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.

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.

Trends in Primary Prevention Statin Use by Cardiovascular Risk Score From 1999 to 2018: A Repeated Cross-Sectional Study

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.

Understanding the Varying Biological Behaviors of Breast and Other Types of Cancer to Avoid Overdiagnosis

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.

Real-World Effectiveness of BNT162b2 Against Infection and Severe Diseases in Children and Adolescents

Background: The efficacy of the BNT162b2 vaccine in pediatrics was assessed by randomized trials before the Omicron variant’s emergence. The long-term durability of vaccine protection in this population during the Omicron period remains limited. Objective: To assess the effectiveness of BNT162b2 in preventing infection and severe diseases with various strains of the SARS-CoV-2 virus in previously uninfected children and adolescents. Design: Comparative effectiveness research accounting for underreported vaccination in 3 study cohorts: adolescents (12 to 20 years) during the Delta phase and children (5 to 11 years) and adolescents (12 to 20 years) during the Omicron phase. Setting: A national collaboration of pediatric health systems (PEDSnet). Participants: 77 392 adolescents (45 007 vaccinated) during the Delta phase and 111 539 children (50 398 vaccinated) and 56 080 adolescents (21 180 vaccinated) during the Omicron phase. Intervention: First dose of the BNT162b2 vaccine versus no receipt of COVID-19 vaccine. Measurements: Outcomes of interest include documented infection, COVID-19 illness severity, admission to an intensive care unit (ICU), and cardiac complications. The effectiveness was reported as (1-relative risk)*100, with confounders balanced via propensity score stratification. Results: During the Delta period, the estimated effectiveness of the BNT162b2 vaccine was 98.4% (95% CI, 98.1% to 98.7%) against documented infection among adolescents, with no statistically significant waning after receipt of the first dose. An analysis of cardiac complications did not suggest a statistically significant difference between vaccinated and unvaccinated groups. During the Omicron period, the effectiveness against documented infection among children was estimated to be 74.3% (CI, 72.2% to 76.2%). Higher levels of effectiveness were seen against moderate or severe COVID-19 (75.5% [CI, 69.0% to 81.0%]) and ICU admission with COVID-19 (84.9% [CI, 64.8% to 93.5%]). Among adolescents, the effectiveness against documented Omicron infection was 85.5% (CI, 83.8% to 87.1%), with 84.8% (CI, 77.3% to 89.9%) against moderate or severe COVID-19, and 91.5% (CI, 69.5% to 97.6%) against ICU admission with COVID-19. The effectiveness of the BNT162b2 vaccine against the Omicron variant declined 4 months after the first dose and then stabilized. The analysis showed a lower risk for cardiac complications in the vaccinated group during the Omicron variant period. Limitation: Observational study design and potentially undocumented infection. Conclusion: This study suggests that BNT162b2 was effective for various COVID-19–related outcomes in children and adolescents during the Delta and Omicron periods, and there is some evidence of waning effectiveness over time. Primary Funding Source: National Institutes of Health.

Outpatient Treatment of Confirmed COVID-19: Living, Rapid Practice Points From the American College of Physicians (Version 2)

An update is available for this article. Description: Evidence for the use of outpatient treatments in adults with confirmed COVID-19 continues to evolve with new data. This is version 2 of the American College of Physicians (ACP) living, rapid practice points focusing on 22 outpatient treatments for COVID-19, specifically addressing the dominant SARS-CoV-2 Omicron variant. Methods: The Population Health and Medical Science Committee (formerly the Scientific Medical Policy Committee) developed this version of the 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). This topic will be maintained as living and rapid by continually monitoring and assessing the impact of new evidence. Practice Point 1: Consider molnupiravir to treat symptomatic patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 days of the onset of symptoms and at a high risk for progressing to severe disease. Practice Point 2: Consider nirmatrelvir–ritonavir combination therapy to treat symptomatic patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 days of the onset of symptoms and at a high risk for progressing to severe disease. Practice Point 3: Do not use ivermectin to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. Practice Point 4: Do not use sotrovimab to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting.

Gene Therapy Versus Common Care for Eligible Individuals With Sickle Cell Disease in the United States: A Cost-Effectiveness Analysis: Annals of Internal Medicine: Vol 177, No 2

Background: Sickle cell disease (SCD) and its complications contribute to high rates of morbidity and early mortality and high cost in the United States and African heritage community. Objective: To evaluate the cost-effectiveness of gene therapy for SCD and its value-based prices (VBPs). Design: Comparative modeling analysis across 2 independently developed simulation models (University of Washington Model for Economic Analysis of Sickle Cell Cure [UW-MEASURE] and Fred Hutchinson Institute Sickle Cell Disease Outcomes Research and Economics Model [FH-HISCORE]) using the same databases. Data Sources: Centers for Medicare & Medicaid Services claims data, 2008 to 2016; published literature. Target Population: Persons eligible for gene therapy. Time Horizon: Lifetime. Perspective: U.S. health care sector and societal. Intervention: Gene therapy versus common care. Outcome Measures: Incremental cost-effectiveness ratios (ICERs), equity-informed VBPs, and price acceptability curves. Results of Base-Case Analysis: At an assumed $2 million price for gene therapy, UW-MEASURE and FH-HISCORE estimated ICERs of $193 000 per QALY and $427 000 per QALY, respectively, under the health care sector perspective. Corresponding estimates from the societal perspective were $126 000 per QALY and $281 000 per QALY. The difference in results between models stemmed primarily from considering a slightly different target population and incorporating the quality-of-life (QOL) effects of splenic sequestration, priapism, and acute chest syndrome in the UW model. From a societal perspective, acceptable (>90% confidence) VBPs ranged from $1 million to $2.5 million depending on the use of alternative effective metrics or equity-informed threshold values. Results of Sensitivity Analysis: Results were sensitive to the costs of myeloablative conditioning before gene therapy, effect on caregiver QOL, and effect of gene therapy on long-term survival. Limitation: The short-term effects of gene therapy on vaso-occlusive events were extrapolated from 1 study. Conclusion: Gene therapy for SCD below a $2 million price tag is likely to be cost-effective when applying a societal perspective at an equity-informed threshold for cost-effectiveness analysis. Primary Funding Source: National Heart, Lung, and Blood Institute.

Development and Validation of the CANHEART Population-Based Laboratory Prediction Models for Atherosclerotic Cardiovascular Disease

Background: Prediction of atherosclerotic cardiovascular disease (ASCVD) in primary prevention assessments exclusively with laboratory results may facilitate automated risk reporting and improve uptake of preventive therapies. Objective: To develop and validate sex-specific prediction models for ASCVD using age and routine laboratory tests and compare their performance with that of the pooled cohort equations (PCEs). Design: Derivation and validation of the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) Lab Models. Setting: Population-based cohort study in Ontario, Canada. Participants: A derivation and internal validation cohort of adults aged 40 to 75 years without cardiovascular disease from April 2009 to December 2015; an external validation cohort of primary care patients from January 2010 to December 2014. Measurements: Age and laboratory predictors measured in the outpatient setting included serum total cholesterol, high-density lipoprotein cholesterol, triglycerides, hemoglobin, mean corpuscular volume, platelets, leukocytes, estimated glomerular filtration rate, and glucose. The ASCVD outcomes were defined as myocardial infarction, stroke, and death from ischemic heart or cerebrovascular disease within 5 years. Results: Sex-specific models were developed and internally validated in 2 160 497 women and 1 833 147 men. They were well calibrated, with relative differences less than 1% between mean predicted and observed risk for both sexes. The c-statistic was 0.77 in women and 0.71 in men. External validation in 31 697 primary care patients showed a relative difference less than 14% and an absolute difference less than 0.3 percentage points in mean predicted and observed risks for both sexes. The c-statistics for the laboratory models were 0.72 for both sexes and were not statistically significantly different from those for the PCEs in women (change in c-statistic, −0.01 [95% CI, −0.03 to 0.01]) or men (change in c-statistic, −0.01 [CI, −0.04 to 0.02]). Limitation: Medication use was not available at the population level. Conclusion: The CANHEART Lab Models predict ASCVD with similar accuracy to more complex models, such as the PCEs. Primary Funding Source: Canadian Institutes of Health Research.