Corticosteroid implants for chronic non-infectious uveitis.

BACKGROUND: Uveitis is a term used to describe a heterogeneous group of intraocular inflammatory diseases of the anterior, intermediate, and posterior uveal tract (iris, ciliary body, choroid). Uveitis is the fifth most common cause of vision loss in high-income countries, accounting for 5% to 20% of legal blindness, with the highest incidence of disease in the working-age population.Corticosteroids are the mainstay of acute treatment for all anatomical subtypes of non-infectious uveitis and can be administered orally, topically with drops or ointments, by periocular (around the eye) or intravitreal (inside the eye) injection, or by surgical implantation. OBJECTIVES: To determine the efficacy and safety of steroid implants in people with chronic non-infectious posterior uveitis, intermediate uveitis, and panuveitis. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (Issue 10, 2015), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2015), EMBASE (January 1980 to November 2015), PubMed (1948 to November 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to November 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched 15 April 2013), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic search for studies. We last searched the electronic databases on 6 November 2015.We also searched reference lists of included study reports, citation databases, and abstracts and clinical study presentations from professional meetings. SELECTION CRITERIA: We included randomized controlled trials comparing either fluocinolone acetonide (FA) or dexamethasone intravitreal implants with standard-of-care therapy with at least six months of follow-up after treatment. We included studies that enrolled participants of all ages who had chronic non-infectious posterior uveitis, intermediate uveitis, or panuveitis with vision that was better than hand-motion. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed studies for inclusion. Two review authors independently extracted data and assessed the risk of bias for each study. MAIN RESULTS: We included data from two studies (619 eyes of 401 participants) that compared FA implants with standard-of-care therapy. Both studies used similar standard-of-care therapy that included administration of prednisolone and, if needed, immunosuppressive agents. The studies included participants from Australia, France, Germany, Israel, Italy, Portugal, Saudi Arabia, Spain, Switzerland, Turkey, the United Kingdom, and the United States. We assessed both studies at high risk of performance and detection bias.Only one study reported our primary outcome, recurrence of uveitis at any point during the study through 24 months. The evidence, judged as moderate-quality, showed that a FA implant probably prevents recurrence of uveitis compared with standard-of-care therapy (risk ratio (RR) 0.29, 95% confidence interval (CI) 0.14 to 0.59; 132 eyes). Both studies reported safety outcomes, and moderate-quality evidence showed increased risks of needing cataract surgery (RR 2.98, 95% CI 2.33 to 3.79; 371 eyes) and surgery to lower intraocular pressure (RR 7.48, 95% CI 3.94 to 14.19; 599 eyes) in the implant group compared with standard-of-care therapy through two years of follow-up. No studies compared dexamethasone implants with standard-of-care therapy. AUTHORS\u27 CONCLUSIONS: After considering both benefits and harms reported from two studies in which corticosteroids implants were compared with standard-of-care therapy, we are unable to conclude that the implants are superior to traditional systemic therapy for the treatment of non-infectious uveitis. These studies exhibited heterogeneity in design and outcomes that measured efficacy. Pooled findings regarding safety outcomes suggest increased risks of post-implant surgery for cataract and high intraocular pressure compared with standard-of-care therapy

A meta-analysis of N-acetylcysteine in contrast-induced nephrotoxicity: unsupervised clustering to resolve heterogeneity

<p>Abstract</p> <p>Background</p> <p>Meta-analyses of N-acetylcysteine (NAC) for preventing contrast-induced nephrotoxicity (CIN) have led to disparate conclusions. Here we examine and attempt to resolve the heterogeneity evident among these trials.</p> <p>Methods</p> <p>Two reviewers independently extracted and graded the data. Limiting studies to randomized, controlled trials with adequate outcome data yielded 22 reports with 2746 patients.</p> <p>Results</p> <p>Significant heterogeneity was detected among these trials (<it>I</it>²= 37%; <it>p </it>= 0.04). Meta-regression analysis failed to identify significant sources of heterogeneity. A modified L'Abbé plot that substituted groupwise changes in serum creatinine for nephrotoxicity rates, followed by model-based, unsupervised clustering resolved trials into two distinct, significantly different (<it>p </it>< 0.0001) and homogeneous populations (<it>I</it>²= 0 and <it>p </it>> 0.5, for both). Cluster 1 studies (<it>n </it>= 18; 2445 patients) showed no benefit (relative risk (RR) = 0.87; 95% confidence interval (CI) 0.68–1.12, <it>p </it>= 0.28), while cluster 2 studies (<it>n </it>= 4; 301 patients) indicated that NAC was highly beneficial (RR = 0.15; 95% CI 0.07–0.33, <it>p </it>< 0.0001). Benefit in cluster 2 was unexpectedly associated with NAC-induced decreases in creatinine from baseline (<it>p </it>= 0.07). Cluster 2 studies were relatively early, small and of lower quality compared with cluster 1 studies (<it>p </it>= 0.01 for the three factors combined). Dialysis use across all studies (five control, eight treatment; <it>p </it>= 0.42) did not suggest that NAC is beneficial.</p> <p>Conclusion</p> <p>This meta-analysis does not support the efficacy of NAC to prevent CIN.</p

New iniciatives in biomedical scholarly communication: removing barriers, enhancing progress

Objective: To review scholarly communication and publication as they have developed in the biomedical academic and research communities; identify changes and new models being explored and implemented; and explore current challenges and new opportunities. Results: We review traditional scholarly communication and publication, as well as factors driving exploration of new models: unsustainable publication and distribution costs; new technologies which offer solutions to existing problems as well as new opportunities for communication of research results; attention to copyright and intellectual property regulations; demands by legislators, patients and researchers for easier, less costly access to research results; and globalization, which creates both new demands for access to information from developing countries and expands collaborative opportunities between developing and developed. Conclusions: No single new model has yet emerged, nor is a single one likely to be the resolution to all issues confronting us today. Researchers and librarians have new opportunities and obligations to shape and control access to biomedical knowledge and new research findings

Can we depend on investigators to identify and register randomized controlled trials?

PURPOSE: To reduce publication bias, systematic reviewers are advised to search conference abstracts to identify randomized controlled trials (RCTs) conducted in humans and not published in full. We assessed the information provided by authors to aid identification of RCTs for reviews. METHODS: We handsearched the Association for Research in Vision and Ophthalmology (ARVO) meeting abstracts for 2004 to 2009 to identify reports of RCTs. We compared our classification with that of authors (requested by ARVO 2004-2006), and authors' report of trial registration (required by ARVO 2007-2009). RESULTS: Authors identified their study as a clinical trial for 169/191 (88%; 95% CI, 84-93) RCTs we identified for 2004, 174/212 (82%; 95% CI, 77-87) for 2005 and 162/215 (75%; 95% CI, 70-81) for 2006. Authors provided registration information for 107/172 (62%; 95% CI, 55-69) RCTs for 2007, 103/153 (67%; 95% CI, 60-75) for 2008, and 126/171 (74%; 95% CI, 67-80) for 2009. Most RCT authors providing a trial register name specified ClinicalTrials.gov (276/312; 88%; 95% CI, 85-92) and provided a valid ClinicalTrials.gov registration number (261/276; 95%; 95% CI, 92-97). Based on information provided by authors, trial registration information would be accessible for 48% (83/172) (95% CI, 41-56) of all ARVO abstracts describing RCTs in 2007, 63% (96/153) (95% CI, 55-70) in 2008, and 70% in 2009 (118/171) (95% CI, 62-76). CONCLUSIONS: Authors of abstracts describing RCTs frequently did not classify them as clinical trials nor comply with reporting trial registration information, as required by the conference organizers. Systematic reviewers cannot rely on authors to identify relevant unpublished trials or report trial registration, if present

Information provided in registration box by authors, compared by RCT status.

<p>Information provided in registration box by authors, compared by RCT status.</p

Abstracts identified by author as controlled trial by study design and year of presentation at ARVO.

*<p>Box checked “Yes” for “human clinical trial”.</p>†<p>Box checked “Yes” for “human controlled clinical trial”.</p>‡<p>Information recorded in trial registration box.</p>§<p>Includes: description of study methods (e.g., methods for measuring outcomes), systematic reviews, theoretical models, studies on correlation between test methods, and studies with historical controls).</p

Reference standard RCTs identified and RCTS identified by author as controlled trial by year of presentation at ARVO.

*<p>Box checked “Yes” for “human clinical trial” (n = 634).</p>†<p>Box checked “Yes” for “human controlled clinical trial” (n = 941).</p>‡<p>Information recorded in trial registration box (n = 797).</p>§<p>Does not include 576 abstracts that were withdrawn and are not included in the analyses.</p

Trial register names provided by authors for randomized trials by year.

<p>Abbreviations used: ISRCTN: International Standard Randomised Controlled Trial Number Register, EudrACT: European Union Drug Regulating Authorities Clinical Trials, ANZCTR: Australian New Zealand Clinical Trials Registry, Trialregister.nl: Nederlands Trial Register, Umin.ac.jp: University Hospital Medical Information Network.</p

A meta-analysis of N-acetylcysteine in contrast-induced nephrotoxicity: unsupervised clustering to resolve heterogeneity-2

<p><b>Copyright information:</b></p><p>Taken from "A meta-analysis of N-acetylcysteine in contrast-induced nephrotoxicity: unsupervised clustering to resolve heterogeneity"</p><p>http://www.biomedcentral.com/1741-7015/5/32</p><p>BMC Medicine 2007;5():32-32.</p><p>Published online 14 Nov 2007</p><p>PMCID:PMC2200657.</p><p></p> identified as contributing most to heterogeneity are noted with open circles and are seen to produce asymmetry in the plot. The summary log RR for all 22 studies is denoted by the open diamond

A meta-analysis of N-acetylcysteine in contrast-induced nephrotoxicity: unsupervised clustering to resolve heterogeneity-4

<p><b>Copyright information:</b></p><p>Taken from "A meta-analysis of N-acetylcysteine in contrast-induced nephrotoxicity: unsupervised clustering to resolve heterogeneity"</p><p>http://www.biomedcentral.com/1741-7015/5/32</p><p>BMC Medicine 2007;5():32-32.</p><p>Published online 14 Nov 2007</p><p>PMCID:PMC2200657.</p><p></p>atment arm (-axis) of each study. Studies are weighted by inverse variance (i.e. larger symbols represent larger studies with less variability). Open circles denote cluster 2 studies [10, 11, 14, 25]. : Box plot of change in creatinine from baseline to study endpoint in the control arm and NAC treatment arm of each study. Boxes represent the 25th, 50th and 75th percentiles. Whiskers are 5th and 95th percentiles. Dashed lines show the mean of each group. Open squares denote cluster 2 studies