Morbidity and Mortality of Hospital-Onset SARS-CoV-2 Infections Due to Omicron Versus Prior Variants: A Propensity-Matched Analysis: Annals of Internal Medicine: Vol 177, No 8

Background: Many hospitals have scaled back measures to prevent nosocomial SARS-CoV-2 infection given large decreases in the morbidity and mortality of SARS-CoV-2 infections for most people. Little is known, however, about the morbidity and mortality of nosocomial SARS-CoV-2 infections for hospitalized patients in the Omicron era. Objective: To estimate the effect of nosocomial SARS-CoV-2 infection on hospitalized patients’ outcomes during the pre-Omicron and Omicron periods. Design: Retrospective matched cohort study. Setting: 5 acute care hospitals in Massachusetts, December 2020 to April 2023. Patients: Adults testing positive for SARS-CoV-2 on or after hospital day 5, after negative SARS-CoV-2 test results on admission and on hospital day 3, were matched to control participants by hospital, service, time period, days since admission, and propensity scores that incorporated demographics, comorbid conditions, vaccination status, primary diagnosis category, vital signs, and laboratory test values. Measurements: Primary outcomes were hospital mortality and time to discharge. Secondary outcomes were intensive care unit (ICU) admission, need for advanced oxygen support, discharge destination, hospital-free days, and 30-day readmissions. Results: There were 274 cases of hospital-onset SARS-CoV-2 infection during the pre-Omicron period and 1037 cases during the Omicron period (0.17 vs. 0.49 cases per 100 admissions). Patients with hospital-onset SARS-CoV-2 infection were older and had more comorbid conditions than those without. During the pre-Omicron period, hospital-onset SARS-CoV-2 infection was associated with increased risk for ICU admission, increased need for high-flow oxygen, longer time to discharge (median difference, 4.7 days [95% CI, 2.9 to 6.6 days]), and higher mortality (risk ratio, 2.0 [CI, 1.1 to 3.8]) versus matched control participants. During the Omicron period, hospital-onset SARS-CoV-2 infection remained associated with increased risk for ICU admission and increased time to discharge (median difference, 4.2 days [CI, 3.6 to 5.0 days]). The association with increased hospital mortality was attenuated but still significant (risk ratio, 1.6 [CI, 1.2 to 2.3]). Limitation: Residual confounding may be present. Conclusion: Hospital-onset SARS-CoV-2 infection during the Omicron period remains associated with increased morbidity and mortality. Primary Funding Source: Harvard Medical School Department of Population Medicine.

Trends in Diet Quality Among U.S. Adults From 1999 to 2020 by Race, Ethnicity, and Socioeconomic Disadvantage

Background: Few data have assessed trends in diet quality among U.S. adults. Objective: To evaluate trends in diet quality by race, ethnicity, and socioeconomic disadvantage. Design: Repeated cross-sectional study. Setting: United States. Participants: Noninstitutionalized adults aged 20 years or older who responded to the 1999–2020 National Health and Nutrition Examination Survey (NHANES). Measurements: The proportion of participants meeting the targets of the validated American Heart Association (AHA) 2020 continuous diet score (based on higher intake of fruits, vegetables, whole grains, fish and shellfish, and nuts, seeds, and legumes and lower intake of sugar-sweetened beverages, processed meat, saturated fat, and sodium) and the Healthy Eating Index (HEI)-2015, and energy-adjusted consumption of their components and other individual food groups and nutrients. Poor diet was defined as less than 40% adherence to the AHA score, intermediate as 40% to 79.9% adherence, and ideal as at least 80% adherence. Results: A total of 51 703 adults were included. From 1999 to 2020, the proportion of U.S. adults with poor diet quality decreased from 48.8% to 37.4% (difference, −11.4 percentage points [95% CI, −16.8 to −5.96 percentage points]), the proportion with intermediate quality increased from 50.6% to 61.1% (difference, 10.5 percentage points [CI, 5.20 to 16.1 percentage points]), and the proportion with ideal quality increased from 0.66% to 1.58% (difference, 0.93 percentage points [CI, 0.35 to 1.51 percentage points]) (P for trend < 0.001 for each). Persistent or worsening disparities in diet quality were observed by age, sex, race and ethnicity, education, income, food security, Supplemental Nutrition Assistance Program participation, and health insurance coverage. For example, the proportion of adults with poor diet quality decreased from 47.9% to 33.0% among those with food security (P for trend < 0.001) but did not change (51.3% to 48.2%) among those experiencing food insecurity (P for trend = 0.140) (P for interaction = 0.001). Findings were similar for HEI-2015. Limitations: Self-reported diet; cross-sectional study design. Conclusion: Diet quality among U.S. adults improved modestly between 1999 and 2020, but the proportion with poor diet quality remains high, and dietary disparities persist or are worsening. Primary Funding Source: National Institutes of Health.

Comparative Effectiveness and Safety of Atorvastatin Versus Rosuvastatin: A Multi-database Cohort Study: Annals of Internal Medicine: Vol 177, No 12

Background: Rosuvastatin and atorvastatin are the most widely prescribed moderate- to high-intensity statins. However, evidence on their efficacy and safety during actual use is limited. Objective: To compare the real-world effectiveness and safety of rosuvastatin and atorvastatin. Design: Active comparator cohort study using target trial emulation. Setting: The China Renal Data System (CRDS) and UK Biobank (UKB) databases. Participants: Adults newly prescribed rosuvastatin or atorvastatin. Measurements: The primary outcome was all-cause mortality. Cox proportional hazards regressions were used after 1:1 multilevel propensity score matching. Results: Among the 285 680 eligible participants in both databases, 6-year all-cause mortality was lower for rosuvastatin than for atorvastatin (2.57 vs. 2.83 per 100 person-years in the CRDS database and 0.66 vs. 0.90 per 100 person-years in the UKB database), with differences in cumulative incidence of −1.03% (95% CI, −1.44% to −0.46%) in the CRDS database and −1.38% (CI, −2.50% to −0.21%) in the UKB database. For secondary outcomes in both databases, rosuvastatin conferred lower risks for major adverse cardiovascular events and major adverse liver outcomes. In the UKB database, the risk for development of type 2 diabetes mellitus was higher with rosuvastatin, and the 2 medications carried similar risks for development of chronic kidney disease and other statin-related adverse effects. Limitation: Possible residual confounding. Conclusion: This study found differences in risks for some important outcomes associated with rosuvastatin and atorvastatin. The differences were relatively small, and many did not meet traditional standards for statistical significance. Further research is needed to understand whether these findings can be used with confidence in clinical practice. Primary Funding Source: National Key R&D Program of China and National Natural Science Foundation of China.

Census Tract Rurality, Predominant Race and Ethnicity, and Distance to Lung Cancer Screening Facilities: An Ecological Study: Annals of Internal Medicine: Vol 178, No 2

Background: The U.S. Preventive Services Task Force recommends annual lung cancer screening (LCS) for adults who meet specific age and smoking history criteria. Objective: To evaluate race-, ethnicity-, and rurality-based differences in distance to the nearest LCS facility. Design: Cross-sectional ecological study. Setting: U.S. census tracts. Participants: 71 691 census tracts. Measurements: The outcome variable was road network distance in miles between a census tract and the nearest LCS facility. Distance was log-transformed, and geometric means are reported. Census tracts were classified as majority (>50%) American Indian/Alaska Native (AI/AN), Asian, Black, non-Hispanic White (NHW), no single race, or Hispanic. Rurality was defined using the rural-urban commuting area codes. Ordinary least-squares regression examined the associations between distance and census tract race, ethnicity, and rurality. Results: Geometric mean distance to the nearest LCS facility was 6.5 miles. Compared with NHW-majority census tracts, distance to the nearest LCS facility was 5.26 times (426%) longer in AI/AN-majority census tracts and 7% to 39% shorter in Asian-, Black-, and Hispanic-majority census tracts. Adjustment for rurality reduced the mean distance in AI/AN-majority census tracts, but the mean distance was still 3.16 times the distance in NHW-majority census tracts. Adjustment for rurality reduced the observed advantage in Asian- and Black-majority census tracts and changed the direction of associations in Hispanic-majority census tracts. Limitation: Analyses did not account for travel time or cost. Conclusion: Differences exist in distance to LCS facilities by race and ethnicity that can only be partially explained by rurality. Primary Funding Source: Lung Ambition Alliance and the Center for Lung Research in Honor of Wayne Gittinger.

Association Between False-Positive Results and Return to Screening Mammography in the Breast Cancer Surveillance Consortium Cohort

Background: False-positive results on screening mammography may affect women’s willingness to return for future screening. Objective: To evaluate the association between screening mammography results and the probability of subsequent screening. Design: Cohort study. Setting: 177 facilities participating in the Breast Cancer Surveillance Consortium (BCSC). Patients: 3 529 825 screening mammograms (3 184 482 true negatives and 345 343 false positives) performed from 2005 to 2017 among 1 053 672 women aged 40 to 73 years without a breast cancer diagnosis. Measurements: Mammography results (true-negative result or false-positive recall with a recommendation for immediate additional imaging only, short-interval follow-up, or biopsy) from 1 or 2 screening mammograms. Absolute differences in the probability of returning for screening within 9 to 30 months of false-positive versus true-negative screening results were estimated, adjusting for race, ethnicity, age, time since last mammogram, BCSC registry, and clustering within women and facilities. Results: Women were more likely to return after a true-negative result (76.9% [95% CI, 75.1% to 78.6%]) than after a false-positive recall for additional imaging only (adjusted absolute difference, −1.9 percentage points [CI, −3.1 to −0.7 percentage points]), short-interval follow-up (−15.9 percentage points [CI, −19.7 to −12.0 percentage points]), or biopsy (−10.0 percentage points [CI, −14.2 to −5.9 percentage points]). Asian and Hispanic/Latinx women had the largest decreases in the probability of returning after a false positive with a recommendation for short-interval follow-up (−20 to −25 percentage points) or biopsy (−13 to −14 percentage points) versus a true negative. Among women with 2 screening mammograms within 5 years, a false-positive result on the second was associated with a decreased probability of returning for a third regardless of the first screening result. Limitation: Women could receive care at non-BCSC facilities. Conclusion: Women were less likely to return to screening after false-positive mammography results, especially with recommendations for short-interval follow-up or biopsy, raising concerns about continued participation in routine screening among these women at increased breast cancer risk. Primary Funding Source: National Cancer Institute.

Comparative Performance of Common Fecal Immunochemical Tests: A Cross-Sectional Study: Annals of Internal Medicine: Vol 177, No 10

Background: Despite widespread use of fecal immunochemical tests (FITs) for colorectal cancer (CRC) screening, data to guide test selection are limited. Objective: To compare the performance characteristics of 5 commonly used FITs, using colonoscopy as the reference standard. Design: Cross-sectional study. (ClinicalTrials.gov: NCT03264898) Setting: Three U.S. academic medical centers and affiliated endoscopy units. Participants: Patients aged 50 to 85 years undergoing screening or surveillance colonoscopy. Intervention: Participants completed 5 different FITs before their colonoscopy, including 4 qualitative tests (Hemoccult ICT, Hemosure iFOB, OC-Light S FIT, QuickVue iFOB) and 1 quantitative test (OC-Auto FIT, which was run at the manufacturer's threshold for positivity of >100 ng/mL). Measurements: The primary outcome was test performance (sensitivity and specificity) for each of the 5 FITs for advanced colorectal neoplasia (ACN), defined as advanced polyps or CRC. Positivity rates, positive and negative predictive values, and rates of unevaluable tests were compared. Multivariable models were used to identify factors affecting sensitivity. Results: A total of 3761 participants were enrolled, with a mean age of 62.1 years (SD, 7.8); 63.2% of participants were female, 5.7% were Black, 86.4% were White, and 28.7% were Hispanic. There were 320 participants with ACN (8.5%), including 9 with CRC (0.2%). The test positivity rate varied 4-fold (3.9% to 16.4%) across FITs. Rates of unevaluable FITs ranged from 0.2% to 2.5%. The sensitivity for ACN varied from 10.1% to 36.7%, and specificity varied from 85.5% to 96.6%. Differences in sensitivity between FITs were all statistically significantly different except between Hemosure iFOB and QuickVue iFOB, and specificity differences were all statistically significantly different from one another. In addition to FIT brand, distal location of ACN was also associated with higher FIT sensitivity. Limitation: The study did not assess the programmatic sensitivity of annual FIT. Conclusion: Although considered a single class, FITs have varying test performance for detecting ACN and should not be considered interchangeable. Primary Funding Source: National Institutes of Health.

The Effect of Denosumab on Risk for Emergently Treated Hypocalcemia by Stage of Chronic Kidney Disease: A Target Trial Emulation: Annals of Internal Medicine: Vol 178, No 1

Background: There is a paucity of data on treatment of osteoporosis in patients with advanced chronic kidney disease (CKD). Objective: To assess the risk for emergently treated hypocalcemia with denosumab by stage of CKD and presence of CKD–mineral and bone disorder (CKD-MBD). Design: Target trial emulation. Setting: Medicare fee-for-service data with prescription drug coverage, 2012 to 2020. Participants: Female patients aged 65 years or older initiating denosumab, oral bisphosphonates, or intravenous (IV) bisphosphonates for osteoporosis. Measurements: Hospital and emergency department admissions (that is, emergent care) for hypocalcemia were assessed in the first 12 treatment weeks. Inverse probability of treatment weighted cumulative incidence and weighted risk differences (RDs) were calculated. Results: A total of 361 453 patients treated with denosumab, 829 044 treated with oral bisphosphonates, and 160 413 treated with IV bisphosphonates were identified. Risk for emergently treated hypocalcemia with denosumab versus oral bisphosphonates increased with worsening CKD stage (P < 0.001), with greatest risk among dialysis-dependent (DD) patients (3.01% vs. 0.00%; RD, 3.01% [95% CI, 2.27% to 3.77%]) and non–dialysis-dependent (NDD) patients with CKD stages 4 and 5 (0.57% vs. 0.03%; RD, 0.54% [CI, 0.41% to 0.68%]). Among patients with stages 4 and 5 CKD (NDD + DD), denosumab had a greater risk for emergently treated hypocalcemia versus oral bisphosphonates in those with CKD-MBD (1.53% vs. 0.02%; RD, 1.51% [CI, 1.21% to 1.78%]) than in those without CKD-MBD (0.22% vs. 0.03%; RD, 0.19% [CI, 0.08% to 0.31%]). Denosumab also showed increased risk compared with IV bisphosphonates. Limitation: Generalizability to men and non-Medicare populations. Conclusion: Risk for emergently treated hypocalcemia with denosumab increased with worsening CKD stage and was highest in DD patients and those with CKD-MBD. Primary Funding Source: U.S. Food and Drug Administration.

Benefits and Risks Associated With Statin Therapy for Primary Prevention in Old and Very Old Adults: Real-World Evidence From a Target Trial Emulation Study: Annals of Internal Medicine: Vol 177, No 6

Background: There is little consensus on using statins for primary prevention of cardiovascular diseases (CVDs) and all-cause mortality in adults aged 75 years or older due to the underrepresentation of this population in randomized controlled trials. Objective: To investigate the benefits and risks of using statins for primary prevention in old (aged 75 to 84 years) and very old (aged ≥85 years) adults. Design: Sequential target trial emulation comparing matched cohorts initiating versus not initiating statin therapy. Setting: Territory-wide public electronic medical records in Hong Kong. Participants: Persons aged 75 years or older who met indications for statin initiation from January 2008 to December 2015 were included. Participants with preexisting diagnosed CVDs at baseline, such as coronary heart disease (CHD), were excluded from the analysis. Among 69 981 eligible persons aged 75 to 84 years and 14 555 persons aged 85 years or older, 41 884 and 9457 had history of CHD equivalents (for example, diabetes) in the respective age groups. Intervention: Initiation of statin therapy. Measurements: Incidence of major CVDs (stroke, myocardial infarction, or heart failure), all-cause mortality, and major adverse events (myopathies and liver dysfunction). Results: Of 42 680 matched person-trials aged 75 to 84 years and 5390 matched person-trials aged 85 years or older (average follow-up, 5.3 years), 9676 and 1600 of them developed CVDs in each age group, respectively. Risk reduction for overall CVD incidence was found for initiating statin therapy in adults aged 75 to 84 years (5-year standardized risk reduction, 1.20% [95% CI, 0.57% to 1.82%] in the intention-to-treat [ITT] analysis; 5.00% [CI, 1.11% to 8.89%] in the per protocol [PP] analysis) and in those aged 85 years or older (ITT: 4.44% [CI, 1.40% to 7.48%]; PP: 12.50% [CI, 4.33% to 20.66%]). No significantly increased risks for myopathies and liver dysfunction were found in both age groups. Limitation: Unmeasured confounders, such as lifestyle factors of diet and physical activity, may exist. Conclusion: Reduction for CVDs after statin therapy were seen in patients aged 75 years or older without increasing risks for severe adverse effects. Of note, the benefits and safety of statin therapy were consistently found in adults aged 85 years or older. Primary Funding Source: Health Bureau, the Government of Hong Kong Special Administrative Region, China, and National Natural Science Foundation of China.

Excessive Alcohol Use and Alcohol Use Disorders: A Policy Brief of the American College of Physicians

Alcohol is used by more people in the United States than tobacco, electronic nicotine delivery systems, or illicit drugs. Several health conditions, including cancer, cardiovascular disease, and liver disease, are associated with excessive alcohol use and alcohol use disorder. Nearly 30 million people aged 12 years or older in the United States reported past-year alcohol use disorder in 2022, but—despite its prevalence—alcohol use disorder is undertreated. In this policy brief, the American College of Physicians outlines the health effects of excessive alcohol use and alcohol use disorder, calls for policy changes to increase the availability of treatment of alcohol use disorder and excessive alcohol use, and recommends alcohol-related public health interventions.

The Effect of Open-Label Semaglutide on Metabolic Dysfunction–Associated Steatotic Liver Disease in People With HIV