Firearm Owners' Preferences for Locking Devices: Results of a National Survey

Comparative Safety Analysis of Oral Antipsychotics for In-Hospital Adverse Clinical Events in Older Adults After Major Surgery: A Nationwide Cohort Study: Annals of Internal Medicine: Vol 176, No 9

Background: Antipsychotics are commonly used to manage postoperative delirium. Recent studies reported that haloperidol use has declined, and atypical antipsychotic use has increased over time. Objective: To compare the risk for in-hospital adverse events associated with oral haloperidol, olanzapine, quetiapine, and risperidone in older patients after major surgery. Design: Retrospective cohort study. Setting: U.S. hospitals in the Premier Healthcare Database. Patients: 17 115 patients aged 65 years and older without psychiatric disorders who were prescribed an oral antipsychotic drug after major surgery from 2009 to 2018. Interventions: Haloperidol (≤4 mg on the day of initiation), olanzapine (≤10 mg), quetiapine (≤150 mg), and risperidone (≤4 mg). Measurements: The risk ratios (RRs) for in-hospital death, cardiac arrhythmia events, pneumonia, and stroke or transient ischemic attack (TIA) were estimated after propensity score overlap weighting. Results: The weighted population had a mean age of 79.6 years, was 60.5% female, and had in-hospital death of 3.1%. Among the 4 antipsychotics, quetiapine was the most prescribed (53.0% of total exposure). There was no statistically significant difference in the risk for in-hospital death among patients treated with haloperidol (3.7%, reference group), olanzapine (2.8%; RR, 0.74 [95% CI, 0.42 to 1.27]), quetiapine (2.6%; RR, 0.70 [CI, 0.47 to 1.04]), and risperidone (3.3%; RR, 0.90 [CI, 0.53 to 1.41]). The risk for nonfatal clinical events ranged from 2.0% to 2.6% for a cardiac arrhythmia event, 4.2% to 4.6% for pneumonia, and 0.6% to 1.2% for stroke or TIA, with no statistically significant differences by treatment group. Limitation: Residual confounding by delirium severity; lack of untreated group; restriction to oral low-to-moderate dose treatment. Conclusion: These results suggest that atypical antipsychotics and haloperidol have similar rates of in-hospital adverse clinical events in older patients with postoperative delirium who receive an oral low-to-moderate dose antipsychotic drug. Primary Funding Source: National Institute on Aging.

Forgiving Physician Debt

Cardiac Arrest During Delivery Hospitalization: A Cohort Study: Annals of Internal Medicine: Vol 176, No 4

Background: Estimates of cardiac arrest occurring during delivery guide evidence-based strategies to reduce pregnancy-related death. Objective: To investigate rate of, maternal characteristics associated with, and survival after cardiac arrest during delivery hospitalization. Design: Retrospective cohort study. Setting: U.S. acute care hospitals, 2017 to 2019. Participants: Delivery hospitalizations among women aged 12 to 55 years included in the National Inpatient Sample database. Measurements: 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. Results: 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). Limitations: 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. Conclusion: 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. Primary Funding Source: None.

Role of Artificial Intelligence in Colonoscopy Detection of Advanced Neoplasias: A Randomized Trial: Annals of Internal Medicine: Vol 176, No 9

Background: The role of computer-aided detection in identifying advanced colorectal neoplasia is unknown. Objective: To evaluate the contribution of computer-aided detection to colonoscopic detection of advanced colorectal neoplasias as well as adenomas, serrated polyps, and nonpolypoid and right-sided lesions. Design: Multicenter, parallel, randomized controlled trial. (ClinicalTrials.gov: NCT04673136) Setting: Spanish colorectal cancer screening program. Participants: 3213 persons with a positive fecal immunochemical test. Intervention: Enrollees were randomly assigned to colonoscopy with or without computer-aided detection. Measurements: Advanced colorectal neoplasia was defined as advanced adenoma and/or advanced serrated polyp. Results: The 2 comparison groups showed no significant difference in advanced colorectal neoplasia detection rate (34.8% with intervention vs. 34.6% for controls; adjusted risk ratio [aRR], 1.01 [95% CI, 0.92 to 1.10]) or the mean number of advanced colorectal neoplasias detected per colonoscopy (0.54 [SD, 0.95] with intervention vs. 0.52 [SD, 0.95] for controls; adjusted rate ratio, 1.04 [99.9% CI, 0.88 to 1.22]). Adenoma detection rate also did not differ (64.2% with intervention vs. 62.0% for controls; aRR, 1.06 [99.9% CI, 0.91 to 1.23]). Computer-aided detection increased the mean number of nonpolypoid lesions (0.56 [SD, 1.25] vs. 0.47 [SD, 1.18] for controls; adjusted rate ratio, 1.19 [99.9% CI, 1.01 to 1.41]), proximal adenomas (0.94 [SD, 1.62] vs. 0.81 [SD, 1.52] for controls; adjusted rate ratio, 1.17 [99.9% CI, 1.03 to 1.33]), and lesions of 5 mm or smaller (polyps in general and adenomas and serrated lesions in particular) detected per colonoscopy. Limitations: The high adenoma detection rate in the control group may limit the generalizability of the findings to endoscopists with low detection rates. Conclusion: Computer-aided detection did not improve colonoscopic identification of advanced colorectal neoplasias. Primary Funding Source: Medtronic.

Physician Turnover in the United States

Background: Medical groups, health systems, and professional associations are concerned about potential increases in physician turnover, which may affect patient access and quality of care. Objective: To examine whether turnover has changed over time and whether it is higher for certain types of physicians or practice settings. Design: The authors developed a novel method using 100% of traditional Medicare billing to create national estimates of turnover. Standardized turnover rates were compared by physician, practice, and patient characteristics. Setting: Traditional Medicare, 2010 to 2020. Participants: Physicians billing traditional Medicare. Measurements: Indicators of physician turnover—physicians who stopped practicing and those who moved from one practice to another—and their sum. Results: The annual rate of turnover increased from 5.3% to 7.2% between 2010 and 2014, was stable through 2017, and increased modestly in 2018 to 7.6%. Most of the increase from 2010 to 2014 came from physicians who stopped practicing increasing from 1.6% to 3.1%; physicians moving increased modestly from 3.7% to 4.2%. Modest but statistically significant (P < 0.001) differences existed across rurality, physician sex, specialty, and patient characteristics. In the second and third quarters of 2020, quarterly turnover was slightly lower than in the corresponding quarters of 2019. Limitation: Measurement was based on traditional Medicare claims. Conclusion: Over the past decade, physician turnover rates have had periods of increase and stability. These early data, covering the first 3 quarters of 2020, give no indication yet of the COVID-19 pandemic increasing turnover, although continued tracking of turnover is warranted. This novel method will enable future monitoring and further investigations into turnover. Primary Funding Source: The Physicians Foundation Center for the Study of Physician Practice and Leadership.

Double-Blind

Hydroxychloroquine Dose and Risk for Incident Retinopathy: A Cohort Study: Annals of Internal Medicine: Vol 176, No 2

Background: Hydroxychloroquine is recommended for all patients with systemic lupus erythematosus and is often used for other inflammatory conditions, but a critical long-term adverse effect is vision-threatening retinopathy. Objective: To characterize the long-term risk for incident hydroxychloroquine retinopathy and examine the degree to which average hydroxychloroquine dose within the first 5 years of treatment predicts this risk. Design: Cohort study. Setting: U.S. integrated health network. Participants: All patients aged 18 years or older who received hydroxychloroquine for 5 or more years between 2004 and 2020 and had guideline-recommended serial retinopathy screening. Measurements: Hydroxychloroquine dose was assessed from pharmacy dispensing records. Incident hydroxychloroquine retinopathy was assessed by central adjudication of spectral domain optical coherence tomography with severity assessment (mild, moderate, or severe). Risk for hydroxychloroquine retinopathy was estimated over 15 years of use according to hydroxychloroquine weight-based dose (>6, 5 to 6, or ≤5 mg/kg per day) using the Kaplan–Meier estimator. Results: Among 3325 patients in the primary study population, 81 developed hydroxychloroquine retinopathy (56 mild, 17 moderate, and 8 severe), with overall cumulative incidences of 2.5% and 8.6% at 10 and 15 years, respectively. The cumulative incidences of retinopathy at 15 years were 21.6% for higher than 6 mg/kg per day, 11.4% for 5 to 6 mg/kg per day, and 2.7% for 5 mg/kg per day or lower. The corresponding risks for moderate to severe retinopathy at 15 years were 5.9%, 2.4%, and 1.1%, respectively. Limitation: Possible misclassifications of dose due to nonadherence to filled prescriptions. Conclusion: In this large, contemporary cohort with active surveillance retinopathy screening, the overall risk for hydroxychloroquine retinopathy was 8.6% after 15 years, and most cases were mild. Higher hydroxychloroquine dose was associated with progressively greater risk for incident retinopathy. Primary Funding Source: National Institutes of Health.

Second-Line Chimeric Antigen Receptor T-Cell Therapy in Diffuse Large B-Cell Lymphoma: A Cost-Effectiveness Analysis: Annals of Internal Medicine: Vol 176, No 12

Background: First-line treatment of diffuse large B-cell lymphoma (DLBCL) achieves durable remission in approximately 60% of patients. In relapsed or refractory disease, only about 20% achieve durable remission with salvage chemoimmunotherapy and consolidative autologous stem cell transplantation (ASCT). The ZUMA-7 (axicabtagene ciloleucel [axi-cel]) and TRANSFORM (lisocabtagene maraleucel [liso-cel]) trials demonstrated superior event-free survival (and, in ZUMA-7, overall survival) in primary-refractory or early-relapsed (high-risk) DLBCL with chimeric antigen receptor T-cell therapy (CAR-T) compared with salvage chemoimmunotherapy and consolidative ASCT; however, list prices for CAR-T exceed $400 000 per infusion. Objective: To determine the cost-effectiveness of second-line CAR-T versus salvage chemoimmunotherapy and consolidative ASCT. Design: State-transition microsimulation model. Data Sources: ZUMA-7, TRANSFORM, other trials, and observational data. Target Population: “High-risk” patients with DLBCL. Time Horizon: Lifetime. Perspective: Health care sector. Intervention: Axi-cel or liso-cel versus ASCT. Outcome Measures: Incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (iNMB) in 2022 U.S. dollars per quality-adjusted life-year (QALY) for a willingness-to-pay (WTP) threshold of $200 000 per QALY. Results of Base-Case Analysis: The increase in median overall survival was 4 months for axi-cel and 1 month for liso-cel. For axi-cel, the ICER was $684 225 per QALY and the iNMB was −$107 642. For liso-cel, the ICER was $1 171 909 per QALY and the iNMB was −$102 477. Results of Sensitivity Analysis: To be cost-effective with a WTP of $200 000, the cost of CAR-T would have to be reduced to $321 123 for axi-cel and $313 730 for liso-cel. Implementation in high-risk patients would increase U.S. health care spending by approximately $6.8 billion over a 5-year period. Limitation: Differences in preinfusion bridging therapies precluded cross-trial comparisons. Conclusion: Neither second-line axi-cel nor liso-cel was cost-effective at a WTP of $200 000 per QALY. Clinical outcomes improved incrementally, but costs of CAR-T must be lowered substantially to enable cost-effectiveness. Primary Funding Source: No research-specific funding.

Outpatient Treatment of Confirmed COVID-19: Living, Rapid Practice Points From the American College of Physicians (Version 1)

An update is available for this article. Description: Strategies to manage COVID-19 in the outpatient setting continue to evolve as new data emerge on SARS-CoV-2 variants and the availability of newer treatments. The Scientific Medical Policy Committee (SMPC) of the American College of Physicians (ACP) developed these living, rapid practice points to summarize the best available evidence on the treatment of adults with confirmed COVID-19 in an outpatient setting. These practice points do not evaluate COVID-19 treatments in the inpatient setting or adjunctive COVID-19 treatments in the outpatient setting. Methods: The SMPC developed these living, rapid practice points on the basis of a living, rapid review done by the ACP Center for Evidence Reviews at Cochrane Austria at the University for Continuing Education Krems (Danube University Krems). The SMPC will maintain these practice points as living by monitoring and assessing the impact of new evidence. Practice Point 1: Consider molnupiravir to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 to 7 days of the onset of symptoms and at high risk for progressing to severe disease. Practice Point 2: Consider nirmatrelvir–ritonavir combination therapy to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 days of the onset of symptoms and at high risk for progressing to severe disease. Practice Point 3: Consider remdesivir to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 7 days of the onset of symptoms and at high risk for progressing to severe disease. Practice Point 4: Do not use azithromycin to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. Practice Point 5: Do not use chloroquine or hydroxychloroquine to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. Practice Point 6: Do not use ivermectin to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. Practice Point 7: Do not use nitazoxanide to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. Practice Point 8: Do not use lopinavir–ritonavir combination therapy to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. Practice Point 9: Do not use casirivimab–imdevimab combination therapy to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting unless it is considered effective against a SARS-CoV-2 variant or subvariant locally in circulation. Practice Point 10: Do not use regdanvimab to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting unless it is considered effective against a SARS-CoV-2 variant or subvariant locally in circulation. Practice Point 11: Do not use sotrovimab to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting unless it is considered effective against a SARS-CoV-2 variant or subvariant locally in circulation. Practice Point 12: Do not use convalescent plasma to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. Practice Point 13: Do not use ciclesonide to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. Practice Point 14: Do not use fluvoxamine to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting.