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Completed Systematic Reviews




Three types of hypoglycemic agents (DPP- 4Is, GLP-1RAs, SGLT-2Is) for patients with type 2 diabetes: effectiveness and safety evaluation network meta-analysis


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Statistics: 9 Studies, 1 Key Question, 1 Extraction Form,
Date Published: Apr 06, 2020 02:51PM
Description: Objective: In view of the development of hypoglycemic agents in recent years and the growth in the number of people with type 2 diabetes mellitus(T2DM), latest information is needed for clinicians and patients to make more reliable decisions. The objective of this systematic review database is to summarize and compare the effectiveness and possible safeties of the current three new types of hypoglycemic agents: dipeptidyl peptidase-4 inhibitors[DPP- 4Is], glucagon-like peptide-1 receptor agonists[GLP-1RAs] and sodium-dependent glucose transporters 2 inhibitors[SGLT-2Is]. Data Sources: We searched the MEDLINE, Embase and Cochrane Library databases for original English-language articles, and collected unpublished studies’ data from clinicaltrial.org and other sources. We included all randomized controlled trials (RCTs) that use any of these three types of hypoglycemic agents as interventions in comparison groups, and the searching process is now updated to March 2019. Results: This systematic review database contains three types of hypoglycemic agents: DDP-4Is, GLP-1RAs and SGLT-2Is, which involved in 441,338 and 573 RCTs respectively. We recorded the baseline characteristics of patients and outcome indicators, which include gender, age, duration of type 2 diabetes, and the level of HbA1c, FPG, PPG, LDL, HDL, TC, body weight, BMI, blood pressure, heart rate, etc. Additionally, we included almost all adverse events that were observed in studies to obtain comprehensive information, for instance: digestive system disorders(e.g. nausea, diarrhea, decreased appetite, hyperchlorhydria); cardiovascular system dysfunctions(e.g. stroke, angina pectoris, arrhythmia, myocardial infarction); liver and renal impairments(e.g. renal stone, acute renal failure, hepatic encephalopathy, hepatic steatosis); musculoskeletal disorders(e.g. arthtitis, fracture, muscular weakness); various types of infections and neural disorders, etc. The data extraction and quality evaluation process now is partly done, and we have been keeping the database updated. Next, we will select the appropriate information from this database for deeper statistical analysis, and complete systematic reviews and meta-analysis. Conclusions: Till today, the existing results of original researches on the effectiveness and safety of three type of hypoglycemic drugs are diverse, and related systematic reviews are still incomplete. For example, study had shown that SGLT-2Is improve cardiovascular function in T2DM patients with coronary artery disease or chronic kidney dysfunction compared to DPP-4Is; DPP-4Is(sitagliptin)may exert a less potent effect on HbA1C, FPG, PPG, and weight reduction than GLP-1 receptor agonists in obese or overweight patients; There are also differences between different drugs in one single type. Observing the effects of hypoglycemic drugs requires studies with large samples and long term observation. Therefore, better evidences are needed to provide a compelling reason for their use in different situations and different population subgroups. All of comprehensive information was included in this database, which is essential for further statistical analysis. Studies that focus on a single outcome have certain limitations. So in the future, we will use this database to explore the benefit-risk of these drugs with multiple outcomes. The models we are interested in are multi-criteria decision analysis (MCDA) model and its derivative model stochastic multicriteria acceptability analysis (SMAA). When we conduct benefit/risk analysis, we will make good use of indirect comparative studies through network meta-analysis. Through the comparison within or between three types of hypoglycemic agents, we may hopefully provide more reliable conclusions for clinicians and patients to develop personalized treatment plans and gain the greatest health benefit for patients.
Contributor(s): Sun feng; Liu fengqi; Yu shuqing; Gao le; Yang zhirong; Wu shanshan; Zhang yuan; Chai sanbao; Ji linong; Zhan siyan.
DOI: DOI pending.
Funding Source: The National Natural Science Foundation of China(Project number:71673003)
Methodology Description: We searched the following databases for primary studies for the periods in parentheses: MEDLINE(1966 to March 2019), Embase(1974 to March 2019), and Cochrane Library(1995 to March 2019). We developed a search strategy based on the purposes of this research and the analysis of MeSH terms. The articles which were selected out from above mentioned databases were exported and gathered into an EndNote library(EndNote version X9). We used the duplication check feature in EndNote to scan for duplicate articles, and deleted duplicates more precisely by two reviewers during screening. Two reviewers screened these articles by their titles and abstracts independently, classified those which meet the criterion, and excluded those which do not. Then detailed data, including study design, treatments for the comparison groups, baseline characteristics, outcome indicators and adverse events, was extracted from each article by using standardized protocols and pooled into ADDIS(Aggregate Data Drug Information System), and the evaluation of the studies’ qualities was summarized into a table in Excel(Microsoft Office 2016). Data analysis were performed by using WinBUGS(version 1.4), STATA(version 13.0), etc.

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Skin Substitutes for Treating Chronic Wounds


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Statistics: 22 Studies, 1 Key Question, 1 Extraction Form,
Date Published: Apr 02, 2020 01:03PM
Description: Systematic review to describe skin substitute products commercially available in the United States used to treat chronic wounds, examine systems used to classify skin substitutes, identify and assess randomized controlled trials (RCTs), and suggest best practices for future studies.
Contributor(s): David L Snyder, Nancy Sullivan, Karen Schoelles
DOI: DOI pending.
Funding Source: Agency for Healthcare Research and Quality
Methodology Description: Systematic review

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Opioid Treatments for Chronic Pain


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Statistics: 175 Studies, 4 Key Questions, 1 Extraction Form,
Date Published: Mar 16, 2020 01:17PM
Description: To assess the effectiveness and harms of opioid therapy for chronic noncancer pain; alternative opioid dosing strategies; and risk mitigation strategies
Contributor(s): Roger Chou, MD Daniel Hartung, PharmD Judith Turner, PhD Ian Blazina, MPH Brian Chan, MD Ximena Levander, MD Marian McDonagh, PharmD Shelley Selph, MD, MPH Miranda Pappas, MA
DOI: DOI pending.
Funding Source: AHRQ Contract No. HHSA-290201500009I
Methodology Description: Predefined criteria were used to select studies of patients with chronic pain prescribed opioids that addressed effectiveness or harms versus placebo, no opioid use, or nonopioid pharmacological therapies; different opioid dosing methods; or risk mitigation strategies. Effects were analyzed at short term (1 to <6 months), intermediate term (≥6 to <12 months), and long term (≥12 months) followup. Studies on the accuracy of risk prediction instruments for predicting opioid use disorder or misuse were also included. Random effects meta-analysis was conducted on short-term trials of opioids versus placebo, opioids versus nonopioids, and opioids plus nonopioids versus an opioid or nonopioid alone. Magnitude of effects was classified as small, moderate, or large using predefined criteria and strength of evidence was assessed.

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Screening for Hepatitis C Virus Infection in Adolescents and Adults: A Systematic Review Update for the U.S. Preventive Services Task Force [Entered Retrospectively]


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Statistics: 94 Studies, 9 Key Questions, 1 Extraction Form,
Date Published: Mar 13, 2020 01:58PM
Description: Background: Prior reviews on hepatitis C (HCV) infection screening and treatment used by the U.S. Preventive Services Task Force (USPSTF) to inform its 2013 recommendation found interferon-containing antiviral therapies associated with sustained virologic response (SVR) rates of 68 percent to 78 percent and an association between SVR after antiviral therapy and improved clinical outcomes. Interferon-containing regimens were associated with a high rate of harms. Since the prior reviews, interferon-containing antiviral therapies have been replaced by all-oral direct acting antiviral (DAA) regimens. Purpose: To systematically review the evidence on screening for HCV infection in asymptomatic adults and adolescents, including effects of DAA regimens and interventions to prevent mother-to-child transmission. Data Sources: We searched the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, Ovid MEDLINE and ClinicalTrials.gov through February 2019, manually reviewed reference lists, and conducted literature surveillance through November 22, 2019. Study Selection: Randomized controlled trials (RCTs), non-randomized trials, and cohort studies of HCV screening, antiviral therapy, and interventions to prevent mother-to-child transmission of HCV infection on SVR and clinical outcomes; and cohort studies on the association between an SVR after antiviral therapy versus no SVR and clinical outcomes. Treatment studies focused on populations without cirrhosis who are more likely to be asymptomatic and identified by screening. Data Extraction: One investigator abstracted data, and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF. Data Synthesis (Results): No study evaluated the benefits of HCV screening versus no screening, or the yield of repeat versus one-time screening. Previously reviewed studies found that HCV screening might be associated with negative psychological and social consequences, but had important methodological limitations; no new studies were identified. One new study found similar diagnostic yield of risk-based and birth cohort screening, but it was retrospective and assumed perfect implementation of risk-based screening. Ten trials reported improvements in some quality of life and functional outcomes following DAA treatment compared with prior to treatment, but differences were small, studies were open-label, and there was no non-DAA comparison group. Forty-nine trials found DAA regimens associated with pooled SVR rates that ranged from 95.5 percent to 98.9 percent across genotypes; rates of serious adverse events (1.9%) and withdrawal due to adverse events (0.4%) were low. Seven trials reported SVR rates in adolescents with DAA therapy similar to those observed in adults. An SVR after antiviral therapy was associated with decreased risk of all-cause mortality (13 studies, pooled hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.28 to 0.56), liver mortality (4 studies, pooled HR 0.11, 95% CI, 0.04 to 0.27), cirrhosis (4 cohorts in 3 studies, pooled HR 0.36, 95% CI, 0.33 to 0.40), and hepatocellular carcinoma (20 studies, pooled HR 0.29, 95% CI, 0.23 to 0.38) versus no SVR, after adjustment for potential confounders. New evidence on interventions to reduce the risk of mother-to-infant transmission was limited and did not change the conclusion from the prior review that no intervention has been clearly demonstrated to reduce risk. Limitations: Most DAA trials were not randomized and did not have a non-DAA comparison group, almost all DAA trials relied on SVR as the main efficacy outcome, observational studies varied in how well they adjusted for confounders, and few studies evaluated the effectiveness of DAA regimens in adolescents. Conclusions: The USPSTF previously determined that HCV screening is highly accurate. Currently recommended all-oral DAA regimens are associated with very high SVR rates (95.5% to 98.9% across genotypes) and few harms relative to older antiviral therapies. An SVR after antiviral therapy is associated with improved clinical outcomes compared with no SVR, after adjusting for potential confounders. Direct evidence on the benefits of HCV screening remains unavailable, and direct evidence on the effects of antiviral therapy on clinical outcomes remains limited but indicates improved long-term outcomes.
Contributor(s): Roger Chou, MD, FACP Tracy Dana, MLS Rongwei Fu, PhD Bernadette Zakher, MBBS, MPH Jesse Wagner, MA Shaun Ramirez, MPH, CPH Sara Grusing, BA Janice H. Jou, MD, MHS
DOI: DOI pending.
Funding Source: This report is based on research conducted by the Pacific Northwest Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. HHSA 290201500009I, Task Order No. 7)
Methodology Description: Study Selection: Randomized controlled trials (RCTs), non-randomized trials, and cohort studies of HCV screening, antiviral therapy, and interventions to prevent mother-to-child transmission of HCV infection on SVR and clinical outcomes; and cohort studies on the association between an SVR after antiviral therapy versus no SVR and clinical outcomes. Treatment studies focused on populations without cirrhosis who are more likely to be asymptomatic and identified by screening. Data Extraction: One investigator abstracted data, and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF.

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Labor Dystocia


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Statistics: 158 Studies, 9 Key Questions, 1 Extraction Form,
Date Published: Feb 27, 2020 06:46PM
Description: Objectives: This review evaluates the comparative effectiveness of different strategies for treating labor dystocia in women with otherwise uncomplicated pregnancies. Data Sources: We searched PubMed®, Embase®, CINAHL®, and the Cochrane Database of Systematic Reviews (CDSR), limiting the searches to studies in the English-language and comparative studies published from January 1, 2005, to February 15,2019. Review Methods: Two investigators screened each abstract and full-text article for inclusion, abstracted data, rated quality and applicability, and graded evidence. When possible, random-effects models were used to compute summary estimates of effects.
Contributor(s): Evan R. Myers, M.D., M.P.H. Gillian D Sanders Ph.D. Remy R. Coeytaux, M.D., Ph.D. Kara A. McElligott, M.D., M.P.H. Patricia G. Moorman, Ph.D., M.S.P.H. Karen Hicklin, Ph.D. Chad Grotegut, M.D., M.H.SC. Margaret Villers, M.D. Adam Goode, DPT, Ph.D. Hilary Campbell, Pharm.D., J.D. Deanna Befus, Ph.D. Amanda J. McBroom, Ph.D. J. Kelly Davis, B.A. Kathryn Lallinger, M.S.L.S. Robyn Fortman, B.A. Andrzej Kosinski, Ph.D.
DOI: DOI pending.
Funding Source: Agency for Healthcare Research and Quality (AHRQ)
Methodology Description: We searched PubMed®, Embase®, CINAHL®, and the Cochrane Database of Systematic Reviews (CDSR), limiting the searches to studies in the English-language and comparative studies published from January 1, 2005, to February15,2019. Two investigators screened each abstract and full-text article for inclusion, abstracted the data, and performed quality ratings and evidence grading. Random-effects models were used to compute summary estimates of effects. See the review protocol (https://effectivehealthcare.ahrq.gov/topics/labor-dystocia/research-protocol) for full details.

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