Colorectal Cancer Screening Completion and Yield in Patients Aged 45 to 50 Years: An Observational Study: Annals of Internal Medicine: Vol 177, No 12

Background: Guidelines now recommend initiating colorectal cancer (CRC) screening at age 45 years rather than 50 years, but little is known about screening completion and yield among people aged 45 to 49 years. Objective: To evaluate fecal immunochemical test (FIT) completion and yield in patients aged 45 to 49 versus 50 years. Design: Retrospective cohort study. Setting: Kaiser Permanente Northern California, Washington, and Colorado. Patients: Those distributed a FIT kit during January to September 2022. Measurements: FIT completion within 3 months, FIT positivity, receipt of colonoscopy within 3 months after a positive FIT result, and colonoscopy yield. Results: A total of 267 732 FIT kits were distributed: 213 928 (79.9%) to patients aged 45 to 49 years, and 53 804 (20.1%) to those aged 50 years. Overall, FIT completion was slightly higher in patients aged 45 to 49 years (38.9% vs. 37.5%; adjusted risk ratio [aRR], 1.05 [95% CI, 1.04 to 1.06]), although at Colorado, those aged 45 to 49 years were substantially less likely to complete a FIT (30.7% vs. 40.2%; aRR, 0.77 [CI, 0.73 to 0.80]). Overall, FIT positivity was lower in patients aged 45 to 49 years (3.6% vs. 4.0%; aRR, 0.91 [CI, 0.84 to 0.98]), and receipt of colonoscopy after a positive FIT result was similar between groups (64.9% vs. 67.4%; aRR, 1.00 [CI, 0.94 to 1.05]). Adenoma detection was lower in the younger group (58.8% vs. 67.7%; aRR, 0.88 [CI, 0.83 to 0.95]). Yields were similar for adenoma with advanced histology (13.2% vs. 15.9%; aRR, 0.86 [CI, 0.69 to 1.07]), polyp with high-grade dysplasia (3.4% vs. 5.1%; aRR, 0.68 [CI, 0.44 to 1.04]), sessile serrated lesion (10.3% vs. 11.7%; aRR, 0.92 [CI, 0.71 to 1.21]), and CRC (2.8% vs. 2.7%; aRR, 1.10 [CI, 0.62 to 1.96]). Limitation: The small number of neoplasia events contributed to wide CIs. Conclusion: Similar FIT completion and yield rates in people aged 45 to 50 years support initiation of CRC screening at age 45 years. Primary Funding Source: Kaiser Permanente Sidney R. Garfield Memorial Fund.

Body Surface Area in Obesity: Clinical Challenges and Call for Improvements

Severe Maternal and Neonatal Morbidity Among Gestational Carriers: A Cohort Study: Annals of Internal Medicine: Vol 177, No 11

Background: Use of a gestational (“surrogate”) carrier is increasingly common. Risk for maternal and neonatal adversity is largely unknown in this birthing population. Objective: To determine the risk for severe maternal morbidity (SMM) and severe neonatal morbidity (SNM) in gestational carriers. Design: Population-based cohort study. Setting: All of Ontario, Canada. Participants: All singleton births at more than 20 weeks’ gestation, from 2012 to 2021. Measurements: Exposure was type of conception, namely, gestational carriage (main exposure), unassisted conception (comparison group 1), and in vitro fertilization (IVF) (comparison group 2). Main composite outcomes were SMM and SNM. Modified Poisson regression models generated weighted relative risks (wRRs) using propensity score–based overlap weighting. Secondary outcomes included hypertensive disorders of pregnancy, cesarean delivery, preterm birth, and postpartum hemorrhage. Results: Of all eligible singleton births, 846 124 (97.6%) were by unassisted conception, 16 087 (1.8%) by IVF, and 806 (0.1%) by gestational carriage. Respective risks for SMM were 2.3%, 4.3%, and 7.8%. The wRRs were 3.30 (95% CI, 2.59 to 4.20) comparing gestational carriage with unassisted conception and 1.86 (CI, 1.36 to 2.55) comparing gestational carriage with IVF. Respective risks for SNM were 5.9%, 8.9%, and 6.6%, generating wRRs of 1.20 (CI, 0.92 to 1.55) for gestational carriage versus unassisted conception and 0.81 (CI, 0.61 to 1.08) for gestational carriage versus IVF. Hypertensive disorders, postpartum hemorrhage, and preterm birth at less than 37 weeks were also significantly higher contrasting gestational carriers to either comparison group. Limitation: Absence of information about indications for choosing a gestational carrier, and oocyte or sperm donor source. Conclusion: Among singleton births of more than 20 weeks’ gestation, a higher risk for SMM and adverse pregnancy outcomes was seen among gestational carriers compared with women who conceived with and without assistance. Although gestational carriage was associated with preterm birth, there was less clear evidence of severe neonatal morbidity. Potential mechanisms for higher maternal morbidity among gestational carriers require elucidation, alongside developing special care plans for gestational carriers. Primary Funding Source: The Canadian Institutes of Health Research.

Heterogeneity of Sepsis Presentations and Mortality Rates

Viral Load–Based Prediction of Hepatocellular Carcinoma Risk in Noncirrhotic Patients With Chronic Hepatitis B: A Multinational Study for the Development and External Validation of a New Prognostic Model: Annals of Internal Medicine: Vol 177, No 10

Background: A nonlinear association between serum hepatitis B virus (HBV) DNA levels and hepatocellular carcinoma (HCC) risk has been suggested in patients with chronic hepatitis B (CHB). Objective: To develop and externally validate a prognostic model for HCC risk in noncirrhotic adult patients with CHB and no notable alanine aminotransferase (ALT) elevation. Design: Multinational cohort study. Setting: A community-based cohort in Taiwan (REVEAL-HBV [Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus]; REACH-B [Risk Estimation for HCC in CHB] model cohort) and 8 hospital-based cohorts from Korea and Hong Kong (GAG-HCC [Guide with Age, Gender, HBV DNA-HCC] and CU-HCC [Chinese University-HCC] cohorts). Participants: Model development: 6949 patients with CHB from a Korean hospital-based cohort. External validation: 7429 patients with CHB combined from the Taiwanese cohort and 7 cohorts from Korea and Hong Kong. Measurements: Incidence of HCC. Results: Over median follow-up periods of 10.0 and 12.2 years, the derivation and validation cohorts identified 435 and 467 incident HCC cases, respectively. Baseline HBV DNA level was one of the strongest predictors of HCC development, demonstrating a nonlinear parabolic association in both cohorts, with moderate viral loads (around 6 log10 IU/mL) showing the highest HCC risk. Additional predictors included in the new model (Revised REACH-B) were age, sex, platelet count, ALT levels, and positive hepatitis B e antigen result. The model exhibited satisfactory discrimination and calibration, with c-statistics of 0.844 and 0.813 in the derivation and validation cohorts with multiple imputation, respectively. The model yielded a greater positive net benefit compared with other strategies in the 0% to 18% threshold. Limitation: Validation in cohorts of other races and receiving antiviral treatment was lacking. Conclusion: Our new prognostic model, based on the nonlinear association between HBV viral loads and HCC risk, provides a valuable tool for predicting and stratifying HCC risk in noncirrhotic patients with CHB who are not currently indicated for antiviral treatment. Primary Funding Source: Korean government.

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.

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.