Citations

Abstract Background The efficacy of lipid-lowering agents on patient-important outcomes in older individuals is unclear. Methods We included randomized trials that enrolled individuals aged 65 years or older and that included at least 1 year of follow-up. Pairs of reviewers selected and appraised the trials. Results We included 23 trials that enrolled 60,194 elderly patients. For primary prevention, statins reduced the risk of coronary artery disease [CAD; relative risk (RR): 0.79, 95% CI: 0.68 to 0.91] and myocardial infarction (MI; RR: 0.45, 95% CI: 0.31 to 0.66) but not all-cause or cardiovascular mortality or stroke. These effects were imprecise in patients with diabetes, but there was no significant interaction between diabetes status and the intervention effect. For secondary prevention, statins reduced all-cause mortality (RR: 0.80, 95% CI: 0.73 to 0.89), cardiovascular mortality (RR: 0.68, 95% CI: 0.58 to 0.79), CAD (RR: 0.68, 95% CI: 0.61 to 0.77), MI (RR: 0.68, 95% CI: 0.59 to 0.79), and revascularization (RR: 0.68, 95% CI: 0.61 to 0.77). Intensive (vs less-intensive) statin therapy reduced the risk of CAD and heart failure. Niacin did not reduce the risk of revascularization, and fibrates did not reduce the risk of stroke, cardiovascular mortality, or CAD. Conclusion High-certainty evidence supports statin use for secondary prevention in older individuals. Evidence for primary prevention is less certain. Data in older individuals with diabetes are limited; however, no empirical evidence has shown a significant difference based on diabetes status.

ObjectiveWe performed a systematic review and meta‐analysis to evaluate the comparative effects of tumor necrosis factor inhibitors (TNFi), non‐TNFi biologics, and conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs) on cardiovascular risk in rheumatoid arthritis (RA).MethodsUsing a systematic search through May 8, 2018, we included 14 observational studies in adults with RA treated with TNFi, non‐TNFi biologics, tofacitinib, or csDMARDs, reporting the risk of major adverse cardiovascular events (MACE) or stroke. Only studies reporting active comparators were included. We performed random effects meta‐analysis and estimated odds ratios (ORs) and 95% confidence intervals (95% CIs).ResultsAs compared to TNFi, tocilizumab was associated with a decreased risk of MACE (OR 0.59 [95% CI 0.34–1.00]), whereas csDMARDs were associated with an increased risk of MACE (csDMARDs including methotrexate OR 1.45 [95% CI 1.09–1.93]; without methotrexate OR 2.57 [95% CI 1.32–5.00]), without heterogeneity (I2 = 0%); there was no difference in risk of MACE between abatacept and TNFi (OR 0.89 [95% CI 0.71–1.11]), or between tocilizumab and abatacept (OR 0.81 [0.57–1.16]). Based on 11 cohorts (n = 135,053 patients), as compared to TNFi, csDMARDs were associated with an increased risk of stroke (OR 1.17 [95% CI 1.01–1.36]); there was no difference in risk of stroke between different biologics (tocilizumab versus TNFi OR 0.98 [95% CI 0.59–1.61]; abatacept versus TNFi OR 1.08 [0.86–1.34]; tocilizumab versus abatacept OR 0.73 [95% CI 0.39–1.38]), without heterogeneity (I2 = 0%). No comparative studies on cardiovascular risk with tofacitinib were identified.ConclusionBased on meta‐analysis, as compared to TNFi, tocilizumab may be associated with a reduced risk of MACE, whereas csDMARDs may be associated with an increased risk of MACE and stroke.

Background. This systematic review was commissioned to identify new variables associated with transplant outcomes that are not currently collected by the Organ Procurement and Transplantation Network (OPTN). Methods. We identified 81 unique studies including 1 193 410 patients with median follow-up of 36 months posttransplant, reporting 108 unique risk factors. Results. Most risk factors (104) were recipient related; few (4) were donor related. Most risk factors were judged to be practical and feasible to routinely collect. Relative association measures were small to moderate for most risk factors (ranging between 1.0 and 2.0). The strongest relative association measure for a heart transplant outcome with a risk factor was 8.6 (recipient with the previous Fontan operation), for a kidney transplant 2.8 (sickle cell nephropathy as primary cause of end-stage renal disease), for a liver transplant 14.3 (recipient serum ferritin >500 µg/L), and for a lung transplant 6.3 (Burkholderia cepacia complex infection for 1 y or less). OPTN may consider some of these 108 variables for future collection to enhance transplant research and clinical care. Conclusions. Evidence-based approaches can be used to determine variables collected in databases and registries. Several candidate variables have been identified for OPTN.

Purpose The authors sought to summarize quantitative and qualitative research addressing electronic knowledge resources and point-of-care learning in a scoping review. Method The authors searched MEDLINE, Embase, PsycINFO, and the Cochrane Database for studies addressing electronic knowledge resources and point-of-care learning. They iteratively revised inclusion criteria and operational definitions of study features and research themes of interest. Two reviewers independently performed each phase of study selection and data extraction. Results Of 10,811 studies identified, 305 were included and reviewed. Most studies (225; 74%) included physicians or medical students. The most frequently mentioned electronic resources were UpToDate (88; 29%), Micromedex (59; 19%), Epocrates (50; 16%), WebMD (46; 15%), MD Consult (32; 10%), and LexiComp (31; 10%). Eight studies (3%) evaluated electronic resources or point-of-care learning using outcomes of patient effects, and 36 studies (12%) reported objectively measured clinician behaviors. Twenty-five studies (8%) examined the clinical or educational impact of electronic knowledge resource use on patient care or clinician knowledge, 124 (41%) compared use rates of various knowledge resources, 69 (23%) examined the quality of knowledge resource content, and 115 (38%) explored the process of point-of-care learning. Two conceptual clarifications were identified, distinguishing the impact on clinical or educational outcomes versus the impact on test setting decision support, and the quality of information content versus the correctness of information obtained by a clinician–user. Conclusions Research on electronic knowledge resources is dominated by studies involving physicians and evaluating use rates. Studies involving nonphysician users, and evaluating resource impact and implementation, are needed.

Abstract Background Females with congenital adrenal hyperplasia (CAH) and atypical genitalia often undergo complex surgeries; however, their outcomes remain largely uncertain. Methods We searched several databases through 8 March 2016 for studies evaluating genital reconstructive surgery in females with CAH. Reviewers working independently and in duplicate selected and appraised the studies. Results We included 29 observational studies (1178 patients, mean age at surgery, 2.7 ± 4.7 years; mostly classic CAH). After an average follow-up of 10.3 years, most patients who had undergone surgery had a female gender identity (88.7%) and were heterosexual (76.2%). Females who underwent surgery reported a sexual function score of 25.13 using the Female Sexual Function Index (maximum score, 36). Many patients continued to complain of substantial impairment of sensitivity in the clitoris, vaginal penetration difficulties, and low intercourse frequency. Most patients were sexually active, although only 48% reported comfortable intercourse. Most patients (79.4%) and treating health care professionals (71.8%) were satisfied with the surgical outcomes. Vaginal stenosis was common (27%), and other surgical complications, such as fistulas, urinary incontinence, and urinary tract infections, were less common. Data on quality of life were sparse and inconclusive. Conclusion The long-term follow-up of females with CAH who had undergone urogenital reconstructive surgery shows variable sexual function. Most patients were sexually active and satisfied with the surgical outcomes; however, some patients still complained of impairment in sexual experience and satisfaction. The certainty in the available evidence is very low.

Summary Objective Surgery is a stressor that can be categorized by duration and severity and induces a systemic stress response that includes increased adrenal cortisol production. However, the precise impact of surgical stress on the cortisol response remains to be defined. Design We performed a systematic review and meta‐analysis to assess the cortisol stress response induced by surgery and to stratify this response according to different parameters. Methods We conducted a comprehensive search in several databases from 1990 to 2016. Pairs of reviewers independently selected studies, extracted data and evaluated the risk of bias. Cortisol concentrations were standardized, pooled in meta‐analysis and plotted over time. Results We included 71 studies reporting peri‐operative serum cortisol measurements in 2953 patients. The cortisol response differed substantially between moderately/highly invasive and minimally invasive surgical procedures. Minimally invasive procedures did not show a peri‐operative cortisol peak, whereas more invasive surgeries caused a cortisol surge that was more pronounced in older subjects, women and patients undergoing open surgery and general anaesthesia. The duration of the procedure and the use of etomidate for induction of anaesthesia did not affect the cortisol response. Conclusions The peri‐operative cortisol stress response is dynamic and influenced by patient‐specific, surgical and anaesthetic features. However, the available evidence is derived from highly heterogeneous studies, with only two of 71 studies measuring cortisol by mass spectrometry, which currently prevents a precise and reproducible definition of this response.

AbstractBackground & AimsAcute liver failure caused by hepatitis E virus genotype 3 and 4 has been rarely described. Because of the presence of a short golden therapeutic window in patients with viral acute liver failure from other causes, it is possible that early recognition and treatment might reduce the morbidity and mortality. We performed a systematic review and pooled analysis of acute liver failure caused by hepatitis E virus genotype 3 and 4.MethodsTwo reviewers appraised studies after searching multiple databases on June 12th, 2017. Appropriate tests were used to compare hepatitis E virus genotype 3 vs 4, suspected vs confirmed genotypes, hepatitis E virus‐RNA positive vs negative, and to discern important mortality risk factors.ResultsWe identified 65 patients, with median age 58 years (range: 3‐79), and a male to female ratio of 1.2:1. The median bilirubin, ALT, AST and alkaline phosphatase (expressed by multiplication of the upper limit of normal) levels were 14.8, 45.3, 34.8 and 1.63 respectively. Antihepatitis E virus IgG, antihepatitis E virus IgM and hepatitis E virus‐RNA were positive in 84%, 91% and 86% of patients respectively. The median interval from symptoms onset to acute liver failure was 23 days, and 16 patients underwent liver transplantation. Final outcome was reported in 58 patients and mortality was 46%. Age was a predictor of poor prognosis in multivariate analysis. No important differences were found between patients infected with genotype 3 vs 4, patients with confirmed vs suspected genotypes, or patients with positive vs negative RNA.ConclusionAcute liver failure caused by hepatitis E virus genotype 3 and 4 is rare, similar between genotypes, occurs commonly in middle‐aged/elderly patients and has a very high mortality. Age is predictive of poor prognosis in multivariate analysis.