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Background Antibiotic stewardship programs (ASPs) have demonstrated success at reducing costs, yet there is limited quality evidence of their effectiveness in reducing infections of high-profile drug-resistant organisms. Methods This retrospective, cohort study included all Kaiser Permanente Southern California (KPSC) members aged ≥18 years hospitalized in 9 KPSC hospitals from 1 January 2008 to 31 December 2016. We measured the impact of staggered ASP implementation on consumption of 18 ASP-targeted antibiotics using generalized linear mixed-effects models. We used multivariable generalized linear mixed-effects models to estimate the adjusted effect of an ASP on rates of infection with drug-resistant organisms. Analyses were adjusted for confounding by time, cluster effects, and patient- and hospital-level characteristics. Results We included 765 111 hospitalizations (288 257 pre-ASP, 476 854 post-ASP). By defined daily dose, we found a 6.1% (−7.5% to −4.7%) overall decrease antibiotic use post-ASP; by days of therapy, we detected a 4.3% (−5.4% to −3.1%) decrease in overall use of antibiotics. The number of prescriptions increased post-ASP (1.04 [1.03–1.05]). In adjusted analyses, we detected an overall increase in vancomycin-resistant enterococci infections post-ASP (1.37 [1.10–1.69]). We did not detect a change in the rates of extended-spectrum beta-lactamase, carbapenem-resistant Enterobacteriaceae, and multidrug-resistant Pseudomonas aeruginosa infections post-ASP. Conclusions ASPs with successful reductions in consumption of targeted antibiotics may not see changes in infection rates with antibiotic-resistant organisms in the 2 to 6 years post-implementation. There are likely differing timescales for reversion to susceptibility across organisms and antibiotics, and unintended consequences from compensatory prescribing may occur.

Background Direct oral anticoagulants (DOACs) are widely used in patients with nonvalvular atrial fibrillation for stroke prevention. However, long‐term adherence to DOACs and clinical outcomes in real‐world clinical practice is not well understood. This study evaluated long‐term medication adherence patterns to DOAC therapy and clinical outcomes in a large US integrated health care system. Methods and Results We included adult patients with nonvalvular atrial fibrillation who newly initiated DOACs between 2012 and 2018 in Kaiser Permanente Southern California. Long‐term (3.5 years) adherence trajectories to DOAC were investigated using monthly proportion of days covered and group‐based trajectory models. Factors associated with long‐term adherence trajectories were investigated. Multivariable Poisson regression analyses were used to investigate thromboembolism and major bleeding events associated with long‐term adherence trajectories. Of 18 920 patients newly initiating DOACs, we identified 3 DOAC adherence trajectories: consistently adherent (85.2%), early discontinuation within 6 months (10.6%), and gradually declining adherence (4.2%). Predictors such as lower CHA 2 DS 2 ‐VASc (0–1 versus ≥5) and previous injurious falls were associated with both early discontinuation and gradually declining adherence trajectories. Early discontinuation of DOAC therapy was associated with a higher risk of thromboembolism (rate ratio, 1.40; 95% CI, 1.05–1.86) especially after 12 months from DOAC initiation but a lower risk of major bleed compared with consistent adherence (rate ratio, 0.48; 95% CI, 0.30–0.75), specifically during the first 12 months following DOAC initiation. A gradual decline in adherence to DOACs was not statistically significantly associated with thromboembolism outcomes compared with consistent adherence. Conclusions Although a large proportion of patients with nonvalvular atrial fibrillation were adherent to DOAC therapy over 3.5 years, early discontinuation of DOAC was associated a higher risk of thromboembolic events. Future tailored interventions for early discontinuers may improve clinical outcomes.

Background Urinary tract infections (UTIs) occur commonly, but recent data on UTI rates are scarce. It is unknown how the growth of virtual healthcare delivery affects outpatient UTI management and trends in the United States. Methods From 1 January 2008 to 31 December 2017, UTIs from outpatient settings (office, emergency, and virtual visits) were identified from electronic health records at Kaiser Permanente Southern California using multiple UTI definitions. Annual rates estimated by Poisson regression were stratified by sex, care setting, age, and race/ethnicity. Annual trends were estimated by linear or piecewise Poisson regression. Results UTIs occurred in 1 065 955 individuals. Rates per 1000 person-years were 53.7 (95% confidence interval [CI], 50.6–57.0) by diagnosis code with antibiotic and 25.8 (95% CI, 24.7–26.9) by positive culture. Compared to office and emergency visits, UTIs were increasingly diagnosed in virtual visits, where rates by diagnosis code with antibiotic increased annually by 21.2% (95% CI, 16.5%–26.2%) in females and 29.3% (95% CI, 23.7%–35.3%) in males. Only 32% of virtual care diagnoses had a culture order. Overall, UTI rates were highest and increased the most in older adults. Rates were also higher in Hispanic and white females and black and white males. Conclusions Outpatient UTI rates increased from 2008 to 2017, especially in virtual care and among older adults. Virtual care is important for expanding access to health services, but strategies are needed in all outpatient care settings to ensure accurate UTI diagnosis and reduce inappropriate antibiotic treatment.

Anticyclic citrullinated peptide (anti-CCP) positivity may be a strong predictor of joint erosion and a potential biomarker for guiding treatment decisions for rheumatoid arthritis (RA). However, limited studies are currently available on the effect of anti-CCP positivity on health care utilization and/or medical costs of RA patients.To investigate short-term and long-term direct health care expenditures associated with anti-CCP positivity in newly diagnosed RA patients.A retrospective cohort study was conducted in adult RA patients within a U.S. integrated health care delivery system (January 1, 2007-June 30, 2015). Patients were required to have 2 RA diagnoses and treatment with a conventional or biologic disease-modifying antirheumatic drug (DMARD) within 12 months. The first RA diagnosis date was labeled as the index date, and patients were followed until they left the health plan, died, or reached the end of the study period. Patient demographics, anti-CCP results, comorbid conditions, and health care resource utilization during baseline (12 months before the index date) and follow-up periods were collected. Nationally recognized direct medical costs were assigned to health care utilization to calculate health care costs in 2015 U.S. dollars. The baseline differences between anti-CCP positivity and negativity and differences in censoring during follow-up were addressed using propensity scores. The mean differences in costs were estimated using recycled prediction methods.2,448 newly diagnosed RA patients were identified and followed for a median of 3.7 years (range = 1-8 years). At baseline, 65.8% of patients were anti-CCP positive. Anti-CCP-positive patients had fewer comorbid conditions at baseline. During the first 12 months of follow-up, median (interquartile range) total health care expenditures for anti-CCP-positive and anti-CCP-negative patients were $6,200 ($3,563-$13,260) and $7,022 ($3,885-$12,995), respectively. After adjusting for baseline differences, total incremental mean cost associated with anti-CCP positivity during the first 12 months was estimated to be $2,163 per patient (P = 0.001). The annual incremental costs in anti-CCP-positive patients became progressively larger over time, from $2,163 during the first year to $5,062 during the fourth year. Anti-CCP positivity was associated with higher prescription, laboratory testing, and rheumatologist utilization. A higher percentage of anti-CCP-positive patients received 1 or more biologic DMARDs (11.6% for anti-CCP-positive vs. 5.7% for anti-CCP negative; P0.001) compared with anti-CCP-negative patients during the 12-month follow-up, which resulted in $2,499 in incremental prescription costs (P0.001). Total additional burden associated with anti-CCP positivity during the first 4 years was estimated to be $14,089 per patient.In newly diagnosed RA patients, higher economic burden associated with anti-CCP positivity was mainly driven by prescription costs.This research and manuscript were funded by Bristol-Myers Squibb (BMS). Alemao and Connolly are employees and shareholders of BMS and participated in the design of the study, interpretation of the data, review/revision of the manuscript, and approval of the final version of the manuscript. An and Cheetham received a grant from BMS for this research. At the time of this study, An was employed by Western University of Health Sciences, and Cheetham was employed by Kaiser Permanente Southern California. Bider-Canfield, Kang, and Lin have nothing to disclose. Some study results were presented as a poster at the American College of Rheumatology Annual Meeting; November 5, 2017; San Diego, CA, and at the International Society for Pharmacoeconomics and Outcomes Research Meeting; May 19, 2018; Baltimore, MD.

Objective To compare maternal and infant outcomes with different antihypertensive medications in pregnancy. Design Retrospective cohort study. Setting Kaiser Permanente, a large healthcare system in the United States. Population Women aged 15–49 years with a singleton birth from 2005–2014 treated for hypertension. Methods We identified medication exposure from automated pharmacy data based on the earliest dispensing after the first prenatal visit. Using logistic regression, we calculated weighted outcome prevalences, adjusted odds ratios (aORs) and 95% confidence intervals, with inverse probability of treatment weighting to address confounding. Main outcome measures Small for gestational age, preterm delivery, neonatal and maternal intensive care unit (ICU) admission, preeclampsia, and stillbirth or termination at > 20 weeks. Results Among 6346 deliveries, 87% with chronic hypertension, the risk of the infant being small for gestational age (birthweight < 10th percentile) was lower with methyldopa than labetalol (prevalence 13.6% vs. 16.6%; aOR 0.77, 95% CI 0.63 to 0.92). For birthweight < 3rd percentile the aOR was 0.57 (0.39 to 0.80). Compared with labetalol (26.0%), risk of preterm delivery was similar for methyldopa (26.5%; aOR 1.10 [0.95 to 1.27]) and slightly higher for nifedipine (28.5%; aOR 1.25 [1.06 to 1.46]) and other β-blockers (31.2%; aOR 1.58 [1.07 to 2.23]). Neonatal ICU admission was more common with nifedipine than labetalol (25.9% vs. 23.3%, aOR 1.21 [1.02 to 1.43]) but not elevated with methyldopa. Risks of other outcomes did not differ by medication. Conclusions Risk of most outcomes was similar comparing labetalol, methyldopa and nifedipine. Risk of the infant being small for gestational age was substantially lower for methyldopa, suggesting this medication may warrant further consideration.

Objective To incorporate blood pressure (BP), diagnoses codes, and medication fills from electronic medical records (EMR) to identify pregnant women with hypertension. Study design A retrospective cohort study of singleton pregnancies at three US integrated health delivery systems during 2005–2014. Main outcome measures Women were considered hypertensive if they had any of the following: (1) ≥2 high BPs (≥140/90 mmHg) within 30 days during pregnancy (High BP); (2) an antihypertensive medication fill in the 120 days before pregnancy and a hypertension diagnosis from 1 year prior to pregnancy through 20 weeks gestation (Treated Chronic Hypertension); or (3) a high BP, a hypertension diagnosis, and a prescription fill within 7 days during pregnancy (Rapid Treatment). We described characteristics of these pregnancies and conducted medical record review to understand hypertension presence and severity. Results Of 566,624 pregnancies, 27,049 (4.8%) met our hypertension case definition: 24,140 (89.2%) with High BP, 5,409 (20.0%) with Treated Chronic Hypertension, and 5,363 (19.8%) with Rapid Treatment (not mutually exclusive). Of hypertensive pregnancies, 19,298 (71.3%) received a diagnosis, 9,762 (36.1%) received treatment and 11,226 (41.5%) had a BP ≥ 160/110. In a random sample (n = 55) of the 7,559 pregnancies meeting the High BP criterion with no hypertension diagnosis, clinical statements about hypertension were found in medical records for 58% of them. Conclusion Incorporating EMR BP identified many pregnant women with hypertension who would have been missed by using diagnosis codes alone. Future studies should seek to incorporate BP to study treatment and outcomes of hypertension in pregnancy.

CONTEXT Screening for HIV infection in medical settings remains suboptimal. OBJECTIVE To examine the real-world effectiveness of an electronic clinician alert on the same-day HIV testing rate and early diagnosis in high-risk populations. DESIGN We identified Kaiser Permanente Southern California Health Plan members aged 14 years or older who received tests for sexually transmitted infections. MAIN OUTCOME MEASURES Encounter-based same-day HIV testing rate, positive test result rate, and CD4+ cell count and HIV viral load at diagnosis. RESULTS We identified 1,800,948 patients who made 2,326,701 health care encounters eligible for HIV testing before implementation (January 1, 2008 - June 30, 2012) and 1,362,479 eligible encounters after implementation (January 1, 2013 - June 30, 2015). The same-day HIV testing rate increased from 36.7% to 44.1% (standardized mean difference = 0.15, significant difference). The alert was associated with a moderate difference and statistically significant increase in the HIV testing rate (adjusted odds ratio = 1.17, 95% confidence interval = 1.16-1.18). The positive test result rate increased from 0.02% to 0.04% (p < 0.001). During the postimplementation period, fewer HIV-infected patients had a CD4+ cell count below 200 and/or an HIV viral load of 10,000 copies/mL or higher at diagnosis. CONCLUSION Implementation of a targeted electronic alert embedded in the electronic medical record improved same-day HIV screening rate and positive test result rates among patients receiving tests for sexually transmitted infections in a large health organization. This intervention has potential for facilitating frequent screening and early identification of HIV infection in high-risk populations.

To compare perioperative outcomes in the three most common partial nephrectomy modalities: robotic (RPN), laparoscopic (LPN), and open (OPN), matched for nephrometry scores. Patients aged 16–85 who underwent RPN, LPN, or OPN from 2007 to 2014 for localized renal carcinoma within our healthcare system were enrolled. Age, sex, body mass index, and Charlson Comorbidity Index (CCI) as well as perioperative outcomes of estimated blood loss (EBL), length of hospital stay (LOS), ischemia time (IT), change in eGFR, positive margin rate, operative time (OT), and emergency room visit rates were compared between RPN, LPN, and OPN using the R.E.N.A.L nephrometry score. A total of 862 patients underwent partial nephrectomy (523 LPN, 176 OPN, and 163 RPN). Patients who underwent OPN were significantly older, and had higher nephrometry scores and CCI. When matched for nephrometry scores, minimally invasive (LPN and RPN) compared to OPN had lower EBL (

Purpose A skilled assistant surgeon is presumed necessary during robot-assisted partial nephrectomy (RAPN) to minimize warm ischemia time (WIT) and to facilitate complex renorrhaphy. Studies observing impact of resident participation have focused on robotic prostatectomies, showing no impact on core surgical outcomes. Herein, we evaluated the level of experience of the bedside assistant and its impact on perioperative outcomes in RAPN. Materials and methods All RAPN cases in our healthcare system from January 2011 to December 2013 were retrospectively reviewed. The cases were divided into teaching and nonteaching hospitals. There were 18 fellowship-trained attending surgeons. At teaching hospitals, surgeries were performed by an attending physician and postgraduate year (PGY)-2 or PGY-3 resident at bedside; at nonteaching hospitals, surgeries were performed by two attending surgeons. We compared age, gender, body mass index, Charlson comorbidity index, operative difficulty by R.E.N.A.L. nephrometry score, and operative outcomes (WIT, estimated blood loss, operative time (OT), positive margin rate, length of stay (LOS), postoperative glomerular filtration rate, and readmission rate). Results Of the 170 patients captured, 162 had R.E.N.A.L. nephrometry score and WIT: 112 from teaching hospitals and 50 from nonteaching hospitals. Patient characteristics were equivalent between both cohorts with the exception of the R.E.N.A.L. score, which was higher (6.3 vs 5.7, p = 0.046) in the teaching hospitals cohort. Regarding operative outcomes, we noted an overall increase in LOS by 1 day (p = 0.001) and OT by 16 minutes (p = 0.011) in the teaching hospitals. Conclusion We observed that increased LOS was the only clinically relevant measure negatively impacted by resident physician involvement during RAPN.

Background Many epidemiology studies report that atopic conditions such as allergies are associated with reduced pancreas cancer risk. The reason for this relationship is not yet understood. This is the first study to comprehensively evaluate the association between variants in atopy-related candidate genes and pancreatic cancer risk. Methods A population-based case-control study of pancreas cancer cases diagnosed during 2011-2012 (via Ontario Cancer Registry), and controls recruited using random digit dialing utilized DNA from 179 cases and 566 controls. Following an exhaustive literature review, SNPs in 180 candidate genes were pre-screened using dbGaP pancreas cancer GWAS data; 147 SNPs in 56 allergy-related immunologic genes were retained and genotyped. Logistic regression was used to estimate age-adjusted odd ratio (AOR) for each variant and false discovery rate was used to adjust Wald p-values for multiple testing. Subsequently, a risk allele score was derived based on statistically significant variants. Results 18 SNPs in 14 candidate genes (CSF2, DENND1B, DPP10, FLG, IL13, IL13RA2, LRP1B, NOD1, NPSR1, ORMDL3, RORA, STAT4, TLR6, TRA) were significantly associated with pancreas cancer risk. After adjustment for multiple comparisons, two LRP1B SNPs remained statistically significant; for example, LRP1B rs1449477 (AA vs. CC: AOR=0.37, 95% CI: 0.22-0.62; p (adjusted)=0.04). Furthermore, the risk allele score was associated with a significant reduction in pancreas cancer risk (p=0.0007). Conclusions Preliminary findings suggest certain atopy-related variants may be associated with pancreas cancer risk. Further studies are needed to replicate this, and to elucidate the biology behind the growing body of epidemiologic evidence suggesting allergies may reduce pancreatic cancer risk.