; for the PCORnet Bariatric Study Collaborative 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.

; for the PCORnet Bariatric Study Collaborative 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 A 1c). 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 A 1c 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.

Following the release of the framework for the Real-World Evidence (RWE) Program, the US Food and Drug Administration (FDA) is actively evaluating and exploring ways to optimize the utility of real-world data (RWD) and RWE to support regulatory decision making. For rare conditions, conducting traditional randomized clinical trials may not always be feasible, and RWD and RWE have played and will continue to play an important role. We use three case examples-cerliponase alfa, asfotase alfa, and uridine triacetate-to illustrate how RWD from disease registries, medical records with chart review, and literature, respectively, have been used to generate RWE to support regulatory decisions for selected rare diseases. These

IMPORTANCEPrior observational studies have suggested that fluoroquinolone use may be associated with more than 2-fold increased risk of aortic aneurysm or aortic dissection (AA/AD). These studies, however, did not fully consider the role of coexisting infections and the risk of fluoroquinolones relative to other antibiotics. OBJECTIVE To estimate the risk of AA/AD associated with infections and to assess the comparative risk of AA/AD associated with fluoroquinolones vs other antibiotics with similar indication profiles among patients with the same types of infections. DESIGNS, SETTINGS, AND PARTICIPANTSThis nested case-control study identified 21 651 176 adult patients from a nationwide population-based health insurance claims database from January 1, 2009, to November 30, 2015. Each incident case of AA/AD was matched with 10 control individuals by age, sex, and follow-up duration in the database using risk-set sampling. Analysis of the data was conducted from April 2019 to March 2020.EXPOSURES Infections and antibiotic use within a 60-day risk window before the occurrence of AA/AD. MAIN OUTCOMES AND MEASURESConditional logistic regression was used to estimate the odds ratios (ORs) and 95% CIs comparing infections for which fluoroquinolones are commonly used with no infection within a 60-day risk window before outcome occurrence, adjusting for baseline confounders and concomitant antibiotic use. The adjusted ORs comparing fluoroquinolones with antibiotics with similar indication profiles within patients with indicated infections were also estimated. RESULTSA total of 28 948 cases and 289 480 matched controls were included (71.37% male; mean [SD] age, 67.41 [15.03] years). Among these, the adjusted OR of AA/AD for any indicated infections was 1.73 (95% CI, 1.66-1.81). Septicemia (OR, 3.16; 95% CI, 2.63-3.78) and intra-abdominal infection (OR, 2.99; 95% CI, 2.45-3.65) had the highest increased risk. Fluoroquinolones were not associated with an increased AA/AD risk when compared with combined amoxicillin-clavulanate or combined ampicillin-sulbactam (OR, 1.01; 95% CI, 0.82-1.24) or with extended-spectrum cephalosporins (OR, 0.88; 95% CI, 0.70-1.11) among patients with indicated infections. The null findings for fluoroquinolone use remained robust in different subgroup and sensitivity analyses.CONCLUSIONS AND RELEVANCE These results highlight the importance of accounting for coexisting infections while examining the safety of antibiotics using real-world data; the findings suggest that concerns about AA/AD risk should not deter fluoroquinolone use for patients with indicated infections.