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.

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.

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.

Using Body Mass Index to Identify and Address Obesity in Asian Americans: One Size Does Not Fit All

Adrenal Incidentalomas: Insights Into Prevalence

Effect of Yoga on Frailty in Older Adults: A Systematic Review: Annals of Internal Medicine: Vol 176, No 4

Background: Yoga, a multicomponent mind–body practice, improves several domains of physical and psychological health and may affect frailty in older adults. Purpose: To evaluate the available trial evidence on the effect of yoga-based interventions on frailty in older adults. Data Sources: MEDLINE, EMBASE, and Cochrane Central from their inception to 12 December 2022. Study Selection: 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. Data Extraction: 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. Data Synthesis: Thirty-three studies (n = 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. Limitation: Heterogeneity in study design and yoga style, small sample sizes, and reporting deficiencies leading to concerns for selection bias. Conclusion: 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). Primary Funding Source: None. (PROSPERO: CRD42020130303)

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

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.

Endemic Mycoses: Underdiagnosed and Underreported