How Would You Treat This Patient With Pulmonary Embolism?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 175, No 8

Pulmonary embolism can be acutely life-threatening and is associated with long-term consequences such as recurrent venous thromboembolism and chronic thromboembolic pulmonary hypertension. In 2020, the American Society of Hematology published updated guidelines on the management of patients with venous thromboembolism. Here, a hematologist and a cardiology and vascular medicine specialist discuss these guidelines in the context of the care of a patient with pulmonary embolism. They discuss advanced therapies such as catheter-directed thrombolysis in the short-term management of patients with intermediate-risk disease, recurrence risk stratification at presentation, and ideal antithrombotic regimens for patients whose pulmonary embolism was associated with a transient minor risk factor.

Population Genomic Screening for Three Common Hereditary Conditions: A Cost-Effectiveness Analysis: Annals of Internal Medicine: Vol 176, No 5

Background: The cost-effectiveness of screening the U.S. population for Centers for Disease Control and Prevention (CDC) Tier 1 genomic conditions is unknown. Objective: To estimate the cost-effectiveness of simultaneous genomic screening for Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), and familial hypercholesterolemia (FH). Design: Decision analytic Markov model. Data Sources: Published literature. Target Population: Separate age-based cohorts (ages 20 to 60 years at time of screening) of racially and ethnically representative U.S. adults. Time Horizon: Lifetime. Perspective: U.S. health care payer. Intervention: Population genomic screening using clinical sequencing with a restricted panel of high-evidence genes, cascade testing of first-degree relatives, and recommended preventive interventions for identified probands. Outcome Measures: Incident breast, ovarian, and colorectal cancer cases; incident cardiovascular events; quality-adjusted survival; and costs. Results of Base-Case Analysis: Screening 100 000 unselected 30-year-olds resulted in 101 (95% uncertainty interval [UI], 77 to 127) fewer overall cancer cases and 15 (95% UI, 4 to 28) fewer cardiovascular events and an increase of 495 quality-adjusted life-years (QALYs) (95% UI, 401 to 757) at an incremental cost of $33.9 million (95% UI, $27.0 million to $41.1 million). The incremental cost-effectiveness ratio was $68 600 per QALY gained (95% UI, $41 800 to $88 900). Results of Sensitivity Analysis: Screening 30-, 40-, and 50-year-old cohorts was cost-effective in 99%, 88%, and 19% of probabilistic simulations, respectively, at a $100 000-per-QALY threshold. The test costs at which screening 30-, 40-, and 50-year-olds reached the $100 000-per-QALY threshold were $413, $290, and $166, respectively. Variant prevalence and adherence to preventive interventions were also highly influential parameters. Limitations: Population averages for model inputs, which were derived predominantly from European populations, vary across ancestries and health care environments. Conclusion: Population genomic screening with a restricted panel of high-evidence genes associated with 3 CDC Tier 1 conditions is likely to be cost-effective in U.S. adults younger than 40 years if the testing cost is relatively low and probands have access to preventive interventions. Primary Funding Source: National Human Genome Research Institute.

Paternal Preconception Diabetes Drugs and Birth Defects in Offspring: A Call for More Conclusive Study

Direct-to-Consumer Generic Drugs: A Maverick Approach or Another Exposure of Market Failures?

Telehealth Strategies for the Delivery of Maternal Health Care: A Rapid Review: Annals of Internal Medicine: Vol 175, No 9

Background: Telehealth strategies to supplement or replace in-person maternity care may affect maternal health outcomes. Purpose: To conduct a rapid review of the effectiveness and harms of telehealth strategies for maternal health care given the recent expansion of telehealth arising from the COVID-19 pandemic, and to produce an evidence map. Data Sources: Systematic searches of MEDLINE, the Cochrane Library, CINAHL, Embase, and Scopus for English-language studies (January 2015 to April 2022). Study Selection: Randomized controlled trials (RCTs) and observational studies of maternal care telehealth strategies versus usual care. Data Extraction: Dual data extraction and risk-of-bias assessment of studies, with disagreements resolved through consensus. Data Synthesis: 28 RCTs and 14 observational studies (n = 44 894) were included. Maternal telehealth interventions supplemented in-person care for most studies of mental health and diabetes during pregnancy, primarily resulting in similar, and sometimes better, clinical and patient-reported outcomes versus usual care. Supplementing in-person mental health care with phone- or web-based platforms or mobile applications resulted in similar or better mental health outcomes versus in-person care. A reduced-visit prenatal care schedule using telehealth to replace in-person general maternity care for low-risk pregnancies resulted in similar clinical outcomes and higher patient satisfaction versus usual care. Overall, telehealth strategies were heterogeneous and resulted in similar obstetric and patient satisfaction outcomes. Few studies addressed disparities, health equity, or harms. Limitations: Interventions varied, and evidence was inadequate for some clinical outcomes. Conclusion: Replacing or supplementing in-person maternal care with telehealth generally results in similar, and sometimes better, clinical outcomes and patient satisfaction compared with in-person care. The effect on access to care, health equity, and harms is unclear. Primary Funding Source: Patient-Centered Outcomes Research Institute. (PROSPERO: CRD42021276347)

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.

Maternal, Infant, and Child Health Outcomes Associated With the Special Supplemental Nutrition Program for Women, Infants, and Children: A Systematic Review: Annals of Internal Medicine: Vol 175, No 10

Background: The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) is intended to improve maternal and child health outcomes. In 2009, the WIC food package changed to better align with national nutrition recommendations. Purpose: To determine whether WIC participation was associated with improved maternal, neonatal–birth, and infant–child health outcomes or differences in outcomes by subgroups and WIC enrollment duration. Data Sources: Search (January 2009 to April 2022) included PubMed, Embase, CINAHL, ERIC, Scopus, PsycInfo, and the Cochrane Central Register of Controlled Trials. Study Selection: Included studies had a comparator of WIC-eligible nonparticipants or comparison before and after the 2009 food package change. Data Extraction: Paired team members independently screened articles for inclusion and evaluated risk of bias. Data Synthesis: We identified 20 observational studies. We found: moderate strength of evidence (SOE) that maternal WIC participation during pregnancy is likely associated with lower risk for preterm birth, low birthweight infants, and infant mortality; low SOE that maternal WIC participation may be associated with a lower likelihood of inadequate gestational weight gain, as well as increased well-child visits and childhood immunizations; and low SOE that child WIC participation may be associated with increased childhood immunizations. We found low SOE for differences in some outcomes by race and ethnicity but insufficient evidence for differences by WIC enrollment duration. We found insufficient evidence related to maternal morbidity and mortality outcomes. Limitation: Data are from observational studies with high potential for selection bias related to the choice to participate in WIC, and participation status was self-reported in most studies. Conclusion: Participation in WIC was likely associated with improved birth outcomes and lower infant mortality, and also may be associated with increased child preventive service receipt. Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42020222452)

Associations of Atrial Fibrillation After Noncardiac Surgery With Stroke, Subsequent Arrhythmia, and Death: A Cohort Study: Annals of Internal Medicine: Vol 175, No 8

Background: Postoperative atrial fibrillation (AF) after noncardiac surgery confers increased risks for ischemic stroke and transient ischemic attack (TIA). How outcomes for postoperative AF after noncardiac surgery compare with those for AF occurring outside of the operative setting is unknown. Objective: To compare the risks for ischemic stroke or TIA and other outcomes in patients with postoperative AF versus those with incident AF not associated with surgery. Design: Cohort study. Setting: Olmsted County, Minnesota. Participants: Patients with incident AF between 2000 and 2013. Measurements: Patients were categorized as having AF occurring within 30 days of a noncardiac surgery (postoperative AF) or having AF unrelated to surgery (nonoperative AF). Results: Of 4231 patients with incident AF, 550 (13%) had postoperative AF as their first-ever documented AF presentation. Over a mean follow-up of 6.3 years, 486 patients had an ischemic stroke or TIA and 2462 had subsequent AF; a total of 2565 deaths occurred. The risk for stroke or TIA was similar between those with postoperative AF and nonoperative AF (absolute risk difference [ARD] at 5 years, 0.1% [95% CI, −2.9% to 3.1%]; hazard ratio [HR], 1.01 [CI, 0.77 to 1.32]). A lower risk for subsequent AF was seen for patients with postoperative AF (ARD at 5 years, −13.4% [CI, −17.8% to −9.0%]; HR, 0.68 [CI, 0.60 to 0.77]). Finally, no difference was seen for cardiovascular death or all-cause death between patients with postoperative AF and nonoperative AF. Limitation: The population consisted predominantly of White patients; caution should be used when extrapolating the results to more racially diverse populations. Conclusion: Postoperative AF after noncardiac surgery is associated with similar risk for thromboembolism compared with nonoperative AF. Our findings have potentially important implications for the early postsurgical and subsequent management of postoperative AF. Primary Funding Source: National Institute on Aging.

Comparing Racial Differences in Emphysema Prevalence Among Adults With Normal Spirometry: A Secondary Data Analysis of the CARDIA Lung Study

Background: Computed tomography (CT) imaging complements spirometry and may provide insight into racial disparities in respiratory health. Objective: To determine the difference in emphysema prevalence between Black and White adults with different measures of normal spirometry results. Design: Observational study using clinical data and spirometry from the CARDIA (Coronary Artery Risk Development in Young Adults) study obtained in 2015 to 2016 and CT scans done in 2010 to 2011. Setting: 4 U.S. centers. Participants: Population-based sample of Black and White adults. Measurements: Self-identified race and visually identified emphysema on CT in participants with different measures of “normal” spirometry results, calculated using standard race-specific and race-neutral reference equations. Results: A total of 2674 participants (485 Black men, 762 Black women, 659 White men, and 768 White women) had both a CT scan and spirometry available for analysis. Among participants with a race-specific FEV1 between 80% and 99% of predicted, 6.5% had emphysema. In this group, emphysema prevalence was 3.9-fold (95% CI, 2.1- to 7.1-fold; 15.5% vs. 4.0%) higher among Black men than White men and 1.9-fold (CI, 1.0- to 3.8-fold; 6.6% vs. 3.4%) higher among Black women than White women. Among participants with a race-specific FEV1 between 100% and 120% of predicted, 4.0% had emphysema. In this category, Black men had a 6.4-fold (CI, 2.2- to 18.7-fold; 13.9% vs. 2.2%) higher prevalence of emphysema than White men, whereas Black and White women had a similar prevalence of emphysema (2.6% and 2.0%, respectively). The use of race-neutral equations to identify participants with an FEV1 percent predicted between 80% and 120% attenuated racial differences in emphysema prevalence among men and eliminated racial differences among women. Limitation: No CT scans were obtained during the most recent study visit (2015 to 2016) when spirometry was done. Conclusion: Emphysema is often present before spirometry findings become abnormal, particularly among Black men. Reliance on spirometry alone to differentiate lung health from lung disease may result in the underrecognition of impaired respiratory health and exacerbate racial disparities. Primary Funding Source: National Institutes of Health.