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Objective: Many guidelines recommend limiting glucocorticoids in patients with rheumatoid arthritis (RA), but 40% of patients remain on glucocorticoids long term. We evaluated the cardiovascular risk of long‐term glucocorticoid prescription by studying patients on stable disease‐modifying antirheumatic drugs (DMARDs). Methods: Using two claims databases, we identified patients with RA on stable DMARD therapy for >180 days. Proportional hazards models with inverse‐probability weights and clustering to account for multiple observations were used to estimate the effect of glucocorticoid dose on composite cardiovascular outcomes (stroke or myocardial infarction [MI]). Results: There were 135,583 patients in Medicare and 39,272 in Optum's de‐identified Clinformatics Data Mart (CDM) database. Medicare and CDM patients had an incidence of 1.3 and 0.8 composite cardiovascular outcomes per 100 person‐years, respectively. In the older, comorbid Medicare cohort, glucocorticoids were associated with a dose‐dependent increase in composite cardiovascular outcomes in adjusted models with predicted one‐year incidence of 1.4% (95% confidence interval [CI] 1.2%–1.6%) for ≤5 mg, 1.6% (95% CI 1.4%–1.9%) for >5 to 10 mg, and 1.8% (95% CI 1.2%–2.5%) for >10 mg versus 1.1% (95% CI 1.1%–1.2%) among patients not receiving glucocorticoids. There was no significant association among the CDM cohort. However, in the subgroup of younger patients with RA and higher cardiovascular risk, glucocorticoids were associated with a dose‐dependent increase in composite cardiovascular outcomes. Conclusion: Among older patients with more comorbidities and younger patients with higher cardiovascular risk with RA on stable DMARD therapy, glucocorticoids were associated with a dose‐dependent increased risk of MI and stroke, even at doses ≤5 mg/day. By contrast, no association was noted among younger, healthier patients with RA. [ABSTRACT FROM AUTHOR]

Purpose: To assess accuracy of administrative claims prescription fill‐based estimates of glucocorticoid use and dose, and approximate bias from glucocorticoid exposure misclassification. Methods: We identified adults with rheumatoid arthritis with linked Medicare and CorEvitas registry data. An algorithm identifying glucocorticoid use and average dose over 90 days from Medicare prescription fills was compared to physician‐reported measures from a CorEvitas visit during the same period, using weighted kappa to compare doses (none, ≤5 mg, 5–10 mg, >10 mg/day). A deterministic sensitivity analysis examined the effect of exposure misclassification on estimated glucocorticoid‐associated infection risk from a prior study. Results: We identified 621 observations among 494 patients. Prescription fills identified glucocorticoid use in 41.9% of observations versus 31.1% identified by CorEvitas physician‐report. For glucocorticoid use (yes/no), prescription fills had sensitivity 88.1% (95% CI 82.7–92.3), specificity 79.0% (74.8–82.7), PPV 65.4% (59.3–71.2), NPV 93.6% (90.6–95.9), and 81.8% agreement with CorEvitas, with kappa 0.61 (moderate to substantial agreement). There was 89.5% agreement between prescription fills and physician‐reported doses, with weighted kappa 0.56 (moderate agreement). Applying these results to a prior Medicare study evaluating glucocorticoid‐associated infection risk [risk ratio 1.44 (95% CI 1.41–1.48)] led to an externally adjusted risk ratio of 1.74 when accounting for exposure misclassification, representing −17% bias in infection risk estimate. Conclusions: This study supports the use of claims data to estimate glucocorticoid use and dose, but investigators should account for exposure misclassification, which may lead to underestimates of glucocorticoid risks. Our results could be applied to adjust risk estimates in other studies that use prescription fills to estimate glucocorticoid use. [ABSTRACT FROM AUTHOR]

Objective: Glucocorticoids are recommended for short‐term use in rheumatoid arthritis (RA), but many patients continue receiving long‐term therapy. We evaluated the variability in glucocorticoid prescribing across rheumatologists to inform interventions to limit long‐term glucocorticoid use to the lowest dose necessary. Methods: Two cohorts were created using Medicare data from 2006 to 2015. Using cohort 1 (RA patients receiving disease‐modifying antirheumatic drugs [DMARDs]), we calculated each rheumatologist's "provider preference" for glucocorticoids (frequency of use compared to other providers), using the ratio of observed to expected number of patients receiving glucocorticoids to account for case mix. In cohort 2 (RA patients receiving stable DMARD therapy), we evaluated whether provider preference for glucocorticoids could independently predict use of ≥5 mg/day of glucocorticoids 6–9 months after initiation of DMARD therapy. Results: Using cohort 1 (1,272,644 yearly observations; 385,597 patients), we calculated provider preference among 6,875 rheumatologists (28,936 yearly observations). Provider preference was highly variable, with physicians at the lowest and upper quartiles prescribing glucocorticoids 33% less often to 31% more often (25th and 75th percentiles, respectively) than expected. In cohort 2 (155,539 patients receiving stable DMARD therapy), provider preference was strongly associated with glucocorticoid use ≥5 mg/day at 6–9 months, with a predicted probability of use of 22% (95% confidence interval [95% CI] 21.7–22.7) versus 11% (95% CI 10.2–10.9) for a patient seeing a provider in the highest versus lowest quintile of preference. Conclusion: Glucocorticoid prescribing for RA varies greatly among rheumatologists, and provider preference is one of the strongest predictors of a patient's long‐term glucocorticoid use. These findings raise quality of care concerns and highlight the need for stronger evidence to guide RA treatment. [ABSTRACT FROM AUTHOR]

Background: Low-dose glucocorticoids are frequently used for the management of rheumatoid arthritis (RA) and other chronic conditions, but the safety of long-term use remains uncertain.Objective: To quantify the risk for hospitalized infection with long-term use of low-dose glucocorticoids in patients with RA receiving stable disease-modifying antirheumatic drug (DMARD) therapy.Design: Retrospective cohort study.Setting: Medicare claims data and Optum's deidentified Clinformatics Data Mart database from 2006 to 2015.Patients: Adults with RA receiving a stable DMARD regimen for more than 6 months.Measurements: Associations between glucocorticoid dose (none, ≤5 mg/d, >5 to 10 mg/d, and >10 mg/d) and hospitalized infection were evaluated using inverse probability-weighted analyses, with 1-year cumulative incidence predicted from weighted models.Results: 247 297 observations were identified among 172 041 patients in Medicare and 58 279 observations among 44 118 patients in Optum. After 6 months of stable DMARD use, 47.1% of Medicare patients and 39.5% of Optum patients were receiving glucocorticoids. The 1-year cumulative incidence of hospitalized infection in Medicare patients not receiving glucocorticoids was 8.6% versus 11.0% (95% CI, 10.6% to 11.5%) for glucocorticoid dose of 5 mg or less per day, 14.4% (CI, 13.8% to 15.1%) for greater than 5 to 10 mg/d, and 17.7% (CI, 16.5% to 19.1%) for greater than 10 mg/d (all P < 0.001 vs. no glucocorticoids). The 1-year cumulative incidence of hospitalized infection in Optum patients not receiving glucocorticoids was 4.0% versus 5.2% (CI, 4.7% to 5.8%) for glucocorticoid dose of 5 mg or less per day, 8.1% (CI, 7.0% to 9.3%) for greater than 5 to 10 mg/d, and 10.6% (CI, 8.5% to 13.2%) for greater than 10 mg/d (all P < 0.001 vs. no glucocorticoids).Limitation: Potential for residual confounding and misclassification of glucocorticoid dose.Conclusion: In patients with RA receiving stable DMARD therapy, glucocorticoids were associated with a dose-dependent increase in the risk for serious infection, with small but significant risks even at doses of 5 mg or less per day. Clinicians should balance the benefits of low-dose glucocorticoids with this potential risk.Primary Funding Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases. [ABSTRACT FROM AUTHOR]

Objectives: The impact of immunosuppression on postoperative outcomes has primarily been studied in patients undergoing joint replacement surgery. We aimed to evaluate the impact of biologics and glucocorticoids on outcomes after other major surgeries.Methods: This retrospective cohort study used Medicare data 2006-2015 to identified adults with rheumatoid arthritis undergoing hip fracture repair, abdominopelvic surgery (cholecystectomy, hysterectomy, hernia, appendectomy, colectomy) or cardiac surgery (coronary artery bypass graft, mitral/aortic valve). Logistic regression with propensity-score-based inverse probability weighting compared 90-day mortality and 30-day readmission in patients receiving methotrexate (without a biologic or targeted synthetic disease-modifying antirheumatic drug (tsDMARD)), a tumour necrosis factor inhibitor (TNFi) or a non-TNFi biologic/tsDMARD <8 weeks before surgery. Similar analyses evaluated associations between glucocorticoids and outcomes.Results: We identified 10 777 eligible surgeries: 3585 hip fracture, 5025 abdominopelvic and 2167 cardiac surgeries. Compared with patients receiving methotrexate, there was no increase in the risk of 90-day mortality or 30-day readmission among patients receiving a TNFi (mortality adjusted OR (aOR) 0.83 (0.67 to 1.02), readmission aOR 0.86 (0.75 to 0.993)) or non-TNFi biologic/tsDMARD (mortality aOR 0.78 (0.49 to 1.22), readmission aOR 1.02 (0.78 to 1.33)). Analyses stratified by surgery category were similar. Risk of mortality and readmission was higher with 5-10 mg/day of glucocorticoids (mortality aOR 1.41 (1.08 to 1.82), readmission aOR 1.26 (1.05 to 1.52)) or >10 mg/day (mortality aOR 1.64 (1.02 to 2.64), readmission aOR 1.60 (1.15 to 2.24)) versus no glucocorticoids, although results varied when stratifying by surgery category.Conclusions: Recent biologic or tsDMARD use was not associated with a greater risk of mortality or readmission after hip fracture, abdominopelvic or cardiac surgery compared with methotrexate. Higher dose glucocorticoids were associated with greater risk. [ABSTRACT FROM AUTHOR]

Objective: Guidelines recommend withholding biologic therapies before hip and knee arthroplasty, yet evidence to inform optimal timing is limited. The aim of this study was to determine whether withholding abatacept infusions is associated with lower risk of adverse postoperative outcomes.Methods: This retrospective cohort study, which used US Medicare and Truven MarketScan administrative data from January 2006 to September 2015, evaluated adults with rheumatoid arthritis who received intravenous abatacept (precisely dated in claims data) within 6 months of elective primary or revision hip or knee arthroplasty. Propensity weighted analyses using inverse probability weights compared the risk of 30-day hospitalized infection and 1-year prosthetic joint infection (PJI) between patients with different abatacept stop timing (time between last infusion and surgery). Secondary analyses evaluated nonurinary hospitalized infections and 30-day readmissions.Results: After 1,939 surgeries among 1,780 patients, there were 175 hospitalized infections (9.0%), 115 nonurinary hospitalized infections (5.9%), 39 PJIs (2.4/100 person-years), and 114/1,815 30-day readmissions (6.3%). There were no significant differences in outcomes with abatacept stop timing <4 weeks (1 dosing interval) versus 4-8 weeks (hospitalized infection odds ratio [OR] 0.93 [95% confidence interval (95% CI) 0.65-1.34]; nonurinary hospitalized infection OR 0.93 [95% CI 0.60-1.44]; PJI hazard ratio 1.29 [95% CI 0.62-2.69]; 30-day readmission OR 1.00 [95% CI 0.65-1.54]). Similarly, there were no significant differences in outcomes with abatacept stop timing <4 weeks versus ≥8 weeks. Glucocorticoid use >7.5 mg/day was associated with greater risk of hospitalized infection (OR 2.19 [95% CI 1.28-3.77]) and nonurinary hospitalized infection (OR 2.38 [95% CI 1.22-4.64]).Conclusion: Compared to continuing intravenous abatacept, withholding abatacept for ≥4 weeks (one dosing interval) before surgery was not associated with a lower risk of hospitalized infection, nonurinary hospitalized infection, PJI, or 30-day readmission. [ABSTRACT FROM AUTHOR]

Background: Patients with rheumatoid arthritis (RA) are at increased risk for infection after arthroplasty, yet risks of specific biologic medications are unknown. Objective: To compare risk for postoperative infection among biologics and to evaluate the risk associated with glucocorticoids. Design: Retrospective cohort study. Setting: Medicare and Truven MarketScan administrative data from January 2006 through September 2015. Patients: Adults with RA who were having elective inpatient total knee or hip arthroplasty, either primary or revision, and had a recent infusion of or prescription for abatacept, adalimumab, etanercept, infliximab, rituximab, or tocilizumab before surgery. Measurements: Propensity-adjusted analyses using inverse probability weights evaluated comparative risks for hospitalized infection within 30 days and prosthetic joint infection (PJI) within 1 year after surgery between biologics or with different dosages of glucocorticoids. Secondary analyses evaluated non–urinary tract hospitalized infections and 30-day readmissions. Results: Among 9911 patients treated with biologics, 10 923 surgical procedures were identified. Outcomes were similar in patients who received different biologics. Compared with an 8.16% risk for hospitalized infection with abatacept, predicted risk from propensity-weighted models ranged from 6.87% (95% CI, 5.30% to 8.90%) with adalimumab to 8.90% (CI, 5.70% to 13.52%) with rituximab. Compared with a 2.14% 1-year cumulative incidence of PJI with abatacept, predicted incidence ranged from 0.35% (CI, 0.11% to 1.12%) with rituximab to 3.67% (CI, 1.69% to 7.88%) with tocilizumab. Glucocorticoids were associated with a dose-dependent increase in postoperative risk for all outcomes. Propensity-weighted models showed that use of more than 10 mg of glucocorticoids per day (vs. no glucocorticoid use) resulted in a predicted risk for hospitalized infection of 13.25% (CI, 9.72% to 17.81%) (vs. 6.78%) and a predicted 1-year cumulative incidence of PJI of 3.83% (CI, 2.13% to 6.87%) (vs. 2.09%). Limitation: Residual confounding is possible, and sample sizes for rituximab and tocilizumab were small. Conclusion: Risks for hospitalized infection, PJI, and readmission after arthroplasty were similar across biologics. In contrast, glucocorticoid use, especially with dosages above 10 mg/d, was associated with greater risk for adverse outcomes. Primary Funding Source: Rheumatology Research Foundation, National Institutes of Health, and Bristol-Myers Squibb. Patients, particularly those with rheumatoid arthritis (RA), are at increased risk for infection after major surgery. In this analysis, the authors examined risk for infection across different biologic medications and with exposure to glucocorticoids in a large sample of patients with RA who underwent a primary or revision total knee or hip arthroplasty. [ABSTRACT FROM AUTHOR]

Objective: The optimal timing of tumor necrosis factor antagonists before elective surgery is unknown. This study evaluated the association between infliximab timing and serious infection after elective hip or knee arthroplasty.Methods: A retrospective cohort study evaluated US Medicare patients with rheumatoid arthritis, inflammatory bowel disease, psoriasis, psoriatic arthritis, or ankylosing spondylitis who received infliximab within 6 months of elective knee or hip arthroplasty from 2007 to 2013. Propensity-adjusted analyses examined whether infliximab stop timing (time between the most recent infusion and surgery) was associated with hospitalized infection within 30 days or prosthetic joint infection (PJI) within 1 year.Results: Hospitalized infection within 30 days occurred after 270 of 4,288 surgeries (6.3%). Infliximab stop timing <4 weeks versus 8-12 weeks was not associated with an increase in infection within 30 days (propensity-adjusted odds ratio [OR] 0.90 [95% confidence interval (95% CI) 0.60-1.34]). The rate of PJI was 2.9 per 100 person-years and was not increased in patients with stop timing <4 weeks versus 8-12 weeks (hazard ratio [HR] 0.98 [95% CI 0.52-1.87]). Glucocorticoid dosage >10 mg/day was associated with increased risk of 30-day infection (OR 2.11 [95% CI 1.30-3.40]) and PJI (HR 2.70 [95% CI 1.30-5.60]). Other risk factors for infection included elderly age, comorbidities, revision surgery, and previous hospitalized infection.Conclusion: Administering infliximab within 4 weeks of elective knee or hip arthroplasty was not associated with a higher risk of short- or long-term serious infection compared to withholding infliximab for longer time periods. Glucocorticoid use, especially >10 mg/day, was associated with an increased infection risk. [ABSTRACT FROM AUTHOR]

Background: Clostridium difficile infection (CDI), the most common health care-associated infection, often recurs. Fecal microbiota transplantation is increasingly used to treat multiply recurrent CDI (mrCDI).Objective: To determine whether the incidence of mrCDI is increasing in proportion to CDI and to identify risk factors for mrCDI.Design: Retrospective cohort study.Setting: United States.Participants: 38 911 718 commercially insured patients in the OptumInsight Clinformatics Database, of whom 45 341 developed CDI.Measurements: Age- and sex-standardized incidence rates for CDI and mrCDI.Results: From 2001 to 2012, the annual incidence of CDI and mrCDI per 1000 person-years increased by 42.7% (from 0.4408 to 0.6289 case) and 188.8% (from 0.0107 to 0.0309 case), respectively. The increase in mrCDI incidence was independent of known risk factors for CDI. Those who developed mrCDI were older (median age, 56.0 vs. 49.0 years; adjusted odds ratio [aOR] per 10-year increase in age, 1.25 [95% CI, 1.21 to 1.29]) and were more likely to be female (63.8% vs. 58.7%; aOR, 1.24 [CI, 1.11 to 1.38]) and to have used antibiotics (72.3% vs. 58.8%; aOR, 1.79 [CI, 1.59 to 2.01]), proton-pump inhibitors (24.6% vs. 18.2%; aOR, 1.14 [CI, 1.01 to 1.29]), or corticosteroids (18.3% vs. 13.7%; aOR, 1.15 [CI, 1.00 to 1.32]) within 90 days of CDI diagnosis. Chronic kidney disease (10.4% vs. 5.6%; aOR, 1.49 [CI, 1.24 to 1.80]) and diagnosis in a nursing home (2.1% vs. 0.6%; aOR, 1.99 [CI, 1.34 to 2.93]) were also associated with increased risk for mrCDI.Limitation: The primary analyses included only commercially insured patients in the United States.Conclusion: Relative to CDI, mrCDI incidence has disproportionately increased, indicating a rising demand for mrCDI therapies.Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Allergy and Infectious Diseases. [ABSTRACT FROM AUTHOR]

Background: Obesity is associated with the development of acute respiratory distress syndrome (ARDS) in at-risk patients. Low plasma levels of adiponectin, a circulating hormone-like molecule, have been implicated as a possible mechanism for this association. The objective of this study was to determine the association of plasma adiponectin level at ICU admission with ARDS and 30-day mortality in patients with severe sepsis and septic shock.Methods: This is a prospective cohort study of patients admitted to the medical ICU at the Hospital of the University of Pennsylvania. Plasma adiponectin was measured at the time of ICU admission. ARDS was defined by Berlin criteria. Multivariable logistic regression was used to determine the association of plasma adiponectin with the development of ARDS and mortality at 30 days.Results: The study included 164 patients. The incidence of ARDS within 5 days of admission was 45%. The median initial plasma adiponectin level was 7.62 mcg/ml (IQR: 3.87, 14.90) in those without ARDS compared to 8.93 mcg/ml (IQR: 4.60, 18.85) in those developing ARDS. The adjusted odds ratio for ARDS associated with each 5 mcg increase in adiponectin was 1.12 (95% CI 1.01, 1.25), p-value 0.025). A total of 82 patients (51%) of the cohort died within 30 days of ICU admission. There was a statistically significant association between adiponectin and mortality in the unadjusted model (OR 1.11, 95% CI 1.00, 1.23, p-value 0.04) that was no longer significant after adjusting for potential confounders.Conclusions: In this study, low levels of adiponectin were not associated with an increased risk of ARDS in patients with severe sepsis and septic shock. This argues against low levels of adiponectin as a mechanism explaining the association of obesity with ARDS. At present, it is unclear whether circulating adiponectin is involved in the pathogenesis of ARDS or simply represents an epiphenomenon of other unknown functions of adipose tissue or metabolic alterations in sepsis. [ABSTRACT FROM AUTHOR]

Background: Prior studies of post–lung transplant acute kidney injury (AKI) have not accounted for confounding effects of primary graft dysfunction (PGD). We sought to test the impact of PGD on AKI risk factors and on the association of AKI with mortality. Methods: We included patients transplanted at the University of Pennsylvania from 2005‐12, defined AKI using consensus criteria during transplant hospitalization, and defined PGD as grade 3 at 48‐72 hours. We used multivariable logistic regression to test the impact of PGD on AKI risk factors and Cox models to test association of AKI with one‐year mortality adjusting for PGD and other confounders. Results: Of 299 patients, 188 (62.9%) developed AKI with 142 (75%) cases occurring by postoperative day 4. In multivariable models, PGD was strongly associated with AKI (OR 3.76, 95% CI 1.72‐8.19, P = .001) but minimally changed associations of other risk factors with AKI. Both AKI (HR 3.64, 95% CI 1.68‐7.88, P = .001) and PGD (HR 2.55, 95% CI 1.40‐4.64, P = .002) were independently associated with one‐year mortality. Conclusions: Post–lung transplant AKI risk factors and association of AKI with mortality were independent of PGD. AKI may therefore be a target for improving lung transplant mortality rather than simply an epiphenomenon of PGD. [ABSTRACT FROM AUTHOR]

Diet may be an important factor in the progression of Crohn's disease (CD). We performed a randomized controlled trial to determine whether reduced consumption of red and processed meats decreases the risk of symptomatic relapse of CD, analyzing results from the Food and Crohn's Disease Exacerbation Study (FACES) trial. Adults with CD were recruited into the FACES trial from IBD Partners, an Internet-based cohort of patients with inflammatory bowel disease, from November 2013 through June 2015. Individuals who were in remission (CD activity index [sCDAI] scores of ≤150), had completed a biannual survey, and reported consumption of red meat at least once weekly were randomly assigned to groups that consumed a minimum of 2 servings/week of red or processed meat (high meat, n = 118) or not more than 1 serving per month (low meat, n = 96) for 49 weeks. The primary outcome was relapse of CD, defined as increase in sCDAI score by ≥70 points and to >150 or a need for CD surgery or new CD medication. A secondary outcome, moderate or severe relapse, was based on an increase in sCDAI to >219. During the trial, the high-meat groups reported consumption of 2 or more servings of red or processed meat during 98.5% of observed weeks compared with 18.8% of weeks for the low-meat group. Any and moderate to severe relapse occurred in 62% of participants in the high-meat group and 42% of participants in the low-meat group. There were no significant differences in time to any (P =.61) or moderate/severe (P =.50) relapse. In an analysis of data from the FACES trial, we found that among patients with CD in remission, level of red and processed meat consumption was not associated with time to symptomatic relapse. ClinicalTrials.gov , Number: NCT0192673. [ABSTRACT FROM AUTHOR]

Background: Chronic pain is common in people living with HIV (PLWH). Few studies have evaluated the association between the diagnoses of chronic pain, substance use disorder (SUD), and HIV-related outcomes in clinical settings over a 10-year period., Methods: Using electronic medical records, the study described psychiatric diagnoses, pain medication, and HIV-related variables in PLWH and examined the factors associated with pain diagnosis and HIV-related outcomes., Results: Among 3528 PLWH, more than one-third exhibited a chronic pain diagnosis and more than one-third a psychiatric disorder. Chronic pain diagnosis has been associated with SUD and mood and anxiety disorders and occurred before SUD or psychiatric disorders about half of the time. Opioids have been commonly prescribed for pain management, more often than nonopioid analgesic, without any change in prescription pattern over the 10-year period. A dual diagnosis of pain and SUD has been associated with more psychiatric disorders and had a negative impact on the pain management by requesting more health care utilization and higher frequency of both opioid and nonopioid medication prescriptions. Chronic pain and SUD had a negative impact on ART adherence. SUD but not chronic pain has been associated with an unsuppressed HIV viral load., Conclusions: In the current intertwining opioid prescription and opioid epidemic, opioids are still commonly prescribed in PLWH in HIV care. A diagnosis of chronic pain and/or SUD worsened the HIV-related outcomes, emphasizing the potential risk of the HIV epidemic. These findings called for a better coordinated care program in HIV clinics.

Background Although intestinal and urinary microbiome perturbations are associated with nephrolithiasis, whether antibiotics are a risk factor for this condition remains unknown. Methods We determined the association between 12 classes of oral antibiotics and nephrolithiasis in a population-based, case-control study nested within 641 general practices providing electronic health record data for >13 million children and adults from 1994 to 2015 in the United Kingdom. We used incidence density sampling to match 25,981 patients with nephrolithiasis to 259,797 controls by age, sex, and practice at date of diagnosis (index date). Conditional logistic regression models were adjusted for the rate of health care encounters, comorbidities, urinary tract infections, and use of thiazide and loop diuretics, proton-pump inhibitors, and statins. Results Exposure to any of five different antibiotic classes 3-12 months before index date was associated with nephrolithiasis. The adjusted odds ratio (95% confidence interval) was 2.33 (2.19 to 2.48) for sulfas, 1.88 (1.75 to 2.01) for cephalosporins, 1.67 (1.54 to 1.81) for fluoroquinolones, 1.70 (1.55 to 1.88) for nitrofurantoin/methenamine, and 1.27 (1.18 to 1.36) for broad-spectrum penicillins. In exploratory analyses, the magnitude of associations was greatest for exposure at younger ages ( P <0.001) and 3-6 months before index date ( P <0.001), with all but broad-spectrum penicillins remaining statistically significant 3-5 years from exposure. Conclusions Oral antibiotics associated with increased odds of nephrolithiasis, with the greatest odds for recent exposure and exposure at younger age. These results have implications for disease pathogenesis and the rising incidence of nephrolithiasis, particularly among children., (Copyright © 2018 by the American Society of Nephrology.)

Objective: To evaluate the risk of serious adverse events among patients with type 2 diabetes mellitus initiating saxagliptin compared with oral antidiabetic drugs (OADs) in classes other than dipeptidyl peptidase-4 (DPP-4) inhibitors., Research Design and Methods: Cohort studies using 2009-2014 data from two UK medical record data sources (Clinical Practice Research Datalink, The Health Improvement Network) and two USA claims-based data sources (HealthCore Integrated Research Database, Medicare). All eligible adult patients newly prescribed saxagliptin (n=110 740) and random samples of up to 10 matched initiators of non-DPP-4 inhibitor OADs within each data source were selected (n=913 384). Outcomes were hospitalized major adverse cardiovascular events (MACE), acute kidney injury (AKI), acute liver failure (ALF), infections, and severe hypersensitivity events, evaluated using diagnostic coding algorithms and medical records. Cox regression was used to determine HRs with 95% CIs for each outcome. Meta-analyses across data sources were performed for each outcome as feasible., Results: There were no increased incidence rates or risk of MACE, AKI, ALF, infection, or severe hypersensitivity reactions among saxagliptin initiators compared with other OAD initiators within any data source. Meta-analyses demonstrated a reduced risk of hospitalization/death from MACE (HR 0.91, 95% CI 0.85 to 0.97) and no increased risk of hospitalization for infection (HR 0.97, 95% CI 0.93 to 1.02) or AKI (HR 0.99, 95% CI 0.88 to 1.11) associated with saxagliptin initiation. ALF and hypersensitivity events were too rare to permit meta-analysis., Conclusions: Saxagliptin initiation was not associated with increased risk of MACE, infection, AKI, ALF, or severe hypersensitivity reactions in clinical practice settings., Trial Registration Number: NCT01086280, NCT01086293, NCT01086319, NCT01086306, and NCT01377935; Results., Competing Interests: Competing interests: VLR, DMC, MES, CWN, JAR, QL, QW, SC, KH, SEK, PPR, DJM, AJA, KRR and BLS received funding from AstraZeneca through their employers. AMG and HB are employees of CPRD and THIN, respectively. KH and DBE are employees of HealthCore. SEK has consulted for Pfizer, Merck and Bayer, all unrelated to this manuscript.

Background and Objective: ABO blood types are determined by antigen modifications on glycoproteins and glycolipids and associated with altered plasma levels of inflammatory and endothelial injury markers implicated in AKI pathogenesis. We sought to determine the association of ABO blood types with AKI risk in critically ill patients with trauma or sepsis., Design, Setting, Participants, & Measurements: We conducted two prospective cohort studies at an urban, academic, level I trauma center and tertiary referral center; 497 patients with trauma admitted to the surgical intensive care unit between 2005 and 2010 with an injury severity score >15 and 759 patients with severe sepsis admitted to the medical intensive care unit between 2008 and 2013 were followed for 6 days for the development of incident AKI. AKI was defined by Acute Kidney Injury Network creatinine and dialysis criteria., Results: Of 497 patients with trauma, 134 developed AKI (27%). In multivariable analysis, blood type A was associated with higher AKI risk relative to type O among patients of European descent (n=229; adjusted risk, 0.28 versus 0.14; risk difference, 0.14; 95% confidence interval, 0.03 to 0.24; P=0.02). Of 759 patients with sepsis, AKI developed in 326 (43%). Blood type A again conferred higher AKI risk relative to type O among patients of European descent (n=437; adjusted risk, 0.53 versus 0.40; risk difference, 0.14; 95% confidence interval, 0.04 to 0.23; P=0.01). Findings were similar when analysis was restricted to those patients who did not develop acute respiratory distress syndrome or were not transfused. We did not detect a significant association between blood type and AKI risk among individuals of African descent in either cohort., Conclusions: Blood type A is independently associated with AKI risk in critically ill patients with trauma or severe sepsis of European descent, suggesting a role for ABO glycans in AKI susceptibility., (Copyright © 2015 by the American Society of Nephrology.)