Cost-Effectiveness of Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Systematic Review of Cost-Effectiveness Studies for the American College of Physicians.

BACKGROUND: In the United States, costs of antidiabetes medications exceed $327 billion. PURPOSE: To systematically review cost-effectiveness analyses (CEAs) of newer antidiabetes medications for type 2 diabetes. DATA SOURCES: Bibliographic databases from 1 January 2010 through 13 July 2023, limited to English. STUDY SELECTION: Nonindustry-funded CEAs, done from a U.S. perspective that estimated cost per quality-adjusted life-year (QALY) gained for newer antidiabetic medications. Two reviewers screened the literature; disagreements were resolved with a third reviewer. DATA EXTRACTION: Cost-effectiveness analyses were reviewed for treatment comparisons, model inputs, and outcomes. Risk of bias (RoB) of the CEAs was assessed using Drummond criteria and certainty of evidence (CoE) was assessed using GRADE (Grading of Recommendations Assessment, Development, and Evaluations). Certainty of evidence was determined using cost per QALY thresholds predetermined by the American College of Physicians Clinical Guidelines Committee; low (>$150 000), intermediate ($50 to $150 000), or high (<$50 000) value per QALY compared with the alternative. DATA SYNTHESIS: Nine CEAs were eligible (2 low, 1 high, and 6 some concerns RoB), evaluating glucagon-like peptide-1 agonists (GLP1a), dipeptidyl peptidase-4 inhibitors (DPP4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucose-dependent insulinotropic peptide agonist (GIP/GLP1a), and insulin. Comparators were metformin, sulfonylureas, neutral protamine Hagedorn (NPH) insulin, and others. Compared with metformin, GLP1a and SGLT2i are low value as first-line therapy (high CoE) but may be of intermediate value when added to metformin or background therapy compared with adding nothing (low CoE). Insulin analogues may be similarly effective but more expensive than NPH insulin (low CoE). The GIP/GLP1a value is uncertain (insufficient CoE). LIMITATIONS: Cost-effectiveness analyses varied in methodological approach, assumptions, and drug comparisons. Risk of bias and GRADE method for CEAs are not well established. CONCLUSION: Glucagon-like peptide-1 agonists and SGLT2i are of low value as first-line therapy but may be of intermediate value when added to metformin or other background therapy compared with adding nothing. Other drugs and comparisons are of low or uncertain value. Results are sensitive to drug effectiveness and cost assumptions. PRIMARY FUNDING SOURCE: American College of Physicians. (PROSPERO: CRD42022382315).

Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Systematic Review and Network Meta-analysis for the American College of Physicians.

BACKGROUND: Newer diabetes medications may have beneficial effects on mortality, cardiovascular outcomes, and renal outcomes. PURPOSE: To evaluate the effectiveness, comparative effectiveness, and harms of sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP1) agonists, dipeptidyl peptidase-4 (DPP4) inhibitors, and long-acting insulins as monotherapy or combination therapy in adults with type 2 diabetes mellitus (T2DM). DATA SOURCES: MEDLINE and EMBASE for randomized controlled trials (RCTs) published from 2010 through January 2023. STUDY SELECTION: RCTs lasting at least 52 weeks that included at least 500 adults with T2DM receiving eligible medications and reported any outcomes of interest. DATA EXTRACTION: Data were abstracted by 1 reviewer and verified by a second. Independent, dual assessments of risk of bias and certainty of evidence (CoE) were done. DATA SYNTHESIS: A total of 130 publications from 84 RCTs were identified. CoE was appraised using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria for direct, indirect, and network meta-analysis (NMA); the highest CoE was reported. Compared with usual care, SGLT2 inhibitors and GLP1 agonists reduce all-cause mortality (high CoE) and major adverse cardiovascular events (MACE) (moderate to high CoE), SGLT2 inhibitors reduce progression of chronic kidney disease (CKD) and heart failure hospitalizations and GLP1 agonists reduce stroke (high CoE), and SGLT2 inhibitors reduce serious adverse events and severe hypoglycemia (high CoE). The threshold for minimally important differences, which was predefined with the American College of Physicians Clinical Guidelines Committee, was not met for these outcomes. Compared with usual care, insulin, tirzepatide, and DPP4 inhibitors do not reduce all-cause mortality (low to high CoE). Compared with insulin, SGLT2 inhibitors and GLP1 agonists reduce all-cause mortality (low to moderate CoE). Compared with DPP4 inhibitors, GLP1 agonists reduce all-cause mortality (moderate CoE). Compared with DPP4 inhibitors and sulfonylurea (SU), SGLT2 inhibitors reduce MACE (moderate to high CoE). Compared with SU and insulin, SGLT2 inhibitors and GLP1 agonists reduce severe hypoglycemia (low to high CoE). LIMITATIONS: Infrequent direct comparisons between drugs of interest; sparse data for NMA on most outcomes; possible incoherence due to differences in baseline patient characteristics and usual care; insufficient data on predefined subgroups, including demographic subgroups, patients with prior cardiovascular disease, and treatment-naive persons. CONCLUSION: In adults with T2DM, SGLT2 inhibitors and GLP1 agonists (but not DPP4 inhibitors, insulin, or tirzepatide) reduce all-cause mortality and MACE compared with usual care. SGLT2 inhibitors reduce CKD progression and heart failure hospitalization and GLP1 agonists reduce stroke compared with usual care. Serious adverse events and severe hypoglycemia are less frequent with SGLT2 inhibitors and GLP1 agonists than with insulin or SU. PRIMARY FUNDING SOURCE: American College of Physicians. (PROSPERO: CRD42022322129).

Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia (BPH): AUA Guideline Amendment 2023.

PURPOSE: The purpose of this American Urological Association (AUA) Guideline amendment is to provide a useful reference on the effective evidence-based management of male lower urinary tract symptoms secondary/attributed to BPH (LUTS/BPH). MATERIALS AND METHODS: The Minnesota Evidence Review Team searched Ovid MEDLINE, the Cochrane Library, and the Agency for Healthcare Research and Quality (AHRQ) database to identify studies relevant to the management of BPH. The guideline was updated in 2023 to capture eligible literature published between September 2020 and October 2022. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. RESULTS: The BPH amendment resulted in changes to statements/supporting text on combination therapy, photoselective vaporization of the prostate (PVP), water vapor thermal therapy (WVTT), laser enucleation, and prostate artery embolization (PAE). A new statement on temporary implanted prostatic devices (TIPD) was added. In addition, statements on transurethral needle ablation (TUNA) and transurethral microwave thermotherapy (TUMT) were removed and information regarding these legacy technologies was added to the background section. References and the accompanying treatment algorithms were updated to align with the updated text. CONCLUSION: This guideline seeks to improve clinicians' ability to evaluate and treat patients with BPH/LUTS based on currently available evidence. Future studies will be essential to further support these statements to improve patient care.

Screening for Colorectal Cancer in Asymptomatic Average-Risk Adults: A Guidance Statement From the American College of Physicians (Version 2).

DESCRIPTION: The purpose of this updated guidance statement is to guide clinicians on screening for colorectal cancer (CRC) in asymptomatic average-risk adults. The intended audience is all clinicians. The population is asymptomatic adults at average risk for CRC. METHODS: This updated guidance statement was developed using recently published and critically appraised clinical guidelines from national guideline developers since the publication of the American College of Physicians' 2019 guidance statement, "Screening for Colorectal Cancer in Asymptomatic Average-Risk Adults." The authors searched for national guidelines from the United States and other countries published in English using PubMed and the Guidelines International Network library from 1 January 2018 to 24 April 2023. The authors also searched for updates of guidelines included in the first version of our guidance statement. The Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument was used to assess the quality of eligible guidelines. Two guidelines were selected for adoption and adaptation by raters on the basis of the highest average overall AGREE II quality scores. The evidence reviews and modeling studies for these 2 guidelines were also used to synthesize the evidence of diagnostic test accuracy, effectiveness, and harms of CRC screening interventions and to develop our guidance statements. GUIDANCE STATEMENT 1: Clinicians should start screening for colorectal cancer in asymptomatic average-risk adults at age 50 years. GUIDANCE STATEMENT 2: Clinicians should consider not screening asymptomatic average-risk adults between the ages of 45 to 49 years. Clinicians should discuss the uncertainty around benefits and harms of screening in this population. GUIDANCE STATEMENT 3: Clinicians should stop screening for colorectal cancer in asymptomatic average-risk adults older than 75 years or in asymptomatic average-risk adults with a life expectancy of 10 years or less. GUIDANCE STATEMENT 4A: Clinicians should select a screening test for colorectal cancer in consultation with their patient based on a discussion of benefits, harms, costs, availability, frequency, and patient values and preferences. GUIDANCE STATEMENT 4B: Clinicians should select among a fecal immunochemical or high-sensitivity guaiac fecal occult blood test every 2 years, colonoscopy every 10 years, or flexible sigmoidoscopy every 10 years plus a fecal immunochemical test every 2 years as a screening test for colorectal cancer. GUIDANCE STATEMENT 4C: Clinicians should not use stool DNA, computed tomography colonography, capsule endoscopy, urine, or serum screening tests for colorectal cancer.

Implementation of Evidence-Based Psychotherapies for Posttraumatic Stress Disorder: A Systematic Review.

Guidelines strongly recommend trauma-focused therapies to treat posttraumatic stress disorder. Implementation of cognitive processing therapy (CPT) and prolonged exposure (PE) in Veterans Health Administration (VHA) and non-VHA settings began in 2006. We conducted a systematic review of implementation facilitators and challenges and strategies to address barriers. We searched MEDLINE, Embase, PsycINFO, and CINAHL from inception until March 2021 for English-language articles. Two individuals reviewed eligibility and rated quality. Quantitative results were abstracted by one reviewer and verified by a second. Qualitative results were independently coded by two reviewers and finalized through consensus. We used RE-AIM and CFIR frameworks to synthesize findings. 29 eligible studies addressed CPT/PE, mostly conducted in VHA. Training/education with audit/feedback was the primary implementation strategy and was linked to improved provider CPT/PE perceptions and self-efficacy. Use was not widespread. Only six studies tested other implementation strategies with mixed impact. Following VHA implementation, strong support for training, perceived effectiveness for patients and benefits for clinics, and positive patient experiences and relationships with providers were reported. However, barriers persisted including perceived protocol inflexibility, complex referral processes and patient complexity and competing needs. In non-VHA settings, providers perceived fewer barriers, but few were CPT/PE trained. Across both settings, fewer studies targeted patient factors. Training/education with audit/feedback improved perceptions and the availability of CPT/PE, but not consistent use. Studies testing implementation strategies to address post-training challenges, including patient-level factors, are needed. A few studies are underway in VHA to test patient-focused and other implementation strategies. Research assessing actual vs perceived barriers in non-VHA settings is needed to elucidate unique challenges experienced.

Evaluation of Implementation Strategies for Cognitive Behavioral Therapy (CBT), Acceptance and Commitment Therapy (ACT), and Mindfulness-Based Stress Reduction (MBSR): a Systematic Review.

BACKGROUND: Improving access to evidence-based psychotherapies (EBPs) is a Veterans Health Administration (VHA) priority. Cognitive behavioral therapy (CBT), acceptance and commitment therapy (ACT), and mindfulness-based stress reduction (MBSR) are effective for chronic pain and several mental health conditions. We synthesized evidence on implementation strategies to increase EBP access and use. METHODS: We searched MEDLINE, Embase, PsycINFO, and CINAHL from inception until March 2021 for articles on EBP implementation within integrated health systems to treat chronic pain or chronic mental health conditions. Reviewers independently screened articles, extracted results, coded qualitative findings, and rated quality using modified criteria from Newcastle-Ottawa (quantitative results) or Critical Appraisal Skills Programme (qualitative results). We categorized implementation strategies using the Expert Recommendations for Implementing Change (ERIC) framework and classified outcomes using RE-AIM domains (Reach, Effectiveness, Adoption, Implementation, Maintenance). RESULTS: Twelve articles (reporting results from 10 studies) evaluated CBT (k = 11) and ACT (k = 1) implementation strategies in large integrated healthcare systems. No studies evaluated MBSR implementation. Eight articles evaluated strategies within VHA. Six articles reported on national VHA EBP implementation programs; all involved training/education, facilitation, and audit/feedback. CBT and ACT implementation demonstrated moderate to large improvements in patient symptoms and quality of life. Trainings increased mental health provider self-efficacy in delivering EBPs, improved provider EBP perceptions, and increased provider EBP use during programs, but had unclear impacts on Reach. It was unclear whether external facilitation added benefit. Provider EBP maintenance was modest; barriers included competing professional time demands and patient barriers. DISCUSSION: Multi-faceted CBT and ACT implementation programs increased provider EBP Adoption but had unclear impacts on Reach. Future implementation efforts should further evaluate Reach, Adoption, and Maintenance; assess the added value of external facilitation; and consider strategies targeting patient barriers. Future work should use implementation frameworks to guide evaluations of barriers and facilitators, processes of change, and outcomes. REGISTRATION: PROSPERO registration number CRD42021252038.

Barriers and Facilitators of Evidence-Based Psychotherapies for Chronic Pain in Adults: A Systematic Review.

Cognitive behavioral therapy (CBT), acceptance and commitment therapy (ACT), and mindfulness-based stress reduction (MBSR) have demonstrated effectiveness for improving outcomes in chronic pain. These evidence-based psychotherapies (EBPs) remain underutilized in clinical practice, however. To identify research gaps and next steps for improving uptake of EBPs, we conducted a systematic review of patient-, provider-, and system-level barriers and facilitators of their use for chronic pain. We searched MEDLINE, Embase, PsycINFO, and CINAHL databases from inception through September 2022. Prespecified eligibility criteria included outpatient treatment of adults with chronic pain; examination of barriers and facilitators and/or evaluation of implementation strategies; conducted in the United States (US), United Kingdom (UK), Ireland, Canada or Australia; and publication in English. Two reviewers independently assessed eligibility and rated quality. We conducted a qualitative synthesis of results using a best-fit framework approach building upon domains of the Consolidated Framework for Implementation Research (CFIR). We identified 34 eligible studies (33 moderate or high quality), most (n = 28) of which addressed patient-level factors. Shared barriers across EBPs included variable patient buy-in to therapy rationale and competing responsibilities for patients; shared facilitators included positive group or patient-therapist dynamics. Most studies examining ACT and all examining MBSR assessed only group formats. No studies compared barriers, facilitators, or implementation strategies of group CBT to individual CBT, or of telehealth to in-person EBPs. Conceptual mismatches of patient knowledge and beliefs with therapy principles were largely analyzed qualitatively, and studies did not explore how these mismatches were addressed to support engagement. Future research on EBPs for chronic pain in real-world practice settings is needed to explore provider and system-level barriers and facilitators, heterogeneity of effects and uptake, and both effects and uptake of EBPs delivered in various formats, including group vs individual therapy and telehealth or asynchronous digital approaches. PERSPECTIVE: This systematic review synthesizes evidence on barriers and facilitators to uptake of cognitive behavioral therapy, acceptance and commitment therapy, and mindfulness-based stress reduction for chronic pain. Findings can guide future implementation work to increase availability and use of evidence-based psychotherapies for treatment of chronic pain. REGISTRATION: PROSPERO number CRD42021252038.

Risk prediction models for diabetic foot ulcer development or amputation: a review of reviews.

BACKGROUND: In adults with diabetes, diabetic foot ulcer (DFU) and amputation are common and associated with significant morbidity and mortality. PURPOSE: Identify tools predicting risk of DFU or amputation that are prognostically accurate and clinically feasible. METHODS: We searched for systematic reviews (SRs) of tools predicting DFU or amputation published in multiple databases from initiation to January, 2023. We assessed risk of bias (ROB) and provided a narrative review of reviews describing performance characteristics (calibration and discrimination) of prognostically accurate tools. For such tools, we additionally reviewed original studies to ascertain clinical applicability and usability (variables included, score calculation, and risk categorization). RESULTS: We identified 3 eligible SRs predicting DFU or amputation risk. Two recent SRs (2020 and 2021) were rated as moderate and low ROB respectively. Four risk prediction models - Boyko, Martins-Mendes (simplified), Martins-Mendes (original), and PODUS 2020 had good prognostic accuracy for predicting DFU or amputation over time horizons ranging from 1- to 5-years. PODUS 2020 predicts absolute average risk (e.g., 6% risk of DFU at 2 years) and consists of 3-binary variables with a simple, summative scoring (0-4) making it feasible for clinic use. The other 3 models categorize risk subjectively (e.g., high-risk for DFU at 3 years), include 2-7 variables, and require a calculation device. No data exist to inform rescreening intervals. Furthermore, the effectiveness of targeted interventions in decreasing incidence of DFU or amputation in response to prediction scores is unknown. CONCLUSIONS: In this review of reviews, we identified 4 prognostically accurate models that predict DFU or amputation in persons with diabetes. The PODUS 2020 model, predicting absolute average DFU risk at 2 years, has the most favorable prognostic accuracy and is clinically feasible. Rescreening intervals and effectiveness of intervention based on prediction score are uncertain.

Nonpharmacologic and Pharmacologic Treatments of Adults in the Acute Phase of Major Depressive Disorder: A Living Clinical Guideline From the American College of Physicians.

DESCRIPTION: The purpose of this guideline from the American College of Physicians (ACP) is to present updated clinical recommendations on nonpharmacologic and pharmacologic interventions as initial and second-line treatments during the acute phase of a major depressive disorder (MDD) episode, based on the best available evidence on the comparative benefits and harms, consideration of patient values and preferences, and cost. METHODS: The ACP Clinical Guidelines Committee based these recommendations on an updated systematic review of the evidence. AUDIENCE AND PATIENT POPULATION: The audience for this guideline includes clinicians caring for adult patients in the acute phase of MDD in ambulatory care. The patient population includes adults in the acute phase of MDD. RECOMMENDATION 1A: ACP recommends monotherapy with either cognitive behavioral therapy or a second-generation antidepressant as initial treatment in patients in the acute phase of moderate to severe major depressive disorder (strong recommendation; moderate-certainty evidence). RECOMMENDATION 1B: ACP suggests combination therapy with cognitive behavioral therapy and a second-generation antidepressant as initial treatment in patients in the acute phase of moderate to severe major depressive disorder (conditional recommendation; low-certainty evidence). The informed decision on the options of monotherapy with cognitive behavioral therapy versus second-generation antidepressants or combination therapy should be personalized and based on discussion of potential treatment benefits, harms, adverse effect profiles, cost, feasibility, patients' specific symptoms (such as insomnia, hypersomnia, or fluctuation in appetite), comorbidities, concomitant medication use, and patient preferences. RECOMMENDATION 2: ACP suggests monotherapy with cognitive behavioral therapy as initial treatment in patients in the acute phase of mild major depressive disorder (conditional recommendation; low-certainty evidence). RECOMMENDATION 3: ACP suggests one of the following options for patients in the acute phase of moderate to severe major depressive disorder who did not respond to initial treatment with an adequate dose of a second-generation antidepressant: • Switching to or augmenting with cognitive behavioral therapy (conditional recommendation; low-certainty evidence) • Switching to a different second-generation antidepressant or augmenting with a second pharmacologic treatment (see Clinical Considerations) (conditional recommendation; low-certainty evidence) The informed decision on the options should be personalized and based on discussion of potential treatment benefits, harms, adverse effect profiles, cost, feasibility, patients' specific symptoms (such as insomnia, hypersomnia, or fluctuation in appetite), comorbidities, concomitant medication use, and patient preferences.

Effects of Nurse Staffing on Resident Outcomes in Nursing Homes: A Systematic Review.

OBJECTIVES: To evaluate the evidence on effects of nurse staffing in nursing homes on resident outcomes. DESIGN: Systematic review. SETTING AND PARTICIPANTS: Studies evaluating the effects of nurse staffing levels, total staffing, or skill mix on pressure ulcers, nursing home associated infections, and pain outcomes for adult residents in US nursing homes. METHODS: We searched MEDLINE, Embase, CINAHL, and the Cochrane Database for English-language articles published between January 2000 and May 2021. We also searched for gray literature and sought expert referrals. Two reviewers participated in determination of eligibility, assessment of methodological quality, and abstraction of data. Abstracted data included study design; setting and population characteristics; and resident outcomes. We rated overall certainty of evidence (very low, low, moderate, and high) for each outcome using GRADE. RESULTS: Of 9152 unique citations, 378 articles underwent full-text review. We identified 22 eligible studies that addressed pressure ulcers (k = 15), COVID-19 cases and/or mortality (k = 4), other infections (k = 8), and moderate-severe pain among residents (k = 7); some examined multiple outcomes. Most studies (k = 17) were rated moderate or high quality. All studies were observational. Overall, registered nurse (RN) staffing was probably associated with fewer pressure ulcers (moderate certainty) and possibly fewer COVID-19 infections/mortality (low certainty), other infections (low certainty) and lower rates of moderate-severe pain (low certainty). Higher skill mix was probably associated with fewer pressure ulcers, higher resident COVID-19 infections, fewer other infections, and lower rates of moderate-severe pain (low certainty for all outcomes). CONCLUSIONS AND IMPLICATIONS: Higher RN staffing and skill mix may be associated with better nursing home resident outcomes, while results were mixed for total staffing. Increasing RN staffing levels and skill mix are one of a variety of approaches to improve nursing home care.

Improving grading of recommendations assessment, development, and evaluation evidence tables part 4: a three-arm noninferiority randomized trial demonstrates improved understanding of content in summary of findings tables with a new format.

OBJECTIVES: To evaluate alternative formats of summary of findings (SoF) tables for single comparison with multiple outcomes. STUDY DESIGN AND SETTING: We conducted a three-arm randomized controlled noninferiority trial (RCT) in the following systematic review (SR) users: researchers, clinical practice guideline developers, health care providers, policymakers, and knowledge transfer organizations to measure understanding, accessibility, satisfaction, and preference across the current grading of recommendations assessment, development, and evaluation (GRADE) SoF, an alternative GRADE SoF, or an adapted evidence-based practice center (EPC) program SoF table. RESULTS: One Hundred Seventy-Nine participants were randomized, and 129 participants completed the RCT (n = 47 current GRADE, n = 41 alternative GRADE, n = 41 adapted EPC). Understanding the certainty of evidence and treatment effect was comparable across groups. The adapted EPC SoF table was inferior for quantifying risk and RD compared to the alternatives (<35% correct vs. >85% correct). Participants reported increased satisfaction when SoF tables presented number needed to treat (NNT), anticipated absolute effect differences, and narrative syntheses for evidence that could not be meta-analyzed. Participants reported accessibility to information as significantly better in both GRADE SoF tables, when compared with the adapted EPC SoF table. Participants preferred the alternative GRADE SoF table format. CONCLUSION: The alternative GRADE SoF table is a promising format for SR users preferring a comprehensive presentation of SR results for single comparisons.

Population- and Community-Based Interventions to Prevent Suicide.

Background: Suicide is estimated to account for 1.4% of deaths worldwide, making it among the leading causes of premature death. Public health approaches to reduce suicide have the potential to reach individuals across the spectrum of suicide risk. Aims: To review the effectiveness of newer community-based or population-level suicide prevention strategies. Methods: We conducted a systematic review of literature published from January 2010 to November 2020 to evaluate the effectiveness of community- and population-level interventions. The US Center for Disease Control framework was used for grouping studies by strategy. Results: We included 56 publications that described 47 unique studies. Interventions that reduce access to lethal means, implement organizational policies and culture in police workplace settings, and involve community screening for depression may reduce suicide deaths. It is unclear if other interventions such as public awareness and education campaigns, crisis lines, and gatekeeper training prevent suicide. Evidence was inconsistent for community-based, multistrategy interventions. The most promising multistrategy intervention was the European Alliance Against Depression. Limitations: Most eligible studies were observational and many lacked concurrent control groups or adjustment for confounding variables. Conclusions: Community-based interventions that may reduce suicide deaths include reducing access to lethal means, implementing organizational policies in workplace settings, screening for depression, and the multistrategy European Alliance Against Depression Program. Evidence was unclear, inconsistent, or lacking regarding the impact of many other single- or multistrategy interventions on suicide deaths.

Inclusion of nonrandomized studies of interventions in systematic reviews of interventions: updated guidance from the Agency for Health Care Research and Quality Effective Health Care program.

OBJECTIVES: We developed guidance to inform decisions regarding the inclusion of nonrandomized studies of interventions (NRSIs) in systematic reviews (SRs) of the effects of interventions. STUDY DESIGN AND SETTING: The guidance workgroup comprised SR experts and used an informal consensus generation method. RESULTS: Instead of recommending NRSI inclusion only if randomized controlled trials (RCTs) are insufficient to address the SR key question, different topics may require different decisions regarding NRSI inclusion. We identified important considerations to inform such decisions from topic refinement through protocol development. During topic scoping and refinement, considerations were related to the clinical decisional dilemma, adequacy of RCTs to address the key questions, risk of bias in NRSIs, and the extent to which NRSIs are likely to complement RCTs. When NRSIs are included, during SR team formation, familiarity with topic-specific data sources and advanced analytic methods for NRSIs should be considered. During protocol development, the decision regarding NRSI inclusion or exclusion should be justified, and potential implications explained. When NRSIs are included, the protocol should describe the processes for synthesizing evidence from RCTs and NRSIs and determining the overall strength of evidence. CONCLUSION: We identified specific considerations for decisions regarding NRSI inclusion in SRs and highlight the importance of flexibility and transparency.

COVID-19 postacute care major organ damage: a systematic review.

BACKGROUND: Major organ complications have been reported in patients hospitalised for COVID-19; most studies lacked controls. OBJECTIVE: Examine major organ damage postdischarge among adults hospitalised for COVID-19 versus non-COVID-19 controls. DATA SOURCES: MEDLINE, Embase and Cochrane Library from 1 January 2020 to 19 May 2021. STUDY ELIGIBILITY CRITERIA: English language studies of adults discharged from hospital for COVID-19; reporting major organ damage. Single review of abstracts; independent dual review of full text. STUDY APPRAISAL AND SYNTHESIS METHODS: Study quality was assessed using the Joanna Briggs Institute Appraisal Checklist for Cohort Studies. Outcome data were not pooled due to heterogeneity in populations, study designs and outcome assessment methods; findings are narratively synthesised. RESULTS: Of 124 studies in a full evidence report, 9 included non-COVID controls and are described here. Four of the nine (three USA, one UK) used large administrative databases. Four of the remaining five studies enrolled <600 COVID-19 patients. Mean or median age ranged from 49 to 70 years with 46%-94% male and 48%-78% White race; 10%-40% had been in intensive care units. Follow-up ranged from 4 weeks to 22 weeks postdischarge. Four used hospitalised controls, three non-hospitalised controls and two were unclear. Studies used various definitions of, and methods to assess, major organ damage outcomes. While the magnitude of effect differed across studies, incident cardiac, pulmonary, liver, acute and chronic kidney, stroke, diabetes, and coagulation disorders were consistently greater in adults hospitalised for COVID-19 compared with non-COVID-19 controls. LIMITATIONS: Applicability to subgroups (age, gender, COVID-19 severity, treatment, vaccination status) and non-hospitalised patients is unknown. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Postacute COVID-19 major organ damage is common and likely higher than controls. However, there is substantial uncertainty. More consistent reporting of clinical outcomes and pre-COVID health status along with careful selection of control groups are needed to address evidence gaps. PROSPERO REGISTRATION NUMBER: CRD42020204788.