Medication-Induced Weight Change Across Common Antidepressant Treatments : A Target Trial Emulation Study.

BACKGROUND: Antidepressants are among the most commonly prescribed medications, but evidence on comparative weight change for specific first-line treatments is limited. OBJECTIVE: To compare weight change across common first-line antidepressant treatments by emulating a target trial. DESIGN: Observational cohort study over 24 months. SETTING: Electronic health record (EHR) data from 2010 to 2019 across 8 U.S. health systems. PARTICIPANTS: 183 118 patients. MEASUREMENTS: Prescription data determined initiation of treatment with sertraline, citalopram, escitalopram, fluoxetine, paroxetine, bupropion, duloxetine, or venlafaxine. The investigators estimated the population-level effects of initiating each treatment, relative to sertraline, on mean weight change (primary) and the probability of gaining at least 5% of baseline weight (secondary) 6 months after initiation. Inverse probability weighting of repeated outcome marginal structural models was used to account for baseline confounding and informative outcome measurement. In secondary analyses, the effects of initiating and adhering to each treatment protocol were estimated. RESULTS: Compared with that for sertraline, estimated 6-month weight gain was higher for escitalopram (difference, 0.41 kg [95% CI, 0.31 to 0.52 kg]), paroxetine (difference, 0.37 kg [CI, 0.20 to 0.54 kg]), duloxetine (difference, 0.34 kg [CI, 0.22 to 0.44 kg]), venlafaxine (difference, 0.17 kg [CI, 0.03 to 0.31 kg]), and citalopram (difference, 0.12 kg [CI, 0.02 to 0.23 kg]); similar for fluoxetine (difference, -0.07 kg [CI, -0.19 to 0.04 kg]); and lower for bupropion (difference, -0.22 kg [CI, -0.33 to -0.12 kg]). Escitalopram, paroxetine, and duloxetine were associated with 10% to 15% higher risk for gaining at least 5% of baseline weight, whereas bupropion was associated with 15% reduced risk. When the effects of initiation and adherence were estimated, associations were stronger but had wider CIs. Six-month adherence ranged from 28% (duloxetine) to 41% (bupropion). LIMITATION: No data on medication dispensing, low medication adherence, incomplete data on adherence, and incomplete data on weight measures across time points. CONCLUSION: Small differences in mean weight change were found between 8 first-line antidepressants, with bupropion consistently showing the least weight gain, although adherence to medications over follow-up was low. Clinicians could consider potential weight gain when initiating antidepressant treatment. PRIMARY FUNDING SOURCE: National Institutes of Health.

Association between SARS-CoV-2 infection and select symptoms and conditions 31 to 150 days after testing among children and adults.

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.

Public Health Surveillance in Electronic Health Records: Lessons From PCORnet.

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.

Preventive Service Usage and New Chronic Disease Diagnoses: Using PCORnet Data to Identify Emerging Trends, United States, 2018-2022.

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 A1c 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.

Racial/Ethnic Disparities in Post-acute Sequelae of SARS-CoV-2 Infection in New York: an EHR-Based Cohort Study from the RECOVER Program.

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.

Validity and Relative Validity of Alternative Methods of Assessing Physical Activity in Epidemiologic Studies: Findings From the Men's Lifestyle Validation Study.

In the Men's Lifestyle Validation Study (2011-2013), we examined the validity and relative validity of a physical activity questionnaire (PAQ), a Web-based 24-hour recall (Activities Completed Over Time in 24 Hours (ACT24)), and an accelerometer by multiple comparison methods. Over the course of 1 year, 609 men completed 2 PAQs, two 7-day accelerometer measurements, at least 1 doubly labeled water (DLW) physical activity level (PAL) measurement (n = 100 with repeat measurements), and 4 ACT24s; they also measured their resting pulse rate. A subset (n = 197) underwent dual-energy x-ray absorptiometry (n = 99 with repeated measurements). The method of triads was used to estimate correlations with true activity using DLW PAL, accelerometry, and the PAQ or ACT24 as alternative comparison measures. Estimated correlations of the PAQ with true activity were 0.60 (95% confidence interval (95% CI): 0.52, 0.68) for total activity, 0.69 (95% CI: 0.61, 0.79) for moderate-to-vigorous physical activity (MVPA), and 0.76 (95% CI: 0.62, 0.93) for vigorous activity. Corresponding correlations for total activity were 0.53 (95% CI: 0.45, 0.63) for the average of 4 ACT24s and 0.68 (95% CI: 0.61, 0.75) for accelerometry. Total activity and MVPA measured by PAQ, ACT24, and accelerometry were all significantly correlated with body fat percentage and resting pulse rate, which are physiological indicators of physical activity. Using a combination of comparison methods, we found the PAQ and accelerometry to have moderate validity for assessing physical activity, especially MVPA, in epidemiologic studies.

Antibiotics prior to age 2 years have limited association with preschool growth trajectory.

BACKGROUND: Prior studies of early antibiotic use and growth have shown mixed results, primarily on cross-sectional outcomes. This study examined the effect of oral antibiotics before age 24 months on growth trajectory at age 2-5 years. METHODS: We captured oral antibiotic prescriptions and anthropometrics from electronic health records through PCORnet, for children with ≥1 height and weight at 0-12 months of age, ≥1 at 12-30 months, and ≥2 between 25 and 72 months. Prescriptions were grouped into episodes by time and by antimicrobial spectrum. Longitudinal rate regression was used to assess differences in growth rate from 25 to 72 months of age. Models were adjusted for sex, race/ethnicity, steroid use, diagnosed asthma, complex chronic conditions, and infections. RESULTS: 430,376 children from 29 health U.S. systems were included, with 58% receiving antibiotics before 24 months. Exposure to any antibiotic was associated with an average 0.7% (95% CI 0.5, 0.9, p < 0.0001) greater rate of weight gain, corresponding to 0.05 kg additional weight. The estimated effect was slightly greater for narrow-spectrum (0.8% [0.6, 1.1]) than broad-spectrum (0.6% [0.3, 0.8], p < 0.0001) drugs. There was a small dose response relationship between the number of antibiotic episodes and weight gain. CONCLUSION: Oral antibiotic use prior to 24 months of age was associated with very small changes in average growth rate at ages 2-5 years. The small effect size is unlikely to affect individual prescribing decisions, though it may reflect a biologic effect that can combine with others.

Racial and Ethnic Disparities in Receipt of Medications for Treatment of COVID-19 - United States, March 2020-August 2021.

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.

Racial and Ethnic Disparities in Outpatient Treatment of COVID-19 - United States, January-July 2022.

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.

Cardiac Complications After SARS-CoV-2 Infection and mRNA COVID-19 Vaccination - PCORnet, United States, January 2021-January 2022.

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.

Natural language processing of head CT reports to identify intracranial mass effect: CTIME algorithm.

BACKGROUND: The Mortality Probability Model (MPM) is used in research and quality improvement to adjust for severity of illness and can also inform triage decisions. However, a limitation for its automated use or application is that it includes the variable "intracranial mass effect" (IME), which requires human engagement with the electronic health record (EHR). We developed and tested a natural language processing (NLP) algorithm to identify IME from CT head reports. METHODS: We obtained initial CT head reports from adult patients who were admitted to the ICU from our ED between 10/2013 and 9/2016. Each head CT head report was labeled yes/no IME by at least two of five independent labelers. The reports were then randomly divided 80/20 into training and test sets. All reports were preprocessed to remove linguistic and style variability, and a dictionary was created to map similar common terms. We tested three vectorization strategies: Term Frequency-Inverse Document frequency (TF-IDF), Word2Vec, and Universal Sentence Encoder to convert the report text to a numerical vector. This vector served as the input to a classification-tree-based ensemble machine learning algorithm (XGBoost). After training, model performance was assessed in the test set using the area under the receiver operating characteristic curve (AUROC). We also divided the continuous range of scores into positive/inconclusive/negative categories for IME. RESULTS: Of the 1202 CT reports in the training set, 308 (25.6%) reports were manually labeled as "yes" for IME. Of the 355 reports in the test set, 108 (30.4%) were labeled as "yes" for IME. The TF-IDF vectorization strategy as an input for the XGBoost model had the best AUROC:-- 0.9625 (95% CI 0.9443-0.9807). TF-IDF score categories were defined and had the following likelihood ratios: "positive" (TF-IDF score > 0.5) LR = 24.59; "inconclusive" (TF-IDF 0.05-0.5) LR = 0.99; and "negative" (TF-IDF < 0.05) LR = 0.05. 82% of reports were classified as either "positive" or "negative". In the test set, only 4 of 199 (2.0%) reports with a "negative" classification were false negatives and only 8 of 93 (8.6%) reports classified as "positive" were false positives. CONCLUSION: NLP can accurately identify IME from free-text reports of head CTs in approximately 80% of records, adequate to allow automatic calculation of MPM based on EHR data for many applications.

A Governance Framework to Integrate Longitudinal Clinical and Community Data in a Distributed Data Network: The Childhood Obesity Data Initiative.

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.

The Childhood Obesity Data Initiative: A Case Study in Implementing Clinical-Community Infrastructure Enhancements to Support Health Services Research and Public Health.

CONTEXT: We describe a participatory framework that enhanced and implemented innovative changes to an existing distributed health data network (DHDN) infrastructure to support linkage across sectors and systems. Our processes and lessons learned provide a potential framework for other multidisciplinary infrastructure development projects that engage in a participatory decision-making process. PROGRAM: The Childhood Obesity Data Initiative (CODI) provides a potential framework for local and national stakeholders with public health, clinical, health services research, community intervention, and information technology expertise to collaboratively develop a DHDN infrastructure that enhances data capacity for patient-centered outcomes research and public health surveillance. CODI utilizes a participatory approach to guide decision making among clinical and community partners. IMPLEMENTATION: CODI's multidisciplinary group of public health and clinical scientists and information technology experts collectively defined key components of CODI's infrastructure and selected and enhanced existing tools and data models. We conducted a pilot implementation with 3 health care systems and 2 community partners in the greater Denver Metro Area during 2018-2020. EVALUATION: We developed an evaluation plan based primarily on the Good Evaluation Practice in Health Informatics guideline. An independent third party implemented the evaluation plan for the CODI development phase by conducting interviews to identify lessons learned from the participatory decision-making processes. DISCUSSION: We demonstrate the feasibility of rapid innovation based upon an iterative and collaborative process and existing infrastructure. Collaborative engagement of stakeholders early and iteratively was critical to ensure a common understanding of the research and project objectives, current state of technological capacity, intended use, and the desired future state of CODI architecture. Integration of community partners' data with clinical data may require the use of a trusted third party's infrastructure. Lessons learned from our process may help others develop or improve similar DHDNs.

Changes in the calorie and nutrient content of purchased fast food meals after calorie menu labeling: A natural experiment.

BACKGROUND: Calorie menu labeling is a policy that requires food establishments to post the calories on menu offerings to encourage healthy food choice. Calorie labeling has been implemented in the United States since May 2018 per the Affordable Care Act, but to the best of our knowledge, no studies have evaluated the relationship between calorie labeling and meal purchases since nationwide implementation of this policy. Our objective was to investigate the relationship between calorie labeling and the calorie and nutrient content of purchased meals after a fast food franchise began labeling in April 2017, prior to the required nationwide implementation, and after nationwide implementation of labeling in May 2018, when all large US chain restaurants were required to label their menus. METHODS AND FINDINGS: We obtained weekly aggregated sales data from 104 restaurants that are part of a fast food franchise for 3 national chains in 3 US states: Louisiana, Mississippi, and Texas. The franchise provided all sales data from April 2015 until April 2019. The franchise labeled menus in April 2017, 1 year prior to the required nationwide implementation date of May 2018 set by the US Food and Drug Administration. We obtained nutrition information for items sold (calories, fat, carbohydrates, protein, saturated fat, sugar, dietary fiber, and sodium) from Menustat, a publicly available database with nutrition information for items offered at the top revenue-generating US restaurant chains. We used an interrupted time series to find level and trend changes in mean weekly calorie and nutrient content per transaction after franchise and nationwide labeling. The analytic sample represented 331,776,445 items purchased across 67,112,342 transactions. Franchise labeling was associated with a level change of -54 calories/transaction (95% confidence interval [CI]: -67, -42, p < 0.0001) and a subsequent 3.3 calories/transaction increase per 4-week period (95% CI: 2.5, 4.1, p < 0.0001). Nationwide implementation was associated with a level decrease of -82 calories/transaction (95% CI: -88, -76, p < 0.0001) and a subsequent -2.1 calories/transaction decrease per 4-week period (95% CI: -2.9, -1.3, p < 0.0001). At the end of the study, the model-based predicted mean calories/transaction was 4.7% lower (change = -73 calories/transaction, 95% CI: -81, -65), and nutrients/transaction ranged from 1.8% lower (saturated fat) to 7.0% lower (sugar) than what we would expect had labeling not been implemented. The main limitations were potential residual time-varying confounding and lack of individual-level transaction data. CONCLUSIONS: In this study, we observed that calorie labeling was associated with small decreases in mean calorie and nutrient content of fast food meals 2 years after franchise labeling and nearly 1 year after implementation of labeling nationwide. These changes imply that calorie labeling was associated with small improvements in purchased meal quality in US chain restaurants.

Reproducibility and Validity of a Semiquantitative Food Frequency Questionnaire in Men Assessed by Multiple Methods.

Among 626 participants of the Men's Lifestyle Validation Study (2011-2013), we evaluated the validity and reproducibility of a self-administered 152-item semiquantitative food frequency questionnaire (SFFQ) using two 7-day dietary records (7DDRs), 4 Automated Self-Administered 24-hour dietary recalls (ASA24s), four 24-hour urine samples, 1 doubly labeled water measurement (repeated in 104 participants), and 2 fasting blood samples, collected over 15 months. Compared with 7DDRs, SFFQs underestimated energy intake, macronutrients, and sodium intake but overestimated some micronutrients. The mean of the Spearman correlation coefficients was 0.66 (range, 0.38-0.88) between 46 energy-adjusted nutrients estimated from 7DDRs and the final SFFQ, deattenuated for within-person variation in the 7DDRs. These deattenuated correlations were similar using ASA24s as the comparison. Relative to biomarkers, SFFQs underestimated energy, sodium, and protein intakes, as well as the sodium:potassium ratio. The energy-adjusted correlations between the final SFFQ and the biomarkers were slightly lower than the correlations between the SFFQ and 7DDRs. Using the method of triads to calculate validity coefficients, the median validity coefficient between SFFQ and true intake was 0.65 and 0.69 using 7DDRs and ASA24s, respectively, as the third method. These data indicate that this SFFQ provided reasonably valid estimates for a wide range of nutrients when evaluated by multiple comparison methods.

Comparing shopper characteristics by online grocery ordering use among households in low-income communities in Maine.

OBJECTIVE: Online grocery shopping could improve access to healthy food, but it may not be equally accessible to all populations - especially those at higher risk for food insecurity. The current study aimed to compare the socio-demographic characteristics of families who ordered groceries online v. those who only shopped in-store. DESIGN: We analysed enrollment survey and 44 weeks of individually linked grocery transaction data. We used univariate χ2 and t-tests and logistic regression to assess differences in socio-demographic characteristics between households that only shopped in-store and those that shopped online with curbside pickup (online only or online and in-store). SETTING: Two Maine supermarkets. PARTICIPANTS: 863 parents or caregivers of children under 18 years old enrolled in two fruit and vegetable incentive trials. RESULTS: Participants had a total of 32 757 transactions. In univariate assessments, online shoppers had higher incomes (P < 0 0001), were less likely to participate in Special Supplemental Nutrition Program for Women, Infants, and Children or Supplemental Nutrition Assistance Program (SNAP; P < 0 0001) and were more likely to be female (P = 0·04). Most online shoppers were 30-39 years old, and few were 50 years or older (P = 0·003). After controlling for age, gender, race/ethnicity, number of children, number of adults, income and SNAP participation, female primary shoppers (OR = 2·75, P = 0·003), number of children (OR = 1·27, P = 0·04) and income (OR = 3·91 for 186-300 % federal poverty line (FPL) and OR = 6·92 for >300 % FPL, P < 0·0001) were significantly associated with likelihood of shopping online. CONCLUSIONS: In the current study of Maine families, low-income shoppers were significantly less likely to utilise online grocery ordering with curbside pickup. Future studies could focus on elucidating barriers and developing strategies to improve access.

Privacy-protecting multivariable-adjusted distributed regression analysis for multi-center pediatric study.

BACKGROUND: Privacy-protecting analytic approaches without centralized pooling of individual-level data, such as distributed regression, are particularly important for vulnerable populations, such as children, but these methods have not yet been tested in multi-center pediatric studies. METHODS: Using the electronic health data from 34 healthcare institutions in the National Patient-Centered Clinical Research Network (PCORnet), we fit 12 multivariable-adjusted linear regression models to assess the associations of antibiotic use <24 months of age with body mass index z-score at 48 to <72 months of age. We ran these models using pooled individual-level data and conventional multivariable-adjusted regression (reference method), as well as using the more privacy-protecting pooled summary-level intermediate statistics and distributed regression technique. We compared the results from these two methods. RESULTS: Pooled individual-level and distributed linear regression analyses produced virtually identical parameter estimates and standard errors. Across all 12 models, the maximum difference in any of the parameter estimates or standard errors was 4.4833 × 10-10. CONCLUSIONS: We demonstrated empirically the feasibility and validity of distributed linear regression analysis using only summary-level information within a large multi-center study of children. This approach could enable expanded opportunities for multi-center pediatric research, especially when sharing of granular individual-level data is challenging.

Effect of an Online Weight Management Program Integrated With Population Health Management on Weight Change: A Randomized Clinical Trial.

Importance: Online programs may help with weight loss but have not been widely implemented in routine primary care. Objective: To compare the effectiveness of a combined intervention, including an online weight management program plus population health management, with the online program only and with usual care. Design, Setting, and Participants: Cluster randomized trial with enrollment from July 19, 2016, through August 10, 2017, at 15 primary care practices in the US. Eligible participants had a scheduled primary care visit and were aged 20 to 70 years, had a body mass index between 27 and less than 40, and had a diagnosis of hypertension or type 2 diabetes. Follow-up ended on May 8, 2019. Interventions: Participants in the usual care group (n = 326) were mailed general information about weight management. Participants in the online program only group (n = 216) and the combined intervention group (n = 298) were registered for the online program. The participants in the combined intervention group also received weight-related population health management, which included additional support from nonclinical staff who monitored their progress in the online program and conducted periodic outreach. Main Outcomes and Measures: The primary outcome was weight change at 12 months based on measured weights recorded in the electronic health record. Weight change at 18 months was a secondary outcome. Results: Among the 840 participants who enrolled (mean age, 59.3 years [SD, 8.6 years]; 60% female; 76.8% White), 732 (87.1%) had a recorded weight at 12 months and the missing weights for the remaining participants were imputed. There was a significant difference in weight change at 12 months by group with a mean weight change of -1.2 kg (95% CI, -2.1 to -0.3 kg) in the usual care group, -1.9 kg (95% CI, -2.6 to -1.1 kg) in the online program only group, and -3.1 kg (95% CI, -3.7 to -2.5 kg) in the combined intervention group (P < .001). The difference in weight change between the combined intervention group and the usual care group was -1.9 kg (97.5% CI, -2.9 to -0.9 kg; P < .001) and the difference between the combined intervention group and the online program only group was -1.2 kg (95% CI, -2.2 to -0.3 kg; P = .01). At 18 months, the mean weight change was -1.9 kg (95% CI, -2.8 to -1.0 kg) in the usual care group, -1.1 kg (95% CI, -2.0 to -0.3 kg) in the online program only group, and -2.8 kg (95% CI, -3.5 to -2.0 kg) in the combined intervention group (P < .001). Conclusions and Relevance: Among primary care patients with overweight or obesity and hypertension or type 2 diabetes, combining population health management with an online program resulted in a small but statistically significant greater weight loss at 12 months compared with usual care or the online program only. Further research is needed to understand the generalizability, scalability, and durability of these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT02656693.

Maternal antibiotic use during pregnancy and childhood obesity at age 5 years.

OBJECTIVE: The benefits of antibiotic treatment during pregnancy are immediate, but there may be long-term risks to the developing child. Prior studies show an association between early life antibiotics and obesity, but few have examined this risk during pregnancy. SUBJECTS: To evaluate the association of maternal antibiotic exposure during pregnancy on childhood BMI-z at 5 years, we conducted a retrospective cohort analysis. Using electronic health record data from seven health systems in PCORnet, a national distributed clinical research network, we included children with same-day height and weight measures who could be linked to mothers with vital measurements during pregnancy. The primary independent variable was maternal outpatient antibiotic prescriptions during pregnancy (any versus none). We examined dose response (number of antibiotic episodes), spectrum and class of antibiotics, and antibiotic episodes by trimester. The primary outcome was child age- and sex-specific BMI-z at age 5 years. RESULTS: The final sample was 53,320 mother-child pairs. During pregnancy, 29.9% of mothers received antibiotics. In adjusted models, maternal outpatient antibiotic prescriptions during pregnancy were not associated with child BMI-z at age 5 years (ß = 0.00, 95% CI -0.03, 0.02). When evaluating timing during pregnancy, dose-response, spectrum and class of antibiotics, there were no associations of maternal antibiotics with child BMI-z at age 5 years. CONCLUSION: In this large observational cohort, provision of antibiotics during pregnancy was not associated with childhood BMI-z at 5 years.

Primary Care Patients' and Providers' Perspectives about an Online Weight Management Program: a Qualitative Study.

BACKGROUND: Primary care providers (PCPs) often take the lead role in caring for patients with overweight and obesity; however, few PCPs counsel patients about weight loss. Online weight management programs that are integrated within primary care may help address this gap in care. OBJECTIVE: To identify perceptions of and experience with online weight management programs in general and with a proposed online program, to identify barriers to use, and to improve the design and content of our intervention, which included an online program plus population health management (PHM) support from primary care practices. DESIGN: A mixed qualitative methods study including three patient focus groups and seven semi-structured interviews with healthcare providers. PARTICIPANTS: A total of 13 adult patients (age range, 20-70) with body mass index (BMI) 27-35 kg/m2 attended the focus groups. In-person semi-structured interviews were conducted with seven healthcare providers (three PCPs, two population health managers, one primary care nurse, and one registered dietitian). MAIN MEASURES: We developed and used semi-structured focus groups and interview guides. The focus group and interviews were recorded and transcribed. Using grounded theory, we analyzed the transcripts to identify and extract common concepts and themes. KEY RESULTS: Although patients and healthcare providers expressed positive opinions about online weight management programs, few patients had experience with them, and providers stated that such programs are not being widely implemented in primary care settings. Some participants highlighted the flexibility and low cost as strengths of online weight management tools compared with in-person programs. All participants had favorable opinions about our proposed intervention and were overwhelmingly positive about the combination of an online program and PHM support. CONCLUSIONS: This study highlights the potential value of online weight management programs and PHM support in primary care. CLINICAL TRIALS REGISTRATION: NCT02656693.