Study Selection Six researchers screened citations in duplicate. We included studies of adults treated for ARAS that reported long-term (6 months) outcomes or adverse events. The outcomes of interest were all-cause mortality; kidney function (renal replacement therapy [RRT] and categorical and continuous changes in glomerular filtration rate [GFR], creatinine clearance, or serum creatinine level); BP control (hypertension and categorical and continuous changes in BP); CVD, including congestive heart failure; and adverse events, including medication-related and procedural complications. We included randomized, controlled trials (RCTs) and nonrandomized, comparative studies (NRCSs) comparing PTRAS versus any medical therapy with at least 10 participants per group. Noncomparative (single-group) studies were eligible only if they reported adverse events or outcome predictors and had at least 30 participants (PTRAS studies) or at least 10 participants (medication-only studies). We also included the 20 most recent (through 2014) case reports of patients with acute ARAS decompensation because of a concern that these patients would not have been included in other studies. Studies of open surgical revascularization and other noncomparative studies are reported elsewhere (11). We excluded studies that evaluated ARAS treatment in patients with kidney transplantation, renal cell or other carcinoma, concurrent aortic or aortoiliac aneurysm repair, or prior revascularization and studies in which more than 20% of the study population had non-ARAS disease. Data Extraction and Assessment Data from each study were extracted by 1 of 6 experienced methodologists and confirmed by at least 1 other. Extracted data included study, participant, and ARAS characteristics; interventions; outcomes; and study design. We applied the Cochrane risk-of-bias tool for RCTs (12) and selected questions from the Newcastle-Ottawa Scale (13) about comparability of cohorts, representativeness of the population, and adjustment for different lengths of follow-up. Two reviewers independently assessed risk of bias at the study level, with notation of specific outcomes at increased risk of bias (for example, due to high attrition). Two reviewers independently categorized the strength of evidence across studies as high, moderate, or low for each outcome category on the basis of the number of studies, study designs, study limitations (such as risk of bias), applicability, consistency of study results, precision of effect estimates, likelihood of reporting bias, other limitations, and summary findings across studies (14). Data Synthesis Meta-analysis was not conducted because of significant clinical heterogeneity. Between-group comparisons are summarized by effect size (expressed as either a hazard ratio [HR] or an odds ratio) and were synthesized qualitatively. Role of the Funding Source The funding agency (AHRQ) participated in protocol development and reviewed the full report. The research team independently conducted the review. Results The literature search retrieved 1560 citations, of which 189 were evaluated as full-text articles in addition to 54 studies from the 2006 and 2007 evidence reports and other systematic reviews and 74 case reports (Appendix Figure 1). In total, 83 studies (33 of which were newly identified) were eligible, including 15 that compared PTRAS with medical therapy; 39 that provided data on adverse events; 28 outcome predictor, subgroup, or co-treatment analyses; and 20 case reports of acute decompensation. Appendix Figure 1. Literature flow diagram. ARAS = atherosclerotic renal artery stenosis; NRCS = nonrandomized, comparative study; PTRAS = percutaneous transluminal renal angioplasty with stent placement; RCT = randomized, controlled trial. * Does not include studies that were screened and excluded for the 2006 report. Studies of open surgical revascularization and other noncomparative studies are reported elsewhere (11). Characteristics of Comparative Studies Fifteen comparative studies with 4006 total patients compared PTRAS with medical therapy for ARAS. Of these, 7 were RCTs (9, 10, 1521) and 8 were NRCSs (2229). The 7 RCTs analyzed a total of 2178 patients. The 2 largest RCTs (CORAL [9] and ASTRAL [10]) reported on 931 and 806 patients, respectively, and the remaining RCTs included a range of 52 to 140 patients (9, 10, 1517, 19, 21). Enrolled patients had uncontrolled BP while receiving at least 2 medications and up to about stage 3 or 4 CKD (Table 1; Supplement Table 2). The definitions of ARAS varied across studies (Supplement Table 3). Only the CORAL trial measured stenosis severity with translesional pressure gradients (9). All trials excluded patients with acute decompensation. Three of the 7 RCTs had high risk of attrition bias, and 2 had unclear risk. Two RCTs have been reported only as conference abstracts (19, 21); both had incomplete study descriptions and high risk of selective outcome reporting, and 1 included only selected patients from a terminated trial (21) (Supplement Table 4). Table 1. Characteristics and Main Results of Comparative Studies of PTRAS Versus Medical Therapy Table 1Continued Eight NRCSs compared PTRAS with medical therapy among 1828 patients (2229). All NRCSs included patients who had uncontrolled BP while receiving at least 2 medications and about stage 3 to 4 CKD. Four studies included patients with acute flash pulmonary edema or acute kidney injury (25, 26, 28, 29). The NRCSs were about evenly divided between high and low risk of selection bias (5 with high risk and 3 with low risk), attrition bias (incomplete outcome data; 3 with high risk and 5 with low risk), and selective reporting bias (3 with high risk, 4 with low risk, and 1 with unclear risk). In all NRCSs, the sample representativeness was rated as having low risk of bias. Reporting of medical therapy was often incomplete, and none of the NRCSs adequately adjusted for potential confounders. Effects of Interventions on Outcomes Mortality We found low strength of evidence of no difference in mortality, but none of the studies was powered to detect differences between PTRAS and medical therapy. Four RCTs (9, 10, 15, 16) reported mortality data for 1 to 5 years of follow-up, and 5 NRCSs (22, 24, 26, 27, 29) reported mortality at 6 months or later (Table 1; Supplement Table 5). Effect sizes ranged from 0.55 to 2.35, with no clear explanation for the heterogeneity (Figure 1). In the 4 RCTs, no statistically significant differences were found between PTRAS and medical therapy alone in all-cause mortality and cardiovascular mortality. Among the 5 NRCSs, only 1 found a statistically significantly reduced risk for death (45% with PTRAS vs. medical therapy) (26). Figure 1. Forest plot of effect size of death in adults w

Prevention and Treatment of Tympanostomy Tube Otorrhea: A Meta-analysis

A systematic review of need for water precautions and the effectiveness of otorrhea treatment with topical drops versus oral antibiotics in children with tympanostomy tubes. CONTEXT: Children with tympanostomy tubes often develop ear discharge. OBJECTIVE: Synthesize evidence about the need for water precautions (ear plugs or swimming avoidance) and effectiveness of topical versus oral antibiotic treatment of otorrhea in children with tympanostomy tubes. DATA SOURCES: Searches in Medline, the Cochrane Central Trials Registry and Cochrane Database of Systematic Reviews, Excerpta Medica Database, and the Cumulative Index to Nursing and Allied Health Literature. STUDY SELECTION: Abstracts and full-text articles independently screened by 2 investigators. DATA EXTRACTION: 25 articles were included. RESULTS: One randomized controlled trial (RCT) in children assigned to use ear plugs versus no precautions reported an odds ratio (OR) of 0.68 (95% confidence interval, 0.37–1.25) for >1 episode of otorrhea. Another RCT reported an OR of 0.71 (95% confidence interval, 0.29–1.76) for nonswimmers versus swimmers. Network meta-analyses suggest that, relative to oral antibiotics, topical antibiotic–glucocorticoid drops were more effective: OR 5.3 (95% credible interval, 1.2–27). The OR for antibiotic-only drops was 3.3 (95% credible interval, 0.74–16). Overall, the topical antibiotic–glucocorticoid and antibiotic-only preparations have the highest probabilities, 0.77 and 0.22 respectively, of being the most effective therapies. LIMITATIONS: Sparse randomized evidence (2 RCTs) and high risk of bias for nonrandomized comparative studies evaluating water precautions. Otorrhea treatments include non–US Food and Drug Administration approved, off-label, and potentially ototoxic antibiotics. CONCLUSIONS: No compelling evidence of a need for water precautions exists. Cure rates are higher for topical drops than oral antibiotics.

Strategies for improving the lives of US women aged 40 and above living with HIV/AIDS: an evidence map

BackgroundWhile in its early years the HIV epidemic affected primarily the male and the young, nowadays, the population living with HIV/AIDS is approximately 24% women, and its age composition has shifted towards older ages. Many of the older women who live with HIV/AIDS also live with the medical and social conditions that accompany aging. This work aims to identify and characterize empirical studies of strategies for the comprehensive management of women over 40, including transgender women, who live with HIV/AIDS. Forty was chosen as an operational age cutoff to identify premenopausal women who are less likely to bear children, as well as peri- and postmenopausal women.MethodsWe conducted a literature search after discussions with a diverse panel of content experts and other stakeholders and developed an evidence map that identified 890 citations that address questions having to do with programs and barriers to engaging with programs, as well as the role of insurance and comorbidities, and have enrolled older women who live with HIV/AIDS.ResultsOf these, only 37 (4%) reported results of interest for women over 40 who live with HIV/AIDS, or examined interactions between gender and older age that would allow predictions in this subgroup. Few of the 37 eligible studies focused on women facing obvious challenges, such as immigrants, transgender, physically abused, or those recently released from prison. No studies focused on women caring for dependents, including children and grandchildren, or those diagnosed after age 40.ConclusionThe evidence base that is directly applicable to women over 40 who live with HIV/AIDS in the USA is limited, and the research need is broad. We propose research prioritization strategies for this population.