Cardiovascular Health of Middle-Aged U.S. Adults by Income Level, 1999 to March 2020: A Serial Cross-Sectional Study: Annals of Internal Medicine: Vol 176, No 12

Background: Although cardiovascular mortality has increased among middle-aged U.S. adults since 2011, how the burden of cardiovascular risk factors has changed for this population by income level over the past 2 decades is unknown. Objective: To evaluate trends in the prevalence, treatment, and control of cardiovascular risk factors among low-income and higher-income middle-aged adults and how social determinants contribute to recent associations between income and cardiovascular health. Design: Serial cross-sectional study. Setting: NHANES (National Health and Nutrition Examination Survey), 1999 to March 2020. Participants: Middle-aged adults (aged 40 to 64 years). Measurements: Age-standardized prevalence of hypertension, diabetes, hyperlipidemia, obesity, and cigarette use; treatment rates for hypertension, diabetes, and hyperlipidemia; and rates of blood pressure, glycemic, and cholesterol control. Results: The study population included 20 761 middle-aged adults. The prevalence of hypertension, diabetes, and cigarette use was consistently higher among low-income adults between 1999 and March 2020. Low-income adults had an increase in hypertension over the study period (37.2% [95% CI, 33.5% to 40.9%] to 44.7% [CI, 39.8% to 49.5%]) but no changes in diabetes or obesity. In contrast, higher-income adults did not have a change in hypertension but had increases in diabetes (7.8% [CI, 5.0% to 10.6%] to 14.9% [CI, 12.4% to 17.3%]) and obesity (33.0% [CI, 26.7% to 39.4%] to 44.0% [CI, 40.2% to 47.7%]). Cigarette use was high and stagnant among low-income adults (33.2% [CI, 28.4% to 38.0%] to 33.9% [CI, 29.6% to 38.3%]) but decreased among their higher-income counterparts (18.6% [CI, 13.5% to 23.7%] to 11.5% [CI, 8.7% to 14.3%]). Treatment and control rates for hypertension were unchanged in both groups (>80%), whereas diabetes treatment rates improved only among the higher-income group (58.4% [CI, 44.4% to 72.5%] to 77.4% [CI, 67.6% to 87.1%]). Income-based disparities in hypertension, diabetes, and cigarette use persisted in more recent years even after adjustment for insurance coverage, health care access, and food insecurity. Limitation: Sample size limitations could preclude detection of small changes in treatment and control rates. Conclusion: Over 2 decades in the United States, hypertension increased in low-income middle-aged adults, whereas diabetes and obesity increased in their higher-income counterparts. Income-based disparities in hypertension, diabetes, and smoking persisted even after adjustment for other social determinants of health. Primary Funding Source: National Institutes of Health.

Asthma Disparities in the United States Narrowed During the COVID-19 Pandemic: Findings From a National Survey, 2019 to 2022

HIV Testing and Preexposure Prophylaxis Prescriptions Among U.S. Commercially Insured Transgender Men and Women, 2014 to 2021

Background: Transgender persons are disproportionately affected by HIV, but preexposure prophylaxis (PrEP) use has been low in this population. Clinical encounters for gender-affirming hormone therapy (GAHT) provide opportunities for HIV prevention. Objective: To estimate the number of commercially insured transgender women (TGW) and transgender men (TGM) in the United States and their use of HIV prevention services. Design: Retrospective analysis of secondary data. Setting: Merative MarketScan commercial databases from 2014 to 2021. Participants: TGW and TGM, defined as those with transgender-related diagnoses and prescriptions for feminizing or masculinizing GAHT. Measurements: HIV testing and PrEP use. Results: A substantially increasing trend was observed in the prevalence of transgender-related diagnosis codes from 2014 to 2021 and in the proportion of persons who used GAHT. The increases were driven by persons aged 18 to 34 years. In 2021, among 10 613 TGW with a test for or a diagnosis of a sexually transmitted infection (STI) in the previous 12 months, 61.1% had an HIV test; among those, 20.2% were prescribed PrEP. Among 4184 TGM with STI risk, 48.3% had an HIV test; among those, 10.2% were prescribed PrEP. The prevalence of TGW and TGM who had a test for or a diagnosis of an STI, had an HIV test, and were prescribed PrEP increased substantially from 2014 to 2021. Limitation: The findings represent only persons with commercial health insurance who sought health care services for GAHT. Conclusion: It is important to identify transgender persons to monitor their receipt of HIV prevention services. Encounters for GAHT provide opportunities to offer HIV prevention and other prevention services. Many HIV prevention opportunities were likely missed at clinical encounters for GAHT. Primary Funding Source: None.

Effectiveness of Recombinant Zoster Vaccine Against Herpes Zoster in a Real-World Setting

Background: A 2-dose series of recombinant zoster vaccine (RZV) was 97% effective against herpes zoster (HZ) in a pivotal clinical trial. Objective: To evaluate real-world effectiveness of RZV against HZ. Design: Prospective cohort study. Setting: Four health care systems in the Vaccine Safety Datalink. Participants: Persons aged 50 years or older. Measurements: The outcome was incident HZ defined by a diagnosis with an antiviral prescription. Cox regression was used to estimate the hazard of HZ in vaccinated persons compared with unvaccinated persons, with adjustment for covariates. Vaccine effectiveness (VE) was calculated as 1 minus the adjusted hazard ratio and was estimated by time since the last RZV dose and by corticosteroid use. Results: The study included nearly 2.0 million persons who contributed 7.6 million person-years of follow-up. After adjustment, VE of 1 dose was 64% and VE of 2 doses was 76%. After 1 dose only, VE was 70% during the first year, 45% during the second year, 48% during the third year, and 52% after the third year. After 2 doses, VE was 79% during the first year, 75% during the second year, and 73% during the third and fourth years. Vaccine effectiveness was 65% in persons who received corticosteroids before vaccination and 77% in those who did not. Limitation: Herpes zoster could not be identified as accurately in these observational data as in the previous clinical trials. Conclusion: Two doses of RZV were highly effective, although less effective than in the previous clinical trials. Two-dose effectiveness waned very little during the 4 years of follow-up. However, 1-dose effectiveness waned substantially after 1 year, underscoring the importance of the second dose. Primary Funding Source: Centers for Disease Control and Prevention.

Accurate Measurements of Gastric Emptying and Gastrointestinal Symptoms in the Evaluation of Glucagon-like Peptide-1 Receptor Agonists

Prevalence of Pharmacologic and Nonpharmacologic Pain Management Therapies Among Adults With Chronic Pain—United States, 2020

Cumulative Incidence of Thiazide-Induced Hyponatremia: A Population-Based Cohort Study: Annals of Internal Medicine: Vol 177, No 1

Background: According to drug labels, the frequency of thiazide-induced hyponatremia is unknown or uncommon to very rare (that is, <1 in 10 000 to <1 in 100), but the exact burden remains unclear. Objective: To estimate the increase in the cumulative incidence of hyponatremia using thiazide diuretics compared with nonthiazide antihypertensive drugs in routine clinical practice. Design: Population and register-based cohort study using target trial emulation. Setting: Denmark, 1 January 2014 to 31 October 2018. Participants: Two target trials were emulated among persons aged 40 years or older who had no recent prescription for any antihypertensive drug, had no previous hyponatremia, and were eligible for the studied antihypertensive treatments. The first target trial emulation compared new use of bendroflumethiazide (BFZ) versus a calcium-channel blocker (CCB). The second target trial emulation compared new use of hydrochlorothiazide plus a renin–angiotensin system inhibitor (HCTZ–RASi; that is, combination pill) versus a RASi alone. Measurements: Two-year cumulative incidences of sodium levels less than 130 mmol/L using stabilized inverse probability of treatment–weighted survival curves. Results: The study compared 37 786 new users of BFZ with 44 963 of a CCB and 11 943 new users of HCTZ–RASi with 85 784 of a RASi. The 2-year cumulative incidences of hyponatremia were 3.83% for BFZ and 3.51% for HCTZ–RASi. The risk differences were 1.35% (95% CI, 1.04% to 1.66%) between BFZ and CCB and 1.38% (CI, 1.01% to 1.75%) between HCTZ–RASi and RASi; risk differences were higher with older age and higher comorbidity burden. The respective hazard ratios were 3.56 (CI, 2.76 to 4.60) and 4.25 (CI, 3.23 to 5.59) during the first 30 days since treatment initiation and 1.26 (CI, 1.09 to 1.46) and 1.29 (CI, 1.05 to 1.58) after 1 year. Limitation: The study assumed that filled prescriptions equaled drug use, and residual confounding is likely. Conclusion: Treatment initiation with thiazide diuretics suggests a more substantial excess risk for hyponatremia, particularly during the first months of treatment, than indicated by drug labeling. Primary Funding Source: Independent Research Fund Denmark.

Association of State Insulin Out-of-Pocket Caps With Insulin Cost-Sharing and Use Among Commercially Insured Patients With Diabetes: A Pre–Post Study With a Control Group: Annals of Internal Medicine: Vol 177, No 4

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: Twenty-five states have implemented insulin out-of-pocket (OOP) cost caps, but their effectiveness is uncertain. Objective: To examine the effect of state insulin OOP caps on insulin use and OOP costs among commercially insured persons with diabetes. Design: Pre–post study with control group. Setting: Eight states implementing insulin OOP caps of $25 to $30, $50, or $100 in January 2021, and 17 control states. Participants: Commercially insured persons with diabetes and insulin users younger than 65 years. Subgroups of particular interest included members from states with insulin OOP caps of $25 to $30, enrollees with health savings accounts (HSAs) that require high insulin OOP payments, and lower-income members. Measurements: Mean monthly 30-day insulin fills and OOP costs. Results: State insulin caps were not associated with changes in insulin use in the overall population (relative change in fills per month, 1.8% [95% CI, −3.2% to 6.9%]). Insulin users in intervention states saw a 17.3% (CI, −22.3% to −12.1%) relative reduction in insulin OOP costs, largely driven by reductions among HSA enrollees; there was no difference in OOP costs among nonaccount plan members. More generous ($25 to $30) state insulin OOP caps were associated with insulin OOP cost reductions of 33.6% (CI, −48.6% to −18.7%), again primarily driven by a larger reduction in the subgroup with HSA plans. Limitations: Single national insurer; 9-month follow-up. Conclusion: Insulin OOP caps were associated with reduced insulin OOP costs but no overall increases in insulin use. A proposed national insulin cap of $35 for commercially insured persons might lead to meaningful insulin OOP savings but have a limited effect on insulin use. Primary Funding Source: Centers for Disease Control and Prevention and National Institute of Diabetes and Digestive and Kidney Diseases.

Deep Learning to Estimate Cardiovascular Risk From Chest Radiographs: A Risk Prediction Study: Annals of Internal Medicine: Vol 177, No 4

Background: Guidelines for primary prevention of atherosclerotic cardiovascular disease (ASCVD) recommend a risk calculator (ASCVD risk score) to estimate 10-year risk for major adverse cardiovascular events (MACE). Because the necessary inputs are often missing, complementary approaches for opportunistic risk assessment are desirable. Objective: To develop and test a deep-learning model (CXR CVD-Risk) that estimates 10-year risk for MACE from a routine chest radiograph (CXR) and compare its performance with that of the traditional ASCVD risk score for implications for statin eligibility. Design: Risk prediction study. Setting: Outpatients potentially eligible for primary cardiovascular prevention. Participants: The CXR CVD-Risk model was developed using data from a cancer screening trial. It was externally validated in 8869 outpatients with unknown ASCVD risk because of missing inputs to calculate the ASCVD risk score and in 2132 outpatients with known risk whose ASCVD risk score could be calculated. Measurements: 10-year MACE predicted by CXR CVD-Risk versus the ASCVD risk score. Results: Among 8869 outpatients with unknown ASCVD risk, those with a risk of 7.5% or higher as predicted by CXR CVD-Risk had higher 10-year risk for MACE after adjustment for risk factors (adjusted hazard ratio [HR], 1.73 [95% CI, 1.47 to 2.03]). In the additional 2132 outpatients with known ASCVD risk, CXR CVD-Risk predicted MACE beyond the traditional ASCVD risk score (adjusted HR, 1.88 [CI, 1.24 to 2.85]). Limitation: Retrospective study design using electronic medical records. Conclusion: On the basis of a single CXR, CXR CVD-Risk predicts 10-year MACE beyond the clinical standard and may help identify individuals at high risk whose ASCVD risk score cannot be calculated because of missing data. Primary Funding Source: None.

SARS-CoV-2 Virologic Rebound With Nirmatrelvir–Ritonavir Therapy: An Observational Study: Annals of Internal Medicine: Vol 176, No 12

Background: Data are conflicting regarding an association between treatment of acute COVID-19 with nirmatrelvir−ritonavir (N-R) and virologic rebound (VR). Objective: To compare the frequency of VR in patients with and without N-R treatment for acute COVID-19. Design: Observational cohort study. Setting: Multicenter health care system in Boston, Massachusetts. Participants: Ambulatory adults with acute COVID-19 with and without use of N-R. Intervention: Receipt of 5 days of N-R treatment versus no COVID-19 therapy. Measurements: The primary outcome was VR, defined as either a positive SARS-CoV-2 viral culture result after a prior negative result or 2 consecutive viral loads above 4.0 log10 copies/mL that were also at least 1.0 log10 copies/mL higher than a prior viral load below 4.0 log10 copies/mL. Results: Compared with untreated persons (n = 55), those taking N-R (n = 72) were older, received more COVID-19 vaccinations, and more commonly had immunosuppression. Fifteen participants (20.8%) taking N-R had VR versus 1 (1.8%) who was untreated (absolute difference, 19.0 percentage points [95% CI, 9.0 to 29.0 percentage points]; P = 0.001). All persons with VR had a positive viral culture result after a prior negative result. In multivariable models, only N-R use was associated with VR (adjusted odds ratio, 10.02 [CI, 1.13 to 88.74]; P = 0.038). Virologic rebound was more common among those who started therapy within 2 days of symptom onset (26.3%) than among those who started 2 or more days after symptom onset (0%) (P = 0.030). Among participants receiving N-R, those who had VR had prolonged shedding of replication-competent virus compared with those who did not have VR (median, 14 vs. 3 days). Eight of 16 participants (50% [CI, 25% to 75%]) with VR also reported symptom rebound; 2 were completely asymptomatic. No post-VR resistance mutations were detected. Limitations: Observational study design with differences between the treated and untreated groups; positive viral culture result was used as a surrogate marker for risk for ongoing viral transmission. Conclusion: Virologic rebound occurred in approximately 1 in 5 people taking N-R, often without symptom rebound, and was associated with shedding of replication-competent virus. Primary Funding Source: National Institutes of Health.