<div><h4>Association of Low-Dose Colchicine With Incidence of Knee and Hip Replacements : Exploratory Analyses From a Randomized, Controlled, Double-Blind Trial.</h4><i>Heijman MWJ, Fiolet ATL, Mosterd A, Tijssen JGP, ... Popa CD, Cornel JH</i><br /><b>Background</b><br />Osteoarthritis is a major contributor to pain and disability worldwide. Given that inflammation plays an important role in the development of osteoarthritis, anti-inflammatory drugs may slow disease progression.<br /><b>Objective</b><br />To examine whether colchicine, 0.5 mg daily, reduces incident total knee replacements (TKRs) and total hip replacements (THRs).<br /><b>Design</b><br />Exploratory analysis of the LoDoCo2 (Low-Dose Colchicine 2) randomized, controlled, double-blind trial. (Australian New Zealand Clinical Trials Registry: ACTRN12614000093684).<br /><b>Setting</b><br />43 centers in Australia and the Netherlands.<br /><b>Patients</b><br />5522 patients with chronic coronary artery disease.<br /><b>Intervention</b><br />Colchicine, 0.5 mg, or placebo once daily.<br /><b>Measurements</b><br />The primary outcome was time to first TKR or THR since randomization. All analyses were performed on an intention-to-treat basis.<br /><b>Results</b><br />A total of 2762 patients received colchicine and 2760 received placebo during a median follow-up of 28.6 months. During the trial, TKR or THR was performed in 68 patients (2.5%) in the colchicine group and 97 (3.5%) in the placebo group (incidence rate, 0.90 vs. 1.30 per 100 person-years; incidence rate difference, -0.40 [95% CI, -0.74 to -0.06] per 100 person-years; hazard ratio, 0.69 [CI, 0.51 to 0.95]). In sensitivity analyses, similar results were obtained when patients with gout at baseline were excluded and when joint replacements that occurred in the first 3 and 6 months of follow-up were omitted.<br /><b>Limitation</b><br />LoDoCo2 was not designed to investigate the effect of colchicine in osteoarthritis of the knee or hip and did not collect information specifically on osteoarthritis.<br /><b>Conclusion</b><br />In this exploratory analysis of the LoDoCo2 trial, use of colchicine, 0.5 mg daily, was associated with a lower incidence of TKR and THR. Further investigation of colchicine therapy to slow disease progression in osteoarthritis is warranted.<br /><b>Primary funding source</b><br />None.<br /><br /><br /><br /><small>Ann Intern Med: 30 May 2023; epub ahead of print</small></div>

<div><h4>Comparison of Hospital Outcomes for Patients Treated by Allopathic Versus Osteopathic Hospitalists : An Observational Study.</h4><i>Miyawaki A, Jena AB, Gross N, Tsugawa Y</i><br /><b>Background</b><br />The United States has 2 types of degree programs that educate physicians: allopathic and osteopathic medical schools.<br /><b>Objective</b><br />To determine whether quality and costs of care differ between hospitalized Medicare patients treated by allopathic or osteopathic physicians.<br /><b>Design</b><br />Retrospective observational study.<br /><b>Setting</b><br />Medicare claims data.<br /><b>Patients</b><br />20% random sample of Medicare fee-for-service beneficiaries hospitalized with a medical condition during 2016 to 2019 and treated by hospitalists.<br /><b>Measurements</b><br />The primary outcome was 30-day patient mortality. The secondary outcomes were 30-day readmission, length of stay (LOS), and health care spending (Part B spending). Multivariable regression models adjusted for patient and physician characteristics and their hospital-level averages (to effectively estimate differences within hospitals) were estimated.<br /><b>Results</b><br />Of 329 510 Medicare admissions, 253 670 (77.0%) and 75 840 (23.0%) received care from allopathic and osteopathic physicians, respectively. The results can rule out important differences in quality and costs of care between allopathic versus osteopathic physicians for patient mortality (adjusted mortality, 9.4% for allopathic physicians vs. 9.5% [reference] for osteopathic hospitalists; average marginal effect [AME], -0.1 percentage point [95% CI, -0.4 to 0.1 percentage point]; <i>P </i>= 0.36), readmission (15.7% vs. 15.6%; AME, 0.1 percentage point [CI, -0.4 to 0.3 percentage point; <i>P </i>= 0.72), LOS (4.5 vs. 4.5 days; adjusted difference, -0.001 day [CI, -0.04 to 0.04 day]; <i>P </i>= 0.96), and health care spending ($1004 vs. $1003; adjusted difference, $1 [CI, -$8 to $10]; <i>P </i>= 0.85).<br /><b>Limitation</b><br />Data were limited to elderly Medicare patients hospitalized with medical conditions.<br /><b>Conclusion</b><br />The quality and costs of care were similar between allopathic and osteopathic hospitalists when they cared for elderly patients and worked as the principal physician in a team of health care professionals that often included other allopathic and osteopathic physicians.<br /><b>Primary funding source</b><br />National Institutes of Health/National Institute on Aging.<br /><br /><br /><br /><small>Ann Intern Med: 30 May 2023; epub ahead of print</small></div>

<div><h4>Distributional Cost-Effectiveness of Equity-Enhancing Gene Therapy in Sickle Cell Disease in the United States.</h4><i>Goshua G, Calhoun C, Ito S, James LP, ... Krishnamurti L, Pandya A</i><br /><b>Background</b><br />Gene therapy is a potential cure for sickle cell disease (SCD). Conventional cost-effectiveness analysis (CEA) does not capture the effects of treatments on disparities in SCD, but distributional CEA (DCEA) uses equity weights to incorporate these considerations.<br /><b>Objective</b><br />To compare gene therapy versus standard of care (SOC) in patients with SCD by using conventional CEA and DCEA.<br /><b>Design</b><br />Markov model.<br /><b>Data sources</b><br />Claims data and other published sources.<br /><b>Target population</b><br />Birth cohort of patients with SCD.<br /><b>Time horizon</b><br />Lifetime.<br /><b>Perspective</b><br />U.S. health system.<br /><b>Intervention</b><br />Gene therapy at age 12 years versus SOC.<br /><b>Outcome measures</b><br />Incremental cost-effectiveness ratio (ICER) (in dollars per quality-adjusted life-years [QALYs] gained) and threshold inequality aversion parameter (equity weight).<br /><b>Results of base-case analysis</b><br />Gene therapy versus SOC for females yielded 25.5 versus 15.7 (males: 24.4 vs. 15.5) discounted lifetime QALYs at costs of $2.8 million and $1.0 million (males: $2.8 million and $1.2 million), respectively, with an ICER of $176 000 per QALY (full SCD population). The inequality aversion parameter would need to be 0.90 for the full SCD population for gene therapy to be preferred per DCEA standards.<br /><b>Results of sensitivity analysis</b><br />SOC was favored in 100.0% (females) and 87.1% (males) of 10 000 probabilistic iterations at a willingness-to-pay threshold of $100 000 per QALY. Gene therapy would need to cost less than $1.79 million to meet conventional CEA standards.<br /><b>Limitation</b><br />Benchmark equity weights (as opposed to SCD-specific weights) were used to interpret DCEA results.<br /><b>Conclusion</b><br />Gene therapy is cost-ineffective per conventional CEA standards but can be an equitable therapeutic strategy for persons living with SCD in the United States per DCEA standards.<br /><b>Primary funding source</b><br />Yale Bernard G. Forget Scholars Program and Bunker Endowment.<br /><br /><br /><br /><small>Ann Intern Med: 30 May 2023; epub ahead of print</small></div>

<div><h4>Temporal Trends in the Use of Computed Tomographic Pulmonary Angiography for Suspected Pulmonary Embolism in the Emergency Department : A Retrospective Analysis.</h4><i>Roussel M, Bloom B, Taalba M, Choquet C, ... Freund Y, Improving Emergency Care (IMPEC) FHU Collaborator Group</i><br /><b>Background</b><br />Recently, validated clinical decision rules have been developed that avoid unnecessary use of computed tomographic pulmonary angiography (CTPA) in patients with suspected pulmonary embolism (PE) in the emergency department (ED).<br /><b>Objective</b><br />To measure any resulting change in CTPA use for suspected PE.<br /><b>Design</b><br />Retrospective analysis.<br /><b>Setting</b><br />26 European EDs in 6 countries.<br /><b>Patients</b><br />Patients with CTPA performed for suspected PE in the ED during the first 7 days of each odd month between January 2015 and December 2019.<br /><b>Measurements</b><br />The primary end points were the CTPAs done for suspected PE in the ED and the number of PEs diagnosed in the ED each year adjusted to an annual census of 100 000 ED visits. Temporal trends were estimated using generalized linear mixed regression models.<br /><b>Results</b><br />8970 CTPAs were included (median age, 63 years; 56% female). Statistically significant temporal trends for more frequent use of CTPA (836 per 100 000 ED visits in 2015 vs. 1112 in 2019; <i>P</i> < 0.001), more diagnosed PEs (138 per 100 000 in 2015 vs. 164 in 2019; <i>P</i> = 0.028), a higher proportion of low-risk PEs (annual percent change [APC], 13.8% [95% CI, 2.6% to 30.1%]) with more ambulatory management (APC, 19.3% [CI, 4.1% to 45.1%]), and a lower proportion of intensive care unit admissions (APC, -8.9% [CI, -17.1% to -0.3%]) were observed.<br /><b>Limitation</b><br />Data were limited to 7 days every 2 months.<br /><b>Conclusion</b><br />Despite the recent validation of clinical decision rules to limit the use of CTPA, an increase in the CTPA rate along with more diagnosed PEs and especially low-risk PEs were instead observed.<br /><b>Primary funding source</b><br />None specific for this study.<br /><br /><br /><br /><small>Ann Intern Med: 23 May 2023; epub ahead of print</small></div>

<div><h4>Population-Wide Screening for Chronic Kidney Disease : A Cost-Effectiveness Analysis.</h4><i>Cusick MM, Tisdale RL, Chertow GM, Owens DK, Goldhaber-Fiebert JD</i><br /><b>Background</b><br />Sodium-glucose cotransporter-2 (SGLT2) inhibitors have the potential to alter the natural history of chronic kidney disease (CKD), and they should be included in cost-effectiveness analyses of screening for CKD.<br /><b>Objective</b><br />To determine the cost-effectiveness of adding population-wide screening for CKD.<br /><b>Design</b><br />Markov cohort model.<br /><b>Data sources</b><br />NHANES (National Health and Nutrition Examination Survey), U.S. Centers for Medicare & Medicaid Services data, cohort studies, and randomized clinical trials, including the DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial.<br /><b>Target population</b><br />Adults.<br /><b>Time horizon</b><br />Lifetime.<br /><b>Perspective</b><br />Health care sector.<br /><b>Intervention</b><br />Screening for albuminuria with and without adding SGLT2 inhibitors to the current standard of care for CKD.<br /><b>Outcome measures</b><br />Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs), all discounted at 3% annually.<br /><b>Results of base-case analysis</b><br />One-time CKD screening at age 55 years had an ICER of $86 300 per QALY gained by increasing costs from $249 800 to $259 000 and increasing QALYs from 12.61 to 12.72; this was accompanied by a decrease in the incidence of kidney failure requiring dialysis or kidney transplant of 0.29 percentage points and an increase in life expectancy from 17.29 to 17.45 years. Other options were also cost-effective. During ages 35 to 75 years, screening once prevented dialysis or transplant in 398 000 people and screening every 10 years until age 75 years cost less than $100 000 per QALY gained.<br /><b>Results of sensitivity analysis</b><br />When SGLT2 inhibitors were 30% less effective, screening every 10 years during ages 35 to 75 years cost between $145 400 and $182 600 per QALY gained, and price reductions would be required for screening to be cost-effective.<br /><b>Limitation</b><br />The efficacy of SGLT2 inhibitors was derived from a single randomized controlled trial.<br /><b>Conclusion</b><br />Screening adults for albuminuria to identify CKD could be cost-effective in the United States.<br /><b>Primary funding source</b><br />Agency for Healthcare Research and Quality, Veterans Affairs Office of Academic Affiliations, and National Institute of Diabetes and Digestive and Kidney Diseases.<br /><br /><br /><br /><small>Ann Intern Med: 23 May 2023; epub ahead of print</small></div>

<div><h4>Risk for Bleeding-Related Hospitalizations During Use of Amiodarone With Apixaban or Rivaroxaban in Patients With Atrial Fibrillation : A Retrospective Cohort Study.</h4><i>Ray WA, Chung CP, Stein CM, Smalley W, ... Dickson AL, Murray KT</i><br /><b>Background</b><br />Amiodarone, the most effective antiarrhythmic drug in atrial fibrillation, inhibits apixaban and rivaroxaban elimination, thus possibly increasing anticoagulant-related risk for bleeding.<br /><b>Objective</b><br />For patients receiving apixaban or rivaroxaban, to compare risk for bleeding-related hospitalizations during treatment with amiodarone versus flecainide or sotalol, antiarrhythmic drugs that do not inhibit these anticoagulants\' elimination.<br /><b>Design</b><br />Retrospective cohort study.<br /><b>Setting</b><br />U.S. Medicare beneficiaries aged 65 years or older.<br /><b>Patients</b><br />Patients with atrial fibrillation began anticoagulant use between 1 January 2012 and 30 November 2018 and subsequently initiated treatment with study antiarrhythmic drugs.<br /><b>Measurements</b><br />Time to event for bleeding-related hospitalizations (primary outcome) and ischemic stroke, systemic embolism, and death with or without recent (past 30 days) evidence of bleeding (secondary outcomes), adjusted with propensity score overlap weighting.<br /><b>Results</b><br />There were 91 590 patients (mean age, 76.3 years; 52.5% female) initiating use of study anticoagulants and antiarrhythmic drugs, 54 977 with amiodarone and 36 613 with flecainide or sotalol. Risk for bleeding-related hospitalizations increased with amiodarone use (rate difference [RD], 17.5 events [95% CI, 12.0 to 23.0 events] per 1000 person-years; hazard ratio [HR], 1.44 [CI, 1.27 to 1.63]). Incidence of ischemic stroke or systemic embolism did not increase (RD, -2.1 events [CI, -4.7 to 0.4 events] per 1000 person-years; HR, 0.80 [CI, 0.62 to 1.03]). The risk for death with recent evidence of bleeding (RD, 9.1 events [CI, 5.8 to 12.3 events] per 1000 person-years; HR, 1.66 [CI, 1.35 to 2.03]) was greater than that for other deaths (RD, 5.6 events [CI, 0.5 to 10.6 events] per 1000 person-years; HR, 1.15 [CI, 1.00 to 1.31]) (HR comparison: <i>P</i> = 0.003). The increased incidence of bleeding-related hospitalizations for rivaroxaban (RD, 28.0 events [CI, 18.4 to 37.6 events] per 1000 person-years) was greater than that for apixaban (RD, 9.1 events [CI, 2.8 to 15.3 events] per 1000 person-years) (<i>P</i> = 0.001).<br /><b>Limitation</b><br />Possible residual confounding.<br /><b>Conclusion</b><br />In this retrospective cohort study, patients aged 65 years or older with atrial fibrillation treated with amiodarone during apixaban or rivaroxaban use had greater risk for bleeding-related hospitalizations than those treated with flecainide or sotalol.<br /><b>Primary funding source</b><br />National Heart, Lung, and Blood Institute.<br /><br /><br /><br /><small>Ann Intern Med: 23 May 2023; epub ahead of print</small></div>

<div><h4>Gatekeepers of Extermination: SS Camp Physicians and Their Scope of Action.</h4><i>Biermanns N</i><br /><AbstractText>The role of camp physicians of the Waffen-SS (\"Armed SS,\" military branch of the Nazi Party\'s <i>Schutzstaffel</i>) in the implementation of the Holocaust has been the subject of limited research, even though they occupied a key position in the extermination process. From 1943 and 1944 onward, SS camp physicians made the individual medical decisions on whether each prisoner was fit for work or was immediately subjected to extermination, not only at the Auschwitz labor and extermination camp but also in pure labor camps like Buchenwald and Dachau. This was due to a functional change in the concentration camp system during World War II, where the selection of prisoners, which had previously been carried out by nonmedical SS camp staff, became a main task of the medical camp staff. The initiative to transfer sole responsibility for the selections came from the physicians themselves and was influenced by structural racism, sociobiologically oriented medical expertise, and pure economic rationality. It can be seen as a further radicalization of the decision making practiced until then in the murder of the sick. However, there was a far-reaching scope of action within the hierarchical structures of the Waffen-SS medical service on both the macro and micro levels. But what can this teach us for medical practice today? The historical experience of the Holocaust and Nazi medicine can provide a moral compass for physicians to be sensitive to the potential for abuse of power and ethical dilemmas inherent in medicine. Thus, the lessons from the Holocaust could be a starting point for reflecting on the value of human life in the modern economized and highly hierarchical medical sector.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 16 May 2023; epub ahead of print</small></div>

<div><h4>Major Update: Masks for Prevention of SARS-CoV-2 in Health Care and Community Settings-Final Update of a Living, Rapid Review.</h4><i>Chou R, Dana T</i><br /><b>Background</b><br />Optimal use of masks for preventing COVID-19 is unclear.<br /><b>Purpose</b><br />To update an evidence synthesis on N95, surgical, and cloth mask effectiveness in community and health care settings for preventing SARS-CoV-2 infection.<br /><b>Data sources</b><br />MEDLINE, EMBASE, medRxiv (3 June 2022 to 2 January 2023), and reference lists.<br /><b>Study selection</b><br />Randomized trials of interventions to increase mask use and risk for SARS-CoV-2 infection and observational studies of mask use that controlled for potential confounders.<br /><b>Data extraction</b><br />Two investigators sequentially abstracted study data and rated quality.<br /><b>Data synthesis</b><br />Three randomized trials and 21 observational studies were included. In community settings, mask use may be associated with a small reduced risk for SARS-CoV-2 infection versus no mask use, on the basis of 2 randomized trials and 7 observational studies. In routine patient care settings, surgical masks and N95 respirators may be associated with similar risk for SARS-CoV-2 infection, on the basis of 1 new randomized trial with some imprecision and 4 observational studies. Evidence from observational studies was insufficient to evaluate other mask comparisons due to methodological limitations and inconsistency.<br /><b>Limitation</b><br />Few randomized trials, studies had methodological limitations and some imprecision, suboptimal adherence and pragmatic aspects of randomized trials potentially attenuated benefits, very limited evidence on harms, uncertain applicability to Omicron variant predominant era, meta-analysis not done due to heterogeneity, unable to formally assess for publication bias, and restricted to English-language articles.<br /><b>Conclusion</b><br />Updated evidence suggests that masks may be associated with a small reduction in risk for SARS-CoV-2 infection in community settings. Surgical masks and N95 respirators may be associated with similar infection risk in routine patient care settings, but a beneficial effect of N95 respirators cannot be ruled out.<br /><b>Primary funding source</b><br />None.<br /><br /><br /><br /><small>Ann Intern Med: 16 May 2023; epub ahead of print</small></div>

<div><h4>Improving COVID-19 Disease Severity Surveillance Measures: Statewide Implementation Experience.</h4><i>Doron S, Monach PA, Brown CM, Branch-Elliman W</i><br /><AbstractText>Measurement of the burden of COVID-19 on U.S. hospitals has been an important element of the public health response to the pandemic. However, because of variation in testing density and policies, the metric is not standardized across facilities. Two types of burdens exist, one related to the infection control measures that patients who test positive for SARS-CoV-2 require and one from the care of severely ill patients receiving treatment of COVID-19. With rising population immunity from vaccination and infection, as well as the availability of therapeutics, severity of illness has declined. Prior research showed that dexamethasone administration was highly correlated with other disease severity metrics and sensitive to the changing epidemiology associated with the emergence of immune-evasive variants. On 10 January 2022, the Massachusetts Department of Public Health began requiring hospitals to expand surveillance to include reports of both the total number of \"COVID-19 hospitalizations\" daily and the number of inpatients who received dexamethasone at any point during their hospital stay. All 68 acute care hospitals in Massachusetts submitted COVID-19 hospitalization and dexamethasone data daily to the Massachusetts Department of Public Health over a 1-year period. A total of 44 196 COVID-19 hospitalizations were recorded during 10 January 2022 to 9 January 2023, of which 34% were associated with dexamethasone administration. The proportion of patients hospitalized with COVID-19 who had received dexamethasone was 49.6% during the first month of surveillance and decreased to a monthly average of approximately 33% by April 2022, where it has remained since (range, 28.7% to 33%). Adding a single data element to mandated reporting to estimate the frequency of severe COVID-19 in hospitalized patients was feasible and provided actionable information for health authorities and policy makers. Updates to surveillance methods are necessary to match data collection with public health response needs.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 16 May 2023; epub ahead of print</small></div>

<div><h4>Misinterpretation of Clinical Research Findings and COVID-19 Mortality.</h4><i>Casadevall A, Pirofski LA</i><br /><AbstractText>The first 3 years of the COVID-19 pandemic witnessed an unprecedented pace of research that dramatically lessened morbidity and mortality due to COVID-19. This commentary discusses research findings that led to clinical practice recommendations that were later associated with excess mortality.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 16 May 2023; epub ahead of print</small></div>

<div><h4>Primary Occurrence of Cardiovascular Events After Adding Sodium-Glucose Cotransporter-2 Inhibitors or Glucagon-like Peptide-1 Receptor Agonists Compared With Dipeptidyl Peptidase-4 Inhibitors: A Cohort Study in Veterans With Diabetes.</h4><i>Richardson TL, Halvorson AE, Hackstadt AJ, Hung AM, ... Elasy TA, Roumie CL</i><br /><b>Background</b><br />The effectiveness of glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) in preventing major adverse cardiac events (MACE) is uncertain for those without preexisting cardiovascular disease.<br /><b>Objective</b><br />To test the hypothesis that MACE incidence was lower with the addition of GLP1RA or SGLT2i compared with dipeptidyl peptidase-4 inhibitors (DPP4i) for primary cardiovascular prevention.<br /><b>Design</b><br />Retrospective cohort study of U.S. veterans from 2001 to 2019.<br /><b>Setting</b><br />Veterans aged 18 years or older receiving care from the Veterans Health Administration, with data linkage to Medicare, Medicaid, and the National Death Index.<br /><b>Patients</b><br />Veterans adding GLP1RA, SGLT2i, or DPP4i onto metformin, sulfonylurea, or insulin treatment alone or in combination. Episodes were stratified by history of cardiovascular disease.<br /><b>Measurements</b><br />Study outcomes were MACE (acute myocardial infarction, stroke, or cardiovascular death) and heart failure (HF) hospitalization. Cox models compared the outcome between medication groups using pairwise comparisons in a weighted cohort adjusted for covariates.<br /><b>Results</b><br />The cohort included 28 759 GLP1RA versus 28 628 DPP4i weighted pairs and 21 200 SGLT2i versus 21 170 DPP4i weighted pairs. Median age was 67 years, and diabetes duration was 8.5 years. Glucagon-like peptide-1 receptor agonists were associated with lower MACE and HF versus DPP4i (adjusted hazard ratio [aHR], 0.82 [95% CI, 0.72 to 0.94]), yielding an adjusted risk difference (aRD) of 3.2 events (CI, 1.1 to 5.0) per 1000 person-years. Sodium-glucose cotransporter-2 inhibitors were not associated with MACE and HF (aHR, 0.91 [CI, 0.78 to 1.08]; aRD, 1.28 [-1.12 to 3.32]) compared with DPP4i.<br /><b>Limitation</b><br />Residual confounding; use of DPP4i, GLP1RA, and SGLT2i as first-line therapies were not examined.<br /><b>Conclusion</b><br />The addition of GLP1RA was associated with primary reductions of MACE and HF hospitalization compared with DPP4i use; SGLT2i addition was not associated with primary MACE prevention.<br /><b>Primary funding source</b><br />VA Clinical Science Research and Development and supported in part by the Centers for Diabetes Translation Research.<br /><br /><br /><br /><small>Ann Intern Med: 09 May 2023; epub ahead of print</small></div>

<div><h4>Population Genomic Screening for Three Common Hereditary Conditions : A Cost-Effectiveness Analysis.</h4><i>Guzauskas GF, Garbett S, Zhou Z, Schildcrout JS, ... Veenstra DL, Peterson JF</i><br /><b>Background</b><br />The cost-effectiveness of screening the U.S. population for Centers for Disease Control and Prevention (CDC) Tier 1 genomic conditions is unknown.<br /><b>Objective</b><br />To estimate the cost-effectiveness of simultaneous genomic screening for Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), and familial hypercholesterolemia (FH).<br /><b>Design</b><br />Decision analytic Markov model.<br /><b>Data sources</b><br />Published literature.<br /><b>Target population</b><br />Separate age-based cohorts (ages 20 to 60 years at time of screening) of racially and ethnically representative U.S. adults.<br /><b>Time horizon</b><br />Lifetime.<br /><b>Perspective</b><br />U.S. health care payer.<br /><b>Intervention</b><br />Population genomic screening using clinical sequencing with a restricted panel of high-evidence genes, cascade testing of first-degree relatives, and recommended preventive interventions for identified probands.<br /><b>Outcome measures</b><br />Incident breast, ovarian, and colorectal cancer cases; incident cardiovascular events; quality-adjusted survival; and costs.<br /><b>Results of base-case analysis</b><br />Screening 100 000 unselected 30-year-olds resulted in 101 (95% uncertainty interval [UI], 77 to 127) fewer overall cancer cases and 15 (95% UI, 4 to 28) fewer cardiovascular events and an increase of 495 quality-adjusted life-years (QALYs) (95% UI, 401 to 757) at an incremental cost of $33.9 million (95% UI, $27.0 million to $41.1 million). The incremental cost-effectiveness ratio was $68 600 per QALY gained (95% UI, $41 800 to $88 900).<br /><b>Results of sensitivity analysis</b><br />Screening 30-, 40-, and 50-year-old cohorts was cost-effective in 99%, 88%, and 19% of probabilistic simulations, respectively, at a $100 000-per-QALY threshold. The test costs at which screening 30-, 40-, and 50-year-olds reached the $100 000-per-QALY threshold were $413, $290, and $166, respectively. Variant prevalence and adherence to preventive interventions were also highly influential parameters.<br /><b>Limitations</b><br />Population averages for model inputs, which were derived predominantly from European populations, vary across ancestries and health care environments.<br /><b>Conclusion</b><br />Population genomic screening with a restricted panel of high-evidence genes associated with 3 CDC Tier 1 conditions is likely to be cost-effective in U.S. adults younger than 40 years if the testing cost is relatively low and probands have access to preventive interventions.<br /><b>Primary funding source</b><br />National Human Genome Research Institute.<br /><br /><br /><br /><small>Ann Intern Med: 09 May 2023; epub ahead of print</small></div>

<div><h4>Care of the Patient With Abnormal Kidney Test Results.</h4><i>Tuot DS, Powe NR</i><br /><AbstractText>Blood and urine tests are commonly performed by clinicians in both ambulatory and hospital settings that detect chronic and acute kidney disease. Thresholds for these tests have been established that signal the presence and severity of kidney injury or dysfunction. In the appropriate clinical context of a patient\'s history and physical examination, an abnormal test result should trigger specific actions for clinicians, including reviewing patient medication use, follow-up testing, prescribing lifestyle modifications, and specialist referral. Tests for kidney disease can also be used to determine the future risk for kidney failure as well as cardiovascular death.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 09 May 2023; epub ahead of print</small></div>

<div><h4>Comparative Efficacy and Safety of Wakefulness-Promoting Agents for Excessive Daytime Sleepiness in Patients With Obstructive Sleep Apnea : A Systematic Review and Network Meta-analysis.</h4><i>Pitre T, Mah J, Roberts S, Desai K, ... Busse JW, Zeraatkar D</i><br /><b>Background</b><br />Excessive daytime sleepiness (EDS) is common among patients with obstructive sleep apnea (OSA). The comparative effectiveness of pharmacologic agents is unknown.<br /><b>Purpose</b><br />To compare the effectiveness of drugs for EDS in OSA using network meta-analysis.<br /><b>Data sources</b><br />MEDLINE, CENTRAL, EMBASE, and ClinicalTrials.gov to 7 November 2022.<br /><b>Study selection</b><br />Reviewers identified randomized trials that enrolled patients with EDS-associated OSA on or eligible for conventional therapy assigned to any pharmacologic intervention.<br /><b>Data extraction</b><br />Paired reviewers independently extracted data addressing effects of drugs on the Epworth Sleepiness Scale (ESS), Maintenance of Wakefulness Test (MWT), and adverse events at the longest reported follow-up. The certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.<br /><b>Data synthesis</b><br />Fourteen trials (3085 patients) were eligible. At 4 weeks, compared with placebo, solriamfetol improves ESS scores (mean difference [MD], -3.85 [95% CI, -5.24 to -2.50]; high certainty), and armodafinil-modafinil (MD, -2.25 [CI, -2.85 to -1.64]; moderate certainty) and pitolisant-H3-autoreceptor blockers (MD, -2.78 [CI, -4.03 to -1.51]; moderate certainty) probably improve ESS scores. At 4 weeks, compared with placebo, solriamfetol (standardized mean difference [SMD], 0.9 [CI, 0.64 to 1.17]) and armodafinil-modafinil (SMD, 0.41 [CI, 0.27 to 0.55]) improve MWT (both high certainty), whereas pitolisant-H3-autoreceptor blockers probably do not (moderate certainty). At 4 weeks, armodafinil-modafinil probably increases the risk for discontinuation due to adverse events (relative risk [RR], 2.01 [CI, 1.14 to 3.51]; moderate certainty); solriamfetol may increase the risk for discontinuation due to adverse events (RR, 2.07 [CI, 0.67 to 6.25]; low certainty). Low certainty evidence suggests these interventions may not increase the risk for serious adverse events.<br /><b>Limitations</b><br />There is limited evidence on long term or effectiveness among patients nonadherent or with mixed adherence to conventional OSA therapies.<br /><b>Conclusion</b><br />Solriamfetol, armodafinil-modafinil, and pitolisant reduce daytime sleepiness for patients with OSA already on conventional therapy, with solriamfetol likely superior. Adverse events probably increase the risk for discontinuation of armodafinil-modafinil and may increase the risk for discontinuation with solriamfetol.<br /><b>Primary funding source</b><br />None.<br /><br /><br /><br /><small>Ann Intern Med: 09 May 2023; epub ahead of print</small></div>

<div><h4>In prediabetes, oral vitamin D reduces progression to new-onset diabetes.</h4><i>Lau D</i><br /><AbstractText>Pittas AG, Kawahara T, Jorde R, et al. <b>Vitamin D and risk for type 2 diabetes in people with prediabetes: a systematic review and meta-analysis of individual participant data from 3 randomized clinical trials.</b> Ann Intern Med. 2023;176:355-363. 36745886.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 02 May 2023; epub ahead of print</small></div>

<div><h4>Challenges in Estimating the Effectiveness of COVID-19 Vaccination Using Observational Data.</h4><i>Hulme WJ, Williamson E, Horne EMF, Green A, ... Hernán MA, Sterne JAC</i><br /><AbstractText>The COVID-19 vaccines were developed and rigorously evaluated in randomized trials during 2020. However, important questions, such as the magnitude and duration of protection, their effectiveness against new virus variants, and the effectiveness of booster vaccination, could not be answered by randomized trials and have therefore been addressed in observational studies. Analyses of observational data can be biased because of confounding and because of inadequate design that does not consider the evolution of the pandemic over time and the rapid uptake of vaccination. Emulating a hypothetical \"target trial\" using observational data assembled during vaccine rollouts can help manage such potential sources of bias. This article describes 2 approaches to target trial emulation. In the sequential approach, on each day, eligible persons who have not yet been vaccinated are matched to a vaccinated person. The single-trial approach sets a single baseline at the start of the rollout and considers vaccination as a time-varying variable. The nature of the confounding depends on the analysis strategy: Estimating \"per-protocol\" effects (accounting for vaccination of initially unvaccinated persons after baseline) may require adjustment for both baseline and \"time-varying\" confounders. These issues are illustrated by using observational data from 2 780 931 persons in the United Kingdom aged 70 years or older to estimate the effect of a first dose of a COVID-19 vaccine. Addressing the issues discussed in this article should help authors of observational studies provide robust evidence to guide clinical and policy decisions.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 02 May 2023; epub ahead of print</small></div>

<div><h4>In persons with constipation or IBS-C, kiwifruit vs. psyllium increased spontaneous bowel movements.</h4><i>Purtle BJ, Cash BD</i><br /><AbstractText>Gearry R, Fukudo S, Barbara G, et al. <b>Consumption of 2 green kiwifruits daily improves constipation and abdominal comfort-results of an international multicenter randomized controlled trial.</b> Am J Gastroenterol. 9 Jan 2023. [Epub ahead of print]. 36537785.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 02 May 2023; epub ahead of print</small></div>

<div><h4>In adults with VTE who received anticoagulants for ≥3 mo, VTE-PREDICT predicted recurrence and bleeding at up to 5 y.</h4><i>White RH</i><br /><AbstractText>de Winter MA, Büller HR, Carrier M, et al; VTE-PREDICT study group. <b>Recurrent venous thromboembolism and bleeding with extended anticoagulation: the VTE-PREDICT risk score.</b> Eur Heart J. 2023;44:1231-1244. 36648242.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 02 May 2023; epub ahead of print</small></div>

<div><h4>In patients with chronic neuropathic pain, cannabinoids improve sleep and reduce pain vs. placebo.</h4><i>Kim J</i><br /><AbstractText>McParland AL, Bhatia A, Matelski J, et al. <b>Evaluating the impact of cannabinoids on sleep health and pain in patients with chronic neuropathic pain: a systematic review and meta-analysis of randomized controlled trials.</b> Reg Anesth Pain Med. 2022;48:180-190. 36598058.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 02 May 2023; epub ahead of print</small></div>

<div><h4>In outpatients with mild to moderate COVID-19, low-dose fluvoxamine did not reduce time to sustained recovery.</h4><i>Clark J, Tong SYC</i><br /><AbstractText>McCarthy MW, Naggie S, Boulware DR, et al. <b>Effect of fluvoxamine vs placebo on time to sustained recovery in outpatients with mild to moderate COVID-19: a randomized clinical trial.</b> JAMA. 2023;329:296-305. 36633838.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 02 May 2023; epub ahead of print</small></div>

<div><h4>In limb or pelvic fracture, aspirin was noninferior to enoxaparin for reducing all-cause death.</h4><i>Griffin M, Lip GYH</i><br /><AbstractText>Major Extremity Trauma Research Consortium (METRC); O\'Toole RV, Stein DM, O\'Hara NN, et al. <b>Aspirin or low-molecular-weight heparin for thromboprophylaxis after a fracture.</b> N Engl J Med. 2023;388:203-213. 36652352.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 02 May 2023; epub ahead of print</small></div>

<div><h4>In mechanically ventilated patients at nutritional risk, high protein did not reduce time to discharge alive.</h4><i>Nanchal R</i><br /><AbstractText>Heyland DK, Patel J, Compher C, et al; EFFORT Protein Trial team. <b>The effect of higher protein dosing in critically ill patients with high nutritional risk (EFFORT Protein): an international, multicentre, pragmatic, registry-based randomised trial.</b> Lancet. 2023;401:568-576. 36708732.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 02 May 2023; epub ahead of print</small></div>

<div><h4>In infection, vonoprazan plus high-dose amoxicillin was noninferior to B-quadruple therapy for eradication.</h4><i>Flynn DJ, Feuerstein JD</i><br /><AbstractText>Qian HS, Li WJ, Dang YN, et al. <b>Ten-day vonoprazan-amoxicillin dual therapy as a first-line treatment of <i>Helicobacter pylori</i> infection compared with bismuth-containing quadruple therapy.</b> Am J Gastroenterol. 2023;118:627-634. 36729890.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 02 May 2023; epub ahead of print</small></div>

<div><h4>Tecovirimat Treatment of People With HIV During the 2022 Mpox Outbreak : A Retrospective Cohort Study.</h4><i>McLean J, Stoeckle K, Huang S, Berardi J, ... Glesby MJ, Zucker J</i><br /><b>Background</b><br />The recent mpox outbreak has disproportionately affected people with HIV (PWH) and resulted in the first widespread use of the novel antiviral tecovirimat. Whether treatment outcomes differ between PWH and those without HIV is unknown.<br /><b>Objective</b><br />To compare the clinical presentation and treatment outcomes of PWH and HIV-negative persons with mpox virus (MPXV) infection treated with tecovirimat.<br /><b>Design</b><br />Retrospective cohort study of patients treated with tecovirimat for confirmed MPXV infection from June to August 2022.<br /><b>Setting</b><br />Two academic medical centers in New York City.<br /><b>Participants</b><br />The study included 196 persons treated with tecovirimat from 20 June to 29 August 2022. Of 154 testing positive for MPXV, 72 were PWH and 4 had a CD4 count lower than 0.20 × 10<sup>9</sup> cells/L.<br /><b>Measurements</b><br />Patient demographic characteristics, clinical presentation, treatment outcomes, and safety data for tecovirimat.<br /><b>Results</b><br />Indications for tecovirimat treatment were similar between the PWH and HIV-negative groups. Four participants had serious adverse events; none were attributed to tecovirimat. Three of these 4 participants had HIV infection, and 2 had CD4 counts less than 0.20 × 10<sup>9</sup> cells/L. Twenty-two percent of participants had nonsevere adverse effects. Groups had similar rates of hospitalization, indications for treatment, and co-occurring infections, but PWH had fewer days from symptom onset to treatment (7.5 vs. 10). There was no difference in treatment outcomes, including days to improvement or rate of persistent symptoms.<br /><b>Limitation</b><br />Patients with mpox who were not treated with tecovirimat were not followed routinely and therefore lacked comparable outcome data, limiting evaluation of efficacy.<br /><b>Conclusion</b><br />In our cohort of patients treated with tecovirimat for severe mpox, HIV status did not seem to affect treatment outcomes.<br /><b>Primary funding source</b><br />National Institutes of Health.<br /><br /><br /><br /><small>Ann Intern Med: 02 May 2023; epub ahead of print</small></div>

<div><h4>Prioritizing Quality Measures in Acute Stroke Care : A Cost-Effectiveness Analysis.</h4><i>Zhu J, Kamel H, Gupta A, Mushlin AI, ... Rosenthal MB, Pandya A</i><br /><b>Background</b><br />The American Heart Association and American Stroke Association (AHA/ASA) endorsed 15 process measures for acute ischemic stroke (AIS) to improve the quality of care. Identifying the highest-value measures could reduce the administrative burden of quality measure adoption while retaining much of the value of quality improvement.<br /><b>Objective</b><br />To prioritize AHA/ASA-endorsed quality measures for AIS on the basis of health impact and cost-effectiveness.<br /><b>Design</b><br />Individual-based stroke simulation model.<br /><b>Data sources</b><br />Published literature.<br /><b>Target population</b><br />U.S. patients with incident AIS.<br /><b>Time horizon</b><br />Lifetime.<br /><b>Perspective</b><br />Health care sector.<br /><b>Intervention</b><br />Current versus complete (100%) implementation at the population level of quality measures endorsed by the AHA/ASA with sufficient clinical evidence (10 of 15).<br /><b>Outcome measures</b><br />Life-years, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios, and incremental net health benefits.<br /><b>Results of base-case analysis</b><br />Discounted life-years gained from complete implementation would range from 472 (tobacco use counseling) to 34 688 (early carotid imaging) for an annual AIS patient cohort. All AIS quality measures were cost-saving or highly cost-effective by AHA standards (<$50 000 per QALY for high-value care). Early carotid imaging and intravenous tissue plasminogen activator contributed the largest fraction of the total potential value of quality improvement (measured as incremental net health benefit), accounting for 72% of the total value. The top 5 quality measures accounted for 92% of the total potential value.<br /><b>Results of sensitivity analysis</b><br />A web-based user interface allows for context-specific sensitivity and scenario analyses.<br /><b>Limitation</b><br />Correlations between quality measures were not incorporated.<br /><b>Conclusion</b><br />Substantial variation exists in the potential net benefit of quality improvement across AIS quality measures. Benefits were highly concentrated among 5 of 10 measures assessed. Our results can help providers and payers set priorities for quality improvement efforts and value-based payments in AIS care.<br /><b>Primary funding source</b><br />National Institute of Neurological Disorders and Stroke.<br /><br /><br /><br /><small>Ann Intern Med: 02 May 2023; epub ahead of print</small></div>

<div><h4>Hypotension-Avoidance Versus Hypertension-Avoidance Strategies in Noncardiac Surgery : An International Randomized Controlled Trial.</h4><i>Marcucci M, Painter TW, Conen D, Lomivorotov V, ... Devereaux PJ, POISE-3 Trial Investigators and Study Groups *</i><br /><b>Background</b><br />Among patients having noncardiac surgery, perioperative hemodynamic abnormalities are associated with vascular complications. Uncertainty remains about what intraoperative blood pressure to target and how to manage long-term antihypertensive medications perioperatively.<br /><b>Objective</b><br />To compare the effects of a hypotension-avoidance and a hypertension-avoidance strategy on major vascular complications after noncardiac surgery.<br /><b>Design</b><br />Partial factorial randomized trial of 2 perioperative blood pressure management strategies (reported here) and tranexamic acid versus placebo. (ClinicalTrials.gov: NCT03505723).<br /><b>Setting</b><br />110 hospitals in 22 countries.<br /><b>Patients</b><br />7490 patients having noncardiac surgery who were at risk for vascular complications and were receiving 1 or more long-term antihypertensive medications.<br /><b>Intervention</b><br />In the hypotension-avoidance strategy group, the intraoperative mean arterial pressure target was 80 mm Hg or greater; before and for 2 days after surgery, renin-angiotensin-aldosterone system inhibitors were withheld and the other long-term antihypertensive medications were administered only for systolic blood pressures 130 mm Hg or greater, following an algorithm. In the hypertension-avoidance strategy group, the intraoperative mean arterial pressure target was 60 mm Hg or greater; all antihypertensive medications were continued before and after surgery.<br /><b>Measurements</b><br />The primary outcome was a composite of vascular death and nonfatal myocardial injury after noncardiac surgery, stroke, and cardiac arrest at 30 days. Outcome adjudicators were masked to treatment assignment.<br /><b>Results</b><br />The primary outcome occurred in 520 of 3742 patients (13.9%) in the hypotension-avoidance group and in 524 of 3748 patients (14.0%) in the hypertension-avoidance group (hazard ratio, 0.99 [95% CI, 0.88 to 1.12]; <i>P</i> = 0.92). Results were consistent for patients who used 1 or more than 1 antihypertensive medication in the long term.<br /><b>Limitation</b><br />Adherence to the assigned strategies was suboptimal; however, results were consistent across different adherence levels.<br /><b>Conclusion</b><br />In patients having noncardiac surgery, our hypotension-avoidance and hypertension-avoidance strategies resulted in a similar incidence of major vascular complications.<br /><b>Primary funding source</b><br />Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and Research Grant Council of Hong Kong.<br /><br /><br /><br /><small>Ann Intern Med: 25 Apr 2023; epub ahead of print</small></div>

<div><h4>Effects of Cognitive Behavioral Therapy and Cash Transfers on Older Persons Living Alone in India : A Randomized Trial.</h4><i>McKelway M, Banerjee A, Grela E, Schilbach F, ... Vaidyanathan G, Duflo E</i><br /><b>Background</b><br />A growing number of older persons in developing countries live entirely alone and are physically, mentally, and financially vulnerable.<br /><b>Objective</b><br />To determine whether phone-based cognitive behavioral therapy (CBT) or a cash transfer reduce functional impairment, depression, or food insecurity in this population.<br /><b>Design</b><br />Randomized controlled trial. (ClinicalTrials.gov: NCT04225845; American Economic Association RCT Registry: AEARCTR-0007582).<br /><b>Setting</b><br />Tamil Nadu, India, 2021.<br /><b>Participants</b><br />1120 people aged 55 years and older and living alone.<br /><b>Interventions</b><br />A 6-week, phone-based CBT and a 1-time cash transfer of 1000 rupees (U.S. $12 at market exchange rates) were evaluated in a factorial design.<br /><b>Measurements</b><br />The World Health Organization Disability Assessment Schedule (WHODAS), the Geriatric Depression Scale, and food security, all measured 3 weeks after CBT for 977 people and 3 months after for 932. Surveyors were blind to treatment assignment.<br /><b>Results</b><br />The WHODAS score (scale 0 to 48, greater values representing more impairment) decreased between baseline and the 3-week follow-up by 2.92 more (95% CI, -5.60 to -0.23) in the group assigned cash only than in the control group, and the depression score (ranging from 0 to 15, higher score indicating more depressive symptoms) decreased by 1.01 more (CI, -2.07 to 0.06). These effects did not persist to the 3-month follow-up, and CBT alone and the 2 together had no significant effects. There were no effects on food security.<br /><b>Limitations</b><br />The study cannot say whether more sustained or in-person therapy would have been effective, how results would translate outside of the COVID-19 period, or whether results in the consented sample differ from those in a larger population. Primary outcomes were self-reported.<br /><b>Conclusion</b><br />Among older people living alone, a small cash transfer was effective in alleviating short-term (3 weeks) functional impairment, produced a small but not clinically or statistically significant reduction in depression, and had no effect on food security. There were no short-term effects from CBT or the 2 interventions together. None of the interventions showed any effect at 3 months.<br /><b>Primary funding source</b><br />National Institute on Aging (NIA).<br /><br /><br /><br /><small>Ann Intern Med: 25 Apr 2023; epub ahead of print</small></div>

<div><h4>Infectious Diseases: What You May Have Missed in 2022.</h4><i>Al Ohaly R, Benoit ME, Schuster MG</i><br /><AbstractText>In 2022, COVID-19 remained the infectious disease at the top of most internal medicine physicians\' minds. However, it was not the only infectious disease that was the topic of clinically relevant research that year. This article highlights some important infectious disease evidence unrelated to COVID-19 that was published in 2022. The literature was screened for sound new evidence relevant to internal medicine specialists and subspecialists whose focus of practice is not infectious diseases. The publications highlighted relate to various organisms in different patient populations. One article provides insight into the role of <i>Helicobacter pylori</i> eradication in the treatment of functional dyspepsia. The descriptive epidemiology of bacterial (<i>Staphylococcus aureus</i>) and viral (mpox) infections are the focus of 2 other articles. Several articles address the management of resistant and difficult-to-treat infections: multidrug-resistant gram-negative infections, resistant HIV-1, rifampin-resistant tuberculosis, cryptococcal meningitis, and invasive fungal infection in the setting of neutropenia. Another article provides data on effective HIV preexposure prophylaxis in women, an understudied population. Finally, given the urgent need to reduce inappropriate use of antibiotics, an article on antibiotic stewardship for hospitalized patients with presumed sepsis in a non-intensive care unit setting is also included.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 25 Apr 2023; epub ahead of print</small></div>

<div><h4>Safety and Efficacy of Combination SARS-CoV-2 Neutralizing Monoclonal Antibodies Amubarvimab Plus Romlusevimab in Nonhospitalized Patients With COVID-19.</h4><i>Evering TH, Chew KW, Giganti MJ, Moser C, ... Daar ES, ACTIV-2/A5401 Study Team</i><br /><b>Background</b><br />Development of safe and effective SARS-CoV-2 therapeutics is a high priority. Amubarvimab and romlusevimab are noncompeting anti-SARS-CoV-2 monoclonal antibodies with an extended half-life.<br /><b>Objective</b><br />To assess the safety and efficacy of amubarvimab plus romlusevimab.<br /><b>Design</b><br />Randomized, placebo-controlled, phase 2 and 3 platform trial. (ClinicalTrials.gov: NCT04518410).<br /><b>Setting</b><br />Nonhospitalized patients with COVID-19 in the United States, Brazil, South Africa, Mexico, Argentina, and the Philippines.<br /><b>Patients</b><br />Adults within 10 days onset of symptomatic SARS-CoV-2 infection who are at high risk for clinical progression.<br /><b>Intervention</b><br />Combination of monoclonal antibodies amubarvimab plus romlusevimab or placebo.<br /><b>Measurements</b><br />Nasopharyngeal and anterior nasal swabs for SARS-CoV-2, COVID-19 symptoms, safety, and progression to hospitalization or death.<br /><b>Results</b><br />Eight-hundred and seven participants who initiated the study intervention were included in the phase 3 analysis. Median age was 49 years (quartiles, 39 to 58); 51% were female, 18% were Black, and 50% were Hispanic or Latino. Median time from symptom onset at study entry was 6 days (quartiles, 4 to 7). Hospitalizations and/or death occurred in 9 (2.3%) participants in the amubarvimab plus romlusevimab group compared with 44 (10.7%) in the placebo group, with an estimated 79% reduction in events (<i>P</i> < 0.001). This reduction was similar between participants with 5 or less and more than 5 days of symptoms at study entry. Grade 3 or higher treatment-emergent adverse events through day 28 were seen less frequently among participants randomly assigned to amubarvimab plus romlusevimab (7.3%) than placebo (16.1%) (<i>P</i> < 0.001), with no severe infusion reactions or drug-related serious adverse events.<br /><b>Limitation</b><br />The study population was mostly unvaccinated against COVID-19 and enrolled before the spread of Omicron variants and subvariants.<br /><b>Conclusion</b><br />Amubarvimab plus romlusevimab was safe and significantly reduced the risk for hospitalization and/or death among nonhospitalized adults with mild to moderate SARS-CoV-2 infection at high risk for progression to severe disease.<br /><b>Primary funding source</b><br />National Institute of Allergy and Infectious Diseases of the National Institutes of Health.<br /><br /><br /><br /><small>Ann Intern Med: 18 Apr 2023; epub ahead of print</small></div>

<div><h4>Oral Fluvoxamine With Inhaled Budesonide for Treatment of Early-Onset COVID-19 : A Randomized Platform Trial.</h4><i>Reis G, Dos Santos Moreira Silva EA, Silva DCM, Thabane L, ... Mills EJ, TOGETHER Investigators*</i><br /><b>Background</b><br />Previous trials have demonstrated the effects of fluvoxamine alone and inhaled budesonide alone for prevention of disease progression among outpatients with COVID-19.<br /><b>Objective</b><br />To determine whether the combination of fluvoxamine and inhaled budesonide would increase treatment effects in a highly vaccinated population.<br /><b>Design</b><br />Randomized, placebo-controlled, adaptive platform trial. (ClinicalTrials.gov: NCT04727424).<br /><b>Setting</b><br />12 clinical sites in Brazil.<br /><b>Participants</b><br />Symptomatic adults with confirmed SARS-CoV-2 infection and a known risk factor for progression to severe disease.<br /><b>Intervention</b><br />Patients were randomly assigned to either fluvoxamine (100 mg twice daily for 10 days) plus inhaled budesonide (800 mcg twice daily for 10 days) or matching placebos.<br /><b>Measurements</b><br />The primary outcome was a composite of emergency setting retention for COVID-19 for more than 6 hours, hospitalization, and/or suspected complications due to clinical progression of COVID-19 within 28 days of randomization. Secondary outcomes included health care attendance (defined as hospitalization for any cause or emergency department visit lasting >6 hours), time to hospitalization, mortality, patient-reported outcomes, and adverse drug reactions.<br /><b>Results</b><br />Randomization occurred from 15 January to 6 July 2022. A total of 738 participants were allocated to oral fluvoxamine plus inhaled budesonide, and 738 received placebo. The proportion of patients observed in an emergency setting for COVID-19 for more than 6 hours or hospitalized due to COVID-19 was lower in the treatment group than the placebo group (1.8% [95% credible interval {CrI}, 1.1% to 3.0%] vs. 3.7% [95% CrI, 2.5% to 5.3%]; relative risk, 0.50 [95% CrI, 0.25 to 0.92]), with a probability of superiority of 98.7%. No relative effects were found between groups for any of the secondary outcomes. More adverse events occurred in the intervention group than the placebo group, but no important differences between the groups were detected.<br /><b>Limitation</b><br />Low event rate overall, consistent with contemporary trials in vaccinated populations.<br /><b>Conclusion</b><br />Treatment with oral fluvoxamine plus inhaled budesonide among high-risk outpatients with early COVID-19 reduced the incidence of severe disease requiring advanced care.<br /><b>Primary funding source</b><br />Latona Foundation, FastGrants, and Rainwater Charitable Foundation.<br /><br /><br /><br /><small>Ann Intern Med: 18 Apr 2023; epub ahead of print</small></div>

<div><h4>Long-Term Health Consequences After Ovarian Removal at Benign Hysterectomy : A Nationwide Cohort Study.</h4><i>Gottschau M, Rosthøj S, Settnes A, Aalborg GL, ... Kjær SK, Mellemkjær L</i><br /><b>Background</b><br />More evidence is needed to substantiate current recommendations about removing ovaries during hysterectomy for benign conditions.<br /><b>Objective</b><br />To compare long-term outcomes in women with and without bilateral salpingo-oophorectomy (BSO) during hysterectomy for benign conditions.<br /><b>Design</b><br />Emulated target trial using data from a population-based cohort.<br /><b>Setting</b><br />Women in Denmark aged 20 years or older during 1977 to 2017.<br /><b>Participants</b><br />142 985 women with hysterectomy for a benign condition, 22 974 with BSO and 120 011 without.<br /><b>Intervention</b><br />Benign hysterectomy with or without BSO.<br /><b>Measurements</b><br />The primary outcomes were overall hospitalization for cardiovascular disease (CVD), overall cancer incidence, and all-cause mortality through December 2018.<br /><b>Results</b><br />Compared with women without BSO, women with BSO who were younger than 45 years at surgery had a higher 10-year cumulative risk for hospitalization for CVD (risk difference [RD], 1.19 percentage points [95% CI, 0.09 to 2.43 percentage points]). Women with BSO had a higher 10-year cumulative risk for cancer for ages 45 to 54 years (RD, 0.73 percentage point [CI, 0.05 to 1.38 percentage points]), 55 to 64 years (RD, 1.92 percentage points [CI, 0.69 to 3.25 percentage points]), and 65 years or older (RD, 2.54 percentage points [CI, 0.91 to 4.25 percentage points]). Women with BSO had higher 10-year mortality in all age groups, although the differences were statistically significant only for ages 45 to 54 years (RD, 0.79 percentage point [CI, 0.27 to 1.30 percentage points]). The mortality at 20 years was inconsistent with that at 10 years in women aged 65 years or older.<br /><b>Limitation</b><br />Age was a proxy for menopausal status.<br /><b>Conclusion</b><br />The authors find that these results support current recommendations for conserving ovaries in premenopausal women without a high risk for ovarian cancer and suggest a cautious approach in postmenopausal women.<br /><b>Primary funding source</b><br />The Danish Cancer Society\'s Scientific Committee and the Mermaid Project.<br /><br /><br /><br /><small>Ann Intern Med: 18 Apr 2023; epub ahead of print</small></div>

<div><h4>Performance Measures for Physicians Providing Clinical Care Using Telemedicine: A Position Paper From the American College of Physicians.</h4><i>Qaseem A, MacLean CH, Tierney S, Cross JT, ... Fitterman N, Performance Measurement Committee of the American College of Physicians*</i><br /><AbstractText>There has been an exponential growth in the use of telemedicine services to provide clinical care, accelerated by the COVID-19 pandemic. Clinical care delivered via telemedicine has become a major and accepted method of health care delivery for many patients. There is an urgent need to understand quality of care in the telemedicine environment. This American College of Physicians position paper presents 6 recommendations to ensure the appropriate use of performance measures to evaluate quality of clinical care provided in the telemedicine environment.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 18 Apr 2023; epub ahead of print</small></div>

<div><h4>The New European Medical Device Regulation: Balancing Innovation and Patient Safety.</h4><i>Bretthauer M, Gerke S, Hassan C, Ahmad OF, Mori Y</i><br /><AbstractText>The European Union has introduced stricter provisions for medical devices under the new Medical Device Regulation (MDR). The MDR increases requirements for clinical trial testing for many devices before they can legally be placed on the market and extends requirements for rigorous clinical surveillance of benefits and harms to the entire life cycle of devices. New \"expert panels\" have been established by the European Commission to advise in the assessment of devices toward certification, and the role of previous \"notified bodies\" (private companies charged by the Commission with ensuring that manufacturers follow the requirements for device testing) is being expanded. The MDR does not contain a grandfathering clause; thus, all existing medical devices must be recertified under the stricter regulation. The recertification deadline has recently been extended to 2027 or 2028, depending on the device\'s risk class. Whether most device manufacturers can meet these new requirements is uncertain, and the MDR will likely have important consequences for manufacturers, researchers, clinicians, and patients. Enhanced collaborations between the medical device industry and physician partners will be needed to meet the new requirements in a timely manner to avoid shortages of existing devices and to mitigate barriers to development of new devices.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 18 Apr 2023; epub ahead of print</small></div>

<div><h4>Universal Masking in Health Care Settings: A Pandemic Strategy Whose Time Has Come and Gone, For Now.</h4><i>Shenoy ES, Babcock HM, Brust KB, Calderwood MS, ... Wright SB, Branch-Elliman W</i><br /><AbstractText>During the COVID-19 pandemic in the United States, the use of facemasks has been mandated in all health care settings for individuals older than 2 years, whether present as health care personnel, patients, or visitors. In this commentary, a group of health care epidemiologists, infectious diseases physicians, and researchers argue for the withdrawal of the universal masking policy given the current status of the COVID-19 pandemic.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 18 Apr 2023; epub ahead of print</small></div>

<div><h4>Estimated Effect of Parathyroidectomy on Long-Term Kidney Function in Adults With Primary Hyperparathyroidism.</h4><i>Seib CD, Ganesan C, Furst A, Pao AC, ... Kebebew E, Tamura MK</i><br /><b>Background</b><br />Multidisciplinary guidelines recommend parathyroidectomy to slow the progression of chronic kidney disease in patients with primary hyperparathyroidism (PHPT) and an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m<sup>2</sup>. Limited data address the effect of parathyroidectomy on long-term kidney function.<br /><b>Objective</b><br />To compare the incidence of a sustained decline in eGFR of at least 50% among patients with PHPT treated with parathyroidectomy versus nonoperative management.<br /><b>Design</b><br />Target trial emulation was done using observational data from adults with PHPT, using an extended Cox model with time-varying inverse probability weighting.<br /><b>Setting</b><br />Veterans Health Administration.<br /><b>Patients</b><br />Patients with a new biochemical diagnosis of PHPT in 2000 to 2019.<br /><b>Measurements</b><br />Sustained decline of at least 50% from pretreatment eGFR.<br /><b>Results</b><br />Among 43 697 patients with PHPT (mean age, 66.8 years), 2928 (6.7%) had a decline of at least 50% in eGFR over a median follow-up of 4.9 years. The weighted cumulative incidence of eGFR decline was 5.1% at 5 years and 10.8% at 10 years in patients managed with parathyroidectomy, compared with 5.1% and 12.0%, respectively, in those managed nonoperatively. The adjusted hazard of eGFR decline did not differ between parathyroidectomy and nonoperative management (hazard ratio [HR], 0.98 [95% CI, 0.82 to 1.16]). Subgroup analyses found no heterogeneity of treatment effect based on pretreatment kidney function. Parathyroidectomy was associated with a reduced hazard of the primary outcome among patients younger than 60 years (HR, 0.75 [CI, 0.59 to 0.93]) that was not evident among those aged 60 years or older (HR, 1.08 [CI, 0.87 to 1.34]).<br /><b>Limitation</b><br />Analyses were done in a predominantly male cohort using observational data.<br /><b>Conclusion</b><br />Parathyroidectomy had no effect on long-term kidney function in older adults with PHPT. Potential benefits related to kidney function should not be the primary consideration for PHPT treatment decisions.<br /><b>Primary funding source</b><br />National Institute on Aging.<br /><br /><br /><br /><small>Ann Intern Med: 11 Apr 2023; epub ahead of print</small></div>

<div><h4>Periprocedural Anticoagulation.</h4><i>Parks AL, Fang MC</i><br /><AbstractText>Management of patients taking anticoagulants around the time of a procedure is a common and complex clinical scenario. Providing evidence-based care requires estimation of risk for thrombosis and bleeding, knowledge of commonly used medications, multidisciplinary communication and collaboration, and patient engagement and education. This review provides a standardized, evidence-based approach to periprocedural management of anticoagulation, based on current evidence and expert clinical guidelines.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 11 Apr 2023; epub ahead of print</small></div>

<div><h4>How Would You Manage This Patient With Benign Prostatic Hyperplasia? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.</h4><i>Smetana GW, Smith CC, Singla A, Libman H</i><br /><AbstractText>Lower urinary tract symptoms due to benign prostatic hyperplasia (BPH) are common in older patients assigned male sex at birth, regardless of gender identity, and treatment of these symptoms is therefore common in primary care practice. In 2021, the American Urological Association published guidelines for management of BPH. They recommend using a standardized scoring system such as the International Prostate Symptom Score to help establish a diagnosis and to monitor the efficacy of interventions, α-blockers as the first-choice pharmacotherapy option, and 5α-reductase inhibitors for patients with prostate size estimated to be at least 30 cc. Tadalafil is another option regardless of erectile dysfunction. Combination therapies with α-blockers and 5α-reductase inhibitors, anticholinergic agents, or β<sub>3</sub>-agonists are effective options. A surgical referral is warranted if the BPH results in chronic kidney disease, refractory urinary retention, or recurrent urinary tract infections; if there is concern for bladder or prostate cancer; or if symptoms do not respond to medical therapy. In this article, a general internal medicine physician and a urologist discuss the treatment options and how they would apply their recommendations to a patient who wishes to learn more about his options.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 11 Apr 2023; epub ahead of print</small></div>

<div><h4>Incremental Health Care Costs of Self-Reported Functional Impairments and Phenotypic Frailty in Community-Dwelling Older Adults : A Prospective Cohort Study.</h4><i>Ensrud KE, Schousboe JT, Kats AM, Taylor BC, Boyd CM, Langsetmo L</i><br /><b>Background</b><br />Health care systems need better strategies to identify older adults at risk for costly care to select target populations for interventions to reduce health care burden.<br /><b>Objective</b><br />To determine whether self-reported functional impairments and phenotypic frailty are associated with incremental health care costs after accounting for claims-based predictors.<br /><b>Design</b><br />Prospective cohort study.<br /><b>Setting</b><br />Index examinations (2002 to 2011) of 4 prospective cohort studies linked with Medicare claims.<br /><b>Participants</b><br />8165 community-dwelling fee-for-service beneficiaries (4318 women, 3847 men).<br /><b>Measurements</b><br />Weighted (Centers for Medicare & Medicaid Services Hierarchical Condition Category index) and unweighted (count of conditions) multimorbidity and frailty indicators derived from claims. Self-reported functional impairments (difficulty performing 4 activities of daily living) and frailty phenotype (operationalized using 5 components) derived from cohort data. Health care costs ascertained for 36 months after index examinations.<br /><b>Results</b><br />Average annualized costs (2020 U.S. dollars) were $13 906 among women and $14 598 among men. After accounting for claims-based indicators, average incremental costs of functional impairments versus no impairment in women (men) were $3328 ($2354) for 1 impairment increasing to $7330 ($11 760) for 4 impairments; average incremental costs of phenotypic frailty versus robust in women (men) were $8532 ($6172). Mean predicted costs adjusted for claims-based indicators in women (men) varied by both functional impairments and the frailty phenotype ranging from $8124 ($11 831) among robust persons without impairments to $18 792 ($24 713) among frail persons with 4 impairments. Compared with the model with claims-derived indicators alone, this model resulted in more accurate cost prediction for persons with multiple impairments or phenotypic frailty.<br /><b>Limitation</b><br />Cost data limited to participants enrolled in the Medicare fee-for-service program.<br /><b>Conclusion</b><br />Self-reported functional impairments and phenotypic frailty are associated with higher subsequent health care expenditures in community-dwelling beneficiaries after accounting for several claims-based indicators of costs.<br /><b>Primary funding source</b><br />National Institutes of Health.<br /><br /><br /><br /><small>Ann Intern Med: 04 Apr 2023; epub ahead of print</small></div>

<div><h4>Facilitating Shared Decision Making Among Black Patients at Risk for Sudden Cardiac Arrest : A Randomized Clinical Trial.</h4><i>Thomas KL, Al-Khatib SM, Kosinski AS, Sears SF, ... Hirsh DS, Peterson ED</i><br /><b>Background</b><br />Racial disparities in implantable cardioverter-defibrillator (ICD) implantation are multifactorial and are partly explained by higher refusal rates.<br /><b>Objective</b><br />To assess the effectiveness of a video decision support tool for Black patients eligible for an ICD.<br /><b>Design</b><br />Multicenter, randomized clinical trial conducted between September 2016 and April 2020. (ClinicalTrials.gov: NCT02819973).<br /><b>Setting</b><br />Fourteen academic and community-based electrophysiology clinics in the United States.<br /><b>Participants</b><br />Black adults with heart failure who were eligible for a primary prevention ICD.<br /><b>Intervention</b><br />An encounter-based video decision support tool or usual care.<br /><b>Measurements</b><br />The primary outcome was the decision regarding ICD implantation. Additional outcomes included patient knowledge, decisional conflict, ICD implantation within 90 days, the effect of racial concordance on outcomes, and the time patients spent with clinicians.<br /><b>Results</b><br />Of the 330 randomly assigned patients, 311 contributed data for the primary outcome. Among those randomly assigned to the video group, assent to ICD implantation was 58.6% compared with 59.4% in the usual care group (difference, -0.8 percentage point [95% CI, -13.2 to 11.1 percentage points]). Compared with usual care, participants in the video group had a higher mean knowledge score (difference, 0.7 [CI, 0.2 to 1.1]) and a similar decisional conflict score (difference, -2.6 [CI, -5.7 to 0.4]). The ICD implantation rate within 90 days was 65.7%, with no differences by intervention. Participants randomly assigned to the video group spent less time with their clinician than those in the usual care group (mean, 22.1 vs. 27.0 minutes; difference, -4.9 minutes [CI, -9.4 to -0.3 minutes]). Racial concordance between video and study participants did not affect study outcomes.<br /><b>Limitation</b><br />The Centers for Medicare & Medicaid Services implemented a requirement for shared decision making for ICD implantation during the study.<br /><b>Conclusion</b><br />A video-based decision support tool increased patient knowledge but did not increase assent to ICD implantation.<br /><b>Primary funding source</b><br />Patient-Centered Outcomes Research Institute.<br /><br /><br /><br /><small>Ann Intern Med: 04 Apr 2023; epub ahead of print</small></div>

<div><h4>In HF with iron deficiency, IV ferric derisomaltose was associated with lower rates of HF hospitalization or CV death.</h4><i>Lerman JB, Newby LK</i><br /><AbstractText>Kalra PR, Cleland JG, Petrie MC, et al. <b>Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN): an investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial.</b> Lancet. 2022;400:2199-209. 36347265.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 04 Apr 2023; epub ahead of print</small></div>

<div><h4>In older patients receiving aspirin, eradication reduced hospitalization or death due to peptic ulcer bleeding at 2.5 y.</h4><i>Perisetti A, Sharma P</i><br /><AbstractText>Hawkey C, Avery A, Coupland CAC, et al; HEAT trialists. <b><i>Helicobacter pylori</i> eradication for primary prevention of peptic ulcer bleeding in older patients prescribed aspirin in primary care (HEAT): a randomised, double-blind, placebo-controlled trial.</b> Lancet. 2022;400:1597-1606. 36335970.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 04 Apr 2023; epub ahead of print</small></div>

<div><h4>In critically ill patients with COVID-19, IL-6 receptor antagonists reduced mortality vs. control at 180 d.</h4><i>Fuller C, Chagla Z</i><br /><AbstractText>Writing Committee for the REMAP-CAP Investigators; Higgins AM, Berry LR, Lorenzi E, et al. <b>Long-term (180-day) outcomes in critically ill patients with COVID-19 in the REMAP-CAP randomized clinical trial.</b> JAMA. 2023;329:39-51. 36525245.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 04 Apr 2023; epub ahead of print</small></div>

<div><h4>In thrombotic antiphospholipid syndrome, DOACs vs. VKAs increase arterial thrombotic events but not major bleeding.</h4><i>Koutroumpakis E, Deswal A</i><br /><AbstractText>Khairani CD, Bejjani A, Piazza G, et al. <b>Direct oral anticoagulants vs vitamin K antagonists in patients with antiphospholipid syndromes: meta-analysis of randomized trials.</b> J Am Coll Cardiol. 2023;81:16-30. 36328154.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 04 Apr 2023; epub ahead of print</small></div>

<div><h4>In BPPV, canalith repositioning maneuver increased symptom resolution vs. vestibular suppressants.</h4><i>Aung K, Htay T</i><br /><AbstractText>Sharif S, Khoujah D, Greer A, et al. <b>Vestibular suppressants for benign paroxysmal positional vertigo: a systematic review and meta-analysis of randomized controlled trials.</b> Acad Emerg Med. 2022. [Epub ahead of print.] 36268806.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 04 Apr 2023; epub ahead of print</small></div>

<div><h4>In symptomatic isolated DVT, 12 wk vs. 6 wk of rivaroxaban reduced recurrent VTE at 24 mo.</h4><i>DeLoughery TG</i><br /><AbstractText>Ageno W, Bertu L, Bucherini E, et al; RIDTS study group. <b>Rivaroxaban treatment for six weeks versus three months in patients with symptomatic isolated distal deep vein thrombosis: randomised controlled trial.</b> BMJ. 2022;379:e072623. 36520715.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 04 Apr 2023; epub ahead of print</small></div>

<div><h4>In pituitary adenoma surgery, no vs. perioperative hydrocortisone was noninferior for new-onset adrenal insufficiency.</h4><i>Gandhi GY</i><br /><AbstractText>Guo X, Zhang D, Pang H, et al. <b>Safety of withholding perioperative hydrocortisone for patients with pituitary adenomas with an intact hypothalamus-pituitary-adrenal axis: a randomized clinical trial.</b> JAMA Netw Open. 2022;5:e2242221. 36383383.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 04 Apr 2023; epub ahead of print</small></div>

<div><h4>After PCI and 6 to 18 mo of DAPT, clopidogrel reduced a composite of clinical events vs. aspirin at 6 y.</h4><i>Lader EW</i><br /><AbstractText>Kang J, Park KW, Lee H, et al. <b>Aspirin versus clopidogrel for long-term maintenance monotherapy after percutaneous coronary intervention: The HOST-EXAM extended study.</b> Circulation. 2023;147:108-17. 36342475.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 04 Apr 2023; epub ahead of print</small></div>

<div><h4>In older adults with hypertension, chlorthalidone vs. hydrochlorothiazide did not reduce major CV events or deaths at 2.4 y.</h4><i>Bavishi C</i><br /><AbstractText>Diuretic Comparison Project Writing Group; Ishani A, Cushman WC, Leatherman SM, et al. <b>Chlorthalidone vs. hydrochlorothiazide for hypertension-cardiovascular events.</b> N Engl J Med. 2022;387:2401-10. 36516076.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 04 Apr 2023; epub ahead of print</small></div>

<div><h4>Evolving Real-World Effectiveness of Monoclonal Antibodies for Treatment of COVID-19 : A Cohort Study.</h4><i>Kip KE, McCreary EK, Collins K, Minnier TE, ... Kip PL, Marroquin OC</i><br /><b>Background</b><br />Treatment guidelines and U.S. Food and Drug Administration emergency use authorizations (EUAs) of monoclonal antibodies (mAbs) for treatment of high-risk outpatients with mild to moderate COVID-19 changed frequently as different SARS-CoV-2 variants emerged.<br /><b>Objective</b><br />To evaluate whether early outpatient treatment with mAbs, overall and by mAb product, presumed SARS-CoV-2 variant, and immunocompromised status, is associated with reduced risk for hospitalization or death at 28 days.<br /><b>Design</b><br />Hypothetical pragmatic randomized trial from observational data comparing mAb-treated patients with a propensity score-matched, nontreated control group.<br /><b>Setting</b><br />Large U.S. health care system.<br /><b>Participants</b><br />High-risk outpatients eligible for mAb treatment under any EUA with a positive SARS-CoV-2 test result from 8 December 2020 to 31 August 2022.<br /><b>Intervention</b><br />Single-dose intravenous mAb treatment with bamlanivimab, bamlanivimab-etesevimab, sotrovimab, bebtelovimab, or intravenous or subcutaneous casirivimab-imdevimab administered within 2 days of a positive SARS-CoV-2 test result.<br /><b>Measurements</b><br />The primary outcome was hospitalization or death at 28 days among treated patients versus a nontreated control group (no treatment or treatment ≥3 days after SARS-CoV-2 test date).<br /><b>Results</b><br />The risk for hospitalization or death at 28 days was 4.6% in 2571 treated patients and 7.6% in 5135 nontreated control patients (risk ratio [RR], 0.61 [95% CI, 0.50 to 0.74]). In sensitivity analyses, the corresponding RRs for 1- and 3-day treatment grace periods were 0.59 and 0.49, respectively. In subgroup analyses, those receiving mAbs when the Alpha and Delta variants were presumed to be predominant had estimated RRs of 0.55 and 0.53, respectively, compared with 0.71 for the Omicron variant period. Relative risk estimates for individual mAb products all suggested lower risk for hospitalization or death. Among immunocompromised patients, the RR was 0.45 (CI, 0.28 to 0.71).<br /><b>Limitations</b><br />Observational study design, SARS-CoV-2 variant presumed by date rather than genotyping, no data on symptom severity, and partial data on vaccination status.<br /><b>Conclusion</b><br />Early mAb treatment among outpatients with COVID-19 is associated with lower risk for hospitalization or death for various mAb products and SARS-CoV-2 variants.<br /><b>Primary funding source</b><br />None.<br /><br /><br /><br /><small>Ann Intern Med: 04 Apr 2023; epub ahead of print</small></div>

<div><h4>Effect of Medicare Advantage on Hospital Readmission and Mortality Rankings.</h4><i>Oseran AS, Wadhera RK, Orav EJ, Figueroa JF</i><br /><b>Background</b><br />Medicare links hospital performance on readmissions and mortality to payment solely on the basis of outcomes among fee-for-service (FFS) beneficiaries. Whether including Medicare Advantage (MA) beneficiaries, who account for nearly half of all Medicare beneficiaries, in the evaluation of hospital performance affects rankings is unknown.<br /><b>Objective</b><br />To determine if the inclusion of MA beneficiaries in readmission and mortality measures reclassifies hospital performance rankings compared with current measures.<br /><b>Design</b><br />Cross-sectional.<br /><b>Setting</b><br />Population-based.<br /><b>Participants</b><br />Hospitals participating in the Hospital Readmissions Reduction Program or Hospital Value-Based Purchasing Program.<br /><b>Measurements</b><br />Using the 100% Medicare files for FFS and MA claims, the authors calculated 30-day risk-adjusted readmissions and mortality for acute myocardial infarction, heart failure, chronic obstructive pulmonary disease, and pneumonia on the basis of only FFS beneficiaries and then both FFS and MA beneficiaries. Hospitals were divided into quintiles of performance based on FFS beneficiaries only, and the proportion of hospitals that were reclassified to a different performance group with the inclusion of MA beneficiaries was calculated.<br /><b>Results</b><br />Of the hospitals in the top-performing quintile for readmissions and mortality based on FFS beneficiaries, between 21.6% and 30.2% were reclassified to a lower-performing quintile with the inclusion of MA beneficiaries. Similar proportions of hospitals were reclassified from the bottom performance quintile to a higher one across all measures and conditions. Hospitals with a higher proportion of MA beneficiaries were more likely to improve in performance rankings.<br /><b>Limitation</b><br />Hospital performance measurement and risk adjustment differed slightly from those used by Medicare.<br /><b>Conclusion</b><br />Approximately 1 in 4 top-performing hospitals is reclassified to a lower performance group when MA beneficiaries are included in the evaluation of hospital readmissions and mortality. These findings suggest that Medicare\'s current value-based programs provide an incomplete picture of hospital performance.<br /><b>Primary funding source</b><br />Laura and John Arnold Foundation.<br /><br /><br /><br /><small>Ann Intern Med: 28 Mar 2023; epub ahead of print</small></div>

<div><h4>Drug Repurposing and Observational Studies: The Case of Antivirals for the Treatment of COVID-19.</h4><i>Hernán MA, Del Amo J</i><br /><AbstractText>Remdesivir and molnupiravir were the only 2 repurposed antivirals that were approved for emergency use during the COVID-19 pandemic. Both drugs received their emergency use authorization on the basis of a single industry-funded phase 3 trial, which was launched after evidence of in vitro activity against SARS-CoV-2. In contrast, for tenofovir disoproxil fumarate (TDF), little in vitro evidence was generated, no randomized trials for early treatment were done, and the drug was not considered for authorization. Yet, by the summer of 2020, observational evidence suggested a substantially lower risk for severe COVID-19 in TDF users compared with nonusers. The decision-making process for the launching of randomized trials for these 3 drugs is reviewed. Observational data in favor of TDF was systematically dismissed, even though no viable alternative explanations were proposed for the lower risk for severe COVID-19 among TDF users. Lessons learned from the TDF example during the first 2 years of the COVID-19 pandemic are described, and the use of observational clinical data to guide decisions about the launch of randomized trials during the next public health emergency is proposed. The goal is that gatekeepers of randomized trials make better use of the available observational evidence for the repurposing of drugs without commercial value.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 28 Mar 2023; epub ahead of print</small></div>

<div><h4>Subclinical Coronary Atherosclerosis and Risk for Myocardial Infarction in a Danish Cohort : A Prospective Observational Cohort Study.</h4><i>Fuchs A, Kühl JT, Sigvardsen PE, Afzal S, ... Køber LV, Kofoed KF</i><br /><b>Background</b><br />Coronary atherosclerosis may develop at an early age and remain latent for many years.<br /><b>Objective</b><br />To define characteristics of subclinical coronary atherosclerosis associated with the development of myocardial infarction.<br /><b>Design</b><br />Prospective observational cohort study.<br /><b>Setting</b><br />Copenhagen General Population Study, Denmark.<br /><b>Participants</b><br />9533 asymptomatic persons aged 40 years or older without known ischemic heart disease.<br /><b>Measurements</b><br />Subclinical coronary atherosclerosis was assessed with coronary computed tomography angiography conducted blinded to treatment and outcomes. Coronary atherosclerosis was characterized according to luminal obstruction (nonobstructive or obstructive [≥50% luminal stenosis]) and extent (nonextensive or extensive [one third or more of the coronary tree]). The primary outcome was myocardial infarction, and the secondary outcome was a composite of death or myocardial infarction.<br /><b>Results</b><br />A total of 5114 (54%) persons had no subclinical coronary atherosclerosis, 3483 (36%) had nonobstructive disease, and 936 (10%) had obstructive disease. Within a median follow-up of 3.5 years (range, 0.1 to 8.9 years), 193 persons died and 71 had myocardial infarction. The risk for myocardial infarction was increased in persons with obstructive (adjusted relative risk, 9.19 [95% CI, 4.49 to 18.11]) and extensive (7.65 [CI, 3.53 to 16.57]) disease. The highest risk for myocardial infarction was noted in persons with obstructive-extensive subclinical coronary atherosclerosis (adjusted relative risk, 12.48 [CI, 5.50 to 28.12]) or obstructive-nonextensive (adjusted relative risk, 8.28 [CI, 3.75 to 18.32]). The risk for the composite end point of death or myocardial infarction was increased in persons with extensive disease, regardless of degree of obstruction-for example, nonobstructive-extensive (adjusted relative risk, 2.70 [CI, 1.72 to 4.25]) and obstructive-extensive (adjusted relative risk, 3.15 [CI, 2.05 to 4.83]).<br /><b>Limitation</b><br />Mostly White persons were studied.<br /><b>Conclusion</b><br />In asymptomatic persons, subclinical, obstructive coronary atherosclerosis is associated with a more than 8-fold elevated risk for myocardial infarction.<br /><b>Primary funding source</b><br />AP Møller og Hustru Chastine Mc-Kinney Møllers Fond.<br /><br /><br /><br /><small>Ann Intern Med: 28 Mar 2023; epub ahead of print</small></div>

<div><h4>Cases in Precision Medicine: Is There an Obligation to Return Reinterpreted Genetic Results to Former Patients?</h4><i>Appelbaum PS, Burke W, Parens E, Roberts J, Berger SM, Chung WK</i><br /><AbstractText>Interpretation of many genetic test results can change over time as new data accumulate. Hence, physicians who order genetic tests may subsequently receive revised reports with important implications for patients\' medical treatment-even for patients who are no longer in their care. Several of the ethical principles underlying medical practice suggest an obligation to reach out to former patients with this information. Discharging that obligation can be accomplished, at a minimum, by attempting to contact the former patient with their last known contact information.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 28 Mar 2023; epub ahead of print</small></div>

<div><h4>Assessing Heterogeneity of Treatment Effect in Real-World Data.</h4><i>Segal JB, Varadhan R, Groenwold RHH, Li X, ... Nyberg F, Burcu M</i><br /><AbstractText>Increasing availability of real-world data (RWD) generated from patient care enables the generation of evidence to inform clinical decisions for subpopulations of patients and perhaps even individuals. There is growing opportunity to identify important heterogeneity of treatment effects (HTE) in these subgroups<i>.</i> Thus, HTE is relevant to all with interest in patients\' responses to interventions, including regulators who must make decisions about products when signals of harms arise postapproval and payers who make coverage decisions based on expected net benefit to their beneficiaries. Prior work discussed HTE in randomized studies. Here, we address methodological considerations when investigating HTE in observational studies. We propose 4 primary goals of HTE analyses and the corresponding approaches in the context of RWD: to confirm subgroup effects, to describe the magnitude of HTE, to discover clinically important subgroups, and to predict individual effects. We discuss other possible goals including exploring prognostic score- and propensity score-based treatment effects, and testing the transportability of trial results to populations different from trial participants. Finally, we outline methodological needs for enhancing real-world HTE analysis.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 21 Mar 2023; epub ahead of print</small></div>

<div><h4>Worsening Spread of in the United States, 2019 to 2021.</h4><i>Lyman M, Forsberg K, Sexton DJ, Chow NA, ... Jackson BR, Chiller T</i><br /><b>Background</b><br /><i>Candida auris</i> is an emerging fungal threat that has been spreading in the United States since it was first reported in 2016.<br /><b>Objective</b><br />To describe recent changes in the U.S. epidemiology of <i>C auris</i> occurring from 2019 to 2021.<br /><b>Design</b><br />Description of national surveillance data.<br /><b>Setting</b><br />United States.<br /><b>Patients</b><br />Persons with any specimen that was positive for <i>C auris</i>.<br /><b>Measurements</b><br />Case counts reported to the Centers for Disease Control and Prevention by health departments, volume of colonization screening, and antifungal susceptibility results were aggregated and compared over time and by geographic region.<br /><b>Results</b><br />A total of 3270 clinical cases and 7413 screening cases of <i>C auris</i> were reported in the United States through 31 December 2021. The percentage increase in clinical cases grew each year, from a 44% increase in 2019 to a 95% increase in 2021. Colonization screening volume and screening cases increased in 2021 by more than 80% and more than 200%, respectively. From 2019 to 2021, 17 states identified their first <i>C auris</i> case. The number of <i>C auris</i> cases that were resistant to echinocandins in 2021 was about 3 times that in each of the previous 2 years.<br /><b>Limitation</b><br />Identification of screening cases depends on screening that is done on the basis of need and available resources. Screening is not conducted uniformly across the United States, so the true burden of <i>C auris</i> cases may be underestimated.<br /><b>Conclusion</b><br /><i>C auris</i> cases and transmission have risen in recent years, with a dramatic increase in 2021. The rise in echinocandin-resistant cases and evidence of transmission is particularly concerning because echinocandins are first-line therapy for invasive <i>Candida</i> infections, including <i>C auris</i>. These findings highlight the need for improved detection and infection control practices to prevent spread of <i>C auris</i>.<br /><b>Primary funding source</b><br />None.<br /><br /><br /><br /><small>Ann Intern Med: 21 Mar 2023; epub ahead of print</small></div>

<div><h4>Assessment of the Risk Evaluation and Mitigation Strategy (REMS) for Phentermine-Topiramate to Prevent Exposure During Pregnancy.</h4><i>Sarayani A, Donahoo WT, Hampp C, Brown JD, Winterstein AG</i><br /><b>Background</b><br />The U.S. Food and Drug Administration approved phentermine-topiramate for obesity in 2012 and required a Risk Evaluation and Mitigation Strategy (REMS) to prevent prenatal exposure. No such requirement was introduced for topiramate.<br /><b>Objective</b><br />To evaluate the rate of prenatal exposure, contraceptive use, and pregnancy testing among patients with phentermine-topiramate compared with topiramate or other antiobesity medications (AOMs).<br /><b>Design</b><br />Retrospective cohort study.<br /><b>Setting</b><br />Nationwide health insurance claims database.<br /><b>Participants</b><br />Females aged 12 to 55 years with no infertility diagnosis or sterilization procedure. Patients with other indications for topiramate were excluded to identify a cohort that was likely treated for obesity.<br /><b>Measurements</b><br />Patients initiated use of phentermine-topiramate, topiramate, or an AOM (liraglutide, lorcaserin, or bupropion-naltrexone). Pregnancy at treatment initiation, conception during treatment, contraceptive use, and pregnancy testing outcomes were ascertained. Measurable confounders were adjusted for, and extensive sensitivity analyses were done.<br /><b>Results</b><br />A total of 156 280 treatment episodes were observed. Adjusted prevalence of pregnancy at treatment initiation was 0.9 versus 1.6 per 1000 episodes (prevalence ratio, 0.54 [95% CI, 0.31 to 0.95]) for phentermine-topiramate versus topiramate. The incidence rate of conception during treatment was 9.1 versus 15.0 per 1000 person-years (rate ratio, 0.61 [CI, 0.40 to 0.91]) for phentermine-topiramate versus topiramate. Both outcomes were similarly lower for phentermine-topiramate compared with AOM. Prenatal exposure was marginally lower in topiramate users compared with AOM users. Approximately 20% of patients in all cohorts had at least 50% of treatment days covered by contraceptives. Few patients had pregnancy tests before treatment (≤5%), but this was more common among phentermine-topiramate users.<br /><b>Limitations</b><br />Outcome misclassification; unmeasured confounding due to lack of prescriber data to account for possible clustering and spillover effects.<br /><b>Conclusion</b><br />Prenatal exposure seemed to be significantly lower among phentermine-topiramate users under the REMS. Pregnancy testing and contraceptive use appeared to be inadequate for all groups, which deserves attention to prevent the remaining potential exposures.<br /><b>Primary funding source</b><br />None.<br /><br /><br /><br /><small>Ann Intern Med: 21 Mar 2023; epub ahead of print</small></div>

<div><h4>Effect of Thromboprophylaxis on Clinical Outcomes After COVID-19 Hospitalization.</h4><i>Wang TY, Wahed AS, Morris A, Kreuziger LB, ... Ortel TL, ACTIV-4C Study Group</i><br /><b>Background</b><br />Patients hospitalized with COVID-19 have an increased incidence of thromboembolism. The role of extended thromboprophylaxis after hospital discharge is unclear.<br /><b>Objective</b><br />To determine whether anticoagulation is superior to placebo in reducing death and thromboembolic complications among patients discharged after COVID-19 hospitalization.<br /><b>Design</b><br />Prospective, randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT04650087).<br /><b>Setting</b><br />Done during 2021 to 2022 among 127 U.S. hospitals.<br /><b>Participants</b><br />Adults aged 18 years or older hospitalized with COVID-19 for 48 hours or more and ready for discharge, excluding those with a requirement for, or contraindication to, anticoagulation.<br /><b>Intervention</b><br />2.5 mg of apixaban versus placebo twice daily for 30 days.<br /><b>Measurements</b><br />The primary efficacy end point was a 30-day composite of death, arterial thromboembolism, and venous thromboembolism. The primary safety end points were 30-day major bleeding and clinically relevant nonmajor bleeding.<br /><b>Results</b><br />Enrollment was terminated early, after 1217 participants were randomly assigned, because of a lower than anticipated event rate and a declining rate of COVID-19 hospitalizations. Median age was 54 years, 50.4% were women, 26.5% were Black, and 16.7% were Hispanic; 30.7% had a World Health Organization severity score of 5 or greater, and 11.0% had an International Medical Prevention Registry on Venous Thromboembolism risk prediction score of greater than 4. Incidence of the primary end point was 2.13% (95% CI, 1.14 to 3.62) in the apixaban group and 2.31% (CI, 1.27 to 3.84) in the placebo group. Major bleeding occurred in 2 (0.4%) and 1 (0.2%) and clinically relevant nonmajor bleeding occurred in 3 (0.6%) and 6 (1.1%) apixaban-treated and placebo-treated participants, respectively. By day 30, thirty-six (3.0%) participants were lost to follow-up, and 8.5% of apixaban and 11.9% of placebo participants permanently discontinued the study drug treatment.<br /><b>Limitations</b><br />The introduction of SARS-CoV-2 vaccines decreased the risk for hospitalization and death. Study enrollment spanned the peaks of the Delta and Omicron variants in the United States, which influenced illness severity.<br /><b>Conclusion</b><br />The incidence of death or thromboembolism was low in this cohort of patients discharged after hospitalization with COVID-19. Because of early enrollment termination, the results were imprecise and the study was inconclusive.<br /><b>Primary funding source</b><br />National Institutes of Health.<br /><br /><br /><br /><small>Ann Intern Med: 21 Mar 2023; epub ahead of print</small></div>

<div><h4>Effect of Yoga on Frailty in Older Adults : A Systematic Review.</h4><i>Loewenthal J, Innes KE, Mitzner M, Mita C, Orkaby AR</i><br /><b>Background</b><br />Yoga, a multicomponent mind-body practice, improves several domains of physical and psychological health and may affect frailty in older adults.<br /><b>Purpose</b><br />To evaluate the available trial evidence on the effect of yoga-based interventions on frailty in older adults.<br /><b>Data sources</b><br />MEDLINE, EMBASE, and Cochrane Central from their inception to 12 December 2022.<br /><b>Study selection</b><br />Randomized controlled trials evaluating the effect of yoga-based interventions, including at least 1 session of physical postures, on a validated frailty scale or single-item markers of frailty in adults aged 65 years or older.<br /><b>Data extraction</b><br />Two authors independently screened articles and extracted data; 1 author assessed risk of bias with review from a second author. Disagreements were resolved through consensus and as-needed input from a third author.<br /><b>Data synthesis</b><br />Thirty-three studies (<i>n</i> = 2384 participants) were identified in varied populations, including community dwellers, nursing home residents, and those with chronic disease. Yoga styles were primarily based on Hatha yoga and most often included Iyengar or chair-based methods. Single-item frailty markers included measures of gait speed, handgrip strength, balance, lower-extremity strength and endurance, and multicomponent physical performance measures; no studies included a validated definition of frailty. When compared with education or inactive control, there was moderate-certainty evidence that yoga improved gait speed and lower-extremity strength and endurance, low-certainty evidence for balance and multicomponent physical function measures, and very low-certainty evidence for handgrip strength.<br /><b>Limitation</b><br />Heterogeneity in study design and yoga style, small sample sizes, and reporting deficiencies leading to concerns for selection bias.<br /><b>Conclusion</b><br />Yoga may affect frailty markers that are associated with clinically meaningful outcomes in older adult populations but may not offer benefit over active interventions (for example, exercise).<br /><b>Primary funding source</b><br />None. (PROSPERO: CRD42020130303).<br /><br /><br /><br /><small>Ann Intern Med: 14 Mar 2023; epub ahead of print</small></div>

<div><h4>Cardiac Amyloidosis.</h4><i>Bloom MW, Gorevic PD</i><br /><AbstractText>Amyloidosis is a pathologic and clinical condition resulting from the accumulation of insoluble aggregates of misfolded proteins in tissues. Extracellular deposition of amyloid fibrils in the myocardium leads to cardiac amyloidosis, which is often overlooked as a cause of diastolic heart failure. Although cardiac amyloidosis was previously believed to have a poor prognosis, recent advances in diagnosis and treatment have emphasized the importance of early recognition and changed management of this condition. This article provides an overview of cardiac amyloidosis and summarizes current screening, diagnosis, evaluation, and treatment options.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 14 Mar 2023; epub ahead of print</small></div>

<div><h4>Cardiac Arrest During Delivery Hospitalization : A Cohort Study.</h4><i>Ford ND, DeSisto CL, Galang RR, Kuklina EV, Sperling LS, Ko JY</i><br /><b>Background</b><br />Estimates of cardiac arrest occurring during delivery guide evidence-based strategies to reduce pregnancy-related death.<br /><b>Objective</b><br />To investigate rate of, maternal characteristics associated with, and survival after cardiac arrest during delivery hospitalization.<br /><b>Design</b><br />Retrospective cohort study.<br /><b>Setting</b><br />U.S. acute care hospitals, 2017 to 2019.<br /><b>Participants</b><br />Delivery hospitalizations among women aged 12 to 55 years included in the National Inpatient Sample database.<br /><b>Measurements</b><br />Delivery hospitalizations, cardiac arrest, underlying medical conditions, obstetric outcomes, and severe maternal complications were identified using codes from the International Classification of Diseases, 10th Revision, Clinical Modification. Survival to hospital discharge was based on discharge disposition.<br /><b>Results</b><br />Among 10 921 784 U.S. delivery hospitalizations, the cardiac arrest rate was 13.4 per 100 000. Of the 1465 patients who had cardiac arrest, 68.6% (95% CI, 63.2% to 74.0%) survived to hospital discharge. Cardiac arrest was more common among patients who were older, were non-Hispanic Black, had Medicare or Medicaid, or had underlying medical conditions. Acute respiratory distress syndrome was the most common co-occurring diagnosis (56.0% [CI, 50.2% to 61.7%]). Among co-occurring procedures or interventions examined, mechanical ventilation was the most common (53.2% [CI, 47.5% to 59.0%]). The rate of survival to hospital discharge after cardiac arrest was lower with co-occurring disseminated intravascular coagulation (DIC) without or with transfusion (50.0% [CI, 35.8% to 64.2%] or 54.3% [CI, 39.2% to 69.5%], respectively).<br /><b>Limitations</b><br />Cardiac arrests occurring outside delivery hospitalizations were not included. The temporality of arrest relative to the delivery or other maternal complications is unknown. Data do not distinguish cause of cardiac arrest, such as pregnancy-related complications or other underlying causes among pregnant women.<br /><b>Conclusion</b><br />Cardiac arrest was observed in approximately 1 in 9000 delivery hospitalizations, among which nearly 7 in 10 women survived to hospital discharge. Survival was lowest during hospitalizations with co-occurring DIC.<br /><b>Primary funding source</b><br />None.<br /><br /><br /><br /><small>Ann Intern Med: 14 Mar 2023; epub ahead of print</small></div>

<div><h4>Effectiveness of Molnupiravir and Nirmatrelvir-Ritonavir in Hospitalized Patients With COVID-19 : A Target Trial Emulation Study.</h4><i>Wan EYF, Yan VKC, Mok AHY, Wang B, ... Wong ICK, Chan EWY</i><br /><b>Background</b><br />Whether hospitalized patients benefit from COVID-19 oral antivirals is uncertain.<br /><b>Objective</b><br />To examine the real-world effectiveness of molnupiravir and nirmatrelvir-ritonavir in hospitalized patients with COVID-19 during the Omicron outbreak.<br /><b>Design</b><br />Target trial emulation study.<br /><b>Setting</b><br />Electronic health databases in Hong Kong.<br /><b>Participants</b><br />The molnupiravir emulated trial included hospitalized patients with COVID-19 aged 18 years or older between 26 February and 18 July 2022 (<i>n</i> = 16 495). The nirmatrelvir-ritonavir emulated trial included hospitalized patients with COVID-19 aged 18 years or older between 16 March and 18 July 2022 (<i>n</i> = 7119).<br /><b>Intervention</b><br />Initiation of molnupiravir or nirmatrelvir-ritonavir within 5 days of hospitalization with COVID-19 versus no initiation of molnupiravir or nirmatrelvir-ritonavir.<br /><b>Measurements</b><br />Effectiveness against all-cause mortality, intensive care unit (ICU) admission, or use of ventilatory support within 28 days.<br /><b>Results</b><br />The use of oral antivirals in hospitalized patients with COVID-19 was associated with a lower risk for all-cause mortality (molnupiravir: hazard ratio [HR], 0.87 [95% CI, 0.81 to 0.93]; nirmatrelvir-ritonavir: HR, 0.77 [CI, 0.66 to 0.90]) but no significant risk reduction in terms of ICU admission (molnupiravir: HR, 1.02 [CI, 0.76 to 1.36]; nirmatrelvir-ritonavir: HR, 1.08 [CI, 0.58 to 2.02]) or the need for ventilatory support (molnupiravir: HR, 1.07 [CI, 0.89 to 1.30]; nirmatrelvir-ritonavir: HR, 1.03 [CI, 0.70 to 1.52]). There was no significant interaction between drug treatment and the number of COVID-19 vaccine doses received, thereby supporting the effectiveness of oral antivirals regardless of vaccination status. No significant interaction between nirmatrelvir-ritonavir treatment and age, sex, or Charlson Comorbidity Index was observed, whereas molnupiravir tended to be more effective in older people.<br /><b>Limitation</b><br />The outcome of ICU admission or need for ventilatory support may not capture all severe COVID-19 cases; unmeasured confounders, such as obesity and health behaviors, may exist.<br /><b>Conclusion</b><br />Molnupiravir and nirmatrelvir-ritonavir reduced all-cause mortality in both vaccinated and unvaccinated hospitalized patients. No significant reduction in ICU admission or the need for ventilatory support was observed.<br /><b>Primary funding source</b><br />Health and Medical Research Fund Research on COVID-19, Government of the Hong Kong Special Administrative Region; Research Grants Council, Collaborative Research Fund; and Health Bureau, Government of the Hong Kong Special Administrative Region.<br /><br /><br /><br /><small>Ann Intern Med: 14 Mar 2023; epub ahead of print</small></div>

<div><h4>Comparison of Over-the-Scope Clips to Standard Endoscopic Treatment as the Initial Treatment in Patients With Bleeding From a Nonvariceal Upper Gastrointestinal Cause : A Randomized Controlled Trial.</h4><i>Lau JYW, Li R, Tan CH, Sun XJ, ... Li P, Chan FKL</i><br /><b>Background</b><br />Current endoscopic methods in the control of acute nonvariceal bleeding have a small but clinically significant failure rate. The role of over-the-scope clips (OTSCs) as the first treatment has not been defined.<br /><b>Objective</b><br />To compare OTSCs with standard endoscopic hemostatic treatments in the control of bleeding from nonvariceal upper gastrointestinal causes.<br /><b>Design</b><br />A multicenter, randomized controlled trial. (ClinicalTrials.gov: NCT03216395).<br /><b>Setting</b><br />University teaching hospitals in Hong Kong, China, and Australia.<br /><b>Patients</b><br />190 adult patients with active bleeding or a nonbleeding visible vessel from a nonvariceal cause on upper gastrointestinal endoscopy.<br /><b>Intervention</b><br />Standard hemostatic treatment (<i>n</i> = 97) or OTSC (<i>n</i> = 93).<br /><b>Measurements</b><br />The primary outcome was 30-day probability of further bleeds. Other outcomes included failure to control bleeding after assigned endoscopic treatment, recurrent bleeding after initial hemostasis, further intervention, blood transfusion, and hospitalization.<br /><b>Results</b><br />The 30-day probability of further bleeding in the standard treatment and OTSC groups was 14.6% (14 of 97) and 3.2% (3 of 93), respectively (risk difference, 11.4 percentage points [95% CI, 3.3 to 20.0 percentage points]; <i>P</i> = 0.006). Failure to control bleeding after assigned endoscopic treatment in the standard treatment and OTSC groups was 6 versus 1 (risk difference, 5.1 percentage points [CI, 0.7 to 11.8 percentage points]), respectively, and 30-day recurrent bleeding was 8 versus 2 (risk difference, 6.6 percentage points [CI, -0.3 to 14.4 percentage points]), respectively. The need for further interventions was 8 versus 2, respectively. Thirty-day mortality was 4 versus 2, respectively. In a post hoc analysis with a composite end point of failure to successfully apply assigned treatment and further bleeds, the event rate was 15 of 97 (15.6%) and 6 of 93 (6.5%) in the standard and OTSC groups, respectively (risk difference, 9.1 percentage points [CI, 0.004 to 18.3 percentage points]).<br /><b>Limitation</b><br />Clinicians were not blinded to treatment and the option of crossover treatment.<br /><b>Conclusion</b><br />Over-the-scope clips, as an initial treatment, may be better than standard treatment in reducing the risk for further bleeding from nonvariceal upper gastrointestinal causes that are amenable to OTSC placement.<br /><b>Primary funding source</b><br />General Research Fund to the University Grant Committee, Hong Kong SAR Government.<br /><br /><br /><br /><small>Ann Intern Med: 07 Mar 2023; epub ahead of print</small></div>

<div><h4> Cluster in Cardiac Surgery Patients Potentially Attributable to a Commercial Water Purification System.</h4><i>Klompas M, Akusobi C, Boyer J, Woolley A, ... Rubin E, Baker MA</i><br /><b>Background</b><br />Nontuberculous mycobacteria are water-avid pathogens that are associated with nosocomial infections.<br /><b>Objective</b><br />To describe the analysis and mitigation of a cluster of <i>Mycobacterium abscessus</i> infections in cardiac surgery patients.<br /><b>Design</b><br />Descriptive study.<br /><b>Setting</b><br />Brigham and Women\'s Hospital, Boston, Massachusetts.<br /><b>Participants</b><br />Four cardiac surgery patients.<br /><b>Intervention</b><br />Commonalities among cases were sought, potential sources were cultured, patient and environmental specimens were sequenced, and possible sources were abated.<br /><b>Measurements</b><br />Description of the cluster, investigation, and mitigation.<br /><b>Results</b><br />Whole-genome sequencing confirmed homology among clinical isolates. Patients were admitted during different periods to different rooms but on the same floor. There were no common operating rooms, ventilators, heater-cooler devices, or dialysis machines. Environmental cultures were notable for heavy mycobacterial growth in ice and water machines on the cluster unit but little or no growth in ice and water machines in the hospital\'s other 2 inpatient towers or in shower and sink faucet water in any of the hospital\'s 3 inpatient towers. Whole-genome sequencing confirmed the presence of a genetically identical element in ice and water machine and patient specimens. Investigation of the plumbing system revealed a commercial water purifier with charcoal filters and an ultraviolet irradiation unit leading to the ice and water machines in the cluster tower but not the hospital\'s other inpatient towers. Chlorine was present at normal levels in municipal source water but was undetectable downstream from the purification unit. There were no further cases after high-risk patients were switched to sterile and distilled water, ice and water machine maintenance was intensified, and the commercial purification system was decommissioned.<br /><b>Limitation</b><br />Transmission pathways were not clearly characterized.<br /><b>Conclusion</b><br />Well-intentioned efforts to modify water management systems may inadvertently increase infection risk for vulnerable patients.<br /><b>Primary funding source</b><br />National Institutes of Health.<br /><br /><br /><br /><small>Ann Intern Med: 07 Mar 2023; epub ahead of print</small></div>

<div><h4>In AF, underdosing of DOACs was not linked to reduced bleeding.</h4><i>Dunn A</i><br /><AbstractText>Caso V, de Groot JR, Sanmartin Fernandez M, et al. <b>Outcomes and drivers of inappropriate dosing of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation: a systematic review and meta-analysis.</b> Heart. 2023;109:178-85. 36316100.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 07 Mar 2023; epub ahead of print</small></div>

<div><h4>In adults with acute HF, high-intensity care vs. usual care reduced a composite of death or HF readmission at 180 d.</h4><i>Levine M</i><br /><AbstractText>Mebazaa A, Davison B, Chioncel O, et al. <b>Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): a multinational, open-label, randomised, trial.</b> Lancet. 2022;400:1938-52. 36356631.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 07 Mar 2023; epub ahead of print</small></div>

<div><h4>SGLT2 inhibitors reduce adverse renal and CV outcomes in patients with or without diabetes.</h4><i>Patel T</i><br /><AbstractText>Nuffield Department of Population Health Renal Studies Group; SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists\' Consortium. <b>Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials.</b> Lancet. 2022;400:1788-801. 36351458.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 07 Mar 2023; epub ahead of print</small></div>

<div><h4>In adults receiving mechanical ventilation, selective decontamination of the digestive tract reduces hospital mortality.</h4><i>O\'Grady NP</i><br /><AbstractText>Hammond NE, Myburgh J, Seppelt I, et al. <b>Association between selective decontamination of the digestive tract and in-hospital mortality in intensive care unit patients receiving mechanical ventilation: a systematic review and meta-analysis.</b> JAMA. 2022;328:1922-34. 36286098.</AbstractText><br /><br /><br /><br /><small>Ann Intern Med: 07 Mar 2023; epub ahead of print</small></div>