Faculty Bibliography

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STUDY OBJECTIVES/OBJECTIVE:Obstructive sleep apnea (OSA) has been associated with more severe acute coronavirus disease-2019 (COVID-19) outcomes. We assessed OSA as a potential risk factor for Post-Acute Sequelae of SARS-CoV-2 (PASC). METHODS:We assessed the impact of preexisting OSA on the risk for probable PASC in adults and children using electronic health record data from multiple research networks. Three research networks within the REsearching COVID to Enhance Recovery initiative (PCORnet Adult, PCORnet Pediatric, and the National COVID Cohort Collaborative [N3C]) employed a harmonized analytic approach to examine the risk of probable PASC in COVID-19-positive patients with and without a diagnosis of OSA prior to pandemic onset. Unadjusted odds ratios (ORs) were calculated as well as ORs adjusted for age group, sex, race/ethnicity, hospitalization status, obesity, and preexisting comorbidities. RESULTS:Across networks, the unadjusted OR for probable PASC associated with a preexisting OSA diagnosis in adults and children ranged from 1.41 to 3.93. Adjusted analyses found an attenuated association that remained significant among adults only. Multiple sensitivity analyses with expanded inclusion criteria and covariates yielded results consistent with the primary analysis. CONCLUSIONS:Adults with preexisting OSA were found to have significantly elevated odds of probable PASC. This finding was consistent across data sources, approaches for identifying COVID-19-positive patients, and definitions of PASC. Patients with OSA may be at elevated risk for PASC after SARS-CoV-2 infection and should be monitored for post-acute sequelae.

Biological age may be estimated by proteomic aging clocks (PACs). Previous published PACs were constructed either in smaller studies or mainly in White individuals, and they used proteomic measures from only one-time point. In the Atherosclerosis Risk in Communities (ARIC) study of about 12,000 persons followed for 30 years (around 75% White, 25% Black), we created de novo PACs and compared their performance to published PACs at two different time points. We measured 4,712 plasma proteins by SomaScan in 11,761 midlife participants, aged 46-70 years (1990-92), and 5,183 late-life pariticpants, aged 66-90 years (2011-13). All proteins were log2-transformed to correct for skewness. We created de novo PACs by training them against chronological age using elastic net regression in two-thirds of healthy participants in midlife and late life and compared their performance to three published PACs. We estimated age acceleration (by regressing each PAC on chronological age) and its change from midlife to late life. We examined their associations with mortality from all-cause, cardiovascular disease (CVD), cancer, and lower respiratory disease (LRD) using Cox proportional hazards regression in all remaining participants irrespective of health. The model was adjusted for chronological age, smoking, body mass index (BMI), and other confounders. The ARIC PACs had a slightly stronger correlation with chronological age than published PACs in healthy participants at each time point. Associations with mortality were similar for the ARIC and published PACs. For late-life and midlife age acceleration for the ARIC PACs, respectively, hazard ratios (HRs) per one standard deviation were 1.65 and 1.38 (both p<0.001) for all-cause mortality, 1.37 and 1.20 (both p<0.001) for CVD mortality, 1.21 (p=0.03) and 1.04 (p=0.19) for cancer mortality, and 1.46 and 1.68 (both p<0.001) for LRD mortality. For the change in age acceleration, HRs for all-cause, CVD, and LRD mortality were comparable to those observed for late-life age acceleration. The association between the change in age acceleration and cancer mortality was insignificant. In this prospective study, the ARIC and published PACs were similarly associated with an increased risk of mortality and advanced testing in relation to various age-related conditions in future studies is suggested.

BACKGROUND:We sought to develop a proteomics-based risk model for lung cancer and evaluate its risk-discriminatory performance in comparison with a smoking-based risk model (PLCOm2012) and a commercially available autoantibody biomarker test. METHODS:We designed a case-control study nested in 6 prospective cohorts, including 624 lung cancer participants who donated blood samples at most 3 years prior to lung cancer diagnosis and 624 smoking-matched cancer free participants who were assayed for 302 proteins. We used 470 case-control pairs from 4 cohorts to select proteins and train a protein-based risk model. We subsequently used 154 case-control pairs from 2 cohorts to compare the risk-discriminatory performance of the protein-based model with that of the Early Cancer Detection Test (EarlyCDT)-Lung and the PLCOm2012 model using receiver operating characteristics analysis and by estimating models' sensitivity. All tests were 2-sided. RESULTS:The area under the curve for the protein-based risk model in the validation sample was 0.75 (95% confidence interval [CI] = 0.70 to 0.81) compared with 0.64 (95% CI = 0.57 to 0.70) for the PLCOm2012 model (Pdifference = .001). The EarlyCDT-Lung had a sensitivity of 14% (95% CI = 8.2% to 19%) and a specificity of 86% (95% CI = 81% to 92%) for incident lung cancer. At the same specificity of 86%, the sensitivity for the protein-based risk model was estimated at 49% (95% CI = 41% to 57%) and 30% (95% CI = 23% to 37%) for the PLCOm2012 model. CONCLUSION/CONCLUSIONS:Circulating proteins showed promise in predicting incident lung cancer and outperformed a standard risk prediction model and the commercialized EarlyCDT-Lung.

IMPORTANCE:Presentation to emergency departments (EDs) with high levels of pediatric readiness is associated with improved pediatric survival. However, it is unclear whether children of all races and ethnicities benefit equitably from increased levels of such readiness. OBJECTIVE:To evaluate the association of ED pediatric readiness with in-hospital mortality among children of different races and ethnicities with traumatic injuries or acute medical emergencies. DESIGN, SETTING, AND PARTICIPANTS:This cohort study of children requiring emergency care in 586 EDs across 11 states was conducted from January 1, 2012, through December 31, 2017. Eligible participants included children younger than 18 years who were hospitalized for an acute medical emergency or traumatic injury. Data analysis was conducted between November 2022 and April 2023. EXPOSURE:Hospitalization for acute medical emergency or traumatic injury. MAIN OUTCOMES AND MEASURES:The primary outcome was in-hospital mortality. ED pediatric readiness was measured through the weighted Pediatric Readiness Score (wPRS) from the 2013 National Pediatric Readiness Project assessment and categorized by quartile. Multivariable, hierarchical, mixed-effects logistic regression was used to evaluate the association of race and ethnicity with in-hospital mortality. RESULTS:The cohort included 633 536 children (median [IQR] age 4 [0-12] years]). There were 557 537 children (98 504 Black [17.7%], 167 838 Hispanic [30.1%], 311 157 White [55.8%], and 147 876 children of other races or ethnicities [26.5%]) who were hospitalized for acute medical emergencies, of whom 5158 (0.9%) died; 75 999 children (12 727 Black [16.7%], 21 604 Hispanic [28.4%], 44 203 White [58.2%]; and 21 609 of other races and ethnicities [27.7%]) were hospitalized for traumatic injuries, of whom 1339 (1.8%) died. Adjusted mortality of Black children with acute medical emergencies was significantly greater than that of Hispanic children, White children, and of children of other races and ethnicities (odds ratio [OR], 1.69; 95% CI, 1.59-1.79) across all quartile levels of ED pediatric readiness; but there were no racial or ethnic disparities in mortality when comparing Black children with traumatic injuries with Hispanic children, White children, and children of other races and ethnicities with traumatic injuries (OR 1.01; 95% CI, 0.89-1.15). When compared with hospitals in the lowest quartile of ED pediatric readiness, children who were treated at hospitals in the highest quartile had significantly lower mortality in both the acute medical emergency cohort (OR 0.24; 95% CI, 0.16-0.36) and traumatic injury cohort (OR, 0.39; 95% CI, 0.25-0.61). The greatest survival advantage associated with high pediatric readiness was experienced for Black children in the acute medical emergency cohort. CONCLUSIONS AND RELEVANCE:In this study, racial and ethnic disparities in mortality existed among children treated for acute medical emergencies but not traumatic injuries. Increased ED pediatric readiness was associated with reduced disparities; it was estimated that increasing the ED pediatric readiness levels of hospitals in the 3 lowest quartiles would result in an estimated 3-fold reduction in disparity for pediatric mortality. However, increased pediatric readiness did not eliminate disparities, indicating that organizations and initiatives dedicated to increasing ED pediatric readiness should consider formal integration of health equity into efforts to improve pediatric emergency care.

OBJECTIVES:Poor medication adherence in low-income and middle-income countries is a major cause of suboptimal hypertension and diabetes control. We aimed to identify key factors associated with medication adherence in western Kenya, with a focus on cost-related and economic wealth factors. SETTING:We conducted a cross-sectional analysis of baseline data of participants enrolled in the Bridging Income Generation with Group Integrated Care study in western Kenya. PARTICIPANTS:All participants were ≥35 years old with either diabetes or hypertension who had been prescribed medications in the past 3 months. PRIMARY AND SECONDARY OUTCOME MEASURES:Baseline data included sociodemographic characteristics, wealth and economic status and medication adherence information. Predictors of medication adherence were separated into the five WHO dimensions of medication adherence: condition-related factors (comorbidities), patient-related factors (psychological factors, alcohol use), therapy-related factors (number of prescription medications), economic-related factors (monthly income, cost of transportation, monthly cost of medications) and health system-related factors (health insurance, time to travel to the health facility). A multivariable analysis, controlling for age and sex, was conducted to determine drivers of suboptimal medication adherence in each overarching category. RESULTS:The analysis included 1496 participants (73.7% women) with a mean age of 60 years (range 35-97). The majority of participants had hypertension (69.2%), 8.8% had diabetes and 22.1% had both hypertension and diabetes. Suboptimal medication adherence was reported by 71.2% of participants. Economic factors were associated with medication adherence. In multivariable analysis that investigated specific subtypes of costs, transportation costs were found to be associated with worse medication adherence. In contrast, we found no evidence of association between monthly medication costs and medication adherence. CONCLUSION:Suboptimal medication adherence is highly prevalent in Kenya, and primary-associated factors include costs, particularly indirect costs of transportation. Addressing all economic factors associated with medication adherence will be important to improve outcomes for non-communicable diseases. TRIAL REGISTRATION NUMBER:NCT02501746.

BACKGROUND:The prevalence of waterpipe smoking among women in southern Iran is significantly higher than women in other regions of Iran. We aimed to explore the effect of several demographic factors, knowledge, attitude, self-efficacy and social norms on a successful cessation of waterpipe smoking in the marginalized women of Bandar Abbas city, in the south of Iran. METHODS:This case-control study was conducted in 2022 among 731 women (246 subjects who successfully quit waterpipe smoking in the case group and 485 who smoked waterpipe in the control group). A cluster sampling method was used to collect the required data through face-to-face interviews and a researcher-made questionnaire. The questionnaire consisted of demographic information, behavioral information about waterpipe smoking and knowledge, attitude, self-efficacy and social norms. The data were analyzed in STATA 14 using univariate and multivariate regression analyses. RESULTS:The mean and standard deviation of age was 39.24 ± 11.93 and 37.18 ± 13.57 in the control and case groups, respectively. With an increase of one score in social norm (OR: 1.046), the odds of cessation were increased for 4%. With an increase of one score in self-efficacy (OR: 1.152), the odds of cessation were increased for 15%. With an increase of one score in knowledge (OR: 1.064), the odds of cessation were increased for 6%. With an increase of one score in attitude (OR: 1.215) the odds of cessation were increased for 21%. CONCLUSION:The present findings revealed personal and interpersonal influential factors in successful waterpipe cessation. Women's knowledge can be increased and their attitude can be changed. Important people in women's lives can be influenced to, consequently, affect women positively and improve their self-esteem.

BACKGROUND:Hearing loss is associated with increased cognitive decline and incident dementia in older adults. We aimed to investigate whether a hearing intervention could reduce cognitive decline in cognitively healthy older adults with hearing loss. METHODS:The ACHIEVE study is a multicentre, parallel-group, unmasked, randomised controlled trial of adults aged 70-84 years with untreated hearing loss and without substantial cognitive impairment that took place at four community study sites across the USA. Participants were recruited from two study populations at each site: (1) older adults participating in a long-standing observational study of cardiovascular health (Atherosclerosis Risk in Communities [ARIC] study), and (2) healthy de novo community volunteers. Participants were randomly assigned (1:1) to a hearing intervention (audiological counselling and provision of hearing aids) or a control intervention of health education (individual sessions with a health educator covering topics on chronic disease prevention) and followed up every 6 months. The primary endpoint was 3-year change in a global cognition standardised factor score from a comprehensive neurocognitive battery. Analysis was by intention to treat. This trial was registered at ClinicalTrials.gov, NCT03243422. FINDINGS:=0·010). Other prespecified sensitivity analyses that varied analytical parameters used in the total cohort did not change the observed results. No significant adverse events attributed to the study were reported with either the hearing intervention or health education control. INTERPRETATION:The hearing intervention did not reduce 3-year cognitive decline in the primary analysis of the total cohort. However, a prespecified sensitivity analysis showed that the effect differed between the two study populations that comprised the cohort. These findings suggest that a hearing intervention might reduce cognitive change over 3 years in populations of older adults at increased risk for cognitive decline but not in populations at decreased risk for cognitive decline. FUNDING:US National Institutes of Health.

BACKGROUND:Epigenetic clocks are promising tools for assessing biological age. We assessed the accuracy of pediatric epigenetic clocks in gestational and chronological age determination. RESULTS:Our study used data from seven tissue types on three DNA methylation profiling microarrays and found that the Knight and Bohlin clocks performed similarly for blood cells, while the Lee clock was superior for placental samples. The pediatric-buccal-epigenetic clock performed the best for pediatric buccal samples, while the Horvath clock is recommended for children's blood cell samples. The NeoAge clock stands out for its unique ability to predict post-menstrual age with high correlation with the observed age in infant buccal cell samples. CONCLUSIONS:Our findings provide valuable guidance for future research and development of epigenetic clocks in pediatric samples, enabling more accurate assessments of biological age.

IMPORTANCE:Medicaid patients with mental illness comprise one of the most high-need and complex patient populations. Value-based reforms aim to improve care, but their efficacy in the Medicaid program is unclear. OBJECTIVE:To investigate if New York state's Medicaid value-based payment reform was associated with improved utilization patterns for patients with mental illness. DESIGN, SETTING, AND PARTICIPANTS:This retrospective cohort study used a difference-in-differences analysis to compare changes in utilization between Medicaid beneficiaries whose outpatient practices participated in value-based payment reform and beneficiaries whose practices did not participate from before (July 1, 2013-June 30, 2015) to after reform (July 1, 2015-June 30, 2019). Participants were Medicaid beneficiaries in New York state aged 18 to 64 years with major depression disorder, bipolar disorder, and/or schizophrenia. Data analysis was performed from April 2021 to July 2023. EXPOSURE:Beneficiaries were exposed to value-based payment reforms if their attributed outpatient practice participated in value-based payment reform at baseline (July 1, 2015). MAIN OUTCOMES AND MEASURES:Primary outcomes were the number of outpatient primary care visits and the number of behavioral health visits per year. Secondary outcomes were the number of mental health emergency department visits and hospitalizations per year. RESULTS:The analytic population comprised 306 290 individuals with depression (67.4% female; mean [SD] age, 38.6 [11.9] years), 85 105 patients with bipolar disorder (59.6% female; mean [SD] age, 38.0 [11.6] years), and 71 299 patients with schizophrenia (45.1% female; mean [SD] age, 40.3 [12.2] years). After adjustment, analyses estimated a statistically significant, positive association between value-based payments and behavioral health visits for patients with depression (0.91 visits; 95% CI, 0.51-1.30) and bipolar disorder (1.01 visits; 95% CI, 0.22-1.79). There was no statistically significant changes to primary care visits for patients with depression and bipolar disorder, but value-based payments were associated with reductions in primary care visits for patients with schizophrenia (-1.31 visits; 95% CI, -2.51 to -0.12). In every diagnostic population, value-based payment was associated with significant reductions in mental health emergency department visits (population with depression: -0.01 visits [95% CI, -0.02 to -0.002]; population with bipolar disorder: -0.02 visits [95% CI, -0.05 to -0.001]; population with schizophrenia: -0.04 visits [95% CI, -0.07 to -0.01]). CONCLUSIONS AND RELEVANCE:In this cohort study, Medicaid value-based payment reform was statistically significantly associated with an increase in behavioral health visits and a reduction in mental health emergency department visits for patients with mental illness. Medicaid value-based payment may be effective at altering health care utilization in patients with mental illness.