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Mark J Pletcher,1,2 Christopher B Forrest,3 Thomas W Carton4 1Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, 2Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, CA, 3Applied Clinical Research Center, Children’s Hospital of Philadelphia, Philadelphia, PA, 4Division of Health Services Research, Louisiana Public Health Institute, New Orleans, LA, USA Abstract: The Patient-Centered Outcomes Research Institute (PCORI) launched a multi-institutional “network of networks” in 2013 – Patient-Centered Clinical Research Network (PCORnet) – that is designed to conduct clinical research that is faster, less expensive, and more responsive to the information needs of patients and clinicians. To enhance cross-network and cross-institutional collaboration and catalyze the use of PCORnet, PCORI has supported formation of 11 Collaborative Research Groups focusing on specific disease types (e.g., ­cardiovascular health and cancer) or particular patient populations (e.g., pediatrics and health disparities). PCORnet’s Collaborative Research Groups are establishing research priorities within these focus areas, establishing relationships with potential funders, and supporting development of specific research projects that will use PCORnet resources. PCORnet remains a complex, multilevel, and heterogeneous network that is still maturing and building a diverse portfolio of observational and interventional people-centered research; engaging with PCORnet can be daunting, particularly for outside investigators. We believe the Collaborative Research Groups are stimulating interest and helping investigators navigate the complexity, but only time will tell if these efforts will bear fruit in terms of funded multicenter PCORnet projects. Keywords: PCORI, PCORnet, network, collaboration, infrastructure

Rationale: Short-term weight loss is possible in a variety of settings. However, long-term, free-living weight loss maintenance following structured weight loss interventions remains elusive., Objective: The purpose was to study body weight trajectories over 2 years of intensive lifestyle intervention (ILI) and up to 4 years of follow-up versus usual care (UC)., Methods: Data were obtained from electronic medical records (EMRs) from participating clinics. Baseline (Day 0) was established as the EMR data point closest but prior to the baseline date of the trial. The sample included 111 ILI and 196 UC patients. The primary statistical analysis focused on differentiating weight loss trajectories between ILI and UC., Results: The ILI group experienced significantly greater weight loss compared with the UC group from Day 100 to Day 700, beyond which there were no significant differences. Intensive lifestyle intervention patients who maintained ≥5% and ≥10% weight loss at 24 months demonstrated significantly greater weight loss ( p  < 0.001) across the active intervention and follow-up., Conclusions: Following 24 months of active intervention, patients with ILI regained weight toward their baseline to the point where ILI versus UC differences were no longer statistically or clinically significant. However, patients in the ILI who experienced ≥5% or ≥10% weight loss at the cessation of the active intervention maintained greater weight loss at the end of the follow-up phase., Clinical Trial Registration: ClinicalTrials.gov: NCT02561221., Competing Interests: PK, RN, CM, RH and DF report NIH grants to their institution. PK, CM and JA report research contracts between WW International and their institution. JA and CM report research grants from USDA, NSF, Lilly, and FFAR, and their institution. CM reports a research grant from Kroger Co. Zero Hunger/Zero Waste Foundation and his institution. JA reports a research grant between the HASS Avocado Board and his institution. DF reports PCORI contracts and CDC grants to his institution. TC reports a research award from PCORI. CM reports speaking honoraria and travel support from Indiana University, UAB, Brigham Young University, University of Kansas Medical Center, and University of Southern California JA reports a speaking honorarium and travel support from WW International/Abbott. DF reports a speaking honorarium from Tulane University. CM reports royalties from ABGIL, consulting fees from Wondr Health, EHE Health, UAB, the Commission on Dietetic Registration, and University of Nebraska, and participation on the DSMB of a weight loss trial at Duke University. No other conflicts of interest were reported., (© 2024 The Author(s). Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

Adults aged ≥65 years experience the highest risk for COVID-19-related hospitalization and death, with risk increasing with increasing age; outpatient antiviral treatment reduces the risk for these severe outcomes. Despite the proven benefit of COVID-19 antiviral treatment, information on differences in use among older adults with COVID-19 by age group is limited. Nonhospitalized patients aged ≥65 years with COVID-19 during April 2022-September 2023 were identified from the National Patient-Centered Clinical Research Network. Differences in use of antiviral treatment among patients aged 65-74, 75-89, and ≥90 years were assessed. Multivariable logistic regression was used to estimate the association between age and nonreceipt of antiviral treatment. Among 393,390 persons aged ≥65 years, 45.9% received outpatient COVID-19 antivirals, including 48.4%, 43.5%, and 35.2% among those aged 65-75, 76-89, and ≥90 years, respectively. Patients aged 75-89 and ≥90 years had 1.17 (95% CI = 1.15-1.19) and 1.54 (95% CI = 1.49-1.61) times the adjusted odds of being untreated, respectively, compared with those aged 65-74 years. Among 12,543 patients with severe outcomes, 2,648 (21.1%) had received an outpatient COVID-19 antiviral medication, compared with 177,874 (46.7%) of 380,847 patients without severe outcomes. Antiviral use is underutilized among adults ≥65 years; the oldest adults are least likely to receive treatment. To prevent COVID-19-associated morbidity and mortality, increased use of COVID-19 antiviral medications among older adults is needed., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Faraz S. Ahmad reports receipt of consulting fees and editorial support from Pfizer. Thomas W. Carton reports receipt of grant support from the Task Force for Global Health. No other potential conflicts of interest were disclosed.

Preventing and treating post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, has become a public health priority. In this study, we examined whether treatment with Paxlovid in the acute phase of COVID-19 helps prevent the onset of PASC. We used electronic health records from the National Covid Cohort Collaborative (N3C) to define a cohort of 426,352 patients who had COVID-19 since April 1, 2022, and were eligible for Paxlovid treatment due to risk for progression to severe COVID-19. We used the target trial emulation (TTE) framework to estimate the effect of Paxlovid treatment on PASC incidence. We estimated overall PASC incidence using a computable phenotype. We also measured the onset of novel cognitive, fatigue, and respiratory symptoms in the post-acute period. Paxlovid treatment did not have a significant effect on overall PASC incidence (relative risk [RR] = 0.98, 95% confidence interval [CI] 0.95-1.01). However, it had a protective effect on cognitive (RR = 0.90, 95% CI 0.84-0.96) and fatigue (RR = 0.95, 95% CI 0.91-0.98) symptom clusters, which suggests that the etiology of these symptoms may be more closely related to viral load than that of respiratory symptoms.

Background: SARS-CoV-2-infected patients may develop new conditions in the period after the acute infection. These conditions, the post-acute sequelae of SARS-CoV-2 infection (PASC, or Long COVID), involve a diverse set of organ systems. Limited studies have investigated the predictability of Long COVID development and its associated risk factors., Methods: In this retrospective cohort study, we used electronic healthcare records from two large-scale PCORnet clinical research networks, INSIGHT (~1.4 million patients from New York) and OneFlorida+ (~0.7 million patients from Florida), to identify factors associated with having Long COVID, and to develop machine learning-based models for predicting Long COVID development. Both SARS-CoV-2-infected and non-infected adults were analysed during the period of March 2020 to November 2021. Factors associated with Long COVID risk were identified by removing background associations and correcting for multiple tests., Results: We observed complex association patterns between baseline factors and a variety of Long COVID conditions, and we highlight that severe acute SARS-CoV-2 infection, being underweight, and having baseline comorbidities (e.g., cancer and cirrhosis) are likely associated with increased risk of developing Long COVID. Several Long COVID conditions, e.g., dementia, malnutrition, chronic obstructive pulmonary disease, heart failure, PASC diagnosis U099, and acute kidney failure are well predicted (C-index > 0.8). Moderately predictable conditions include atelectasis, pulmonary embolism, diabetes, pulmonary fibrosis, and thromboembolic disease (C-index 0.7-0.8). Less predictable conditions include fatigue, anxiety, sleep disorders, and depression (C-index around 0.6)., Conclusions: This observational study suggests that association patterns between investigated factors and Long COVID are complex, and the predictability of different Long COVID conditions varies. However, machine learning-based predictive models can help in identifying patients who are at risk of developing a variety of Long COVID conditions., (© 2024. The Author(s).)

Introduction: PCORnet, the National Patient-Centered Clinical Research Network, is a large research network of health systems that map clinical data to a standardized data model. In 2018, we expanded existing infrastructure to facilitate use for public health surveillance. We describe benefits and challenges of using PCORnet for surveillance and describe case studies., Methods: In 2018, infrastructure enhancements included addition of a table to store patients' residential zip codes and expansion of a modular program to generate population health statistics across conditions. Chronic disease surveillance case studies conducted in 2019 assessed atrial fibrillation (AF) and cirrhosis. In April 2020, PCORnet established an infrastructure to support COVID-19 surveillance with institutions frequently updating their electronic health record data., Results: By August 2023, 53 PCORnet sites (84%) had a 5-digit zip code available on at least 95% of their patient populations. Among 148,223 newly diagnosed AF patients eligible for oral anticoagulant (OAC) therapy, 43.3% were on any OAC (17.8% warfarin, 28.5% any novel oral anticoagulant) within a year of the AF diagnosis. Among 60,268 patients with cirrhosis (2015-2019), common documented etiologies included unknown (48%), hepatitis C infection (23%), and alcohol use (22%). During October 2022 through December 2023, across 34 institutions, the proportion of COVID-19 patients who were cared for in the inpatient setting was 9.1% among 887,051 adults aged 20 years or older and 6.0% among 139,148 children younger than 20 years., Conclusions: PCORnet provides important data that may augment traditional public health surveillance programs across diverse conditions. PCORnet affords longitudinal population health assessments among large catchments of the population with clinical, treatment, and geographic information, with capabilities to deliver rapid information needed during public health emergencies.

Background: Data modernization efforts to strengthen surveillance capacity could help assess trends in use of preventive services and diagnoses of new chronic disease during the COVID-19 pandemic, which broadly disrupted health care access., Methods: This cross-sectional study examined electronic health record data from US adults aged 21 to 79 years in a large national research network (PCORnet), to describe use of 8 preventive health services (N = 30,783,825 patients) and new diagnoses of 9 chronic diseases (N = 31,588,222 patients) during 2018 through 2022. Joinpoint regression assessed significant trends, and health debt was calculated comparing 2020 through 2022 volume to prepandemic (2018 and 2019) levels., Results: From 2018 to 2022, use of some preventive services increased (hemoglobin A 1c and lung computed tomography, both P < .05), others remained consistent (lipid testing, wellness visits, mammograms, Papanicolaou tests or human papillomavirus tests, stool-based screening), and colonoscopies or sigmoidoscopies declined (P < .01). Annual new chronic disease diagnoses were mostly stable (6% hypertension; 4% to 5% cholesterol; 4% diabetes; 1% colonic adenoma; 0.1% colorectal cancer; among women, 0.5% breast cancer), although some declined (lung cancer, cervical intraepithelial neoplasia or carcinoma in situ, cervical cancer, all P < .05). The pandemic resulted in health debt, because use of most preventive services and new diagnoses of chronic disease were less than expected during 2020; these partially rebounded in subsequent years. Colorectal screening and colonic adenoma detection by age group aligned with screening recommendation age changes during this period., Conclusion: Among over 30 million patients receiving care during 2018 through 2022, use of preventive services and new diagnoses of chronic disease declined in 2020 and then rebounded, with some remaining health debt. These data highlight opportunities to augment traditional surveillance with EHR-based data.

Importance: The frequency and characteristics of post-acute sequelae of SARS-CoV-2 infection (PASC) may vary by SARS-CoV-2 variant., Objective: To characterize PASC-related conditions among individuals likely infected by the ancestral strain in 2020 and individuals likely infected by the Delta variant in 2021., Design: Retrospective cohort study of electronic medical record data for approximately 27 million patients from March 1, 2020-November 30, 2021., Setting: Healthcare facilities in New York and Florida., Participants: Patients who were at least 20 years old and had diagnosis codes that included at least one SARS-CoV-2 viral test during the study period., Exposure: Laboratory-confirmed COVID-19 infection, classified by the most common variant prevalent in those regions at the time., Main Outcome(s) and Measure(s): Relative risk (estimated by adjusted hazard ratio [aHR]) and absolute risk difference (estimated by adjusted excess burden) of new conditions, defined as new documentation of symptoms or diagnoses, in persons between 31-180 days after a positive COVID-19 test compared to persons without a COVID-19 test or diagnosis during the 31-180 days after the last negative test., Results: We analyzed data from 560,752 patients. The median age was 57 years; 60.3% were female, 20.0% non-Hispanic Black, and 19.6% Hispanic. During the study period, 57,616 patients had a positive SARS-CoV-2 test; 503,136 did not. For infections during the ancestral strain period, pulmonary fibrosis, edema (excess fluid), and inflammation had the largest aHR, comparing those with a positive test to those without a COVID-19 test or diagnosis (aHR 2.32 [95% CI 2.09 2.57]), and dyspnea (shortness of breath) carried the largest excess burden (47.6 more cases per 1,000 persons). For infections during the Delta period, pulmonary embolism had the largest aHR comparing those with a positive test to a negative test (aHR 2.18 [95% CI 1.57, 3.01]), and abdominal pain carried the largest excess burden (85.3 more cases per 1,000 persons)., Conclusions and Relevance: We documented a substantial relative risk of pulmonary embolism and a large absolute risk difference of abdomen-related symptoms after SARS-CoV-2 infection during the Delta variant period. As new SARS-CoV-2 variants emerge, researchers and clinicians should monitor patients for changing symptoms and conditions that develop after infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Varma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Little is known about post-acute sequelae of SARS-CoV-2 infection (PASC) after acquiring SARS-CoV-2 infection during pregnancy. We aimed to evaluate the association between acquiring SARS-CoV-2 during pregnancy compared with acquiring SARS-CoV-2 outside of pregnancy and the development of PASC., Methods: This retrospective cohort study from the Researching COVID to Enhance Recovery (RECOVER) Initiative Patient-Centred Clinical Research Network (PCORnet) used electronic health record (EHR) data from 19 U.S. health systems. Females aged 18-49 years with lab-confirmed SARS-CoV-2 infection from March 2020 through June 2022 were included. Validated algorithms were used to identify pregnancies with a delivery at >20 weeks' gestation. The primary outcome was PASC, as previously defined by computable phenotype in the adult non-pregnant PCORnet EHR dataset, identified 30-180 days post-SARS-CoV-2 infection. Secondary outcomes were the 24 component diagnoses contributing to the PASC phenotype definition. Univariable comparisons were made for baseline characteristics between individuals with SARS-CoV-2 infection acquired during pregnancy compared with outside of pregnancy. Using inverse probability of treatment weighting to adjust for baseline differences, the association between SARS-CoV-2 infection acquired during pregnancy and the selected outcomes was modelled. The incident risk is reported as the adjusted hazard ratio (aHR) with 95% confidence intervals., Findings: In total, 83,915 females with SARS-CoV-2 infection acquired outside of pregnancy and 5397 females with SARS-CoV-2 infection acquired during pregnancy were included in analysis. Non-pregnant females with SARS-CoV-2 infection were more likely to be older and have comorbid health conditions. SARS-CoV-2 infection acquired in pregnancy as compared with acquired outside of pregnancy was associated with a lower incidence of PASC (25.5% vs 33.9%; aHR 0.85, 95% CI 0.80-0.91). SARS-CoV-2 infection acquired in pregnant females was associated with increased risk for some PASC component diagnoses including abnormal heartbeat (aHR 1.67, 95% CI 1.43-1.94), abdominal pain (aHR 1.34, 95% CI 1.16-1.55), and thromboembolism (aHR 1.88, 95% CI 1.17-3.04), but decreased risk for other diagnoses including malaise (aHR 0.35, 95% CI 0.27-0.47), pharyngitis (aHR 0.36, 95% CI 0.26-0.48) and cognitive problems (aHR 0.39, 95% CI 0.27-0.56)., Interpretation: SARS-CoV-2 infection acquired during pregnancy was associated with lower risk of development of PASC at 30-180 days after incident SARS-CoV-2 infection in this nationally representative sample. These findings may be used to counsel pregnant and pregnant capable individuals, and direct future prospective study., Funding: National Institutes of Health (NIH) Other Transaction Agreement (OTA) OT2HL16184., Competing Interests: Dr. Metz is the site Principal Investigator (PI) for a Pfizer RSV vaccination study that is now complete and a Pfizer pharmacokinetic study of Paxlovid for mild to moderate COVID-19 in pregnancy. She also served on the Medical Advisory Board and is a site PI for a Pfizer SARS-CoV-2 vaccination study in pregnancy. Megan Fitzgerald was compensated for work evaluating COVID re-infections funded through the Patient Lead Research Collaborative. This content is solely the responsibility of the authors and does not necessarily represent the official views of the RECOVER Programme, the National Institutes of Health (NIH), or other funders. This study is part of the NIH Researching COVID to Enhance Recovery (RECOVER) Initiative, which seeks to understand, treat, and prevent the post-acute sequelae of SARS-CoV-2 infection (PASC). For more information on RECOVER, visit https://recovercovid.org/., (© 2024 The Author(s).)

Context: Electronic health records (EHRs) are an emerging chronic disease surveillance data source and facilitating this data sharing is complex., Program: Using the experience of the Multi-State EHR-Based Network for Disease Surveillance (MENDS), this article describes implementation of a governance framework that aligns technical, statutory, and organizational requirements to facilitate EHR data sharing for chronic disease surveillance., Implementation: MENDS governance was cocreated with data contributors and health departments representing Texas, New Orleans, Louisiana, Chicago, Washington, and Indiana through engagement from 2020 to 2022. MENDS convened a governance body, executed data-sharing agreements, and developed a master governance document to codify policies and procedures., Results: The MENDS governance committee meets regularly to develop policies and procedures on data use and access, timeliness and quality, validation, representativeness, analytics, security, small cell suppression, software implementation and maintenance, and privacy. Resultant policies are codified in a master governance document., Discussion: The MENDS governance approach resulted in a transparent governance framework that cultivates trust across the network. MENDS's experience highlights the time and resources needed by EHR-based public health surveillance networks to establish effective governance., Competing Interests: The authors declare no conflicts of interest.

Background: An increasing number of studies have described new and persistent symptoms and conditions as potential post-acute sequelae of SARS-CoV-2 infection (PASC). However, it remains unclear whether certain symptoms or conditions occur more frequently among persons with SARS-CoV-2 infection compared with those never infected with SARS-CoV-2. We compared the occurrence of specific COVID-associated symptoms and conditions as potential PASC 31- to 150-day following a SARS-CoV-2 test among adults and children with positive and negative test results., Methods: We conducted a retrospective cohort study using electronic health record (EHR) data from 43 PCORnet sites participating in a national COVID-19 surveillance program. This study included 3,091,580 adults (316,249 SARS-CoV-2 positive; 2,775,331 negative) and 675,643 children (62,131 positive; 613,512 negative) who had a SARS-CoV-2 laboratory test during March 1, 2020-May 31, 2021 documented in their EHR. We used logistic regression to calculate the odds of having a symptom and Cox models to calculate the risk of having a newly diagnosed condition associated with a SARS-CoV-2 positive test., Results: After adjustment for baseline covariates, hospitalized adults and children with a positive test had increased odds of being diagnosed with ≥ 1 symptom (adults: adjusted odds ratio[aOR], 1.17[95% CI, 1.11-1.23]; children: aOR, 1.18[95% CI, 1.08-1.28]) or shortness of breath (adults: aOR, 1.50[95% CI, 1.38-1.63]; children: aOR, 1.40[95% CI, 1.15-1.70]) 31-150 days following a SARS-CoV-2 test compared with hospitalized individuals with a negative test. Hospitalized adults with a positive test also had increased odds of being diagnosed with ≥ 3 symptoms or fatigue compared with those testing negative. The risks of being newly diagnosed with type 1 or type 2 diabetes (adjusted hazard ratio[aHR], 1.25[95% CI, 1.17-1.33]), hematologic disorders (aHR, 1.19[95% CI, 1.11-1.28]), or respiratory disease (aHR, 1.44[95% CI, 1.30-1.60]) were higher among hospitalized adults with a positive test compared with those with a negative test. Non-hospitalized adults with a positive test also had higher odds or increased risk of being diagnosed with certain symptoms or conditions., Conclusions: Patients with SARS-CoV-2 infection, especially those who were hospitalized, were at higher risk of being diagnosed with certain symptoms and conditions after acute infection., (© 2024. The Author(s).)

Oral nirmatrelvir/ritonavir is approved as treatment for acute COVID-19, but the effect of treatment during acute infection on risk of Long COVID is unknown. We hypothesized that nirmatrelvir treatment during acute SARS-CoV-2 infection reduces risk of developing Long COVID and rebound after treatment is associated with Long COVID. We conducted an observational cohort study within the Covid Citizen Science (CCS) study, an online cohort study with over 100 000 participants. We included vaccinated, nonhospitalized, nonpregnant individuals who reported their first SARS-CoV-2 positive test March-August 2022. Oral nirmatrelvir/ritonavir treatment was ascertained during acute SARS-CoV-2 infection. Patient-reported Long COVID symptoms, symptom rebound and test-positivity rebound were asked on subsequent surveys at least 3 months after SARS-CoV-2 infection. A total of 4684 individuals met the eligibility criteria, of whom 988 (21.1%) were treated and 3696 (78.9%) were untreated; 353/988 (35.7%) treated and 1258/3696 (34.0%) untreated responded to the Long COVID survey (n = 1611). Among 1611 participants, median age was 55 years and 66% were female. At 5.4 ± 1.3 months after infection, nirmatrelvir treatment was not associated with subsequent Long COVID symptoms (odds ratio [OR]: 1.15; 95% confidence interval [CI]: 0.80-1.64; p = 0.45). Among 666 treated who answered rebound questions, rebound symptoms or test positivity were not associated with Long COVID symptoms (OR: 1.34; 95% CI: 0.74-2.41; p = 0.33). Within this cohort of vaccinated, nonhospitalized individuals, oral nirmatrelvir treatment during acute SARS-CoV-2 infection and rebound after nirmatrelvir treatment were not associated with Long COVID symptoms more than 90 days after infection., (© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Background Hypertension and diabetes are associated with increased COVID-19 severity. The association between level of control of these conditions and COVID-19 severity is less well understood. Methods and Results This retrospective cohort study identified adults with COVID-19, March 2020 to February 2022, in 43 US health systems in the National Patient-Centered Clinical Research Network. Hypertension control was categorized as blood pressure (BP) <130/80, 130 to 139/80 to 89, 140 to 159/90 to 99, or ≥160/100 mm Hg, and diabetes control as glycated hemoglobin <7%, 7% to <9%, ≥9%. Adjusted, pooled logistic regression assessed associations between hypertension and diabetes control and severe COVID-19 outcomes. Among 1 494 837 adults with COVID-19, 43% had hypertension and 12% had diabetes. Among patients with hypertension, the highest baseline BP was associated with greater odds of hospitalization (adjusted odds ratio [aOR], 1.30 [95% CI, 1.23-1.37] for BP ≥160/100 versus BP <130/80), critical care (aOR, 1.30 [95% CI, 1.21-1.40]), and mechanical ventilation (aOR, 1.32 [95% CI, 1.17-1.50]) but not mortality (aOR, 1.08 [95% CI, 0.98-1.12]). Among patients with diabetes, the highest glycated hemoglobin was associated with greater odds of hospitalization (aOR, 1.61 [95% CI, 1.47-1.76] for glycated hemoglobin ≥9% versus <7%), critical care (aOR, 1.42 [95% CI, 1.31-1.54]), mechanical ventilation (aOR, 1.12 [95% CI, 1.02-1.23]), and mortality (aOR, 1.18 [95% CI, 1.09-1.27]). Black and Hispanic adults were more likely than White adults to experience severe COVID-19 outcomes, independent of comorbidity score and control of hypertension or diabetes. Conclusions Among 1.5 million patients with COVID-19, higher BP and glycated hemoglobin were associated with more severe COVID-19 outcomes. Findings suggest that adults with poorest control of hypertension or diabetes might benefit from efforts to prevent and initiate early treatment of COVID-19.

Introduction: Modernizing chronic disease surveillance with electronic health record (EHR) data may provide better data to improve hypertension prevention and control, but no consensus exists for an EHR-based surveillance definition for hypertension. The Multi-State EHR-Based Network for Disease Surveillance (MENDS) pilot surveillance system was used to develop and test an electronic phenotype for hypertension., Methods: We used MENDS data from 1,671,279 patients in Louisiana to examine the effect of different analytic decisions on estimates of hypertension prevalence. Decisions included 1) whether to restrict surveillance to patients with recent blood pressure measurements, 2) varying the number and recency of encounters to define the population at risk of hypertension, 3) how to define hypertension (diagnosis codes, antihypertensive medication, blood pressure measurements, or combinations of these), and 4) how to handle multiple blood pressure measurements on the same day. Results were compared with independent estimates of hypertension prevalence in Louisiana from the Behavioral Risk Factor Surveillance System (BRFSS)., Results: Applying varying criteria resulted in hypertension prevalence estimates ranging from 19.7% to 59.3%. A hypertension surveillance strategy that includes a population with at least 1 clinical encounter with measured blood pressure in the previous 2 years and identifies hypertension using all available data (≥1 diagnosis code, ≥1 antihypertensive medication, and ≥2 elevated blood pressure values ≥140/90 mm Hg on separate days) generated estimates in line with population-based survey data. This definition estimated the crude 2019 hypertension prevalence in the state of Louisiana as 43.4% (age-adjusted, 41.0%), comparable with the crude BRFSS estimate of 39.7% (age adjusted, 37.1%)., Conclusion: Applying different criteria to define hypertension using EHR data has a large effect on hypertension prevalence estimates. The proposed electronic phenotype generates hypertension prevalence estimates that align with independent estimates from BRFSS.

Background: Little is known about whether people who use both tobacco and cannabis (co-use) are more or less likely to have mental health disorders than single substance users or non-users. We aimed to examine associations between use of tobacco and/or cannabis with anxiety and depression., Methods: We analyzed data from the COVID-19 Citizen Science Study, a digital cohort study, collected via online surveys during 2020-2022 from a convenience sample of 53,843 US adults (≥ 18 years old) nationwide. Past 30-day use of tobacco and cannabis was self-reported at baseline and categorized into four exclusive patterns: tobacco-only use, cannabis-only use, co-use of both substances, and non-use. Anxiety and depression were repeatedly measured in monthly surveys. To account for multiple assessments of mental health outcomes within a participant, we used Generalized Estimating Equations to examine associations between the patterns of tobacco and cannabis use with each outcome., Results: In the total sample (mean age 51.0 years old, 67.9% female), 4.9% reported tobacco-only use, 6.9% cannabis-only use, 1.6% co-use, and 86.6% non-use. Proportions of reporting anxiety and depression were highest for the co-use group (26.5% and 28.3%, respectively) and lowest for the non-use group (10.6% and 11.2%, respectively). Compared to non-use, the adjusted odds of mental health disorders were highest for co-use (Anxiety: OR = 1.89, 95%CI = 1.64-2.18; Depression: OR = 1.77, 95%CI = 1.46-2.16), followed by cannabis-only use, and tobacco-only use. Compared to tobacco-only use, co-use (OR = 1.35, 95%CI = 1.08-1.69) and cannabis-only use (OR = 1.17, 95%CI = 1.00-1.37) were associated with higher adjusted odds for anxiety, but not for depression. Daily use (vs. non-daily use) of cigarettes, e-cigarettes, and cannabis were associated with higher adjusted odds for anxiety and depression., Conclusions: Use of tobacco and/or cannabis, particularly co-use of both substances, were associated with poor mental health. Integrating mental health support with tobacco and cannabis cessation may address this co-morbidity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Nguyen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Recent studies have investigated post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID) using real-world patient data such as electronic health records (EHR). Prior studies have typically been conducted on patient cohorts with specific patient populations which makes their generalizability unclear. This study aims to characterize PASC using the EHR data warehouses from two large Patient-Centered Clinical Research Networks (PCORnet), INSIGHT and OneFlorida+, which include 11 million patients in New York City (NYC) area and 16.8 million patients in Florida respectively. With a high-throughput screening pipeline based on propensity score and inverse probability of treatment weighting, we identified a broad list of diagnoses and medications which exhibited significantly higher incidence risk for patients 30-180 days after the laboratory-confirmed SARS-CoV-2 infection compared to non-infected patients. We identified more PASC diagnoses in NYC than in Florida regarding our screening criteria, and conditions including dementia, hair loss, pressure ulcers, pulmonary fibrosis, dyspnea, pulmonary embolism, chest pain, abnormal heartbeat, malaise, and fatigue, were replicated across both cohorts. Our analyses highlight potentially heterogeneous risks of PASC in different populations., (© 2023. The Author(s).)

Background: Compared to white individuals, Black and Hispanic individuals have higher rates of COVID-19 hospitalization and death. Less is known about racial/ethnic differences in post-acute sequelae of SARS-CoV-2 infection (PASC)., Objective: Examine racial/ethnic differences in potential PASC symptoms and conditions among hospitalized and non-hospitalized COVID-19 patients., Design: Retrospective cohort study using data from electronic health records., Participants: 62,339 patients with COVID-19 and 247,881 patients without COVID-19 in New York City between March 2020 and October 2021., Main Measures: New symptoms and conditions 31-180 days after COVID-19 diagnosis., Key Results: The final study population included 29,331 white patients (47.1%), 12,638 Black patients (20.3%), and 20,370 Hispanic patients (32.7%) diagnosed with COVID-19. After adjusting for confounders, significant racial/ethnic differences in incident symptoms and conditions existed among both hospitalized and non-hospitalized patients. For example, 31-180 days after a positive SARS-CoV-2 test, hospitalized Black patients had higher odds of being diagnosed with diabetes (adjusted odds ratio [OR]: 1.96, 95% confidence interval [CI]: 1.50-2.56, q<0.001) and headaches (OR: 1.52, 95% CI: 1.11-2.08, q=0.02), compared to hospitalized white patients. Hospitalized Hispanic patients had higher odds of headaches (OR: 1.62, 95% CI: 1.21-2.17, q=0.003) and dyspnea (OR: 1.22, 95% CI: 1.05-1.42, q=0.02), compared to hospitalized white patients. Among non-hospitalized patients, Black patients had higher odds of being diagnosed with pulmonary embolism (OR: 1.68, 95% CI: 1.20-2.36, q=0.009) and diabetes (OR: 2.13, 95% CI: 1.75-2.58, q<0.001), but lower odds of encephalopathy (OR: 0.58, 95% CI: 0.45-0.75, q<0.001), compared to white patients. Hispanic patients had higher odds of being diagnosed with headaches (OR: 1.41, 95% CI: 1.24-1.60, q<0.001) and chest pain (OR: 1.50, 95% CI: 1.35-1.67, q < 0.001), but lower odds of encephalopathy (OR: 0.64, 95% CI: 0.51-0.80, q<0.001)., Conclusions: Compared to white patients, patients from racial/ethnic minority groups had significantly different odds of developing potential PASC symptoms and conditions. Future research should examine the reasons for these differences., (© 2023. The Author(s).)

Post-acute sequelae of SARS-CoV-2 infection (PASC) affects a wide range of organ systems among a large proportion of patients with SARS-CoV-2 infection. Although studies have identified a broad set of patient-level risk factors for PASC, little is known about the association between "exposome"-the totality of environmental exposures and the risk of PASC. Using electronic health data of patients with COVID-19 from two large clinical research networks in New York City and Florida, we identified environmental risk factors for 23 PASC symptoms and conditions from nearly 200 exposome factors. The three domains of exposome include natural environment, built environment, and social environment. We conducted a two-phase environment-wide association study. In Phase 1, we ran a mixed effects logistic regression with 5-digit ZIP Code tabulation area (ZCTA5) random intercepts for each PASC outcome and each exposome factor, adjusting for a comprehensive set of patient-level confounders. In Phase 2, we ran a mixed effects logistic regression for each PASC outcome including all significant (false positive discovery adjusted p-value < 0.05) exposome characteristics identified from Phase I and adjusting for confounders. We identified air toxicants (e.g., methyl methacrylate), particulate matter (PM 2.5 ) compositions (e.g., ammonium), neighborhood deprivation, and built environment (e.g., food access) that were associated with increased risk of PASC conditions related to nervous, blood, circulatory, endocrine, and other organ systems. Specific environmental risk factors for each PASC condition and symptom were different across the New York City area and Florida. Future research is warranted to extend the analyses to other regions and examine more granular exposome characteristics to inform public health efforts to help patients recover from SARS-CoV-2 infection., Competing Interests: We declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Context: Electronic health record (EHR) data can potentially make chronic disease surveillance more timely, actionable, and sustainable. Although use of EHR data can address numerous limitations of traditional surveillance methods, timely surveillance data with broad population coverage require scalable systems. This report describes implementation, challenges, and lessons learned from the Multi-State EHR-Based Network for Disease Surveillance (MENDS) to help inform how others work with EHR data to develop distributed networks for surveillance., Program: Funded by the Centers for Disease Control and Prevention (CDC), MENDS is a data modernization demonstration project that aims to develop a timely national chronic disease sentinel surveillance system using EHR data. It facilitates partnerships between data contributors (health information exchanges, other data aggregators) and data users (state and local health departments). MENDS uses query and visualization software to track local emerging trends. The program also uses statistical and geospatial methods to generate prevalence estimates of chronic disease risk measures at the national and local levels. Resulting data products are designed to inform public health practice and improve the health of the population., Implementation: MENDS includes 5 partner sites that leverage EHR data from 91 health system and clinic partners and represents approximately 10 million patients across the United States. Key areas of implementation include governance, partnerships, technical infrastructure and support, chronic disease algorithms and validation, weighting and modeling, and workforce education for public health data users., Discussion: MENDS presents a scalable distributed network model for implementing national chronic disease surveillance that leverages EHR data. Priorities as MENDS matures include producing prevalence estimates at various geographic and subpopulation levels, developing enhanced data sharing and interoperability capacity using international data standards, scaling the network to improve coverage nationally and among underrepresented geographic areas and subpopulations, and expanding surveillance of additional chronic disease measures and social determinants of health., Competing Interests: The authors declare that they have no conflicts of interest.

Background: Few prospective studies of Long COVID risk factors have been conducted. The purpose of this study was to determine whether sociodemographic factors, lifestyle, or medical history preceding COVID-19 or characteristics of acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are associated with Long COVID., Methods: In March 26, 2020, the COVID-19 Citizen Science study, an online cohort study, began enrolling participants with longitudinal assessment of symptoms before, during, and after SARS-CoV-2 infection. Adult participants who reported a positive SARS-CoV-2 test result before April 4, 2022 were surveyed for Long COVID symptoms. The primary outcome was at least 1 prevalent Long COVID symptom greater than 1 month after acute infection. Exposures of interest included age, sex, race/ethnicity, education, employment, socioeconomic status/financial insecurity, self-reported medical history, vaccination status, variant wave, number of acute symptoms, pre-COVID depression, anxiety, alcohol and drug use, sleep, and exercise., Results: Of 13 305 participants who reported a SARS-CoV-2 positive test, 1480 (11.1%) responded. Respondents' mean age was 53 and 1017 (69%) were female. Four hundred seventy-six (32.2%) participants reported Long COVID symptoms at a median 360 days after infection. In multivariable models, number of acute symptoms (odds ratio [OR], 1.30 per symptom; 95% confidence interval [CI], 1.20-1.40), lower socioeconomic status/financial insecurity (OR, 1.62; 95% CI, 1.02-2.63), preinfection depression (OR, 1.08; 95% CI, 1.01-1.16), and earlier variants (OR = 0.37 for Omicron compared with ancestral strain; 95% CI, 0.15-0.90) were associated with Long COVID symptoms., Conclusions: Variant wave, severity of acute infection, lower socioeconomic status, and pre-existing depression are associated with Long COVID symptoms., Competing Interests: Potential conflicts of interest. MJPe has received consulting fees from Gilead Sciences and AstraZeneca and serves on a data safety monitoring board for American Gene Technologies. AD is employed by CVS Health. EO has received research funding to their institution from Pfizer. HK is a consultant for Novo Nordisk. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The post-acute sequelae of SARS-CoV-2 infection (PASC) refers to a broad spectrum of symptoms and signs that are persistent, exacerbated or newly incident in the period after acute SARS-CoV-2 infection. Most studies have examined these conditions individually without providing evidence on co-occurring conditions. In this study, we leveraged the electronic health record data of two large cohorts, INSIGHT and OneFlorida+, from the national Patient-Centered Clinical Research Network. We created a development cohort from INSIGHT and a validation cohort from OneFlorida+ including 20,881 and 13,724 patients, respectively, who were SARS-CoV-2 infected, and we investigated their newly incident diagnoses 30-180 days after a documented SARS-CoV-2 infection. Through machine learning analysis of over 137 symptoms and conditions, we identified four reproducible PASC subphenotypes, dominated by cardiac and renal (including 33.75% and 25.43% of the patients in the development and validation cohorts); respiratory, sleep and anxiety (32.75% and 38.48%); musculoskeletal and nervous system (23.37% and 23.35%); and digestive and respiratory system (10.14% and 12.74%) sequelae. These subphenotypes were associated with distinct patient demographics, underlying conditions before SARS-CoV-2 infection and acute infection phase severity. Our study provides insights into the heterogeneity of PASC and may inform stratified decision-making in the management of PASC conditions., (© 2022. The Author(s).)

In December 2021 and early 2022, four medications received emergency use authorization (EUA) by the Food and Drug Administration for outpatient treatment of mild-to-moderate COVID-19 in patients who are at high risk for progressing to severe disease; these included nirmatrelvir/ritonavir (Paxlovid) and molnupiravir (Lagevrio) (both oral antivirals), expanded use of remdesivir (Veklury; an intraveneous antiviral), and bebtelovimab (a monoclonal antibody [mAb]).* Reports have documented disparities in mAb treatment by race and ethnicity (1) and in oral antiviral treatment by zip code-level social vulnerability (2); however, limited data are available on racial and ethnic disparities in oral antiviral treatment. † Using electronic health record (EHR) data from 692,570 COVID-19 patients aged ≥20 years who sought medical care during January-July 2022, treatment with Paxlovid, Lagevrio, Veklury, and mAbs was assessed by race and ethnicity, overall and among high-risk patient groups. During 2022, the percentage of COVID-19 patients seeking medical care who were treated with Paxlovid increased from 0.6% in January to 20.2% in April and 34.3% in July; the other three medications were used less frequently (0.7%-5.0% in July). During April-July 2022, when Paxlovid use was highest, compared with White patients, Black or African American (Black) patients were prescribed Paxlovid 35.8% less often, multiple or other race patients 24.9% less often, American Indian or Alaska Native and Native Hawaiian or other Pacific Islander (AIAN/NHOPI) patients 23.1% less often, and Asian patients 19.4% less often; Hispanic patients were prescribed Paxlovid 29.9% less often than non-Hispanic patients. Racial and ethnic disparities in Paxlovid treatment were generally somewhat higher among patients at high risk for severe COVID-19, including those aged ≥50 years and those who were immunocompromised. The expansion of programs focused on equitable awareness of and access to outpatient COVID-19 treatments, as well as COVID-19 vaccination, including updated bivalent booster doses, can help protect persons most at risk for severe illness and facilitate equitable health outcomes., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. William E. Trick reports institutional support from PCORnet, the National Patient-Centered Clinical Research Network. Anuradha Paranjape reports serving as the uncompensated president of the Association of Chiefs & Leaders of General Internal Medicine. Michael D. Kappelman reports consulting fees from Abbvie, Takeda, Janssen, and Pfizer, and stock ownership in Johnson & Johnson. Joshua L. Denson reports research funding from the American Diabetes Association, the Society of Critical Care Medicine, and the National Institutes of Health (NIH) (Grant funding the Louisiana Clinical and Translational Science Center Roadmap Scholars Award). Thomas W. Carton and Jason P. Block report grant support from NIH, as part of the Researching COVID to Enhance Recovery (RECOVER) research program. No other potential conflicts of interest were disclosed.

Introduction: Hypertension and diabetes are associated with increased COVID-19 severity, yet less is known about COVID-19 outcomes across levels of disease control for these conditions., Methods: All adults aged ≥20 years with COVID-19 between March 1, 2020 and March 15, 2021 in 42 healthcare systems in National Patient-Centered Clinical Research Network were identified., Results: Among 656,049 adults with COVID-19, 41% had hypertension, and 13% had diabetes. Of patients with classifiable hypertension, 35% had blood pressure <130/80 mmHg, 40% had blood pressure of 130‒139/80‒89 mmHg, 21% had blood pressure of 140‒159/90‒99 mmHg, and 6% had blood pressure ≥160/100 mmHg. Severe COVID-19 outcomes were more prevalent among those with blood pressure of ≥160/100 than among those with blood pressure of 130-139/80-89, including hospitalization (23.7% [95% CI=23.0, 24.4] vs 11.7% [95% CI=11.5, 11.9]), receipt of critical care (5.5% [95% CI=5.0, 5.8] vs 2.4% [95% CI=2.3, 2.5]), receipt of mechanical ventilation (3.0% [95% CI=2.7, 3.3] vs 1.2% [95% CI=1.1, 1.3]), and 60-day mortality (4.6% [95% CI=4.2, 4.9] vs 1.8% [95% CI=1.7, 1.9]). Of patients with classifiable diabetes, 44% had HbA1c <7%, 35% had HbA1c 7% to <9%, and 21% had HbA1c ≥9%. Hospitalization prevalence was 31.3% (95% CI=30.7, 31.9) among those with HbA1c <7% vs 40.2% (95% CI=39.4, 41.1) among those with HbA1c ≥9%; other outcomes did not differ substantially by HbA1c., Conclusions: These findings highlight the importance of appropriate management of hypertension and diabetes, including during public health emergencies such as the COVID-19 pandemic.

Background: The evidence based on the inclusion of patients and other stakeholders as partners in the clinical research process has grown substantially. However, little has been reported on how stakeholders are engaged in the governance of large-scale clinical research networks and the infrastructure used by research networks to support engagement in network-affiliated activities., Objectives: The objective was to document engagement activities and practices emerging from Clinical Research Networks (CRNs) participating in PCORnet, the National Patient-Centered Clinical Research Network, specifically regarding governance and engagement infrastructure., Methods: We conducted an environmental scan of PCORnet CRN engagement structures, assets, and services, focusing on network oversight structures for policy development and strategic decision-making. The scan included assets and services for supporting patient/stakeholder engagement. Data were collected by searching web-based literature and tool repositories, review of CRN Engagement Plans, analysis of previously collected key informant interviews, and CRN-based iterative review of structured worksheets., Results: We identified 87 discrete engagement structures, assets, and services across nine CRNs. All CRNs engage patients/stakeholders in their governance, maintain workgroups and/or staff dedicated to overseeing engagement strategies, and offer one or more services to non-CRN researchers to enhance conducting engaged clinical research., Conclusions: This work provides an important resource for the research community to explore engagement across peers, reflect on progress, consider opportunities to leverage existing infrastructure, and identify new collaborators. It also serves to highlight PCORnet as a resource for non-CRN researchers seeking to efficiently conduct engaged clinical research and a venue for advancing the science of engagement., Competing Interests: There are no potential conflicts of interest or corporate sponsors for this work., (© 2022 The Authors. Learning Health Systems published by Wiley Periodicals LLC on behalf of University of Michigan.)

Cardiac complications, particularly myocarditis and pericarditis, have been associated with SARS-CoV-2 (the virus that causes COVID-19) infection (1-3) and mRNA COVID-19 vaccination (2-5). Multisystem inflammatory syndrome (MIS) is a rare but serious complication of SARS-CoV-2 infection with frequent cardiac involvement (6). Using electronic health record (EHR) data from 40 U.S. health care systems during January 1, 2021-January 31, 2022, investigators calculated incidences of cardiac outcomes (myocarditis; myocarditis or pericarditis; and myocarditis, pericarditis, or MIS) among persons aged ≥5 years who had SARS-CoV-2 infection, stratified by sex (male or female) and age group (5-11, 12-17, 18-29, and ≥30 years). Incidences of myocarditis and myocarditis or pericarditis were calculated after first, second, unspecified, or any (first, second, or unspecified) dose of mRNA COVID-19 (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) vaccines, stratified by sex and age group. Risk ratios (RR) were calculated to compare risk for cardiac outcomes after SARS-CoV-2 infection to that after mRNA COVID-19 vaccination. The incidence of cardiac outcomes after mRNA COVID-19 vaccination was highest for males aged 12-17 years after the second vaccine dose; however, within this demographic group, the risk for cardiac outcomes was 1.8-5.6 times as high after SARS-CoV-2 infection than after the second vaccine dose. The risk for cardiac outcomes was likewise significantly higher after SARS-CoV-2 infection than after first, second, or unspecified dose of mRNA COVID-19 vaccination for all other groups by sex and age (RR 2.2-115.2). These findings support continued use of mRNA COVID-19 vaccines among all eligible persons aged ≥5 years., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Jason P. Block, Christopher B. Forrest, Grace M. Lee, and Thomas W. Carton report support from the National Institutes of Health (NIH) as part of the Researching COVID to Enhance Recovery (RECOVER) program. Nidhi Ghildayal reports NIH funding for a postdoctoral position. Michael D. Kappelman reports grants from NIH, PCORI, Helmsley Trust, Abbvie, Arenapharm, Boehringer Ingelheim, Bristol Myers Squibb, Celtrion, Eli Lilly, Genentech, Janssen (a subsidiary of Johnson & Johnson, Pfizer, and Takeda) and consulting fees from Abbvie, Janssen, Takeda, and Pfizer; payment for service on a data safety monitoring board for Eli Lilly, and payment for service on the editorial board of the American Journal of Gastroenterology. Kenneth H. Mayer reports grant support from NIH’s COVID-19 Vaccine Trials Network for a Phase III AstraZeneca SARS-CoV-2 vaccine trial. Matthew E. Oster reports institutional support from NIH’s National Heart, Lung, and Blood Institute. No other potential conflicts of interest were disclosed.

Background: African Americans have nearly double the rate of posttraumatic stress disorder (PTSD) compared with other racial/ethnic groups., Objective: To understand whether trauma-informed collaborative care (TICC) is effective for improving PTSD among African Americans in New Orleans who receive their care in Federally Qualified Health Centers (FQHCs)., Design and Method: In this pilot randomized controlled trial, we assigned patients within a single site to either TICC or to enhanced usual care (EUC). We performed intent to treat analysis by nonparametric exact tests for small sample sizes., Participants: We enrolled 42 patients from October 12, 2018, through July 2, 2019. Patients were eligible if they considered the clinic their usual source of care, had no obvious physical or cognitive obstacles that would prevent participation, were age 18 or over, self-identified as African American, and had a provisional diagnosis of PTSD., Measures: Our primary outcome measures were PTSD measured as both a symptom score and a provisional diagnosis based on the PTSD Checklist for DSM-5 (PCL-5)., Key Results: Nine months following baseline, both PTSD symptom scores and provisional PTSD diagnosis rates decreased substantially more for patients in TICC than in EUC. The decreases were by 26 points in EUC and 36 points in TICC for symptoms (P=0.08) and 33% in EUC and 57% in TICC for diagnosis rates (P=0.27). We found no effects for mediator variables., Conclusions: TICC shows promise for addressing PTSD in this population. A larger-scale trial is needed to fully assess the effectiveness of this approach in these settings., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Context: Integrating longitudinal data from community-based organizations (eg, physical activity programs) with electronic health record information can improve capacity for childhood obesity research., Objective: A governance framework that protects individual privacy, accommodates organizational data stewardship requirements, and complies with laws and regulations was developed and implemented to support the harmonization of data from disparate clinical and community information systems., Participants and Setting: Through the Childhood Obesity Data Initiative (CODI), 5 Colorado-based organizations collaborated to expand an existing distributed health data network (DHDN) to include community-generated data and assemble longitudinal patient records for research., Design: A governance work group expanded an existing DHDN governance infrastructure with CODI-specific data use and exchange policies and procedures that were codified in a governance plan and a delegated-authority, multiparty, reciprocal agreement., Results: A CODI governance work group met from January 2019 to March 2020 to conceive an approach, develop documentation, and coordinate activities. Governance requirements were synthesized from the CODI use case, and a customized governance approach was constructed to address governance gaps in record linkage, a procedure to request data, and harmonizing community and clinical data. A Master Sharing and Use Agreement (MSUA) and Memorandum of Understanding were drafted and executed to support creation of linked longitudinal records of clinical- and community-derived childhood obesity data. Furthermore, a multiparty infrastructure protocol was approved by the local institutional review board (IRB) to expedite future CODI research by simplifying IRB research applications., Conclusion: CODI implemented a clinical-community governance strategy that built trust between organizations and allowed efficient data exchange within a DHDN. A thorough discovery process allowed CODI stakeholders to assess governance capacity and reveal regulatory and organizational obstacles so that the governance infrastructure could effectively leverage existing knowledge and address challenges. The MSUA and complementary governance documents can inform similar efforts., Competing Interests: The authors have indicated no potential conflicts of interest to disclose., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc.)

Importance: New symptoms and conditions can develop following SARS-CoV-2 infection. Whether they occur more frequently among persons with SARS-CoV-2 infection compared with those without is unclear., Objective: To compare the prevalence of new diagnoses of select symptoms and conditions between 31 and 150 days after testing among persons who tested positive vs negative for SARS-CoV-2., Design, Setting, and Participants: This cohort study analyzed aggregated electronic health record data from 40 health care systems, including 338 024 persons younger than 20 years and 1 790 886 persons aged 20 years or older who were tested for SARS-CoV-2 during March to December 2020 and who had medical encounters between 31 and 150 days after testing., Main Outcomes and Measures: International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes were used to capture new symptoms and conditions that were recorded 31 to 150 days after a SARS-CoV-2 test but absent in the 18 months to 7 days prior to testing. The prevalence of new symptoms and conditions was compared between persons with positive and negative SARS-CoV-2 tests stratified by age (20 years or older and young than 20 years) and care setting (nonhospitalized, hospitalized, or hospitalized and ventilated)., Results: A total of 168 701 persons aged 20 years or older and 26 665 younger than 20 years tested positive for SARS-CoV-2, and 1 622 185 persons aged 20 years or older and 311 359 younger than 20 years tested negative. Shortness of breath was more common among persons with a positive vs negative test result among hospitalized patients (≥20 years: prevalence ratio [PR], 1.89 [99% CI, 1.79-2.01]; <20 years: PR, 1.72 [99% CI, 1.17-2.51]). Shortness of breath was also more common among nonhospitalized patients aged 20 years or older with a positive vs negative test result (PR, 1.09 [99% CI, 1.05-1.13]). Among hospitalized persons aged 20 years or older, the prevalence of new fatigue (PR, 1.35 [99% CI, 1.27-1.44]) and type 2 diabetes (PR, 2.03 [99% CI, 1.87-2.19]) was higher among those with a positive vs a negative test result. Among hospitalized persons younger than 20 years, the prevalence of type 2 diabetes (PR, 2.14 [99% CI, 1.13-4.06]) was higher among those with a positive vs a negative test result; however, the prevalence difference was less than 1%., Conclusions and Relevance: In this cohort study, among persons hospitalized after a positive SARS-CoV-2 test result, diagnoses of certain symptoms and conditions were higher than among those with a negative test result. Health care professionals should be aware of symptoms and conditions that may develop after SARS-CoV-2 infection, particularly among those hospitalized after diagnosis.

The COVID-19 pandemic has magnified longstanding health care and social inequities, resulting in disproportionately high COVID-19-associated illness and death among members of racial and ethnic minority groups (1). Equitable use of effective medications (2) could reduce disparities in these severe outcomes (3). Monoclonal antibody (mAb) therapies against SARS-CoV-2, the virus that causes COVID-19, initially received Emergency Use Authorization (EUA) from the Food and Drug Administration (FDA) in November 2020. mAbs are typically administered in an outpatient setting via intravenous infusion or subcutaneous injection and can prevent progression of COVID-19 if given after a positive SARS-CoV-2 test result or for postexposure prophylaxis in patients at high risk for severe illness. † Dexamethasone, a commonly used steroid, and remdesivir, an antiviral drug that received EUA from FDA in May 2020, are used in inpatient settings and help prevent COVID-19 progression § (2). No large-scale studies have yet examined the use of mAb by race and ethnicity. Using COVID-19 patient electronic health record data from 41 U.S. health care systems that participated in the PCORnet, the National Patient-Centered Clinical Research Network, ¶ this study assessed receipt of medications for COVID-19 treatment by race (White, Black, Asian, and Other races [including American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, and multiple or Other races]) and ethnicity (Hispanic or non-Hispanic). Relative disparities in mAb** treatment among all patients †† (805,276) with a positive SARS-CoV-2 test result and in dexamethasone and remdesivir treatment among inpatients §§ (120,204) with a positive SARS-CoV-2 test result were calculated. Among all patients with positive SARS-CoV-2 test results, the overall use of mAb was infrequent, with mean monthly use at 4% or less for all racial and ethnic groups. Hispanic patients received mAb 58% less often than did non-Hispanic patients, and Black, Asian, or Other race patients received mAb 22%, 48%, and 47% less often, respectively, than did White patients during November 2020-August 2021. Among inpatients, disparities were different and of lesser magnitude: Hispanic inpatients received dexamethasone 6% less often than did non-Hispanic inpatients, and Black inpatients received remdesivir 9% more often than did White inpatients. Vaccines and preventive measures are the best defense against infection; use of COVID-19 medications postexposure or postinfection can reduce morbidity and mortality and relieve strain on hospitals but are not a substitute for COVID-19 vaccination. Public health policies and programs centered around the specific needs of communities can promote health equity (4). Equitable receipt of outpatient treatments, such as mAb and antiviral medications, and implementation of prevention practices are essential to reducing existing racial and ethnic inequities in severe COVID-19-associated illness and death., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Amy K. Feehan receives research support from the Louisiana Public Health Institute. Joshua L. Denson reports grants from the American Diabetes Association, research funding from the Gordon and Betty Moore Foundation, the Society of Critical Care Medicine, and the National Institutes of Health (NIH); and personal fees from Astrazeneca, GlaxoSmithKline, and Guidepoint Global, outside the current work. Jason P. Block reports a grant from the National Institute of Diabetes and Digestive and Kidney Diseases, NIH and receipt of honoraria for participating in a panel discussion for the Kenner Foundation on “Early Detection of Pancreatic Cancer.” No other potential conflicts of interest were disclosed.

Background: The COVID-19 pandemic has catalyzed a global public response and innovation in clinical study methods., Objective: The COVID-19 Citizen Science study was designed to generate knowledge about participant-reported COVID-19 symptoms, behaviors, and disease occurrence., Methods: COVID-19 Citizen Science is a longitudinal cohort study launched on March 26, 2020, on the Eureka Research Platform. This study illustrates important advances in digital clinical studies, including entirely digital study participation, targeted recruitment strategies, electronic consent, recurrent and time-updated assessments, integration with smartphone-based measurements, analytics for recruitment and engagement, connection with partner studies, novel engagement strategies such as participant-proposed questions, and feedback in the form of real-time results to participants., Results: As of February 2021, the study has enrolled over 50,000 participants. Study enrollment and participation are ongoing. Over the lifetime of the study, an average of 59% of participants have completed at least one survey in the past 4 weeks., Conclusions: Insights about COVID-19 symptoms, behaviors, and disease occurrence can be drawn through digital clinical studies. Continued innovation in digital clinical study methods represents the future of clinical research., International Registered Report Identifier (irrid): DERR1-10.2196/28169., (©Alexis L Beatty, Noah D Peyser, Xochitl E Butcher, Thomas W Carton, Jeffrey E Olgin, Mark J Pletcher, Gregory M Marcus. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 30.08.2021.)

Background: The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy., Methods: Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis., Results: A total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922])., Conclusions: In this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily. (Funded by the Patient-Centered Outcomes Research Institute; ADAPTABLE ClinicalTrials.gov number, NCT02697916.)., (Copyright © 2021 Massachusetts Medical Society.)

Objective: To describe PCORnet, a clinical research network developed for patient-centered outcomes research on a national scale., Study Design and Setting: Descriptive study of the current state and future directions for PCORnet. We conducted cross-sectional analyses of the health systems and patient populations of the 9 Clinical Research Networks and 2 Health Plan Research Networks that are part of PCORnet., Results: Within the Clinical Research Networks, electronic health data are currently collected from 337 hospitals, 169,695 physicians, 3,564 primary care practices, 338 emergency departments, and 1,024 community clinics. Patients can be recruited for prospective studies from any of these clinical sites. The Clinical Research Networks have accumulated data from 80 million patients with at least one visit from 2009 to 2018. The PCORnet Health Plan Research Network population of individuals with a valid enrollment segment from 2009 to 2019 exceeds 60 million individuals, who on average have 2.63 years of follow-up., Conclusion: PCORnet's infrastructure comprises clinical data from a diverse cohort of patients and has the capacity to rapidly access these patient populations for pragmatic clinical trials, epidemiological research, and patient-centered research on rare diseases., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

PCORnet, the Patient-Centered Outcomes Research Network, is comprised of health systems and health plans that transform electronic health records (EHRs) and claims data to a common data model (CDM) to facilitate real-world clinical research. Because patients receive health care in multiple care delivery settings, linking health records across systems and health plan claims would provide a more comprehensive and accurate picture of health care for patients. The current study expanded on a PCORnet Antibiotics and Childhood Growth (ABX) study to (1) identify and implement a privacy-preserving patient linkage solution among a clinical data research network and a health plan network within the ABX Study, and (2) assess overlap in prescribed and dispensed antibiotics and additional data gained from claims among the linked patients. This manuscript describes the linkage process and resulting overlap analysis. The authors identified 549 patients from the EHR record study cohort who had claims records with the health plan. Sixty percent (n = 329) of patients had consistent antibiotic exposure data across the 2 sources, indicating antibiotic exposure (44.3%) or nonexposure (15.7%). Among total antibiotic prescribing records, 43.1% had a matched claims record for dispensing within 60 days. Among antibiotic dispense records 26.5% were not associated with a prescribing record in the linked health systems. These findings showcase the feasibility of linking health plan claims data to PCORnet CDM in a privacy-preserving manner while also demonstrating continued gaps in data that may occur. The study highlights the importance of combining multiple health data sources for comprehensive clinical research.

Objectives: We used treatment for alcohol withdrawal syndrome as an objective surrogate marker to investigate the relationship between alcohol-related health outcomes and home neighborhood alcohol outlet density and alcohol advertising density. Methods: Mixed effects logistic regression examined whether alcohol outlet density or alcohol advertisement density within either one-quarter mile or one-half mile of individuals' home address was associated with treatment for alcohol withdrawal. Results: Adjusted models showed outlet and advertising density, particularly off-sale outlet density within one-quarter mile of the home, increased the risk of hospital admission for alcohol withdrawal syndrome (AOR = 1.15). Conclusion/impact: These data inform public policy initiatives to reduce the harmful effects of alcohol by regulating the neighborhood alcohol environment.

This study examined the representativeness of the County Health Rankings and Roadmaps (CHR) measure of potentially preventable hospitalizations, which is derived from Medicare inpatient claims data, as an indicator of potentially preventable hospitalizations for adults aged ≥18 years. Potentially preventable hospitalizations were evaluated using rates of ambulatory care sensitive conditions (ACSCs). CHR rates of hospitalization for ACSCs based on Medicare data for 2010, Agency for Healthcare Research and Quality Prevention Quality Indicator #90 Overall Composite (PQI #90 Composite) rates of ACSCs based on hospital inpatient data for adults aged ≥18 years for 2011, and 2011 total mortality rates for adults aged ≥18 years for 212 counties in 3 US states were evaluated. Pearson correlation analyses were used to assess the linear association between the PQI #90 Composite and CHR rates of hospitalization for ACSCs as well as associations of these measures with total mortality. Steiger's Z-test was conducted to examine whether the PQI #90 Composite and CHR measures of health care quality were similarly correlated with total mortality. The age- and sex-adjusted PQI #90 Composite for adults ≥18 years was moderately correlated with the CHR rate of hospitalization for ACSCs. The PQI #90 Composite and CHR measures of hospitalization for ACSCs were similarly correlated with mortality. These findings suggest that in the absence of easily accessible, high-quality data for adults aged ≥18 years, the CHR measure of potentially preventable hospitalizations provides a modest but acceptable approximation of county-level disparities in potentially preventable hospitalizations for the US adult population.

Background: Louisiana has one of the highest rates of overweight and obese children in the United States. The Healthy School Food Collaborative (HSFC) was created to allow New Orleans's schools to select their own healthy school Food Service Provider (FSP) with requirements for higher nutritional standards than traditional options. The goal of this cross-sectional study was to examine whether HSFC membership was associated with lunch consumption rates in elementary school children., Methods: An 8-week plate waste study examining 18,070 trays of food among fourth and fifth graders was conducted. Participants included 7 schools and the 3 FSPs (2 HSFC and 1 non-HSFC member) that serviced them. Mixed models analysis examined whether consumption rates of food items differed among FSPs., Results: On average, students consumed 307 cal during lunch. Analyses showed significant differences in consumption rates of entrée, vegetables, fruit, and milk between the 3 FSPs (p < .01). The highest consumption rate was among entrées at 65%. One HSFC provider had consumption levels consistent with the non-HSFC FSP., Conclusions: Overall, students consumed less than 60% of the US Department of Agriculture recommended calories for school lunch. While overall caloric consumption was higher among the non-HSFC schools, interventions to increase lunch consumption across all schools are needed., (© 2018, American School Health Association.)

Background: While school foods have become healthier under the Healthy, Hunger Free Kids Act, research suggests there is still substantial food waste in cafeterias. It is therefore necessary to study factors that can impact food consumption, including holding recess before lunch ("reverse recess") and starting lunch periods very early or very late., Objective: This study examined the association between the timing of recess (pre-lunch vs post-lunch recess), the timing of the lunch period, and food consumed by students at lunch., Design: We conducted a secondary data analysis from a repeated cross-sectional design., Participants/setting: An 8-week plate waste study examining 20,183 trays of food was conducted in New Orleans, LA, in 2014. The study involved 1,036 fourth- and fifth-grade students from eight public schools., Main Outcome Measures: We measured percent of entrées, fruit, vegetables, and milk consumed by students at lunch., Statistical Analyses Performed: We used mixed-model analyses, controlling for student sex, grade, and the timing of the lunch period, and examined the association between reverse recess and student lunch consumption. Mixed-model analyses controlling for student sex, grade, and recess status examined whether the timing of the lunch period was associated with student lunch consumption., Results: On average, students with reverse recess consumed 5.1% more of their fruit than students with post-lunch recess (P=0.009), but there were no significant differences in entrées, vegetables, or milk intake. Compared to students with "midday" lunch periods, on average students with "early" lunch periods consumed 5.8% less of their entrées (P<0.001) and 4.5% less of their milk (P=0.047). Students with "late" lunch periods consumed 13.8% less of their entrées (P<0.001) and 15.9% less of their fruit (P<0.001)., Conclusions: Reverse recess was associated with increased fruit consumption. "Early" lunch periods were associated with decreased entrée and milk consumption, and "late" lunch periods were associated with decreased entrée and fruit consumption. Additional research is recommended to determine whether these associations are causal., (Copyright © 2017 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Background: The relationship between mental health status and smoking is complicated and often confounded by bi-directionality, yet most research on this relationship assumes exogeneity., Objectives: The goal of this article is to implement an instrumental variable approach to (1) test the exogeneity assumption and (2) report on the association between mental health status and smoking post-disaster., Methods: This analysis utilizes the 2006 and 2007 Louisiana Behavioral Risk Factor Surveillance Survey to examine the link between mental distress and smoking in areas affected by Hurricanes Katrina and Rita. Residence in a hurricane-affected parish (county) was used as an instrumental variable for mental distress., Results: Just over 22% of the sample resided in a hurricane-affected parish. Residents of hurricane-affected parishes were significantly more likely to report occasional and frequent mental distress. Residence in a hurricane-affected parish was not significantly associated with smoking status. With residence established as a salient instrumental variable for mental distress, the exogeneity assumption was tested and confirmed in this sample. A dose-response relationship existed between mental distress and smoking, with smoking prevalence increasing directly (and non-linearly) with mental distress., Conclusions: In this sample, the relationship between mental distress and smoking status was exogenous and followed a dose-response relationship, suggesting that the disasters did not result in an uptake of smoking initiation, but that the higher amounts of mental distress may lead to increased use among smokers. The findings suggest that tobacco control programs should devise unique strategies to address mentally distressed populations.

Satisfaction with body image is a factor related to health outcomes. The purpose of this study is to examine the relationship between body image satisfaction and body size perception in an urban, Black community sample in New Orleans, Louisiana. Only 42.2% of respondents were satisfied with their body image and 44.1% correctly perceived their body size. Most respondents chose an ideal image in the normal body mass index range with over half choosing an ideal image smaller than their actual size. Misperception was greatest among the heaviest respondents. Females, those who overestimated their size, those with an education beyond high school, and those who were active in order to lose weight were less likely to be satisfied ( p < .001). Those who were active but not trying to lose weight were more likely to be satisfied ( p < .001). This suggests that perception of and satisfaction with body size may play a role in health behavior decisions.

Objective: Exposure to environmental tobacco smoke (ETS) in smoky venues puts patrons and employees at risk for immediate respiratory symptoms. Although much literature focuses on outcomes associated with chronic ETS exposure, the current study assesses changes in lung function after acute exposure., Methods: Ninety-six nonsmoking, healthy adults were exposed to ETS at a bar. Lung function [eg, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1)] was assessed at baseline, immediately after 3 hours of ETS exposure, and 2 hours after exiting the bar. PM2.5 recordings were also measured., Results: Repeated-measures analysis of variance found significant decreases in FEV1, FVC and FEF25-75%, and peak expiratory flow after ETS exposure compared with baseline that remained significantly decreased after a 2-hour recovery period., Conclusions: Acute exposure to ETS in a natural environment significantly attenuates lung function. A subgroup experienced heightened reductions in lung function.

Evidence-based approaches are needed to address the high levels of sexual risk behavior and associated HIV infection among orphaned and vulnerable adolescents. This study recruited adolescents from a support program for HIV-affected families and randomly assigned them by cluster to receive one of the following: (1) a structured group-based behavioral health intervention; (2) interpersonal psychotherapy group sessions; (3) both interventions; or (4) no new interventions. With 95% retention, 1014 adolescents were interviewed three times over a 22-month period. Intent-to-treat analyses, applying multivariate difference-in-difference probit regressions, were performed separately for boys and girls to assess intervention impacts on sexual risk behaviors. Exposure to a single intervention did not impact behaviors. Exposure to both interventions was associated with risk-reduction behaviors, but the outcomes varied by gender: boys reported fewer risky sexual partnerships (β = -.48, p = .05) and girls reported more consistent condom (β = 1.37, p = .02). There was no difference in the likelihood of sexual debut for either gender. Providing both psychological and behavioral interventions resulted in long-term changes in sexual behavior that were not present when either intervention was provided in isolation. Multifaceted approaches for reducing sexual risk behaviors among vulnerable adolescents hold significant promise for mitigating the HIV epidemic among this priority population.

Background: There is expert consensus that delivery at a health facility substantially reduces the risk of maternal death. By increasing the use of antenatal (ANC), postnatal care (PNC) and family planning, the risk of maternal death can be further reduced. There has been little investigation of factors associated with the use of these services in Pakistan., Methods: A representative household survey was conducted in rural areas of Jhang district, Pakistan, to determine the effect of demographic, economic and program factors on the utilization of maternal health services. Married women who had children ages 12 months or younger were interviewed. Data was collected from 2,018 women on socio-demographic characteristics and the utilization of health services. Logistic regression analysis was conducted to identify the correlates of health services use. Marginal effects quantify the impact of various factors on service utilization., Results: Parity and education had the largest impact on institutional delivery: women were substantially less likely to deliver at a health facility after their first birth; women with primary or higher education were much more likely to have an institutional delivery. Age, autonomy, household wealth, proximity to a health facility and exposure to mass media were also important drivers of institutional delivery. The use of family planning within a year of delivery was low, with parity, education and husband's approval being the strongest determinants of use., Conclusions: The findings suggest that rural women are likely to respond to well-designed interventions that remove financial and physical barriers to accessing maternal health services and motivate women by emphasizing the benefits of these services. Interventions should specifically target women who have two or more living children, little formal education and are from the poorest households.