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.

Facilitating Shared Decision Making Among Black Patients at Risk for Sudden Cardiac Arrest: A Randomized Clinical Trial: Annals of Internal Medicine: Vol 176, No 5

Background: Racial disparities in implantable cardioverter-defibrillator (ICD) implantation are multifactorial and are partly explained by higher refusal rates. Objective: To assess the effectiveness of a video decision support tool for Black patients eligible for an ICD. Design: Multicenter, randomized clinical trial conducted between September 2016 and April 2020. (ClinicalTrials.gov: NCT02819973) Setting: Fourteen academic and community-based electrophysiology clinics in the United States. Participants: Black adults with heart failure who were eligible for a primary prevention ICD. Intervention: An encounter-based video decision support tool or usual care. Measurements: 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. Results: 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. Limitation: The Centers for Medicare & Medicaid Services implemented a requirement for shared decision making for ICD implantation during the study. Conclusion: A video-based decision support tool increased patient knowledge but did not increase assent to ICD implantation. Primary Funding Source: Patient-Centered Outcomes Research Institute.

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

Background: 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. Objective: 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. Design: Retrospective cohort study of U.S. veterans from 2001 to 2019. Setting: Veterans aged 18 years or older receiving care from the Veterans Health Administration, with data linkage to Medicare, Medicaid, and the National Death Index. Patients: Veterans adding GLP1RA, SGLT2i, or DPP4i onto metformin, sulfonylurea, or insulin treatment alone or in combination. Episodes were stratified by history of cardiovascular disease. Measurements: 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. Results: 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. Limitation: Residual confounding; use of DPP4i, GLP1RA, and SGLT2i as first-line therapies were not examined. Conclusion: 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. Primary Funding Source: VA Clinical Science Research and Development and supported in part by the Centers for Diabetes Translation Research.

Incremental Health Care Costs of Self-Reported Functional Impairments and Phenotypic Frailty in Community-Dwelling Older Adults: A Prospective Cohort Study: Annals of Internal Medicine: Vol 176, No 4

Background: 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. Objective: To determine whether self-reported functional impairments and phenotypic frailty are associated with incremental health care costs after accounting for claims-based predictors. Design: Prospective cohort study. Setting: Index examinations (2002 to 2011) of 4 prospective cohort studies linked with Medicare claims. Participants: 8165 community-dwelling fee-for-service beneficiaries (4318 women, 3847 men). Measurements: 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. Results: 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. Limitation: Cost data limited to participants enrolled in the Medicare fee-for-service program. Conclusion: 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. Primary Funding Source: National Institutes of Health.

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.

Cancer Screening Guidelines Are Not Simple, But They Could Be Less Complex

Short-Term Adverse Outcomes After Mifepristone–Misoprostol Versus Procedural Induced Abortion: A Population-Based Propensity-Weighted Study: Annals of Internal Medicine: Vol 176, No 2

Background: Prior studies comparing first-trimester pharmaceutical induced abortion (IA) with procedural IA were prone to selection bias, were underpowered to assess serious adverse events (SAEs), and did not account for confounding by indication. Starting in 2017, mifepristone–misoprostol was dispensed at no cost in outpatient pharmacies across Ontario, Canada. Objective: To compare short-term risk for adverse outcomes after early IA by mifepristone–misoprostol versus by procedural IA. Design: Population-based cohort study. Setting: Ontario, Canada. Patients: All women who had first-trimester IA. Measurements: A total of 39 856 women dispensed mifepristone–misoprostol as outpatients were compared with 65 176 women undergoing procedural IA at 14 weeks' gestation or earlier within nonhospital outpatient clinics (comparison 1). A total of 39 856 women prescribed mifepristone–misoprostol were compared with 8861 women undergoing ambulatory hospital-based procedural IA at an estimated 9 weeks' gestation or less (comparison 2). The primary composite outcome was any SAE within 42 days after IA, including severe maternal morbidity, end-organ damage, intensive care unit admission, or death. A coprimary broader outcome comprised any SAE, hemorrhage, retained products of conception, infection, or transfusion. Stabilized inverse probability of treatment weighting accounted for confounding between exposure groups. Results: Mean age at IA was about 29 years (SD, 7); 33% were primigravidae. Six percent resided in rural areas, and 25% resided in low-income neighborhoods. In comparison 1, SAEs occurred among 133 women after mifepristone–misoprostol IA (3.3 per 1000) versus 114 after procedural IA (1.8 per 1000) (relative risk [RR], 1.87 [95% CI, 1.44 to 2.43]; absolute risk difference [ARD], 1.5 per 1000 [CI, 0.9 to 2.2]). The respective rates of any adverse event were 28.9 versus 12.4 per 1000 (RR, 2.33 [CI, 2.11 to 2.57]; ARD, 16.5 per 1000 [CI, 14.5 to 18.4]). In comparison 2, SAEs occurred among 133 (3.4 per 1000) and 27 (3.3 per 1000) women, respectively (RR, 1.04 [CI, 0.61 to 1.78]). The respective rates of any adverse event were 31.2 versus 24.9 per 1000 (RR, 1.25 [CI, 1.04 to 1.51]). Limitation: A woman prescribed mifepristone–misoprostol may not have taken the medication, and the exact gestational age at IA was not always known. Conclusion: Although rare, short-term adverse events are more likely after mifepristone–misoprostol IA than procedural IA, especially for less serious adverse outcomes. Primary Funding Source: Canadian Institutes of Health Research.

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.

Prevalence and Correlates of Patient Rationing of Insulin in the United States: A National Survey

Symptom and Viral Rebound in Untreated SARS-CoV-2 Infection

Background: Although symptom and viral rebound have been reported after nirmatrelvir–ritonavir treatment, the trajectories of symptoms and viral load during the natural course of COVID-19 have not been well described. Objective: To characterize symptom and viral rebound in untreated outpatients with mild to moderate COVID-19. Design: Retrospective analysis of participants in a randomized, placebo-controlled trial. (ClinicalTrials.gov: NCT04518410) Setting: Multicenter trial. Patients: 563 participants receiving placebo in the ACTIV-2/A5401 (Adaptive Platform Treatment Trial for Outpatients With COVID-19) platform trial. Measurements: Participants recorded the severity of 13 symptoms daily between days 0 and 28. Nasal swabs were collected for SARS-CoV-2 RNA testing on days 0 to 14, 21, and 28. Symptom rebound was defined as a 4-point increase in total symptom score after improvement any time after study entry. Viral rebound was defined as an increase of at least 0.5 log10 RNA copies/mL from the immediately preceding time point to a viral load of 3.0 log10 copies/mL or higher. High-level viral rebound was defined as an increase of at least 0.5 log10 RNA copies/mL to a viral load of 5.0 log10 copies/mL or higher. Results: Symptom rebound was identified in 26% of participants at a median of 11 days after initial symptom onset. Viral rebound was detected in 31% and high-level viral rebound in 13% of participants. Most symptom and viral rebound events were transient, because 89% of symptom rebound and 95% of viral rebound events occurred at only a single time point before improving. The combination of symptom and high-level viral rebound was observed in 3% of participants. Limitation: A largely unvaccinated population infected with pre-Omicron variants was evaluated. Conclusion: Symptom or viral relapse in the absence of antiviral treatment is common, but the combination of symptom and viral rebound is rare. Primary Funding Source: National Institute of Allergy and Infectious Diseases.