Adenoma Detection Rate and Colorectal Cancer Risk in Fecal Immunochemical Test Screening Programs: An Observational Cohort Study: Annals of Internal Medicine: Vol 176, No 3

Background: Colorectal cancer (CRC) screening programs based on fecal immunochemical tests (FITs) represent the standard of care for population-based interventions. Their benefit depends on the identification of neoplasia at colonoscopy after FIT positivity. Colonoscopy quality measured by adenoma detection rate (ADR) may affect screening program effectiveness. Objective: To examine the association between ADR and postcolonoscopy CRC (PCCRC) risk in a FIT-based screening program. Design: Retrospective population-based cohort study. Setting: Fecal immunochemical test–based CRC screening program between 2003 and 2021 in northeastern Italy. Patients: All patients with a positive FIT result who had a colonoscopy were included. Measurements: The regional cancer registry supplied information on any PCCRC diagnosed between 6 months and 10 years after colonoscopy. Endoscopists' ADR was categorized into 5 groups (20% to 39.9%, 40% to 44.9%, 45% to 49.9%, 50% to 54.9%, and 55% to 70%). To examine the association of ADR with PCCRC incidence risk, Cox regression models were fitted to estimate hazard ratios (HRs) and 95% CIs. Results: Of the 110 109 initial colonoscopies, 49 626 colonoscopies done by 113 endoscopists between 2012 and 2017 were included. After 328 778 person-years follow-up, 277 cases of PCCRC were diagnosed. Mean ADR was 48.3% (range, 23% and 70%). Incidence rates of PCCRC from lowest to highest ADR group were 13.13, 10.61, 7.60, 6.01, and 5.78 per 10 000 person-years. There was a significant inverse association between ADR and PCCRC incidence risk, with a 2.35-fold risk increase (95% CI, 1.63 to 3.38) in the lowest group compared with the highest. The adjusted HR for PCCRC associated with 1% increase in ADR was 0.96 (CI, 0.95 to 0.98). Limitation: Adenoma detection rate is partly determined by FIT positivity cutoff; exact values may vary in different settings. Conclusion: In a FIT-based screening program, ADR is inversely associated with PCCRC incidence risk, mandating appropriate colonoscopy quality monitoring in this setting. Increasing endoscopists' ADR may significantly reduce PCCRC risk. Primary Funding Source: None.

Would You Recommend a Statin to This Patient for Primary Prevention of Cardiovascular Disease?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 175, No 6

Cardiovascular disease (CVD) is the leading cause of death in the United States. Hypercholesterolemia is a principal modifiable risk factor for the primary prevention of CVD. In addition to lifestyle modification, statins are an important tool to reduce risk for CVD in selected patients. A useful strategy to identify candidates for statins is to estimate the 10-year risk for CVD through the use of a validated risk calculator. Commonly used calculators include the Framingham risk score and the pooled cohort equation. Multiple randomized controlled trials have shown that statins reduce the risk for CVD in patients without known CVD. Two recent guidelines have proposed an approach to the use of statins in primary prevention of CVD. The American College of Cardiology/American Heart Association and the U.S. Department of Veterans Affairs guidelines form the basis for this discussion. The guidelines differ on the use of advanced testing to modify the 10-year CVD risk estimate and on the need for low-density lipoprotein cholesterol targets to establish the efficacy of statins. Advanced testing with coronary artery calcium measurement may be helpful for patients who are potentially eligible for statin therapy but who are uncertain if they wish to take a statin. In this paper, 2 experts, a preventive cardiologist and a general internist, discuss their approach to the use of statins for primary prevention of CVD and how they would apply the guidelines to an individual patient.

Benefits and Risks Associated With Continuation of Anti–Tumor Necrosis Factor After 24 Weeks of Pregnancy in Women With Inflammatory Bowel Disease: A Nationwide Emulation Trial: Annals of Internal Medicine: Vol 175, No 10

Background: Continuation of biologics for inflammatory disorders during pregnancy is still a difficult decision. Many women with inflammatory bowel diseases (IBDs) stop anti–tumor necrosis factor (anti-TNF) treatment after 24 weeks. Objective: To evaluate the benefits and risks of anti-TNF continuation after 24 weeks of pregnancy for mothers with IBD and their offspring. Design: Target trial emulation between 2010 and 2020. Setting: Nationwide population-based study using the Système National des Données de Santé. Patients: All pregnancies with birth exposed to anti-TNF between conception and 24 weeks of pregnancy in women with IBD. Intervention: Continuation of anti-TNF after 24 weeks of pregnancy. Measurements: Occurrence of maternal IBD relapse up to 6 months after pregnancy, adverse pregnancy outcomes, and serious infections in the offspring during the first 5 years of life was compared according to anti-TNF continuation after 24 weeks of pregnancy using inverse probability–weighted marginal models. Results: A total of 5293 pregnancies were included; among them, anti-TNF treatment was discontinued before 24 weeks for 2890 and continued beyond 24 weeks for 2403. Continuation of anti-TNF was associated with decreased frequencies of maternal IBD relapse (35.8% vs. 39.0%; adjusted risk ratio [aRR], 0.93 [95% CI, 0.86 to 0.99]) and prematurity (7.6% vs. 8.9%; aRR, 0.82 [CI, 0.68 to 0.99]). No difference according to anti-TNF continuation was found regarding stillbirths (0.4% vs. 0.2%; aRR, 2.16 [CI, 0.64 to 7.81]), small weight for gestational age births (13.1% vs. 12.9%; aRR, 1.01 [CI, 0.88 to 1.17]), and serious infections in the offspring (54.2 vs. 50.2 per 1000 person-years; adjusted hazard ratio, 1.08 [CI, 0.94 to 1.25]). Limitation: Algorithms rather than clinical data were used to identify patients with IBD, pregnancies, and serious infections. Conclusion: Continuation of anti-TNF after 24 weeks of pregnancy appears beneficial regarding IBD activity and prematurity, while not affecting neonatal outcomes and serious infections in the offspring. Primary Funding Source: None.

Periconception Red Blood Cell Folate and Offspring Congenital Heart Disease: Nested Case–Control and Mendelian Randomization Studies: Annals of Internal Medicine: Vol 175, No 9

Background: Periconception folic acid supplementation has been suggested to protect against congenital heart disease (CHD), but the association between maternal red blood cell (RBC) folate, the gold-standard biomarker of folate exposure, and subsequent offspring CHD risk is lacking. Objective: To quantify the association between periconception maternal RBC folate and offspring CHD risk. Design: Prospective, nested, case–control study and 1-sample Mendelian randomization. (ClinicalTrials.gov: NCT02737644) Setting: 29 maternity institutions in 12 districts of Greater Shanghai, China. Participants: All 197 mothers of offspring with CHD and 788 individually matched mothers of unaffected offspring from the SPCC (Shanghai Preconception Cohort). Measurements: Maternal RBC folate was measured before or at early pregnancy. Odds ratios [ORs] were estimated using conditional logistic regression after adjustment for covariates. Mendelian randomization was done using the methylenetetrahydrofolate reductase (MTHFR) C677T as the genetic instrument. Results: Case patients had lower median maternal RBC folate concentrations than control participants (714 nmol/L [interquartile range, 482 to 1008 nmol/L] vs. 788 nmol/L [557 to 1094 nmol/L]). Maternal RBC folate concentrations were inversely associated with offspring CHD (adjusted OR per 100 nmol/L, 0.93 [95% CI, 0.89 to 0.99]). The adjusted OR for mothers with periconception RBC folate of 906 nmol/L or more (vs. <906 nmol/L) was 0.61 (CI, 0.40 to 0.93). Mendelian randomization showed that each 100-nmol increase in maternal RBC folate concentrations was significantly associated with reduced offspring CHD risk (OR, 0.75 [CI, 0.61 to 0.92]). Limitation: Potential confounding due to unmeasured covariates in the nested case–control study. Conclusion: Higher maternal RBC folate is associated with reduced offspring CHD risk. For primary CHD prevention, higher target RBC folate levels than currently recommended for neural tube defect prevention may be needed and warrant further study. Primary Funding Source: National Key Research and Development Program of China, National Natural Science Foundation of China, China Postdoctoral Science Foundation, and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences.

Increasing Motivation for Lifestyle Change Is Not Enough to Treat Obesity

How the Gender Wage Gap for Primary Care Physicians Differs by Compensation Approach: A Microsimulation Study: Annals of Internal Medicine: Vol 175, No 8

Background: The physician gender wage gap may be due, in part, to productivity-based compensation models that undervalue female practice patterns. Objective: To determine how primary care physician (PCP) compensation by gender differs when applying existing productivity-based and alternative compensation models. Design: Microsimulation. Setting: 2016 to 2019 national clinical registry of 1222 primary care practices. Participants: Male and female PCPs matched on specialty, years since medical school graduation, practice site, and sessions worked. Measurements: Net annual, full-time-equivalent compensation for male versus female PCPs, under productivity-based fee-for-service, panel size–based capitation without or with risk adjustment, and hybrid payment models. Microsimulation inputs included patient and visit characteristics and overhead expenses. Results: Among 1435 matched male (n = 881) and female (n = 554) PCPs, female PCP panels included patients who were, on average, younger, had lower diagnosis-based risk scores, were more often female, and were more often uninsured or insured by Medicaid rather than by Medicare. Under productivity-based payment, female PCPs earned a median of $58 829 (interquartile range [IQR], $39 553 to $120 353; 21%) less than male PCPs. This gap was similar under capitation ($58 723 [IQR, $42 141 to $140 192]). It was larger under capitation risk-adjusted for age alone ($74 695 [IQR, $42 884 to $152 423]), for diagnosis-based scores alone ($114 792 [IQR, $49 080 to $215 326] and $89 974 [IQR, $26 175 to $173 760]), and for age-, sex-, and diagnosis-based scores ($83 438 [IQR, $28 927 to $129 414] and $66 195 [IQR, $11 899 to $96 566]). The gap was smaller and nonsignificant under capitation risk-adjusted for age and sex ($36 631 [IQR, $12 743 to $73 898]). Limitation: Panel attribution based on office visits. Conclusion: The gender wage gap varied by compensation model, with capitation risk-adjusted for patient age and sex resulting in a smaller gap. Future models might better align with primary care effort and outcomes. Primary Funding Source: None.

Quantifying Individual-Level Inaccuracy in Glomerular Filtration Rate Estimation: A Cross-Sectional Study: Annals of Internal Medicine: Vol 175, No 8

Background: Although the population-level differences between estimated glomerular filtration rate (eGFR) and measured glomerular filtration rate (mGFR) are well recognized, the magnitude and potential clinical implications of individual-level differences are unknown. Objective: To quantify the magnitude and consequences of the individual-level differences between mGFRs and eGFRs. Design: Cross-sectional study. Setting: Four U.S. community-based epidemiologic cohort studies with mGFR. Patients: 3223 participants in 4 studies. Measurements: The GFRs were measured using urinary iothalamate and plasma iohexol clearance; the eGFR was calculated from serum creatinine concentration alone (eGFRCR) and with cystatin C. All GFR results are presented as mL/min/1.73 m2. Results: The participants' mean age was 59 years; 32% were Black, 55% were women, and the mean mGFR was 68. The population-level differences between mGFR and eGFRCR were small; the median difference (mGFR − eGFR) was −0.6 (95% CI, −1.2 to −0.2); however, the individual-level differences were large. At an eGFRCR of 60, 50% of mGFRs ranged from 52 to 67, 80% from 45 to 76, and 95% from 36 to 87. At an eGFRCR of 30, 50% of mGFRs ranged from 27 to 38, 80% from 23 to 44, and 95% from 17 to 54. Substantial disagreement in chronic kidney disease staging by mGFR and eGFRCR was present. Among those with eGFRCR of 45 to 59, 36% had mGFR greater than 60 whereas 20% had mGFR less than 45; among those with eGFRCR of 15 to 29, 30% had mGFR greater than 30 and 5% had mGFR less than 15. The eGFR based on cystatin C did not provide substantial improvement. Limitation: Single measurement of mGFR and serum markers without short-term replicates Conclusion: A substantial individual-level discrepancy exists between the mGFR and the eGFR. Laboratories reporting eGFR should consider including the extent of this uncertainty to avoid misinterpretation of eGFR as an mGFR replacement. Primary Funding Source: National Institutes of Health.

Heterogeneity in Obesity Prevalence Among Asian American Adults

Background: Obesity increases the risk for metabolic and cardiovascular disease, and this risk occurs at lower body mass index (BMI) thresholds in Asian adults than in White adults. The degree to which obesity prevalence varies across heterogeneous Asian American subgroups is unclear because most obesity estimates combine all Asian Americans into a single group. Objective: To quantify obesity prevalence in Asian American subgroups among U.S. adults using both standard BMI categorizations and categorizations tailored to Asian populations. Design: Cross-sectional. Setting: United States, 2013 to 2020. Participants: The analytic sample included 2 882 158 adults aged 18 years or older in the U.S. Behavioral Risk Factor Surveillance System surveys (2013 to 2020). Participants self-identified as non-Hispanic White ([NHW] n = 2 547 965); non-Hispanic Black ([NHB] n = 263 136); or non-Hispanic Asian ([NHA] n = 71 057), comprising Asian Indian (n = 13 916), Chinese (n = 11 686), Filipino (n = 11 815), Japanese (n = 12 473), Korean (n = 3634), and Vietnamese (n = 2618) Americans. Measurements: Obesity prevalence adjusted for age and sex calculated using both standard BMI thresholds (≥30 kg/m2) and BMI thresholds modified for Asian adults (≥27.5 kg/m2), based on self-reported height and weight. Results: Adjusted obesity prevalence (by standard categorization) was 11.7% (95% CI, 11.2% to 12.2%) in NHA, 39.7% (CI, 39.4% to 40.1%) in NHB, and 29.4% (CI, 29.3% to 29.5%) in NHW participants; the prevalence was 16.8% (CI, 15.2% to 18.5%) in Filipino, 15.3% (CI, 13.2% to 17.5%) in Japanese, 11.2% (CI, 10.2% to 12.2%) in Asian Indian, 8.5% (CI, 6.8% to 10.5%) in Korean, 6.5% (CI, 5.5% to 7.5%) in Chinese, and 6.3% (CI, 5.1% to 7.8%) in Vietnamese Americans. The prevalence using modified criteria (BMI ≥27.5 kg/m2) was 22.4% (CI, 21.8% to 23.1%) in NHA participants overall and 28.7% (CI, 26.8% to 30.7%) in Filipino, 26.7% (CI, 24.1% to 29.5%) in Japanese, 22.4% (CI, 21.1% to 23.7%) in Asian Indian, 17.4% (CI, 15.2% to 19.8%) in Korean, 13.6% (CI, 11.7% to 15.9%) in Vietnamese, and 13.2% (CI, 12.0% to 14.5%) in Chinese Americans. Limitation: Body mass index estimates rely on self-reported data. Conclusion: Substantial heterogeneity in obesity prevalence exists among Asian American subgroups in the United States. Future studies and public health efforts should consider this heterogeneity. Primary Funding Source: National Heart, Lung, and Blood Institute.

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Comparative Effectiveness and Safety Between Apixaban, Dabigatran, Edoxaban, and Rivaroxaban Among Patients With Atrial Fibrillation: A Multinational Population-Based Cohort Study: Annals of Internal Medicine: Vol 175, No 11

Background: Current guidelines recommend using direct oral anticoagulants (DOACs) over warfarin in patients with atrial fibrillation (AF), but head-to-head trial data do not exist to guide the choice of DOAC. Objective: To do a large-scale comparison between all DOACs (apixaban, dabigatran, edoxaban, and rivaroxaban) in routine clinical practice. Design: Multinational population-based cohort study. Setting: Five standardized electronic health care databases, which covered 221 million people in France, Germany, the United Kingdom, and the United States. Participants: Patients who were newly diagnosed with AF from 2010 through 2019 and received a new DOAC prescription. Measurements: Database-specific hazard ratios (HRs) of ischemic stroke or systemic embolism, intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), and all-cause mortality between DOACs were estimated using a Cox regression model stratified by propensity score and pooled using a random-effects model. Results: A total of 527 226 new DOAC users met the inclusion criteria (apixaban, n = 281 320; dabigatran, n = 61 008; edoxaban, n = 12 722; and rivaroxaban, n = 172 176). Apixaban use was associated with lower risk for GIB than use of dabigatran (HR, 0.81 [95% CI, 0.70 to 0.94]), edoxaban (HR, 0.77 [CI, 0.66 to 0.91]), or rivaroxaban (HR, 0.72 [CI, 0.66 to 0.79]). No substantial differences were observed for other outcomes or DOAC–DOAC comparisons. The results were consistent for patients aged 80 years or older. Consistent associations between lower GIB risk and apixaban versus rivaroxaban were observed among patients receiving the standard dose (HR, 0.72 [CI, 0.64 to 0.82]), those receiving a reduced dose (HR, 0.68 [CI, 0.61 to 0.77]), and those with chronic kidney disease (HR, 0.68 [CI, 0.59 to 0.77]). Limitation: Residual confounding is possible. Conclusion: Among patients with AF, apixaban use was associated with lower risk for GIB and similar rates of ischemic stroke or systemic embolism, ICH, and all-cause mortality compared with dabigatran, edoxaban, and rivaroxaban. This finding was consistent for patients aged 80 years or older and those with chronic kidney disease, who are often underrepresented in clinical trials. Primary Funding Source: None.