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).

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.

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.

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.

Care Coordination Models and Tools-Systematic Review and Key Informant Interviews.

BACKGROUND: Care coordination (CC) interventions involve systematic strategies to address fragmentation and enhance continuity of care. However, it remains unclear whether CC can sufficiently address patient needs and improve outcomes. METHODS: We searched MEDLINE, CINAHL, Embase, Cochrane Database of Systematic Reviews, AHRQ Evidence-based Practice Center, and VA Evidence Synthesis Program, from inception to September 2019. Two individuals reviewed eligibility and rated quality using modified AMSTAR 2. Eligible systematic reviews (SR) examined diverse CC interventions for community-dwelling adults with ambulatory care sensitive conditions and/or at higher risk for acute care. From eligible SR and relevant included primary studies, we abstracted the following: study and intervention characteristics; target population(s); effects on hospitalizations, emergency department (ED) visits, and/or patient experience; setting characteristics; and tools and approaches used. We also conducted semi-structured interviews with individuals who implemented CC interventions. RESULTS: Of 2324 unique citations, 16 SR were eligible; 14 examined case management or transitional care interventions; and 2 evaluated intensive primary care models. Two SR highlighted selection for specific risk factors as important for effectiveness; one of these also indicated high intensity (e.g., more patient contacts) and/or multidisciplinary plans were key. Most SR found inconsistent effects on reducing hospitalizations or ED visits; few reported on patient experience. Effective interventions were implemented in multiple settings, including rural community hospitals, academic medical centers (in urban settings), and public hospitals serving largely poor, uninsured populations. Primary studies reported variable approaches to improve patient-provider communication, including health coaching and role-playing. SR, primary studies, and key informant interviews did not identify tools for measuring patient trust or care team integration. Sustainability of CC interventions varied and some were adapted over time. DISCUSSION: CC interventions have inconsistent effects on reducing hospitalizations and ED visits. Future work should address how they should be adapted to different healthcare settings and which tools or approaches are most helpful for implementation. TRIAL REGISTRATION: PROSPERO #CRD42020156359.

The Effect of Medical Scribes in Emergency Departments: A Systematic Review.

BACKGROUND: Integrating medical scribes with clinicians has been suggested to improve access, quality of care, enhance patient/clinician satisfaction, and increase productivity revenue. OBJECTIVE: Conduct a systematic review to evaluate the effects of medical scribes in emergency departments. METHODS: Electronic databases from 2010 through December 2019. Two individuals independently reviewed study eligibility, rated risk of bias, and determined overall certainty of evidence. Data abstracted included study and population characteristics, outcomes (efficiency, patient or clinician satisfaction, financial productivity, documentation quality, cost, and training time), and the effect of compensation structure, qualifications, duties, and setting on outcomes. RESULTS: Twenty studies (18 observational) were included; 12 from two institutions. All utilized in-person rather than virtual scribes. Fifteen were rated as serious or critical risk of bias; five were rated moderate. Findings indicate that scribes may increase patients seen per day and decrease length of stay; however, effects were small and may vary by setting and outcome measured (low certainty). Scribes may increase financial productivity; however, costs associated with developing, implementing, and maintaining scribe programs were not adequately reported. Results were mixed for door-to-room or door-to-provider time, patients left without being seen, and patient/clinician satisfaction. No studies examined the effects of scribes based on compensation structure, qualifications or duties. CONCLUSIONS: Although information quality, quantity, and applicability are limited, in-person medical scribes may improve emergency department efficiency and financial productivity. There was no information on virtual scribes. There was little information on patient or clinician satisfaction, scribe documentation quality, or whether results vary by in-house vs. contracted hiring and training.

Therapies for Clinically Localized Prostate Cancer: A Comparative Effectiveness Review.

PURPOSE: We sought to identify new information evaluating clinically localized prostate cancer therapies. MATERIALS AND METHODS: Bibliographic databases (2013-January 2020), ClinicalTrials.gov and systematic reviews were searched for controlled studies of treatments for clinically localized prostate cancer with duration ≥5 years for mortality and metastases, and ≥1 year for harms. RESULTS: We identified 67 eligible references. Among patients with clinically, rather than prostate specific antigen, detected localized prostate cancer, watchful waiting may increase mortality and metastases but decreases urinary and erectile dysfunction vs radical prostatectomy. Comparative mortality effect may vary by tumor risk and age but not by race, health status, comorbidities or prostate specific antigen. Active monitoring probably results in little to no mortality difference in prostate specific antigen detected localized prostate cancer vs radical prostatectomy or external beam radiation plus androgen deprivation regardless of tumor risk. Metastases were slightly higher with active monitoring. Harms were greater with radical prostatectomy than active monitoring and mixed between external beam radiation plus androgen deprivation vs active monitoring. 3-Dimensional conformal radiation and androgen deprivation plus low dose rate brachytherapy provided small mortality reductions vs 3-dimensional conformal radiation and androgen deprivation but little to no difference on metastases. External beam radiation plus androgen deprivation vs external beam radiation alone may result in small mortality and metastasis reductions in higher risk disease but may increase sexual harms. Few new data exist on other treatments. CONCLUSIONS: Radical prostatectomy reduces mortality vs watchful waiting in clinically detected localized prostate cancer but causes more harms. Effectiveness may be limited to younger men and those with intermediate risk disease. Active monitoring results in little to no mortality difference vs radical prostatectomy or external beam radiation plus androgen deprivation. Few new data exist on other treatments.

Interventions to Prevent or Delay Long-Term Nursing Home Placement for Adults with Impairments-a Systematic Review of Reviews.

BACKGROUND: With continued growth in the older adult population, US federal and state costs for long-term care services are projected to increase. Recent policy changes have shifted funding to home and community-based services (HCBS), but it remains unclear whether HCBS can prevent or delay long-term nursing home placement (NHP). METHODS: We searched MEDLINE (OVID), Sociological Abstracts, PsycINFO, CINAHL, and Embase (from inception through September 2018); and Cochrane Database of Systematic Reviews, Joanna Briggs Institute Database, AHRQ Evidence-based Practice Center, and VA Evidence Synthesis Program reports (from inception through November 2018) for English-language systematic reviews. We also sought expert referrals. Eligible reviews addressed HCBS for community-dwelling adults with, or at risk of developing, physical and/or cognitive impairments. Two individuals rated quality (using modified AMSTAR 2) and abstracted review characteristics, including definition of NHP and interventions. From a prioritized subset of the highest-quality and most recent reviews, we abstracted intervention effects and strength of evidence (as reported by review authors). RESULTS: Of 47 eligible reviews, most focused on caregiver support (n = 10), respite care and adult day programs (n = 9), case management (n = 8), and preventive home visits (n = 6). Among 20 prioritized reviews, 12 exclusively included randomized controlled trials, while the rest also included observational studies. Prioritized reviews found no overall benefit or inconsistent effects for caregiver support (n = 2), respite care and adult day programs (n = 3), case management (n = 4), and preventive home visits (n = 2). For caregiver support, case management, and preventive home visits, some reviews highlighted that a few studies of higher-intensity models reduced NHP. Reviews on other interventions (n = 9) generally found a lack of evidence examining NHP. DISCUSSION: Evidence indicated no benefit or inconsistent effects of HCBS in preventing or delaying NHP. Demonstration of substantial impacts on NHP may require longer-term studies of higher-intensity interventions that can be adapted for a variety of settings. Registration PROSPERO # CRD42018116198.

Evidence Map: Reporting of Results by Sex or Gender in Randomized, Controlled Trials with Women Veteran Participants (2008 to 2018).

BACKGROUND: Higher participation of women in randomized, controlled trials (RCTs) has not led to significantly improved reporting of sex-stratified results. A recent evidence map of research on women veterans revealed that many studies did not report results by sex or gender. This study's objectives were to compare characteristics of RCTs with women veteran participants that did or did not report results by sex or gender and to assess how sex and gender are addressed in research with women veterans. METHODS: We extended the prior evidence map with a systematic search for RCTs with women veterans, published between 2008 and 2018. We compared the characteristics of RCTs that reported results by sex or gender with those of RCTs that did not, and reviewed methodology and reporting of sex/gender analyses. RESULTS: In addition to 11 studies from the prior evidence map, we assessed 1,820 abstracts for relevance and ultimately included 45 unique RCTs. Five trials included only women and 40 included both men and women (median, 14.3% women). Ten studies reported results by sex or gender. These trials were larger (median study size of n = 343.5 vs. n = 125.5) and included a higher median proportion of women participants (16.8% vs. 11.2%) than studies without sex/gender results. Ten of 11 trials that tested pharmacologic or device interventions did not report results by sex or gender. CONCLUSIONS: Reporting of results by sex or gender remains low in veteran research, but may improve with larger studies and increased recruitment of women veterans into trials. Trials of pharmacologic or device interventions may be targets for future reporting requirements. Standardization could improve attention to sex and gender in methodology and reporting.

Long-Term Drug Therapy and Drug Discontinuations and Holidays for Osteoporosis Fracture Prevention: A Systematic Review.

Background: Optimal long-term osteoporosis drug treatment (ODT) is uncertain. Purpose: To summarize the effects of long-term ODT and ODT discontinuation and holidays. Data Sources: Electronic bibliographic databases (January 1995 to October 2018) and systematic review bibliographies. Study Selection: 48 studies that enrolled men or postmenopausal women aged 50 years or older who were being investigated or treated for fracture prevention, compared long-term ODT (>3 years) versus control or ODT continuation versus discontinuation, reported incident fractures (for trials) or harms (for trials and observational studies), and had low or medium risk of bias (ROB). Data Extraction: Two reviewers independently rated ROB and strength of evidence (SOE). One extracted data; another verified accuracy. Data Synthesis: Thirty-five trials (9 unique studies) and 13 observational studies (11 unique studies) had low or medium ROB. In women with osteoporosis, 4 years of alendronate reduced clinical fractures (hazard ratio [HR], 0.64 [95% CI, 0.50 to 0.82]) and radiographic vertebral fractures (both moderate SOE), whereas 4 years of raloxifene reduced vertebral but not nonvertebral fractures. In women with osteopenia or osteoporosis, 6 years of zoledronic acid reduced clinical fractures (HR, 0.73 [CI, 0.60 to 0.90]), including nonvertebral fractures (high SOE) and clinical vertebral fractures (moderate SOE). Long-term bisphosphonates increased risk for 2 rare harms: atypical femoral fractures (low SOE) and osteonecrosis of the jaw (mostly low SOE). In women with unspecified osteoporosis status, 5 to 7 years of hormone therapy reduced clinical fractures (high SOE), including hip fractures (moderate SOE), but increased serious harms. After 3 to 5 years of treatment, bisphosphonate continuation versus discontinuation reduced radiographic vertebral fractures (zoledronic acid; low SOE) and clinical vertebral fractures (alendronate; moderate SOE) but not nonvertebral fractures (low SOE). Limitation: No trials studied men, clinical fracture data were sparse, methods for estimating harms were heterogeneous, and no trials compared sequential treatments or different durations of drug holidays. Conclusion: Long-term alendronate and zoledronic acid therapies reduce fracture risk in women with osteoporosis. Long-term bisphosphonate treatment may increase risk for rare adverse events, and continuing treatment beyond 3 to 5 years may reduce risk for vertebral fractures. Long-term hormone therapy reduces hip fracture risks but has serious harms. Primary Funding Source: National Institutes of Health and Agency for Healthcare Research and Quality. (PROSPERO: CRD42018087006).

Hospitalization-Associated Change in Gait Speed and Risk of Functional Limitations for Older Adults.

BACKGROUND: Hospitalization-associated functional decline is a common problem for older adults, but it is unclear how hospitalizations affect physical performance measures such as gait speed. We sought to determine hospitalization-associated change in gait speed and likelihood of new limitations in mobility and activities of daily living (ADLs). METHODS: We used longitudinal data over 5 years from the Health, Aging and Body Composition Study, a prospective cohort of black and white community-dwelling men and women, aged 70-79 years, who had no limitations in mobility (difficulty walking 1/4 mile or climbing 10 steps) or ADLs (transferring, bathing, dressing, and eating) at baseline. Gait speed, and new self-reported limitations in mobility and ADLs were assessed annually. Selected participants (n = 2,963) had no limitations at the beginning of each 1-year interval. Hospitalizations were self-reported every 6 months and verified with medical record data. Generalized estimating equations were used to examine hospitalization-associated change in gait speed and odds of new limitations over each 1-year interval. Fully adjusted models included demographics, hospitalization within the past year, health conditions, symptoms, body mass index, and health-related behaviors. RESULTS: In fully adjusted models, any hospitalization was associated with decrease in gait speed (-0.04 m/s; 95% confidence interval [CI]: -0.05 to -0.03) and higher odds of new limitations in mobility or ADLs (odds ratio = 1.97, 95% CI: 1.70-2.28), and separately with increased odds of new mobility limitation (odds ratio = 2.22, 95% CI: 1.90-2.60) and new ADL limitations (odds ratio = 1.84, 95% CI: 1.53-2.21). Multiple hospitalizations within a year were associated with gait speed decline (-0.06 m/s; 95% CI: -0.08 to -0.04) and greater odds of new limitations in mobility or ADLs (odds ratio = 2.96, 95% CI: 2.23-3.95). CONCLUSIONS: Functionally independent older adults experienced hospitalization-associated declines in gait speed and new limitations in mobility and ADLs.

Evidence Review-Social Determinants of Health for Veterans.

BACKGROUND: Veterans Health Administration (VHA) is committed to providing high-quality care and addressing health disparities for vulnerable Veterans. To meet these goals, VA policymakers need guidance on how to address social determinants in operations planning and day-to-day clinical care for Veterans. METHOD: MEDLINE (OVID), CINAHL, PsycINFO, and Sociological Abstracts were searched from inception to January 2017. Additional articles were suggested by peer reviewers and/or found through search of work associated with US and VA cohorts. Eligible articles compared Veterans vs non-Veterans, and/or Veterans engaged with those not engaged in VA healthcare. Our evidence maps summarized study characteristics, social determinant(s) addressed, and whether health behaviors, health services utilization, and/or health outcomes were examined. Qualitative syntheses and quality assessment were performed for articles on rurality, trauma exposure, and sexual orientation. RESULTS: We screened 7242 citations and found 131 eligible articles-99 compared Veterans vs non-Veterans, and 40 included engaged vs non-engaged Veterans. Most articles were cross-sectional and addressed socioeconomic factors (e.g., education and income). Fewer articles addressed rurality (N = 20), trauma exposure (N = 17), or sexual orientation (N = 2); none examined gender identity. We found no differences in rural residence between Veterans and non-Veterans, nor between engaged and non-engaged Veterans (moderate strength evidence). There was insufficient evidence for role of rurality in health behaviors, health services utilization, or health outcomes. Trauma exposures, including from events preceding military service, were more prevalent for Veterans vs non-Veterans and for engaged vs non-engaged Veterans (low-strength evidence); exposures were associated with smoking (low-strength evidence). DISCUSSION: Little published literature exists on some emerging social determinants. We found no differences in rural residence between our groups of interest, but trauma exposure was higher in Veterans (vs non-Veterans) and engaged (vs non-engaged). We recommend consistent measures for social determinants, clear conceptual frameworks, and analytic strategies that account for the complex relationships between social determinants and health.