Evaluation of person-level heterogeneity of treatment effects in published multiperson N-of-1 studies: systematic review and reanalysis.

OBJECTIVE:Individual patients with the same condition may respond differently to similar treatments. Our aim is to summarise the reporting of person-level heterogeneity of treatment effects (HTE) in multiperson N-of-1 studies and to examine the evidence for person-level HTE through reanalysis. STUDY DESIGN:Systematic review and reanalysis of multiperson N-of-1 studies. DATA SOURCES:Medline, Cochrane Controlled Trials, EMBASE, Web of Science and review of references through August 2017 for N-of-1 studies published in English. STUDY SELECTION:N-of-1 studies of pharmacological interventions with at least two subjects. DATA SYNTHESIS:Citation screening and data extractions were performed in duplicate. We performed statistical reanalysis testing for person-level HTE on all studies presenting person-level data. RESULTS:We identified 62 multiperson N-of-1 studies with at least two subjects. Statistical tests examining HTE were described in only 13 (21%), of which only two (3%) tested person-level HTE. Only 25 studies (40%) provided person-level data sufficient to reanalyse person-level HTE. Reanalysis using a fixed effect linear model identified statistically significant person-level HTE in 8 of the 13 studies (62%) reporting person-level treatment effects and in 8 of the 14 studies (57%) reporting person-level outcomes. CONCLUSIONS:Our analysis suggests that person-level HTE is common and often substantial. Reviewed studies had incomplete information on person-level treatment effects and their variation. Improved assessment and reporting of person-level treatment effects in multiperson N-of-1 studies are needed

A Web-based archive of systematic review data

Systematic reviews have become increasingly critical to informing healthcare policy; however, they remain a time-consuming and labor-intensive activity. The extraction of data from constituent studies comprises a significant portion of this effort, an activity which is often needlessly duplicated, such as when attempting to update a previously conducted review or in reviews of overlapping topics

Mycophenolic acid versus azathioprine as primary immunosuppression for kidney transplant recipients

Background Modern immunosuppressive regimens after kidney transplantation usually use a combination of two or three agents of different classes to prevent rejection and maintain graft function. Most frequently, calcineurin‐inhibitors (CNI) are combined with corticosteroids and a proliferation‐inhibitor, either azathioprine (AZA) or mycophenolic acid (MPA). MPA has largely replaced AZA as a first line agent in primary immunosuppression, as MPA is believed to be of stronger immunosuppressive potency than AZA. However, treatment with MPA is more costly, which calls for a comprehensive assessment of the comparative effects of the two drugs. Objectives This review of randomised controlled trials (RCTs) aimed to look at the benefits and harms of MPA versus AZA in primary immunosuppressive regimens after kidney transplantation. Both agents were compared regarding their efficacy for maintaining graft and patient survival, prevention of acute rejection, maintaining graft function, and their safety, including infections, malignancies and other adverse events. Furthermore, we investigated potential effect modifiers, such as transplantation era and the concomitant immunosuppressive regimen in detail. Search methods We searched Cochrane Kidney and Transplant's Specialised Register (to 21 September 2015) through contact with the Trials' Search Co‐ordinator using search terms relevant to this review. Selection criteria All RCTs about MPA versus AZA in primary immunosuppression after kidney transplantation were included, without restriction on language or publication type. Data collection and analysis Two authors independently determined study eligibility, assessed risk of bias and extracted data from each study. Statistical analyses were performed using the random‐effects model and the results were expressed as risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). Main results We included 23 studies (94 reports) that involved 3301 participants. All studies tested mycophenolate mofetil (MMF), an MPA, and 22 studies reported at least one outcome relevant for this review. Assessment of methodological quality indicated that important information on factors used to judge susceptibility for bias was infrequently and inconsistently reported. MMF treatment reduced the risk for graft loss including death (RR 0.82, 95% CI 0.67 to 1.0) and for death‐censored graft loss (RR 0.78, 95% CI 0.62 to 0.99, P < 0.05). No statistically significant difference for MMF versus AZA treatment was found for all‐cause mortality (16 studies, 2987 participants: RR 0.95, 95% CI 0.70 to 1.29). The risk for any acute rejection (22 studies, 3301 participants: RR 0.65, 95% CI 0.57 to 0.73, P < 0.01), biopsy‐proven acute rejection (12 studies, 2696 participants: RR 0.59, 95% CI 0.52 to 0.68) and antibody‐treated acute rejection (15 studies, 2914 participants: RR 0.48, 95% CI 0.36 to 0.65, P < 0.01) were reduced in MMF treated patients. Meta‐regression analyses suggested that the magnitude of risk reduction of acute rejection may be dependent on the control rate (relative risk reduction (RRR) 0.34, 95% CI 0.10 to 1.09, P = 0.08), AZA dose (RRR 1.01, 95% CI 1.00 to 1.01, P = 0.10) and the use of cyclosporin A micro‐emulsion (RRR 1.27, 95% CI 0.98 to 1.65, P = 0.07). Pooled analyses failed to show a significant and meaningful difference between MMF and AZA in kidney function measures. Data on malignancies and infections were sparse, except for cytomegalovirus (CMV) infections. The risk for CMV viraemia/syndrome (13 studies, 2880 participants: RR 1.06, 95% CI 0.85 to 1.32) was not statistically significantly different between MMF and AZA treated patients, whereas the likelihood of tissue‐invasive CMV disease was greater with MMF therapy (7 studies, 1510 participants: RR 1.70, 95% CI 1.10 to 2.61). Adverse event profiles varied: gastrointestinal symptoms were more likely in MMF treated patients and thrombocytopenia and elevated liver enzymes were more common in AZA treatment. Authors' conclusions MMF was superior to AZA for improvement of graft survival and prevention of acute rejection after kidney transplantation. These benefits must be weighed against potential harms such as tissue‐invasive CMV disease. However, assessment of the evidence on safety outcomes was limited due to rare events in the observation periods of the studies (e.g. malignancies) and inconsistent reporting and definitions (e.g. infections, adverse events). Thus, balancing benefits and harms of the two drugs remains a major task of the transplant physician to decide which agent the individual patient should be started on

Changes to Prenatal Care Visit Frequency and Telehealth : A Systematic Review of Qualitative Evidence

Peer reviewedPublisher PD

Schedule of Visits and Televisits for Routine Antenatal Care : A Systematic Review

This report is based on research conducted by the Brown Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 75Q80120D00001). The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.Publisher PD

Comparison of Vaginal Hysterectomy Techniques and Interventions for Benign Indications: A Systematic Review

OBJECTIVE: To create evidence-based clinical practice guidelines based on a systematic review of published literature regarding the risks and benefits of available preoperative, intraoperative, and postoperative technical steps and interventions at the time of vaginal hysterectomy for benign indications. DATA SOURCES: We systematically searched the literature to identify studies that compared technical steps or interventions during the preoperative, intraoperative, and postoperative periods surrounding vaginal hysterectomy. We searched MEDLINE, Cochrane Central Register of Controlled Trials, Health Technology Assessments, and ClinicalTrials.gov from their inception until April 10, 2016, using the MeSH term "Hysterectomy, Vaginal" and associated text words. We included comparative studies, single-group studies, and systematic reviews published in English. METHODS OF STUDY SELECTION: We double-screened 4,250 abstracts, identifying 60 eligible studies. Discrepancies were adjudicated by a third reviewer. We followed standard systematic review methodology and the Grades for Recommendation, Assessment, Development and Evaluation approach to evaluate the evidence and generate guideline recommendations. TABULATION, INTEGRATION, AND RESULTS: Because of limited literature, only 16 perioperative risks, technical steps, and interventions were identified: obesity, large uteri, prior surgery, gonadotropin-releasing hormone agonists, vaginal antisepsis, bilateral salpingo-oophorectomy, morcellation, apical closure, uterine sealers, hemostatic injectants, hot cone, retractor, cystoscopy, vaginal packing, bladder management, and accustimulation. We organized and reported these as four domains: patient selection, preoperative, intraoperative, and postoperative. We did not identify any patient characteristics precluding a vaginal approach; chlorhexidine or povidone is appropriate for vaginal antisepsis; vasopressin decreases blood loss by 130 cc; tissue-sealing devices decrease blood loss by 44 cc and operative time by 15 minutes with uncertain complication implications; vertical cuff closure results in 1-cm increased vaginal length; either peritoneum or epithelium can be used for colpotomy closure; and routine vaginal packing is not advised. CONCLUSION: Minimal data exist to guide surgeons with respect to planning and performing a vaginal hysterectomy. This study identifies available information and future areas for investigation

Antibiotic prophylaxis for selected gynecologic surgeries

BackgroundAntibiotic prophylaxis for surgery is commonly used and is recommended by multiple organizations.ObjectiveTo critically review gynecology‐specific data regarding surgical antibiotic prophylaxis in selected benign gynecologic surgeries.Search strategyMEDLINE and Cochrane databases were searched from inception to July 2010.Selection criteriaRandomized controlled trials of benign vaginal, cervical, transcervical, abdominal, or laparoscopic procedures other than hysterectomy comparing prophylactic antibiotic use with placebo or with another antibiotic. Outcomes of interest were postoperative infections, additional treatments, and adverse events.Data collection and analysisIn total, 19 trials met the inclusion criteria. Studies were individually assessed for methodologic quality, then grouped by procedure and evaluated for evidence quality.Main resultsThere was no difference in infectious outcome for loop electrosurgical excision, hysteroscopic ablation, or laparoscopy, although evidence quality was poor. Fair evidence supports antibiotic prophylaxis for suction curettage or laparotomy. There were insufficient data regarding vaginal surgery prophylaxis.ConclusionAntibiotic prophylaxis may be beneficial in first‐trimester suction curettage and laparotomy. No advantage was found for loop electrosurgical excision, hysteroscopy, or laparoscopic gynecologic surgery. Newer procedures and vaginal surgery lack research and merit study.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135267/1/ijgo10.pd

Improving the utility of evidence synthesis for decision makers in the face of insufficient evidence.

OBJECTIVE: To identify and suggest strategies to make insufficient evidence ratings in systematic reviews more actionable. STUDY DESIGN AND SETTING: A workgroup comprising members from the Evidence-Based Practice (EPC) Program of the Agency for Healthcare Research and Quality convened throughout 2020. We conducted iterative discussions considering information from three data sources: a literature review for relevant publications and frameworks, a review of a convenience sample of past systematic reviews conducted by the EPCs, and an audit of methods used in past EPC technical briefs. RESULTS: We identified five strategies for supplementing systematic review findings when evidence on benefits or harms is expected to be, or found to be, insufficient: 1) reconsider eligible study designs, 2) summarize indirect evidence, 3) summarize contextual and implementation evidence, 4) consider modelling, and 5) incorporate unpublished health system data in the evidence synthesis. While these strategies may not increase the strength of evidence, they may improve the utility of reports for decision makers. Adopting these strategies depends on feasibility, timeline, funding, and expertise of the systematic reviewers. CONCLUSION: Throughout the process of evidence synthesis of early scoping, protocol development, review conduct, and review presentation, authors can consider these five strategies to supplement evidence with insufficient rating to make it more actionable for end-users