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.

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.

Monkeypox in Montréal: Epidemiology, Phylogenomics, and Public Health Response to a Large North American Outbreak

Background: Monkeypox, a viral zoonotic disease, is causing a global outbreak outside of endemic areas. Objective: To characterize the outbreak of monkeypox in Montréal, the first large outbreak in North America. Design: Epidemiologic and laboratory surveillance data and a phylogenomic analysis were used to describe and place the outbreak in a global context. Setting: Montréal, Canada. Patients: Probable or confirmed cases of monkeypox. Measurements: Epidemiologic, clinical, and demographic data were aggregated. Whole-genome sequencing and phylogenetic analysis were performed for a set of outbreak sequences. The public health response and its evolution are described. Results: Up to 18 October 2022, a total of 402 cases of monkeypox were reported mostly among men who have sex with men (MSM), most of which were suspected to be acquired through sexual contact. All monkeypox genomes nested within the B.1 lineage. Montréal Public Health worked closely with the affected communities to control the outbreak, becoming the first jurisdiction to offer 1 dose of the Modified Vaccinia Ankara-Bavarian Nordic vaccine as preexposure prophylaxis (PrEP) to those at risk in early June 2022. Two peaks of cases were seen in early June and July (43 and 44 cases per week, respectively) followed by a decline toward near resolution of the outbreak in October. Reasons for the biphasic peak are not fully elucidated but may represent the tempo of vaccination and/or several factors related to transmission dynamics and case ascertainment. Limitations: Clinical data are self-reported. Limited divergence among sequences limited genomic epidemiologic conclusions. Conclusion: A large outbreak of monkeypox occurred in Montréal, primarily among MSM. Successful control of the outbreak rested on early and sustained engagement with the affected communities and rapid offer of PrEP vaccination to at-risk persons. Primary Funding Source: None.

Association Between Age and Low-Density Lipoprotein Cholesterol Response to Statins: A Danish Nationwide Cohort Study: Annals of Internal Medicine: Vol 176, No 8

Background: There is large patient-to-patient variability in the low-density lipoprotein cholesterol (LDL-C) response to statin treatment. The reduction in LDL-C may depend on the age of the patient treated—particularly in older adults, who have been substantially underrepresented in randomized controlled trials. Objective: To investigate the association between age and the LDL-C reduction by statins. Design: Nationwide, register-based cohort study. Setting: Denmark, 2008 to 2018. Participants: 82 958 simvastatin or atorvastatin initiators with LDL-C measurements before and during statin use. Measurements: Statin response, defined as percentage reduction in prestatin LDL-C level, and percentage reduction differences (PRDs) according to age and simvastatin or atorvastatin dose based on a longitudinal model for LDL-C. Results: Among 82 958 statin initiators, 10 388 (13%) were aged 75 years or older. With low- to moderate-intensity statins, initiators aged 75 years or older had greater mean LDL-C percentage reductions than initiators younger than 50 years—for example, 39.0% versus 33.8% for simvastatin, 20 mg, and 44.2% versus 40.2% for atorvastatin, 20 mg. The adjusted PRD for initiators aged 75 years compared with initiators aged 50 years was 2.62 percentage points. This association was consistent for primary prevention (2.54 percentage points) and secondary prevention (2.32 percentage points) but smaller for initiators of high-intensity statins (atorvastatin, 40 mg: 1.36 percentage points; atorvastatin, 80 mg: −0.58 percentage point). Limitation: Use of administrative data, observational pre–post comparison with a moderately high proportion of missing data, lack of information on body mass index, and the mainly White study population may limit generalizability. Conclusion: Low- to moderate-intensity statins were associated with a greater reduction in LDL-C levels in older persons than younger persons and may be more appealing as initial treatment in older adults who are at increased risk for adverse events. Primary Funding Source: The Independent Research Fund Denmark, Brødrene Hartmanns Fond, and Fonden til Lægevidenskabens Fremme.

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.

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.

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.

Health Care During Incarceration: A Policy Position Paper From the American College of Physicians

The American College of Physicians (ACP) has a long-standing commitment to improving the health of all Americans and opposes any form of discrimination in the delivery of health care services. ACP is committed to working toward fully understanding and supporting the unique needs of the incarcerated population and eliminating health disparities for these persons. In this position paper, ACP offers recommendations to policymakers and administrators to improve the health and well-being of persons incarcerated in adult correctional facilities.

Unintended Consequences of SCOTUS Abortion Decision for Patients With Rheumatic Diseases

Estimated Effect of Parathyroidectomy on Long-Term Kidney Function in Adults With Primary Hyperparathyroidism

Background: 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 m2. Limited data address the effect of parathyroidectomy on long-term kidney function. Objective: To compare the incidence of a sustained decline in eGFR of at least 50% among patients with PHPT treated with parathyroidectomy versus nonoperative management. Design: Target trial emulation was done using observational data from adults with PHPT, using an extended Cox model with time-varying inverse probability weighting. Setting: Veterans Health Administration. Patients: Patients with a new biochemical diagnosis of PHPT in 2000 to 2019. Measurements: Sustained decline of at least 50% from pretreatment eGFR. Results: 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]). Limitation: Analyses were done in a predominantly male cohort using observational data. Conclusion: 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. Primary Funding Source: National Institute on Aging.