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).

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.

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.

Major Update 2: Remdesivir for Adults With COVID-19: A Living Systematic Review and Meta-analysis for the American College of Physicians Practice Points.

BACKGROUND: Remdesivir is approved for the treatment of adults hospitalized with COVID-19. PURPOSE: To update a living review of remdesivir for adults with COVID-19. DATA SOURCES: Several electronic U.S. Food and Drug Administration, company, and journal websites from 1 January 2020 through 19 October 2021. STUDY SELECTION: English-language, randomized controlled trials (RCTs) of remdesivir for COVID-19. DATA EXTRACTION: One reviewer abstracted, and a second reviewer verified data. The Cochrane Risk of Bias Tool and GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used. DATA SYNTHESIS: Since the last update (search date 9 August 2021), 1 new RCT and 1 new subtrial comparing a 10-day course of remdesivir with control (placebo or standard care) were identified. This review summarizes and updates the evidence on the cumulative 5 RCTs and 2 subtrials for this comparison. Our updated results confirm a 10-day course of remdesivir, compared with control, probably results in little to no mortality reduction (5 RCTs). Updated results also confirm that remdesivir probably results in a moderate increase in the proportion of patients recovered by day 29 (4 RCTs) and may reduce time to clinical improvement (2 RCTs) and hospital length of stay (4 RCTs). New RCTs, by increasing the strength of evidence, lead to an updated conclusion that remdesivir probably results in a small reduction in the proportion of patients receiving ventilation or extracorporeal membrane oxygenation at specific follow-up times (4 RCTs). New RCTs also alter the conclusions for harms-remdesivir, compared with control, may lead to a small reduction in serious adverse events but may lead to a small increase in any adverse event. LIMITATION: The RCTs differed in definitions of COVID-19 severity and outcomes reported. CONCLUSION: In hospitalized adults with COVID-19, the findings confirm that remdesivir probably results in little to no difference in mortality and increases the proportion of patients recovered. Remdesivir may reduce time to clinical improvement and may lead to small reductions in serious adverse events but may result in a small increase in any adverse event. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs.

Newer Minimally Invasive Treatment Modalities to Treat Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia.

CONTEXT: Several newer device-based procedures have recently become available for treating men with lower urinary tract symptoms attributed to benign prostatic hyperplasia, but their effectiveness remains uncertain. OBJECTIVE: To assess the longer-term comparative effectiveness (defined as >12 mo of follow-up) of the newer treatment modalities prostatic urethral lift (PUL), transurethral prostate convective radiofrequency water vapor (Rezum), Aquablation, and prostatic arterial embolization (PAE). EVIDENCE ACQUISITION: Ovid Medline, the Cochrane Central Register of Controlled Trials (CENTRAL), and the Agency for Healthcare Research and Quality databases were searched through September 30, 2019; hand searches of references of relevant studies were also performed. Eligible studies were randomized controlled trials (RCTs) published in English language. We excluded observational studies. EVIDENCE SYNTHESIS: One RCT (n = 91) found that patients undergoing PUL may be less likely to respond (risk ratio [RR] 0.8; 95% confidence interval [CI] 0.7-1.0; low certainty of evidence [CoE]) and have a higher mean International Prostate Symptom Score (IPSS; mean difference 6.1; 95% CI 2.2-10.0; low CoE) than those undergoing transurethral resection of the prostate (TURP). Among patients undergoing PAE, one small RCT (n = 30) reported similar IPSS response rates (RR 0.9; 95% CI 0.7-1.1; low CoE) and one trial (n = 107) found similar mean IPSS (-0.7; 95% CI -1.3 to 2.7; moderate CoE) scores to those among patients undergoing TURP. A single study on Aquablation reported 12 mo of follow-up only, and a single 3-mo trial compared Rezum with sham treatment. CONCLUSIONS: The current best evidence underlying these newer therapies is limited to few trials (PUL and PAE), short-term follow-up of 12 mo (Aquablation and Rezum), or sham comparison only (Rezum). PATIENT SUMMARY: Evidence for four of the newer surgical treatments for men with an enlarged prostate is limited to few small trials with short-term follow-up; only one trial compared a new treatment modality with sham surgery.

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.

Effectiveness and Harms of High-Flow Nasal Oxygen for Acute Respiratory Failure: An Evidence Report for a Clinical Guideline From the American College of Physicians.

BACKGROUND: Use of high-flow nasal oxygen (HFNO) for treatment of adults with acute respiratory failure (ARF) has increased. PURPOSE: To assess HFNO versus noninvasive ventilation (NIV) or conventional oxygen therapy (COT) for ARF in hospitalized adults. DATA SOURCES: English-language searches of MEDLINE, Embase, CINAHL, and Cochrane Library from January 2000 to July 2020; systematic review reference lists. STUDY SELECTION: 29 randomized controlled trials evaluated HFNO versus NIV (k = 11) or COT (k = 21). DATA EXTRACTION: Data extraction by a single investigator was verified by a second, 2 investigators assessed risk of bias, and evidence certainty was determined by consensus. DATA SYNTHESIS: Results are reported separately for HFNO versus NIV, for HFNO versus COT, and by initial or postextubation management. Compared with NIV, HFNO may reduce all-cause mortality, intubation, and hospital-acquired pneumonia and improve patient comfort in initial ARF management (low-certainty evidence) but not in postextubation management. Compared with COT, HFNO may reduce reintubation and improve patient comfort in postextubation ARF management (low-certainty evidence). LIMITATIONS: Trials varied in populations enrolled, ARF causes, and treatment protocols. Trial design, sample size, duration of treatment and follow-up, and results reporting were often insufficient to adequately assess many outcomes. Protocols, clinician and health system training, cost, and resource use were poorly characterized. CONCLUSION: Compared with NIV, HFNO as initial ARF management may improve several clinical outcomes. Compared with COT, HFNO as postextubation management may reduce reintubations and improve patient comfort; HFNO resulted in fewer harms than NIV or COT. Broad applicability, including required clinician and health system experience and resource use, is not well known. PRIMARY FUNDING SOURCE: American College of Physicians. (PROSPERO: CRD42019146691).

Major Update: Remdesivir for Adults With COVID-19 : A Living Systematic Review and Meta-analysis for the American College of Physicians Practice Points.

BACKGROUND: Remdesivir is being studied and used for treatment of coronavirus disease 2019 (COVID-19). PURPOSE: To update a previous review of remdesivir for adults with COVID-19, including new meta-analyses of patients with COVID-19 of any severity compared with control. DATA SOURCES: Several sources from 1 January 2020 through 7 December 2020. STUDY SELECTION: English-language, randomized controlled trials (RCTs) of remdesivir for COVID-19. New evidence is incorporated by using living review methods. DATA EXTRACTION: 1 reviewer abstracted data; a second reviewer verified the data. The Cochrane Risk of Bias Tool and GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used. DATA SYNTHESIS: The update includes 5 RCTs, incorporating data from a new large RCT and the final results of a previous RCT. Compared with control, a 10-day course of remdesivir probably results in little to no reduction in mortality (risk ratio [RR], 0.93 [95% CI, 0.82 to 1.06]; 4 RCTs) but may result in a small reduction in the proportion of patients receiving mechanical ventilation (RR, 0.71 [CI, 0.56 to 0.90]; 3 RCTs). Remdesivir probably results in a moderate increase in the percentage of patients who recovered and a moderate decrease in serious adverse events and may result in a large reduction in time to recovery. Effect on hospital length of stay or percentage remaining hospitalized is mixed. Compared with a 10-day course for those not requiring ventilation at baseline, a 5-day course may reduce mortality, the need for ventilation, and serious adverse events while increasing the percentage of patients who recovered or clinically improved. LIMITATION: Summarizing findings was challenging because of varying disease severity definitions and outcomes. CONCLUSION: In hospitalized adults with COVID-19, remdesivir probably results in little to no mortality difference but probably improves the percentage recovered and reduces serious harms and may result in a small reduction in the proportion receiving ventilation. For patients not receiving ventilation, a 5-day course may provide greater benefits and fewer harms with lower drug costs than a 10-day course. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs.

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.

Remdesivir for Adults With COVID-19 : A Living Systematic Review for American College of Physicians Practice Points.

BACKGROUND: Few treatments exist for coronavirus disease 2019 (COVID-19). PURPOSE: To evaluate the effectiveness and harms of remdesivir for COVID-19. DATA SOURCES: Several databases, tables of contents of journals, and U.S. Food and Drug Administration and company websites were searched from 1 January through 31 August 2020. STUDY SELECTION: English-language, randomized trials of remdesivir treatments for adults with suspected or confirmed COVID-19. New evidence will be incorporated using living review methods. DATA EXTRACTION: Single-reviewer abstraction and risk-of-bias assessment verified by a second reviewer; GRADE (Grading of Recommendations Assessment, Development and Evaluation) methods used for certainty-of-evidence assessments. DATA SYNTHESIS: Four randomized trials were included. In adults with severe COVID-19, remdesivir compared with placebo probably improves recovery by a large amount (absolute risk difference [ARD] range, 7% to 10%) and may result in a small reduction in mortality (ARD range, -4% to 1%) and a shorter time to recovery or clinical improvement. Remdesivir may have little to no effect on hospital length of stay. Remdesivir probably reduces serious adverse events by a moderate amount (ARD range, -6% to -8%). Compared with a 10-day remdesivir course, a 5-day course may reduce mortality, increase recovery or clinical improvement by small to moderate amounts, reduce time to recovery, and reduce serious adverse events among hospitalized patients not requiring mechanical ventilation. Recovery due to remdesivir may not vary by age, sex, symptom duration, or disease severity. LIMITATIONS: Low-certainty evidence with few published trials, including 1 preliminary report and 2 open-label trials. Trials excluded pregnant women and adults with severe kidney or liver disease. CONCLUSION: In hospitalized adults with COVID-19, remdesivir probably improves recovery and reduces serious adverse events and may reduce mortality and time to clinical improvement. For adults not receiving mechanical ventilation or extracorporeal membrane oxygenation, a 5-day course of remdesivir may provide similar benefits to and fewer harms than a 10-day course. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs, Veterans Health Administration Office of Research and Development, Health Services Research and Development Service, and Evidence Synthesis Program.

Simulating the End of AIDS in New York: Using Participatory Dynamic Modeling to Improve Implementation of the Ending the Epidemic Initiative.

OBJECTIVES: In 2014, the governor of New York announced the Ending the Epidemic (ETE) plan to reduce annual new HIV infections from 3000 to 750, achieve a first-ever decrease in HIV prevalence, and reduce AIDS progression by the end of 2020. The state health department undertook participatory simulation modeling to develop a baseline for comparing epidemic trends and feedback on ETE strategies. METHODS: A dynamic compartmental model projected the individual and combined effects of 3 ETE initiatives: enhanced linkage to and retention in HIV treatment, increased preexposure prophylaxis (PrEP) among men who have sex with men, and expanded housing assistance. Data inputs for model calibration and low-, medium-, and high-implementation scenarios (stakeholders' rollout predictions, and lower and upper bounds) came from surveillance and program data through 2014, the literature, and expert judgment. RESULTS: Without ETE (baseline scenario), new HIV infections would decline but remain >750, and HIV prevalence would continue to increase by 2020. Concurrently implementing the 3 programs would lower annual new HIV infections by 16.0%, 28.1%, and 45.7% compared with baseline in the low-, medium-, and high-implementation scenarios, respectively. In all concurrent implementation scenarios, although annual new HIV infections would remain >750, there would be fewer new HIV infections than deaths, yielding the first-ever decrease in HIV prevalence. PrEP and enhanced linkage and retention would confer the largest population-level changes. CONCLUSIONS: New York State will achieve 1 ETE benchmark under the most realistic (medium) implementation scenario. Findings facilitated framing of ETE goals and underscored the need to prioritize men who have sex with men and maintain ETE's multipronged approach, including other programs not modeled here.

Deprescribing for Community-Dwelling Older Adults: a Systematic Review and Meta-analysis.

BACKGROUND: Polypharmacy and use of inappropriate medications have been linked to increased risk of falls, hospitalizations, cognitive impairment, and death. The primary objective of this review was to evaluate the effectiveness, comparative effectiveness, and harms of deprescribing interventions among community-dwelling older adults. METHODS: We searched OVID MEDLINE Embase, CINAHL, and the Cochrane Library from 1990 through February 2019 for controlled clinical trials comparing any deprescribing intervention to usual care or another intervention. Primary outcomes were all-cause mortality, hospitalizations, health-related quality of life, and falls. The secondary outcome was use of potentially inappropriate medications (PIMs). Interventions were categorized as comprehensive medication review, educational initiatives, and computerized decision support. Data abstracted by one investigator were verified by another. We used the Cochrane criteria to rate risk of bias for each study and the GRADE system to determine certainty of evidence (COE) for primary outcomes. RESULTS: Thirty-eight low and medium risk of bias clinical trials were included. Comprehensive medication review may have reduced all-cause mortality (OR 0.74, 95% CI: 0.58 to 0.95, I2 = 0, k = 12, low COE) but probably had little to no effect on falls, health-related quality of life, or hospitalizations (low to moderate COE). Nine of thirteen trials reported fewer PIMs in the intervention group. Educational interventions probably had little to no effect on all-cause mortality, hospitalizations, or health-related quality of life (low to moderate COE). The effect on falls was uncertain (very low COE). All 11 education trials that included PIMs reported fewer in the intervention than in the control groups. Two of 4 computerized decision support trials reported fewer PIMs in the intervention arms; none included any primary outcomes. DISCUSSION: In community-dwelling people aged 65 years and older, medication deprescribing interventions may provide small reductions in mortality and use of potentially inappropriate medications. REGISTRY INFORMATION: PROSPERO - CRD42019132420.

Benefits and Harms of Prescription Drugs and Supplements for Treatment of Clinical Alzheimer-Type Dementia.

BACKGROUND: Effects of drug treatment of clinical Alzheimer-type dementia (CATD) are uncertain. PURPOSE: To summarize evidence on the effects of prescription drugs and supplements for CATD treatment. DATA SOURCES: Electronic bibliographic databases (inception to November 2019), ClinicalTrials.gov (to November 2019), and systematic review bibliographies. STUDY SELECTION: English-language trials of prescription drug and supplement treatment in older adults with CATD that report cognition, function, global measures, behavioral and psychological symptoms of dementia (BPSD), or harms. Minimum treatment was 24 weeks (≥2 weeks for selected BPSD). DATA EXTRACTION: Studies with low or medium risk of bias (ROB) were analyzed. Two reviewers rated ROB. One reviewer extracted data; another verified extraction accuracy. DATA SYNTHESIS: Fifty-five studies reporting non-BPSD outcomes (most ≤26 weeks) and 12 reporting BPSD (most ≤12 weeks) were analyzed. Across CATD severity, mostly low-strength evidence suggested that, compared with placebo, cholinesterase inhibitors produced small average improvements in cognition (median standardized mean difference [SMD], 0.30 [range, 0.24 to 0.52]), no difference to small improvement in function (median SMD, 0.19 [range, -0.10 to 0.22]), no difference in the likelihood of at least moderate improvement in global clinical impression (median absolute risk difference, 4% [range, 2% to 4%]), and increased withdrawals due to adverse events. In adults with moderate to severe CATD receiving cholinesterase inhibitors, low- to insufficient-strength evidence suggested that, compared with placebo, add-on memantine inconsistently improved cognition and improved global clinical impression but not function. Evidence was mostly insufficient about prescription drugs for BPSD and about supplements for all outcomes. LIMITATION: Most drugs had few trials without high ROB, especially for supplements, active drug comparisons, BPSD, and longer trials. CONCLUSION: Cholinesterase inhibitors and memantine slightly reduced short-term cognitive decline, and cholinesterase inhibitors slightly reduced reported functional decline, but differences versus placebo were of uncertain clinical importance. Evidence was mostly insufficient on drug treatment of BPSD and on supplements for all outcomes. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018117897).

Effectiveness and harms of high-flow nasal oxygen (HFNO) for acute respiratory failure: a systematic review protocol.

INTRODUCTION: High-flow nasal oxygen (HFNO) use in adults hospitalised with acute respiratory failure (ARF) is increasing. However, evidence to support widespread use of HFNO compared with non-invasive ventilation (NIV) and conventional oxygen therapy (COT) is unclear. This protocol describes the methods for a systematic evidence review regarding the comparative effectiveness and harms of HFNO compared with NIV or COT for the management of ARF in hospitalised adult patients. METHODS AND ANALYSIS: We will search MEDLINE, Embase, CINAHL and Cochrane Library for randomised-controlled trials (RCTs) of adult patients hospitalised with ARF or who developed ARF while hospitalised. ARF will be defined as SpO 2 <90%, PaO 2 :FiO 2 ratio ≤300, PaO 2 ≤60 mm Hg, or PaCO 2 ≥45 mm Hg. The intervention is HFNO (humidified oxygen, flow rate ≥20 L/min) compared separately to NIV or COT. The critical outcomes are: all-cause mortality, hospital-acquired pneumonia, intubation/reintubation (days of intubation), intensive care unit admission/transfers, patient comfort and hospital length of stay. The important outcomes are: delirium, 30-day hospital readmissions, barotrauma, compromised nutrition (enteral or parenteral nutrition), gastric dysfunction, functional independence at discharge and skin breakdown or pressure ulcers. We will calculate risk ratios and Peto ORs (for rare events) and corresponding 95% CIs for categorical outcomes. Mean and standardised mean difference will be calculated for continuous outcomes. Where possible and appropriate, meta-analysis will be performed for each outcome. CONCLUSION: This systematic review will provide a comprehensive evaluation of the evidence regarding the comparative effectiveness and harms of HFNO compared with NIV or COT for the management of ARF in hospitalised adult patients to inform clinical practice and to identify research gaps in the management of ARF in hospitalised adults. The results will inform the work of the American College of Physicians-Clinical Guidelines Committee in their development of a clinical guideline related to use of HFNO in adult patients with ARF. ETHICS AND DISSEMINATION: No ethical approval will be needed because we will be using data from previously published studies in which informed consent was obtained by the primary investigators. We will publish our results in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42019146691.

Efficacy and Safety of Testosterone Treatment in Men: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians.

Background: Testosterone treatment rates in adult men have increased in the United States over the past 2 decades. Purpose: To assess the benefits and harms of testosterone treatment for men without underlying organic causes of hypogonadism. Data Sources: English-language searches of multiple electronic databases (January 1980 to May 2019) and reference lists from systematic reviews. Study Selection: 38 randomized controlled trials (RCTs) of at least 6 months' duration that evaluated transdermal or intramuscular testosterone therapies versus placebo or no treatment and reported prespecified patient-centered outcomes, as well as 20 long-term observational studies, U.S. Food and Drug Administration review data, and product labels that reported harms information. Data Extraction: Data extraction by a single investigator was confirmed by a second, 2 investigators assessed risk of bias, and evidence certainty was determined by consensus. Data Synthesis: Studies enrolled mostly older men who varied in age, symptoms, and testosterone eligibility criteria. Testosterone therapy improved sexual functioning and quality of life in men with low testosterone levels, although effect sizes were small (low- to moderate-certainty evidence). Testosterone therapy had little to no effect on physical functioning, depressive symptoms, energy and vitality, or cognition. Harms evidence reported in trials was judged to be insufficient or of low certainty for most harm outcomes. No trials were powered to assess cardiovascular events or prostate cancer, and trials often excluded men at increased risk for these conditions. Observational studies were limited by confounding by indication and contraindication. Limitation: Few trials exceeded a 1-year duration, minimum important outcome differences were often not established or reported, RCTs were not powered to assess important harms, few data were available in men aged 18 to 50 years, definitions of low testosterone varied, and study entry criteria varied. Conclusion: In older men with low testosterone levels without well-established medical conditions known to cause hypogonadism, testosterone therapy may provide small improvements in sexual functioning and quality of life but little to no benefit for other common symptoms of aging. Long-term efficacy and safety are unknown. Primary Funding Source: American College of Physicians. (PROSPERO: CRD42018096585).

Prevalence and Severity of Psychiatric Disorders and Suicidal Behavior in Service Members and Veterans With and Without Traumatic Brain Injury: Systematic Review.

OBJECTIVES: Assess prevalence and severity of posttraumatic stress disorder, suicidal behavior, and depressive, substance use, and anxiety disorders in US service members or Veterans with and without a deployment-related mild traumatic brain injury (TBI) (mTBI). DESIGN: Systematic review using multiple databases (January 2000 to October 2017). We included national or geographically diverse samples. MAIN MEASURE: Prevalence and severity of psychiatric conditions based on diagnostic codes, clinician assessments, and self-report measures with results stratified by sample type. RESULTS: We identified 11 studies on the basis of national samples and 22 studies on the basis of geographically diverse samples. Traumatic brain injury severity was not always ascertained or reported. In national studies, posttraumatic stress disorder, depressive disorder, substance use disorder, and anxiety disorder prevalence were higher in those with TBI than in those without. One national sample reported prevalence of suicide attempts. Across psychiatric conditions, strength of evidence ranged from insufficient to moderate. In geographically diverse samples, the pattern of findings was similar. National studies provided insufficient evidence on psychiatric condition severity; geographically diverse studies found greater severity of posttraumatic stress disorder symptoms with mixed results for symptoms of depressive or substance use disorders. CONCLUSIONS: Service members and Veterans with TBI history have higher prevalence and possibly severity of selected psychiatric conditions.

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).