Citations

Abstract Introduction Steroid refractory chronic graft-versus-host-disease (SR-cGVHD) is the leading cause of late morbidity and mortality in allogeneic transplant patients. Safety of extracorporeal photophoresis (ECP) has led to multiple studies evaluating its role in SR-cGVHD. Overall and organ specific response rates (RR) of SR-cGVHD have varied significantly between studies. We conducted a systemic review and meta-analysis to assess the efficacy of ECP in SR-cGVHD. Methods A comprehensive search of several databases (Ovid Medline In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Central register of Controlled Trials,, Scopus) for articles published in any language between 1984-2012 was conducted. Unpublished studies using electronic databases from the annual meetings abstracts of hematology/transplant societies were searched. Experts in the field were also contacted for selection of studies and missing data from selected trials. End points included complete response rate (CR), overall RR (ORR), and organ-specific RR's. Results Initial search generated 312 studies, out of which 18 studies (4 prospective) met selection criteria (N=595). Random effects model was used for pooled rates. Pooled CR rate (11 studies) was 29% (CI 19%-42%). Pooled ORR (16 studies) was 64% (CI 65-82%). 1 year overall survival was 49% (CI 29-70%). There was significant heterogeneity between studies (I²=72) likely due to differences in ECP schedules utilized, and a variety of scales used to measure outcomes. Pooled RR's for SR-cGVHD of skin was 74% (CI 60-85%), liver was 68% (CI 57-77%), ocular was 60% (CI 40-78%), oral was 72% (CI 51-86%), lung was 48% (CI 33-63%), gastrointestinal (GI) was 53% (CI 21-83%), and musculoskeletal (MSK) was 64% (CI 18-94%). No significant differences in responses to ECP for pediatric and adult populations were found. Sensitivity analysis could not be done due to limited number of prospective studies. Conclusions ECP is an effective therapy for oral, skin & liver SR-cGVHD, with modest activity in lung and GI SR-cGVHD. Further studies must report standardized outcomes with a uniform schedule of ECP. Disclosures: No relevant conflicts of interest to declare.

OBJECTIVES: Although systemic sclerosis (SSc) is known to affect the gastrointestinal (GI) tract, most of the literature focuses on esophageal, small intestinal, or anorectal manifestations. There have been no reviews focused on large bowel SSc complications in over 30 years. The aim of this study is to perform a systematic review of colonic manifestations and complications of SSc. METHODS: An experienced librarian conducted a search of databases, including English and Spanish articles. The search used keywords including “systemic sclerosis,” “scleroderma,” and “colon.” A systematic review was performed using Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Case reports/series were screened for validity by adapting from criteria published elsewhere. RESULTS: Of 1,890 articles, 74 met selection criteria. Fifty-nine of the 77 articles were case reports/series. The most common article topics on colonic SSc complications were constipation/dysmotility (15), colonic volvulus (8), inflammatory bowel disease (7), microscopic colitis (6), megacolon (6), and telangiectasia (6). Colonic manifestations constituted 24% of articles on GI complications of SSc. There were a total of 85 cases (84% women, with a median age of onset of colon complication of 52 years). Limited cutaneous SSc phenotype (65.6%) was more common than diffuse (26.2%). Patients frequently had poor outcomes with high mortality related to colonic complications (27%). Recent studies explore contemporary topics such as the microbiome in SSc and prucalopride for chronic constipation in SSc. DISCUSSION: Colonic complications comprise a large proportion of the published reports on GI symptoms afflicting patients with SSc and require raised diagnostic suspicion and deliberate action to avoid potentially serious complications including death.

Abstract Context The extent to which some pharmacological interventions reduce or increase the risk of biochemical conversion to type 2 diabetes mellitus (T2DM) in at-risk individuals is unclear. Methods We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus through 24 August 2017 for randomized controlled trials evaluating the effect of drugs suspected to modify the risk of biochemical conversion to T2DM. Results We included 43 trials with 192,156 subjects (mean age, 60 years; 56% men; mean body mass index, 30.4 kg/m2). α-Glucosidase inhibitors, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, metformin, orlistat, phentermine/topiramate, and pioglitazone significantly reduced the risk of biochemical conversion to T2DM, whereas statins and nateglinide increased the risk. There was insufficient direct evidence regarding the effects of sulfonylureas, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and sodium-glucose cotransporter-2 inhibitors. Most trials were brief and evaluated this outcome during treatment without a withdrawal or washout period. Conclusions Several drugs modify the risk of biochemical conversation to T2DM, although whether this effect is persistent and clinically relevant is unclear. Future studies need to focus on cardiovascular disease prevention, mortality, and patient-important outcomes instead of biochemical conversion to T2DM.

Abstract Rationale Prompt diagnosis of invasive fungal infections is important because of the associated morbidity and mortality; however, diagnosis is challenging because of the nonspecific symptoms and radiographic findings. Objectives To conduct a systematic review and meta-analysis of studies that evaluated the diagnostic accuracy of serum and bronchoalveolar lavage (BAL) galactomannan (GM) and serum or BAL polymerase chain reaction (PCR) in patients with suspected invasive aspergillosis (IA), β-d-glucan in critically ill patients at risk for candidiasis or candidemia, and serology testing and antigen detection in patients with endemic mycoses (histoplasmosis, blastomycosis, and coccidioidomycosis). Methods Studies were selected and appraised by pairs of reviewers. Bivariate random effects meta-analysis was used to generate pooled sensitivity, specificity, and diagnostic likelihood ratios. Results Serum GM in patients with impaired immunity suspected of having IA had sensitivity of 0.71 (95% confidence interval [CI], 0.64–0.78) and specificity of 0.89 (95% CI, 0.84–0.92). A cutoff of 1 optical density index yielded optimal sensitivity and specificity. BAL GM in patients with impaired immunity suspected of having IA had sensitivity of 0.84 (95% CI, 0.73–0.91) and specificity of 0.88 (95% CI, 0.81–0.91). Serum or whole-blood PCR in immunocompromised patients with suspected IA had sensitivity of 0.81 (95% CI, 0.73–0.86) and specificity of 0.79 (95% CI, 0.68–0.86). BAL PCR in patients at high risk for IA had high sensitivity of 0.90 (95% CI, 0.77–0.96) and specificity of 0.96 (95% CI, 0.93–0.98) for diagnosing IA. β-d-glucan assay in patients in the intensive care unit at risk for invasive candidiasis or candidemia had sensitivity of 0.81 (95% CI, 0.74–0.86) and specificity of 0.60 (95% CI, 0.49–0.71). Data on diagnostic accuracy of antigen detection and serology testing for endemic mycoses were limited and heterogeneous (varied according to test, patient immunity, and suspected endemic disease). Conclusions The diagnosis of invasive fungal infections remains a challenge. Various serum and BAL markers can aid in diagnosis. This evidence supports the development of clinical practice recommendations by the American Thoracic Society.

Background The benefits of aerobic exercise are well-studied; there is no consensus on the association between resistance training and major adverse cardiovascular outcomes. This systematic review and meta-analysis aimed to address this issue. Design and methods We searched for randomized trials and cohort studies that evaluated the association between resistance training and mortality and cardiovascular events. Two investigators screened the identified abstracts and full-texts independently and in duplicate. Cochrane tools were used to assess the risk of bias. We calculated hazard ratios and 95% confidence intervals using random effect models. Results From the 1430 studies identified, 11 (one randomized trial and 10 cohort studies) met the inclusion criteria, totaling 370,256 participants with mean follow-up of 8.85 years. The meta-analysis showed that, compared with no exercise, resistance training was associated with 21% (hazard ratio (95% confidence interval (CI)), 0.79 (0.69–0.91)) and 40% (hazard ratio (95% CI), 0.60 (0.49–0.72)) lower all-cause mortality alone and when combined with aerobic exercise, respectively. Furthermore, resistance training had a borderline association with lower cardiovascular mortality (hazard ratio (95% CI), 0.83 (0.67–1.03)). In addition, resistance training showed no significant association with cancer mortality. Risk of bias was low to intermediate in the included studies. One cohort study looked at the effect of resistance training on coronary heart disease events in men and found a 23% risk reduction (risk ratio, 0.77, CI: 0.61–0.98). Conclusion Resistance training is associated with lower mortality and appears to have an additive effect when combined with aerobic exercise. There are insufficient data to determine the potential beneficial effect of resistance training on non-fatal events or the effect of substituting aerobic exercise with resistance training.

Introduction Chronic obstructive pulmonary disease (COPD) is a progressive lung disease, usually caused by tobacco smoking, but other important risk factors include exposures to combustion products of biomass fuels and environmental pollution. The introduction of several new (combination) inhaler therapies, increasing uncertainty about the role of inhaled corticosteroids and a rapid proliferation of the literature on management of stable COPD in general, call for novel ways of evidence synthesis in this area. A systematic review and evidence map can provide the basis for shared decision-making tools and help to establish a future research agenda. Methods and analysis This systematic review will follow an umbrella systematic review design (also called overview of reviews). We plan to conduct a comprehensive literature search of Ovid MEDLINE (including epub ahead of print, in process and other non-indexed citations), Ovid Embase, Ovid Cochrane Database of Systematic Reviews and Scopus from database inception to the present. We will include systematic reviews that assessed the effectiveness of any pharmacological or non-pharmacological intervention on one or more patient-important outcomes and/or lung function in patients with stable COPD. For every intervention/outcome pair, one systematic review will be included. An a priori protocol will guide, which systematic reviews will be chosen, how their credibility will be evaluated, and how the quality of the body of evidence will be rated. Data will be synthesised into an evidence map that will present a matrix that depicts each available treatment for stable COPD with a quantitative estimate on symptoms/outcomes from the patient perspective, along with an indication of the size and certainty in the evidence. Ethics and dissemination Approval by a research ethics committee is not required since the review will only include published data. The systematic review will be published in a peer-reviewed journal. PROSPERO registration number CRD42018095079