Potential Medicare Part D Savings on Generic Drugs From the Mark Cuban Cost Plus Drug Company

Ethical Considerations in Precision Medicine and Genetic Testing in Internal Medicine Practice: A Position Paper From the American College of Physicians

This American College of Physicians position paper aims to inform ethical decision making for the integration of precision medicine and genetic testing into clinical care. Although the positions are primarily intended for practicing physicians, they may apply to other health care professionals and can also inform how health care systems, professional schools, and residency programs integrate genomics into educational and clinical settings. Addressing the challenges of precision medicine and genetic testing will guide ethical and responsible implementation to improve health outcomes.

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.

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)

Effect of Molnupiravir on Biomarkers, Respiratory Interventions, and Medical Services in COVID-19: A Randomized, Placebo-Controlled Trial: Annals of Internal Medicine: Vol 175, No 8

Background: In the MOVe-OUT trial, molnupiravir showed a clinically meaningful reduction in the risk for hospitalization or death in adults with mild to moderate COVID-19 and risk factors for progression to severe disease. Objective: To identify other potential clinical benefits of molnupiravir versus placebo. Design: Secondary analysis of the randomized, double-blind, placebo-controlled phase 3 component of MOVe-OUT. (ClinicalTrials.gov: NCT04575597) Setting: 107 sites globally. Participants: 1433 nonhospitalized adults aged 18 years or older with mild to moderate COVID-19. Intervention: Molnupiravir, 800 mg, or placebo every 12 hours for 5 days. Measurements: Changes from baseline in C-reactive protein (CRP) concentration and oxygen saturation (Spo 2), need for respiratory interventions (including invasive mechanical ventilation), and need for medical services in all randomly assigned participants through day 29, and need for respiratory interventions and time to discharge in the subgroup of participants who were hospitalized after randomization. Results: Participants receiving molnupiravir showed faster normalization of CRP and Spo 2, with improvements observed on day 3 of therapy, compared with placebo. Molnupiravir-treated participants had a decreased need for respiratory interventions versus placebo-treated participants (relative risk reduction [RRR], 34.3% [95% CI, 4.3% to 54.9%]), with similar findings in participants who were hospitalized after randomization (RRR, 21.3% [CI, 0.2% to 38.0%]). Hospitalized participants who received molnupiravir were discharged a median of 3 days before those who received placebo. Acute care visits (7.2% vs. 10.6%; RRR, 32.1% [CI, 4.4% to 51.7%]) and COVID-19–related acute care visits (6.6% vs. 10.0%; RRR, 33.8% [CI, 5.6% to 53.6%]) were less frequent in molnupiravir- versus placebo-treated participants. Limitations: Some analyses were performed post hoc. Longer-term benefits of molnupiravir therapy were not evaluated. Participants were not immunized against SARS-CoV-2. Conclusion: The findings suggest there are additional important clinical benefits of molnupiravir beyond reduction in hospitalization or death. Primary Funding Source: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.

Health Equity and Critical Care Survivorship: Where Do We Go From Here?

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.

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)