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Completed Systematic Reviews




Therapies for Clinically Localized Prostate Cancer [Entered Retrospectively]


Public Project Complete

Statistics: 67 Studies, 1 Key Question, 1 Extraction Form,
Date Published: Aug 10, 2020 12:58PM
Description: Structured Abstract Objective. To identify new information that updates findings from previous AHRQ and AUA funded reviews evaluating therapies for clinically localized prostate cancer (CLPC). Sources. Bibliographic databases (2013-January 2020); ClinicalTrials.gov; systematic reviews Methods. Controlled studies of CLPC (T1-T3a) treatments with duration ≥5 years for mortality and metastases and ≥1 year for quality of life and harms. Interventions included watchful waiting (WW), active surveillance or monitoring (AS, AM), androgen deprivation (AD), focal and whole gland therapies or combinations. We evaluated how patient and tumor characteristics modify treatment outcomes and how provider/hospital characteristics modify effectiveness of radical prostatectomy (RP) compared to other therapies. One investigator rated risk of bias (ROB), extracted data, and assessed certainty of evidence; a second checked accuracy. We analyzed English-language studies with low or medium ROB. We incorporated findings from RCTs identified in the 2014 AHRQ and 2016 AUA funded reviews if new RCTs provided information on the same intervention comparison. We derived thresholds defining “small”, “moderate” and “large” effect, summarize key findings from prior reviews and the impact of new research. Results. We identified 67 eligible references; 17 unique RCTs. Among clinically, rather than PSA detected CLPC, WW may increase overall and prostate-cancer mortality, and metastases versus RP at 20+ years. Urinary and erectile dysfunction were lower with WW versus RP. WW‘s effect on mortality may have varied by tumor risk and age but not by race, health status, comorbidities or PSA. AM probably results in little to no difference in overall or prostate-cancer mortality in PSA detected CLPC versus RP or EBR plus AD through 10 years regardless of tumor risk. Metastases were infrequent but slightly higher with AM. Harms were greater with RP than AM and mixed between EBR plus AD versus AM. 3D-Conformal EBR and AD plus low-dose-rate brachytherapy (BT) provided a small reduction in all-cause mortality versus 3D-CRT and AD but little to no difference on metastases. EBR plus AD versus EBR alone may have resulted in a small reduction in overall and prostate-cancer mortality and metastases in higher risk disease but may increase sexual harms. EBR plus initiating neoadjuvant AD versus EBR plus initiating concurrent AD may result in little to no difference in mortality at 12 years and genitourinary toxicity at 3 years. Conventionally fractionated EBR versus ultra-hypofractionated EBR may result in little to no difference in mortality and metastasis at 5 years and urinary and bowel toxicity at 2 years. Limited evidence suggested that AS results in fewer harms than photodynamic therapy and laparoscopic RP resulted in more harms than robotic-assisted RP. There was little to no information on long-term comparative effectiveness of other treatments. No studies evaluated WW or AS in screen detected CLPC or MRI for risk assessment or were conducted since effective pharmacologic therapies for advanced disease. No studies assessed provider or hospital factors of RP comparative effectiveness. Conclusions. RP reduces mortality versus WW in clinically detected CLPC but causes more harms. Effectiveness may be limited to younger men, those with intermediate risk disease and requires many years to occur. AM results in little to no mortality difference versus RP or EBR plus AD. EBR plus AD reduces mortality versus EBR alone in higher risk CLPC but may worsen sexual function. Adding low-dose-rate BT to 3D-Conformal EBR and AD may reduce mortality in higher risk CLPC. Little information exists on other treatments or the effects of patient, tumor and provider factors. Large, long-term RCTs in PSA-detected and MRI staged CLPC are needed.
Contributor(s): Philipp Dahm, M.D., M.H.S.C. Michelle Brasure, Ph.D., M.S.P.H., M.L.I.S. Elizabeth Ester, M.D. Eric J. Linskens, B.S. Roderick MacDonald, M.S. Victoria A. Nelson, M.Sc. Charles Ryan, M.D. Jayati Saha, Ph.D. Shahnaz Sultan, M.D., M.H.S.C. Kristen E. Ullman, M.P.H. Timothy J. Wilt, M.D., M.P.H.
DOI: DOI pending.
Funding Source: AHRQ Contract HHSA290201500008I
Methodology Description: None Provided

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The effect of IDH inhibitors in AML patients.


Public Project Complete

Statistics: 4 Studies, 2 Key Questions, 1 Extraction Form,
Date Published: Jul 28, 2020 04:27PM
Description: 12% of patients with AML harbor mutation at Isocitrate dehydrogenase enzyme (IDH).Mutations at these enzymes result in high level of R2 hydroxyglutarate which competes with 2-alpha-hydroxygluterate resulted in DNA and histone hypermethylation. DNA and histone hypermethylation inhibits cell differentiation and promotes leukemic transformation. Ivosidenib and Enasidenib are IDH inhibitors that promotes cell differentiation and showed promising activity in phase1 and 2 trials in relapse/refractory AML patients and in elderly patients who are not candidate for traditional induction regimens. In this systematic review and meta-analysis, we intend to integrate the results of phase1 and 2 trials that looked at the efficacy and the side effects of IDH inhibitor. Therefore,we will have a clearer picture regarding the efficacy and side effect of these medications.
Contributor(s): Yanal Alnimer, MD Munther Mansour, MD Ayman Qasrawi, MD
DOI: DOI pending.
Funding Source: N/A
Methodology Description: We will use the ("Metaprop") package in R in order to integrate the results pertaining to the Objective response, Complete remission, and other response outcomes in addition to grade 3 and 4 Treatment Emergent Adverse Events (TEAE) in these trials.

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Masks for Prevention of COVID-19 in Community and Healthcare Settings: A Living Rapid Review


Public Project Complete

Statistics: 40 Studies, 2 Key Questions, 1 Extraction Form,
Date Published: Jul 27, 2020 01:39PM
Description: To address the comparative effectiveness of various types of face masks in healthcare workers and in the community and to address the effectiveness and safety of mask reuse. Surveillance Report, July 20, 2020 Version 2, June 24, 2020 Version 1, June 18, 2020
Contributor(s): Roger Chou, M.D., FACP; Tracy Dana, M.L.S.; Rebecca Jungbauer, Dr.P.H.; Chandler Weeks, M.P.H.; Marian S. McDonagh, Pharm.D.
DOI: DOI pending.
Funding Source: Agency for Healthcare Research and Quality. Prepared by the Pacific Northwest Evidence-based Practice Center, Oregon Health & Science University. AHRQ Publication No. 20-EHC016.
Methodology Description: We initially searched PubMed MEDLINE and Elsevier Embase (from 2003 through April 14, 2020) and conducted ongoing search updates to identify new studies (surveillance). The WHO Database of Publications on Coronavirus Disease, and the medRxiv preprint server were also searched initially. Reference lists of systematic reviews and included studies were reviewed for additional studies.

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The Use of Chloroquine and Hydroxychloroquine for Prophylaxis and Treatment of COVID-19


Public Project Complete

Statistics: 24 Studies, 1 Key Question, 1 Extraction Form,
Date Published: May 29, 2020 06:30PM
Description: The purpose of this review is to determine if hydroxychloroquine or chloroquine is effective and safe when used alone or when combined with azithromycin for the prophylaxis and treatment of COVID-19.
Contributor(s): Adrian V. Hernandez, MD, PhD; Yuani M. Roman, MD, MPH; Vinay Pasupuleti, MD, MS, PhD; Joshuan J. Barboza, MSc; C. Michael White, PharmD.
DOI: DOI pending.
Funding Source: Prepared by the University of Connecticut Evidence-based Practice Center under Contract No. HHSA290-2015-00012I | Task Order 1
Methodology Description: On May 8, 2020, we comprehensively searched: PubMed-Medline, EMBASE-OVID, Scopus, Web of Science, the Cochrane Library, pre-prints and pre-proofs from the following web pages: http://eppi.ioe.ac.uk/COVID19_MAP/covid_map_v3.html, https://connect.biorxiv.org/relate/content/181, https://www.preprints.org/, and Trial registry websites of the WHO, USA, and China: https://www.who.int/ictrp/en/, www.clinicaltrials.gov, and http://www.chictr.org.cn/. The searches were very broad containing the agents under investigation “hydroxychloroquine or chloroquine” and the virus or disease state “SARS-CoV-2 or COVID-19”. As such, it would capture efficacy and harm outcome studies as well as active treatment and prophylaxis studies. We did not predefine outcomes to allow the broadest assessment of the literature base available. Three investigators independently selected studies, and disagreements were resolved by discussion. We used a pre-defined extraction sheet that was modified dynamically as new outcomes were identified in the studies. Extractions were performed independently by two authors and revised by two other authors. Discrepancies in extractions were resolved by discussion. Risk of bias assessments were performed independently by two investigators in comparative studies using the ROBINS-I tool for non-randomized studies of interventions and the Cochrane risk of bias 2.0 tool for randomized controlled trials. Discrepancies in risk of bias assessments were resolved by discussion. We only performed random effects meta-analyses of two RCTs for dichotomous outcomes. The inverse variance method was used, and effects were described as relative risks (RR) and their 95% confidence intervals. Heterogeneity of effects between RCTs were described with the I2 statistic, being a value >60% considered high heterogeneity. The certainty or quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach (27). GRADE profile v2 tables were developed in GRADEpro Guideline Development Tool.

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Interventions for Substance Use Disorders in Adolescents: A Systematic Review


Public Project Complete

Statistics: 118 Studies, 1 Key Question, 1 Extraction Form,
Date Published: May 19, 2020 09:56PM
Description: The review aims to inform health care providers, policymakers, and a clinical practice guideline update from the American Academy of Child and Adolescent Psychiatry (AACAP) about the currently available evidence on interventions for adolescents to reduce or cease substance use. The review addresses both behavioral and pharmacological interventions used for adolescents or young adults with problematic substance use or a diagnosis of a substance use disorder (SUD), excluding tobacco.
Contributor(s): Dale W. Steele, Sara J. Becker, Kristin J. Danko, Ethan M. Balk, Ian J. Saldanha, Gaelen P. Adam, Sarah M. Bagley, Catherine Friedman. Anthony Spirito, Kelli Scott, Evangelia E. Ntzani, Iman Saeed, Bryant Smith, Jonah Popp, Thomas A. Trikalinos
DOI: DOI pending.
Funding Source: HHSA 290-2015-00002-I
Methodology Description: We conducted literature searches in MEDLINE, the Cochrane CENTRAL Trials Registry, Embase, CINAHL, and PsycINFO databases (all from inception) to identify primary studies meeting our criteria through April 11, 2019. As a part of an independent methods project, an interim search of MEDLINE was undertaken using text mining tools on October 30, 2018. A separate search for SRs of interventions for alcohol disorders/problematic alcohol use in the college setting was conducted in MEDLINE, Cochrane Database of Systematic Reviews, and Epistemonikos also through April 11, 2019; after discussion with the Technical Expert Panel (TEP), it was decided to restrict the review of this topic to existing SRs because the literature is vast and has been extensively reviewed. The literature search yielded 33,272 citations. We found 118 randomized controlled trials that evaluated treatment of adolescents or young adults with problematic substance use or substance use disorders.

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