Comparative Risk of Angioedema With Sacubitril-Valsartan vs Renin-Angiotensin-Aldosterone Inhibitors.

BACKGROUND: Data on angioedema risk among sacubitril-valsartan (SV) users in real-world settings are limited. OBJECTIVES: We sought to evaluate the risk of angioedema among SV new users compared with angiotensin-converting enzyme (ACE) inhibitor and angiotensin-receptor-blocker (ARB) new users separately. METHODS: We conducted a propensity score-matched cohort study, comparing SV new users (no use of SV, ACE inhibitor, ARB 6 months before) and SV new users with prior use (within 183 or 14 days) of ACE inhibitor or ARB (ACE inhibitor-SV and ARB-SV users; recent ACE inhibitor-SV and recent ARB-SV users, respectively) vs ACE inhibitor and ARB new users separately. RESULTS: Compared with ACE inhibitor, SV new (HR: 0.18; 95% CI: 0.11-0.29) and ACE inhibitor-SV users (HR: 0.31; 95% CI: 0.23-0.43) showed lower risk of angioedema. On the other hand, there was no difference in angioedema risk when SV new users (HR: 0.59; 95% CI: 0.35-1.01) or ARB-SV users (HR: 0.85; 95% CI: 0.58-1.26) were compared with ARB new users. Compared with SV new users, ACE inhibitor-SV users (HR: 1.62; 95% CI: 0.91-2.89) trended toward higher angioedema risk, which intensified when the ACE inhibitor to SV switch occurred within 14 days (recent ACE inhibitor-SV) (HR: 1.98; 95% CI: 1.11-3.53). Similarly, ARB-SV users (HR: 2.03; 95% CI: 1.16-3.54) experienced an increased risk compared with SV new users, which intensified for the more recent switchers (recent ARB-SV) (HR: 2.45; 95% CI: 1.36-4.43). CONCLUSIONS: We did not observe an increased risk of angioedema among SV new users compared with ACE inhibitor or ARB users. However, there was an increased risk of angioedema among SV users who recently switched from ACE inhibitor or ARB compared with SV new users.

Preoperative Depression Status and 5 Year Metabolic and Bariatric Surgery Outcomes in the PCORnet Bariatric Study Cohort.

OBJECTIVE: To examine whether depression status before metabolic and bariatric surgery (MBS) influenced 5-year weight loss, diabetes, and safety/utilization outcomes in the PCORnet Bariatric Study. SUMMARY OF BACKGROUND DATA: Research on the impact of depression on MBS outcomes is inconsistent with few large, long-term studies. METHODS: Data were extracted from 23 health systems on 36,871 patients who underwent sleeve gastrectomy (SG; n=16,158) or gastric bypass (RYGB; n=20,713) from 2005-2015. Patients with and without a depression diagnosis in the year before MBS were evaluated for % total weight loss (%TWL), diabetes outcomes, and postsurgical safety/utilization (reoperations, revisions, endoscopy, hospitalizations, mortality) at 1, 3, and 5 years after MBS. RESULTS: 27.1% of SG and 33.0% of RYGB patients had preoperative depression, and they had more medical and psychiatric comorbidities than those without depression. At 5 years of follow-up, those with depression, versus those without depression, had slightly less %TWL after RYGB, but not after SG (between group difference = 0.42%TWL, P = 0.04). However, patients with depression had slightly larger HbA1c improvements after RYGB but not after SG (between group difference = - 0.19, P = 0.04). Baseline depression did not moderate diabetes remission or relapse, reoperations, revision, or mortality across operations; however, baseline depression did moderate the risk of endoscopy and repeat hospitalization across RYGB versus SG. CONCLUSIONS: Patients with depression undergoing RYGB and SG had similar weight loss, diabetes, and safety/utilization outcomes to those without depression. The effects of depression were clinically small compared to the choice of operation.

Comparative Safety and Effectiveness of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy for Weight Loss and Type 2 Diabetes Across Race and Ethnicity in the PCORnet Bariatric Study Cohort.

Importance: Bariatric surgery is the most effective treatment for severe obesity; yet it is unclear whether the long-term safety and comparative effectiveness of these operations differ across racial and ethnic groups. Objective: To compare outcomes of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) across racial and ethnic groups in the National Patient-Centered Clinical Research Network (PCORnet) Bariatric Study. Design, Setting, and Participants: This was a retrospective, observational, comparative effectiveness cohort study that comprised 25 health care systems in the PCORnet Bariatric Study. Patients were adults and adolescents aged 12 to 79 years who underwent a primary (first nonrevisional) RYGB or SG operation between January 1, 2005, and September 30, 2015, at participating health systems. Patient race and ethnicity included Black, Hispanic, White, other, and unrecorded. Data were analyzed from July 1, 2021, to January 17, 2022. Exposure: RYGB or SG. Outcomes: Percentage total weight loss (%TWL); type 2 diabetes remission, relapse, and change in hemoglobin A1c (HbA1c) level; and postsurgical safety and utilization outcomes (operations, interventions, revisions/conversions, endoscopy, hospitalizations, mortality, 30-day major adverse events) at 1, 3, and 5 years after surgery. Results: A total of 36 871 patients (mean [SE] age, 45.0 [11.7] years; 29 746 female patients [81%]) were included in the weight analysis. Patients identified with the following race and ethnic categories: 6891 Black (19%), 8756 Hispanic (24%), 19 645 White (53%), 826 other (2%), and 783 unrecorded (2%). Weight loss and mean reductions in HbA1c level were larger for RYGB than SG in all years for Black, Hispanic, and White patients (difference in 5-year weight loss: Black, -7.6%; 95% CI, -8.0 to -7.1; P < .001; Hispanic, -6.2%; 95% CI, -6.6 to -5.9; P < .001; White, -5.9%; 95% CI, -6.3 to -5.7; P < .001; difference in change in year 5 HbA1c level: Black, -0.29; 95% CI, -0.51 to -0.08; P = .009; Hispanic, -0.45; 95% CI, -0.61 to -0.29; P < .001; and White, -0.25; 95% CI, -0.40 to -0.11; P = .001.) The magnitude of these differences was small among racial and ethnic groups (1%-3% of %TWL). Black and Hispanic patients had higher risk of hospitalization when they had RYGB compared with SG (hazard ratio [HR], 1.45; 95% CI, 1.17-1.79; P = .001 and 1.48; 95% CI, 1.22-1.79; P < .001, respectively). Hispanic patients had greater risk of all-cause mortality (HR, 2.41; 95% CI, 1.24-4.70; P = .01) and higher odds of a 30-day major adverse event (odds ratio, 1.92; 95% CI, 1.38-2.68; P < .001) for RYGB compared with SG. There was no interaction between race and ethnicity and operation type for diabetes remission and relapse. Conclusions and Relevance: Variability of the comparative effectiveness of operations for %TWL and HbA1c level across race and ethnicity was clinically small; however, differences in safety and utilization outcomes were clinically and statistically significant for Black and Hispanic patients who had RYGB compared with SG. These findings can inform shared decision-making regarding bariatric operation choice for different racial and ethnic groups of patients.

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.

Early Life Antibiotic Prescriptions and Weight Outcomes in Children 10 Years of Age.

OBJECTIVE: We previously found that antibiotic use at <24 months of age was associated with slightly higher body weight at 5 years of age. In this study, we examine associations of early life antibiotic prescriptions with weight outcomes at 108 to 132 months of age ("10 years"). METHODS: We used electronic health record data from 2009 through 2016 from 10 health systems in PCORnet, a national distributed clinical research network. We examined associations of any (vs no) antibiotics at <24 months of age with body mass index z-score (BMI-z) at 10 years adjusted for confounders selected a priori. We further examined dose response (number of antibiotic episodes) and antibiotic spectrum (narrow and broad). RESULTS: Among 56,727 included children, 57% received any antibiotics at <24 months; at 10 years, mean (standard deviation) BMI-z was 0.54 (1.14), and 36% had overweight or obesity. Any versus no antibiotic use at <24 months was associated with a slightly higher BMI-z at 10 years among children without a complex chronic condition (ß 0.03; 95% confidence interval [CI] 0.01, 0.05) or with a complex chronic condition (ß 0.09; 95% CI 0.03, 0.15). Any versus no antibiotic use was not associated with odds of overweight or obesity at 10 years among children without (odds ratio 1.02; 95% CI 0.97, 1.07) or with a complex chronic condition (odds ratio 1.07; 95% CI 0.96, 1.19). CONCLUSIONS: The small and likely clinically insignificant associations in this study are consistent with our previous 5-year follow-up results, suggesting that, if this relationship is indeed causal, early increases in weight are small but maintained over time.

Complementary Use of U.S. FDA's Adverse Event Reporting System and Sentinel System to Characterize Direct Oral Anticoagulants-Associated Cutaneous Small Vessel Vasculitis.

BACKGROUND: Cutaneous small vessel vasculitis (CSVV) has been reported after exposure to direct oral anticoagulants (DOACs), such as dabigatran, rivaroxaban, apixaban, and edoxaban. OBJECTIVE: We used the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) to describe clinical characteristics associated with CSVV among DOAC-exposed patients. Furthermore, we characterized this signal in the Sentinel System to relate the clinical data from the individual FAERS cases to population-based electronic healthcare data. METHODS: We queried FAERS for all cases of CSVV associated with DOACs from U.S. approval date of each DOAC through March 16, 2018. Within the Sentinel System, we identified incident CSVV cases using ICD-9 and ICD-10 diagnosis codes among adults aged ≥ 30 years who received a DOAC in the prior 90 days between January 1, 2010, and June 30, 2018. We excluded patients with evidence of select autoimmune diagnoses in the 183 days prior to their CSVV diagnoses and reported patient characteristics in the 183-day period prior to CSVV diagnoses. RESULTS: In FAERS, we identified 50 cases of CSVV reported with rivaroxaban (n=26), apixaban (n=14), dabigatran (n=9), and edoxaban (n=1). Approximately 50% of the cases reported time to onset within 10 days after DOAC exposure. When specified, the predominant type of CSVV reported was leukocytoclastic vasculitis (n=31), followed by Henoch-Schonlein purpura (n=4). Hospitalization occurred in most of the cases (n=37). Switching of the offending agent after the development of CSVV was reported (n=26). Three rivaroxaban (n=3) cases and one dabigatran case (n=1) reported positive rechallenge. In the Sentinel system, we identified 3659 CSVV cases with prior DOAC exposure, with 85% of events occurring within 10 days. CONCLUSIONS: The assessment of FAERS cases, combined with the temporal clustering of the Sentinel System cases suggest a possible causal relationship of DOACs and CSVV. Future efforts should characterize the risk of CSVV among the various DOAC users.

Comparing the 5-Year Diabetes Outcomes of Sleeve Gastrectomy and Gastric Bypass: The National Patient-Centered Clinical Research Network (PCORNet) Bariatric Study.

Importance: Bariatric surgery can lead to substantial improvements in type 2 diabetes (T2DM), but outcomes vary across procedures and populations. It is unclear which bariatric procedure has the most benefits for patients with T2DM. Objective: To evaluate associations of bariatric surgery with T2DM outcomes. Design, Setting, and Participants: This cohort study was conducted in 34 US health system sites in the National Patient-Centered Clinical Research Network Bariatric Study. Adult patients with T2DM who had bariatric surgery between January 1, 2005, and September 30, 2015, were included. Data analysis was conducted from April 2017 to August 2019. Interventions: Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Main Outcome and Measures: Type 2 diabetes remission, T2DM relapse, percentage of total weight lost, and change in glycosylated hemoglobin (hemoglobin A1c). Results: A total of 9710 patients were included (median [interquartile range] follow-up time, 2.7 [2.9] years; 7051 female patients [72.6%]; mean [SD] age, 49.8 [10.5] years; mean [SD] BMI, 49.0 [8.4]; 6040 white patients [72.2%]). Weight loss was significantly greater with RYGB than SG at 1 year (mean difference, 6.3 [95% CI, 5.8-6.7] percentage points) and 5 years (mean difference, 8.1 [95% CI, 6.6-9.6] percentage points). The T2DM remission rate was approximately 10% higher in patients who had RYGB (hazard ratio, 1.10 [95% CI, 1.04-1.16]) than those who had SG. Estimated adjusted cumulative T2DM remission rates for patients who had RYGB and SG were 59.2% (95% CI, 57.7%-60.7%) and 55.9% (95% CI, 53.9%-57.9%), respectively, at 1 year and 86.1% (95% CI, 84.7%-87.3%) and 83.5% (95% CI, 81.6%-85.1%) at 5 years postsurgery. Among 6141 patients who experienced T2DM remission, the subsequent T2DM relapse rate was lower for those who had RYGB than those who had SG (hazard ratio, 0.75 [95% CI, 0.67-0.84]). Estimated relapse rates for those who had RYGB and SG were 8.4% (95% CI, 7.4%-9.3%) and 11.0% (95% CI, 9.6%-12.4%) at 1 year and 33.1% (95% CI, 29.6%-36.5%) and 41.6% (95% CI, 36.8%-46.1%) at 5 years after surgery. At 5 years, compared with baseline, hemoglobin A1c was reduced 0.45 (95% CI, 0.27-0.63) percentage points more for patients who had RYGB vs patients who had SG. Conclusions and Relevance: In this large multicenter study, patients who had RYGB had greater weight loss, a slightly higher T2DM remission rate, less T2DM relapse, and better long-term glycemic control compared with those who had SG. These findings can help inform patient-centered surgical decision-making.

Interventions and Operations 5 Years After Bariatric Surgery in a Cohort From the US National Patient-Centered Clinical Research Network Bariatric Study.

Importance: Additional data comparing longer-term problems associated with various bariatric surgical procedures are needed for shared decision-making. Objective: To compare the risks of intervention, operation, endoscopy, hospitalization, and mortality up to 5 years after 2 bariatric surgical procedures. Design, Setting, and Participants: Adults who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) between January 1, 2005, and September 30, 2015, within the National Patient-Centered Clinical Research Network. Data from 33 560 adults at 10 centers within 4 clinical data research networks were included in this cohort study. Information was extracted from electronic health records using a common data model and linked to insurance claims and mortality indices. Analyses were conducted from January 2018 through October 2019. Exposures: Bariatric surgical procedures. Main Outcomes and Measures: The primary outcome was time until operation or intervention. Secondary outcomes included endoscopy, hospitalization, and mortality rates. Results: Of 33 560 adults, 18 056 (54%) underwent RYGB, and 15 504 (46%) underwent SG. The median (interquartile range) follow-up for operation or intervention was 3.4 (1.6-5.0) years for RYGB and 2.2 (0.9-3.6) years for SG. The overall mean (SD) patient age was 45.0 (11.5) years, and the overall mean (SD) patient body mass index was 49.1 (7.9). The cohort was composed predominantly of women (80%) and white individuals (66%), with 26% of Hispanic ethnicity. Operation or intervention was less likely for SG than for RYGB (hazard ratio, 0.72; 95% CI, 0.65-0.79; P < .001). The estimated, adjusted cumulative incidence rates of operation or intervention at 5 years were 8.94% (95% CI, 8.23%-9.65%) for SG and 12.27% (95% CI, 11.49%-13.05%) for RYGB. Hospitalization was less likely for SG than for RYGB (hazard ratio, 0.82; 95% CI, 0.78-0.87; P < .001), and the 5-year adjusted cumulative incidence rates were 32.79% (95% CI, 31.62%-33.94%) for SG and 38.33% (95% CI, 37.17%-39.46%) for RYGB. Endoscopy was less likely for SG than for RYGB (hazard ratio, 0.47; 95% CI, 0.43-0.52; P < .001), and the adjusted cumulative incidence rates at 5 years were 7.80% (95% CI, 7.15%-8.43%) for SG and 15.83% (95% CI, 14.94%-16.71%) for RYGB. There were no differences in all-cause mortality between SG and RYGB. Conclusions and Relevance: Interventions, operations, and hospitalizations were relatively common after bariatric surgical procedures and were more often associated with RYGB than SG. Trial Registration: ClinicalTrials.gov identifier: NCT02741674.

Use of Intrauterine Devices and Risk of Human Immunodeficiency Virus Acquisition Among Insured Women in the United States.

Concerns have been raised about progestin-containing contraceptives and the risk of human immunodeficiency virus (HIV) acquisition. Based on health insurance data from women in the United States with intrauterine device (IUD) insertions during 2011-2018, there was no increased risk of incident HIV diagnosis for levonorgestrel-releasing IUDs versus copper IUDs.

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.

Use of Sodium-Glucose Cotransporter 2 Inhibitors in Patients With Type 1 Diabetes and Rates of Diabetic Ketoacidosis.

OBJECTIVE: To estimate real-world off-label use of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 1 diabetes, estimate rates of diabetic ketoacidosis (DKA), and compare them with DKA rates observed in sotagliflozin clinical trials. RESEARCH DESIGN AND METHODS: We identified initiators of SGLT2 inhibitors in the Sentinel System from March 2013 to June 2018, determined the prevalence of type 1 diabetes using a narrow and a broad definition, and measured rates of DKA using administrative claims data. Standardized incidence ratios (SIRs) were calculated using age- and sex-specific follow-up time in Sentinel and age- and sex-specific DKA rates from sotagliflozin trials 309, 310, and 312. RESULTS: Among 475,527 initiators of SGLT2 inhibitors, 0.50% and 0.92% met narrow and broad criteria for type 1 diabetes, respectively. Rates of DKA in the narrow and broad groups were 7.3/100 person-years and 4.5/100 person-years, respectively. Among patients who met narrow criteria for type 1 diabetes, rates of DKA were highest for patients aged 25-44 years, especially females aged 25-44 years (19.7/100 person-years). More DKA events were observed during off-label use of SGLT2 inhibitors in Sentinel than would be expected based on sotagliflozin clinical trials (SIR = 1.83; 95% CI 1.45-2.28). CONCLUSIONS: Real-world off-label use of SGLT2 inhibitors among patients with type 1 diabetes accounted for a small proportion of overall SGLT2 inhibitor use. However, the risk for DKA during off-label use was notable, especially among young, female patients. Although real-word rates of DKA exceeded the expectation based on clinical trials, results should be interpreted with caution due to differences in study methods, patient samples, and study drugs.

Comparing Prescribing and Dispensing Data of the PCORnet Common Data Model Within PCORnet Antibiotics and Childhood Growth Study.

Researchers often use prescribing data from electronic health records (EHR) or dispensing data from medication or medical claims to determine medication utilization. However, neither source has complete information on medication use. We compared antibiotic prescribing and dispensing records for 200,395 patients in the National Patient-Centered Clinical Research Network (PCORnet) Antibiotics and Childhood Growth Study. We stratified analyses by delivery system type [closed integrated (cIDS) and non-cIDS]; 90.5 percent and 39.4 percent of prescribing records had matching dispensing records, and 92.7 percent and 64.0 percent of dispensing records had matching prescribing records at cIDS and non-cIDS, respectively. Most of the dispensings without a matching prescription did not have same-day encounters in the EHR, suggesting they were medications given outside the institution providing data, such as those from urgent care or retail clinics. The sensitivity of prescriptions in the EHR, using dispensings as a gold standard, was 99.1 percent and 89.9 percent for cIDS and non-cIDS, respectively. Only 0.7 percent and 6.1 percent of patients at cIDS and non-cIDS, respectively, were classified as false-negative, i.e. entirely unexposed to antibiotics when they in fact had dispensings. These patients were more likely to have a complex chronic condition or asthma. Overall, prescription records worked well to identify exposure to antibiotics. EHR data, such as the data available in PCORnet, is a unique and vital resource for clinical research. Closing data gaps by understanding why prescriptions may not be captured can improve this type of data, making it more robust for observational research.

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.

Combining distributed regression and propensity scores: a doubly privacy-protecting analytic method for multicenter research.

PURPOSE: Sharing of detailed individual-level data continues to pose challenges in multi-center studies. This issue can be addressed in part by using analytic methods that require only summary-level information to perform the desired multivariable-adjusted analysis. We examined the feasibility and empirical validity of 1) conducting multivariable-adjusted distributed linear regression and 2) combining distributed linear regression with propensity scores, in a large distributed data network. PATIENTS AND METHODS: We compared percent total weight loss 1-year postsurgery between Roux-en-Y gastric bypass and sleeve gastrectomy procedure among 43,110 patients from 36 health systems in the National Patient-Centered Clinical Research Network. We adjusted for baseline demographic and clinical variables as individual covariates, deciles of propensity scores, or both, in three separate outcome regression models. We used distributed linear regression, a method that requires only summary-level information (specifically, sums of squares and cross products matrix) from sites, to fit the three ordinary least squares linear regression models. A comparison set of analyses that used pooled deidentified individual-level data from sites served as the reference. RESULTS: Distributed linear regression produced results identical to those from the corresponding pooled individual-level data analysis for all variables in all three models. The maximum numerical difference in the parameter estimate or standard error for all the variables was 3×10-11 across three models. CONCLUSION: Distributed linear regression analysis is a feasible and valid analytic method in multicenter studies for one-time continuous outcomes. Combining distributed regression with propensity scores via modeling offers more privacy protection and analytic flexibility.

Comparative Effectiveness and Safety of Bariatric Procedures for Weight Loss: A PCORnet Cohort Study.

Background: There has been a dramatic shift in use of bariatric procedures, but little is known about their long-term comparative effectiveness. Objective: To compare weight loss and safety among bariatric procedures. Design: Retrospective observational cohort study, January 2005 to September 2015. (ClinicalTrials.gov: NCT02741674). Setting: 41 health systems in the National Patient-Centered Clinical Research Network. Participants: 65 093 patients aged 20 to 79 years with body mass index (BMI) of 35 kg/m2 or greater who had bariatric procedures. Intervention: 32 208 Roux-en-Y gastric bypass (RYGB), 29 693 sleeve gastrectomy (SG), and 3192 adjustable gastric banding (AGB) procedures. Measurements: Estimated percent total weight loss (TWL) at 1, 3, and 5 years; 30-day rates of major adverse events. Results: Total numbers of eligible patients with weight measures at 1, 3, and 5 years were 44 978 (84%), 20 783 (68%), and 7159 (69%), respectively. Thirty-day rates of major adverse events were 5.0% for RYGB, 2.6% for SG, and 2.9% for AGB. One-year mean TWLs were 31.2% (95% CI, 31.1% to 31.3%) for RYGB, 25.2% (CI, 25.1% to 25.4%) for SG, and 13.7% (CI, 13.3% to 14.0%) for AGB. At 1 year, RYGB patients lost 5.9 (CI, 5.8 to 6.1) percentage points more weight than SG patients and 17.7 (CI, 17.3 to 18.1) percentage points more than AGB patients, and SG patients lost 12.0 (CI, 11.6 to 12.5) percentage points more than AGB patients. Five-year mean TWLs were 25.5% (CI, 25.1% to 25.9%) for RYGB, 18.8% (CI, 18.0% to 19.6%) for SG, and 11.7% (CI, 10.2% to 13.1%) for AGB. Patients with diabetes, those with BMI less than 50 kg/m2, those aged 65 years or older, African American patients, and Hispanic patients lost less weight than patients without those characteristics. Limitation: Potential unobserved confounding due to nonrandomized design; electronic health record databases had missing outcome data. Conclusion: Adults lost more weight with RYGB than with SG or AGB at 1, 3, and 5 years; however, RYGB had the highest 30-day rate of major adverse events. Small subgroup differences in weight loss outcomes were observed. Primary Funding Source: Patient-Centered Outcomes Research Institute.

Early Antibiotic Exposure and Weight Outcomes in Young Children.

: media-1vid110.1542/5839981580001PEDS-VA_2018-0290Video Abstract OBJECTIVES: To determine the association of antibiotic use with weight outcomes in a large cohort of children. METHODS: Health care data were available from 2009 to 2016 for 35 institutions participating in the National Patient-Centered Clinical Research Network. Participant inclusion required same-day height and weight measurements at 0 to <12, 12 to <30, and 48 to <72 months of age. We assessed the association between any antibiotic use at <24 months of age with BMI z score and overweight or obesity prevalence at 48 to <72 months (5 years) of age, with secondary assessments of antibiotic spectrum and age-period exposures. We included children with and without complex chronic conditions. RESULTS: Among 1 792 849 children with a same-day height and weight measurement at <12 months of age, 362 550 were eligible for the cohort. One-half of children (52%) were boys, 27% were African American, 18% were Hispanic, and 58% received ≥1 antibiotic prescription at <24 months of age. At 5 years, the mean BMI z score was 0.40 (SD 1.19), and 28% of children had overweight or obesity. In adjusted models for children without a complex chronic condition at 5 years, we estimated a higher mean BMI z score by 0.04 (95% confidence interval [CI] 0.03 to 0.05) and higher odds of overweight or obesity (odds ratio 1.05; 95% CI 1.03 to 1.07) associated with obtaining any (versus no) antibiotics at <24 months. CONCLUSIONS: Antibiotic use at <24 months of age was associated with a slightly higher body weight at 5 years of age.

Comparative effectiveness of bariatric procedures among adolescents: the PCORnet bariatric study.

BACKGROUND: Bariatric surgery has been used for treatment of severe obesity in adolescents but most studies have been small and limited in follow-up. OBJECTIVES: We hypothesized that electronic health record data could be used to compare effectiveness of bariatric procedures in adolescents. SETTING: Data were obtained from clinical research networks using a common data model to extract data from each site. METHODS: Adolescents who underwent a primary bariatric procedure from 2005 through 2015 were identified. The percent change in body mass index (BMI) at 1, 3, and 5 years was estimated using random effects linear regression for patients undergoing all operations. Propensity score adjusted estimates and 95% confidence intervals were estimated for procedures with >25 patients at each time period. RESULTS: This cohort of 544 adolescents was predominantly female (79%) and White (66%), with mean (±standard deviation) age of 17.3 (±1.6) years and mean BMI of 49.8 (± 7.8) kg/m2. Procedures included Roux-en-Y gastric bypass (RYGB; n = 177), sleeve gastrectomy (SG; n = 306), and laparoscopic adjustable gastric banding (n = 61). For those undergoing RYGB, SG, and laparoscopic adjustable gastric banding, mean (95% confidence interval) BMI changes of -31% (-30% to -33%), -28% (-27% to -29%), and -10% (-8% to -12%), were estimated at 1 year. For RYGB and SG, BMI changes of -29% (-26% to -33%) and -25% (-22% to -28%) were estimated at 3 years. CONCLUSIONS: Adolescents undergoing SG and RYGB experienced greater declines in BMI at 1- and 3-year follow-up time points, while laparoscopic adjustable gastric banding was significantly less effective for BMI reduction.

PCORnet Antibiotics and Childhood Growth Study: Process for Cohort Creation and Cohort Description.

OBJECTIVES: The National Patient-Centered Clinical Research Network (PCORnet) supports observational and clinical research using health care data. The PCORnet Antibiotics and Childhood Growth Study is one of PCORnet's inaugural observational studies. We sought to describe the processes used to integrate and analyze data from children across 35 participating institutions, the cohort characteristics, and prevalence of antibiotic use. METHODS: We included children in the cohort if they had at least one same-day height and weight measured in each of 3 age periods: 1) before 12 months, 2) 12 to 30 months, and 3) after 24 months. We distributed statistical queries that each institution ran on its local version of the PCORnet Common Data Model, with aggregate data returned for analysis. We defined overweight or obesity as age- and sex-specific body mass index ≥85th percentile, obesity ≥95th percentile, and severe obesity ≥120% of the 95th percentile. RESULTS: A total of 681,739 children met the cohort inclusion criteria, and participants were racially/ethnically diverse (24.9% black, 17.5% Hispanic). Before 24 months of age, 55.2% of children received at least one antibiotic prescription; 21.3% received a single antibiotic prescription; 14.3% received 4 or more; and 33.3% received a broad-spectrum antibiotic. Overweight and obesity prevalence was 27.6% at age 4 to <6 years (n = 362,044) and 36.2% at 9 to <11 years (n = 58,344). CONCLUSIONS: The PCORnet Antibiotics and Childhood Growth Study is a large national longitudinal observational study in a diverse population that will examine the relationship between early antibiotic use and subsequent growth patterns in children.

The National Patient-Centered Clinical Research Network (PCORnet) Bariatric Study Cohort: Rationale, Methods, and Baseline Characteristics.

BACKGROUND: Although bariatric procedures are commonly performed in clinical practice, long-term data on the comparative effectiveness and safety of different procedures on sustained weight loss, comorbidities, and adverse effects are limited, especially in important patient subgroups (eg, individuals with diabetes, older patients, adolescents, and minority patients). OBJECTIVE: The objective of this study was to create a population-based cohort of patients who underwent 3 commonly performed bariatric procedures-adjustable gastric band (AGB), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG)-to examine the long-term comparative effectiveness and safety of these procedures in both adults and adolescents. METHODS: We identified adults (20 to 79 years old) and adolescents (12 to 19 years old) who underwent a primary (first observed) AGB, RYGB, or SG procedure between January 1, 2005 and September 30, 2015 from 42 health systems participating in the Clinical Data Research Networks within the National Patient-Centered Clinical Research Network (PCORnet). We extracted information on patient demographics, encounters with healthcare providers, diagnoses recorded and procedures performed during these encounters, vital signs, and laboratory test results from patients' electronic health records (EHRs). The outcomes of interest included weight change, incidence of major surgery-related adverse events, and diabetes remission and relapse, collected for up to 10 years after the initial bariatric procedure. RESULTS: A total of 65,093 adults and 777 adolescents met the eligibility criteria of the study. The adult subcohort had a mean age of 45 years and was predominantly female (79.30%, 51,619/65,093). Among adult patients with non-missing race or ethnicity information, 72.08% (41,248/57,227) were White, 21.13% (12,094/57,227) were Black, and 20.58% (13,094/63,637) were Hispanic. The average highest body mass index (BMI) recorded in the year prior to surgery was 49 kg/m2. RYGB was the most common bariatric procedure among adults (49.48%, 32,208/65,093), followed by SG (45.62%, 29,693/65,093) and AGB (4.90%, 3192/65,093). The mean age of the adolescent subcohort was 17 years and 77.5% (602/777) were female. Among adolescent patients with known race or ethnicity information, 67.3% (473/703) were White, 22.6% (159/703) were Black, and 18.0% (124/689) were Hispanic. The average highest recorded BMI in the year preceding surgery was 53 kg/m2. The majority of the adolescent patients received SG (60.4%, 469/777), followed by RYGB (30.8%, 239/777) and AGB (8.9%, 69/777). A BMI measurement (proxy for follow-up) was available in 84.31% (44,978/53,351), 68.09% (20,783/30,521), and 68.56% (7159/10,442) of the eligible adult patients at 1, 3, and 5 years of follow-up, respectively. The corresponding proportion was 82.0% (524/639), 49.9% (174/349), and 38.8% (47/121) in the adolescent subcohort. CONCLUSIONS: Our study cohort is one of the largest cohorts of patients with bariatric procedures in the United States. Patients are geographically and demographically diverse, which improves the generalizability of the research findings and allows examination of treatment effect heterogeneity. Ongoing and planned investigations will provide real-world evidence on the long-term benefits and risks of these most commonly used bariatric procedures in current clinical practice.