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BackgroundTo determine the clinical importance of pneumatosis intestinalis (PI) on surgical decision-making and patient outcomes.MethodsA matched cohort observational study was conducted including all clinical encounters for both ambulatory and inpatient care at UCLA Health between February 15, 2006 and January 31, 2023. Patients were initially identified using encounter diagnostic codes for "other specified diseases of intestine." A radiologic diagnosis of PI was then assessed using natural language processing techniques followed by confirmation using manual chart review. Patients who did not have PI served as a control group. Patient comorbidity was assessed using Elixhauser comorbidity scores. Logistic regression and Cox hazard analyses were used to assess associations between PI and mortality. The main outcome was 90-day all-cause mortality. Secondary outcomes were the proportion of patients undergoing surgery and, of those, how many required bowel resections.ResultsOf the 16,728 patients identified by diagnostic coding, 315 were confirmed to have a diagnosis of PI. The 90-day mortality rate for all patients with PI was 29%. Surgery was performed for 62 patients (20%), of whom 46 (72%) underwent bowel resection and 16 (28%) underwent abdominal exploration alone. Most patients underwent surgery for peritonitis (37%), bowel obstruction (31%), and/or pneumoperitoneum (23%) in association with PI; whereas only 8% of patients received surgery exclusively for PI. There was no statistically significant association between PI and mortality with logistic regression conditioned on other risk factors for mortality. In contrast, survival analysis of a matched cohort demonstrated a small effect of PI on mortality (hazard ratio = 1.24: 95% confidence interval = 1.16-1.32, P = 0.021).ConclusionsMost patients with a diagnosis of PI survive without requiring surgery. Of those who undergo surgery, nearly all have indications for laparotomy exclusive of PI. Mortality in patients who have pneumatosis is strongly associated with comorbid disease, with little to no independent association with PI. Our findings suggest that the presence of PI should not be a primary indication for surgical intervention.

PURPOSE: To determine the relationship between abdominal hernia and obesity. Although obesity is frequently cited as a risk factor for abdominal hernia, few studies have confirmed this association (Menzo et al. Surg Obes Relat Dis 14:1221-1232. 10.1016/j.soard.2018.07.005, 2018). METHODS: A cross-sectional study of primary care ambulatory patients aged older than 16 years treated at UCLA Health from 01/01/2018 to 06/06/2023. Abdominal hernia was identified by clinic encounter ICD-10 codes (K40-K46). RESULTS: There were 41,703 hernias identified among 1,362,440 patients (306.1 per10,000) with a mean age of 62.5 ± 16.1 years, and 57.6% were men. Nearly half (44.7%) of all abdominal hernias were diaphragmatic. There was an approximately equal distribution of the ventral (28.7%) and inguinal (24.3%) hernia. Each hernia type had a different relationship with obesity: The odds of having a ventral hernia increased with BMI in both sexes: BMI 25-29.9 kg/m2 odds ratio (OR) = 1.65, (CI 1.56-1.74); BMI 30-39.9 kg/m2 OR = 2.42 (CI 2.29-2.56), BMI 40-49.9 kg/m2 OR = 2.28 (CI 2.05-2.54) and BMI >  = 50 kg/m2 OR = 2.54 (CI 2.03-3.17) all relative to normal BMI. In contrast, the odds of having an inguinal hernia decreased with obesity relative to normal weight [obesity (BMI 30-39.9 kg/m2): OR = 0.60 (CI 0.56-0.65)], morbid obesity (BMI 40-49.9 kg/m2): OR = 0.29 (CI 0.23-0.37). The OR for diaphragmatic hernia peaks with obesity in women and overweight status in men but was found to decrease with morbid obesity [OR = 1.18 (CI 1.07-1.30)]. There was no significant difference between men and women in the prevalence of femoral hernia (men: 0.7/per10,000, women: 0.9/per10,000, p = 0.19). CONCLUSIONS: The relationship between hernia and obesity is complex with some hernias decreasing in prevalence as obesity increases. Further research is needed to better understand this paradoxical relationship.

BackgroundUniversity of California at Los Angeles Health implemented a Best Practice Advisory (BPA) alert for the initiation of an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB) for individuals with diabetes. The BPA alert was configured with a “chart closure” hard stop, which demanded a response before closing the chart. ObjectiveThe aim of the study was to evaluate whether the implementation of the BPA was associated with changes in ACEI and ARB prescribing during primary care encounters for patients with diabetes. MethodsWe defined ACEI and ARB prescribing opportunities as primary care encounters in which the patient had a diabetes diagnosis, elevated blood pressure in recent encounters, no active ACEI or ARB prescription, and no contraindications. We used a multivariate logistic regression model to compare the change in the probability of an ACEI or ARB prescription during opportunity encounters before and after BPA implementation in primary care sites that did (n=30) and did not (n=31) implement the BPA. In an additional subgroup analysis, we compared ACEI and ARB prescribing in BPA implementation sites that had also implemented a pharmacist-led medication management program. ResultsWe identified a total of 2438 opportunity encounters across 61 primary care sites. The predicted probability of an ACEI or ARB prescription increased significantly from 11.46% to 22.17% during opportunity encounters in BPA implementation sites after BPA implementation. However, in the subgroup analysis, we only observed a significant improvement in ACEI and ARB prescribing in BPA implementation sites that had also implemented the pharmacist-led program. Overall, the change in the predicted probability of an ACEI or ARB prescription from before to after BPA implementation was significantly greater in BPA implementation sites compared with nonimplementation sites (difference-in-differences of 11.82; P

Introduction: Urinary incontinence (UI) affects an estimated 51% of US adult women. This is a comparative effectiveness study of practice-based interventions to improve UI care quality and reduce health disparities. Objectives: Compare the effectiveness of two nonsurgical UI interventions on care quality, shared decision making (SDM), patient-centered outcomes and knowledge. Determine if interventions reduce care disparities and knowledge gaps in underserved Spanish-speaking Latinas. Methods: Sixty primary care physicians (PCPs) from 3 health systems will be randomized into two arms. In Arm 1,patients are co-managed by urology advanced practice provider (APP) and PCP. APP provides UI care, education, and self-management by telemedicine. In Arm 2, patients are co-managed by PCP and urologist. Urologist electronically reviews referral for appropriate primary UI care and provide recommendations if indicated. In both arms, PCPs receive academic detailing and electronic clinical decision support. Shared decision making, patient-reported UI outcomes and knowledge will be assessed using validated questionnaires. Will compare the care quality by site, provider characteristics (sex and years in practice), and racial/ethnic patient groups. Results: Study funding began in October 2022. 181 primary care clinics are eligible for participation. Recruitment began April 2023. Preliminary analysis found 21.1% of women who screened positive for UI discussed UI with PCP. EHR clinical decision support tools are implemented to prompt PCPs to discuss UI patients who screen positive. Conclusions: Successful intervention(s) may lead to wide-scale implementation of effective, cost-saving, quality improvement methods to improve patient satisfaction and streamline UI care.

Objective: Examine the impact of a primary care-embedded clinical pharmacist-led intervention (UCMyRx) on hemoglobin A1C and blood pressure control, relative to usual care, among patients with Type 2 diabetes (TD2) and Medicaid, in a large healthcare system. Methods: We used data extracted from the Electronic Health Records system and a Difference-In-Differences study design with a 2:1 propensity-matched comparison group to evaluate the impact of UCMyRx on HbA1c and systolic blood pressure among patients with TD2 and Medicaid, relative to usual care. Results: Having at least one UCMyRx clinical pharmacist visit was associated with a significant reduction in HbA1c; (-.27%, P-value= .03) but no impact on SBP. We do not find differential UCMyRx effects on HbA1c or SBP among the subpopulations with baseline HbA1C ≥9% or SBP ≥150 mmHg, respectively. In Charlson Comorbidity Index (CCI)-stratified analyses we found stronger UCMyRx effects on HbA1C (-.47%, P-value< .02) among the CCI tercile with the lowest comorbidity score (CC1 ≤ 5). Significant UCMyRx effects are only observed among the subpopulation of Medicaid beneficiaries without Medicare (-.35%, P-value= .02). Conclusions: The UCMyRx intervention is a useful strategy for improving HbA1c control among patients with TD2 and Medicaid.

BackgroundIn 2011, the American Board of Medical Specialties established clinical informatics (CI) as a subspecialty in medicine, jointly administered by the American Board of Pathology and the American Board of Preventive Medicine. Subsequently, many institutions created CI fellowship training programs to meet the growing need for informaticists. Although many programs share similar features, there is considerable variation in program funding and administrative structures.ObjectivesThe aim of our study was to characterize CI fellowship program features, including governance structures, funding sources, and expenses.MethodsWe created a cross-sectional online REDCap survey with 44 items requesting information on program administration, fellows, administrative support, funding sources, and expenses. We surveyed program directors of programs accredited by the Accreditation Council for Graduate Medical Education between 2014 and 2021.ResultsWe invited 54 program directors, of which 41 (76%) completed the survey. The average administrative support received was $27,732/year. Most programs (85.4%) were accredited to have two or more fellows per year. Programs were administratively housed under six departments: Internal Medicine (17; 41.5%), Pediatrics (7; 17.1%), Pathology (6; 14.6%), Family Medicine (6; 14.6%), Emergency Medicine (4; 9.8%), and Anesthesiology (1; 2.4%). Funding sources for CI fellowship program directors included: hospital or health systems (28.3%), clinical departments (28.3%), graduate medical education office (13.2%), biomedical informatics department (9.4%), hospital information technology (9.4%), research and grants (7.5%), and other sources (3.8%) that included philanthropy and external entities.ConclusionCI fellowships have been established in leading academic and community health care systems across the country. Due to their unique training requirements, these programs require significant resources for education, administration, and recruitment. There continues to be considerable heterogeneity in funding models between programs. Our survey findings reinforce the need for reformed federal funding models for informatics practice and training.

ObjectivePatient portals are increasingly used to recruit patients in research studies, but communication response rates remain low without tactics such as financial incentives or manual outreach. We evaluated a new method of study enrollment by embedding a study information sheet and HIPAA authorization form (HAF) into the patient portal preCheck-in (where patients report basic information like allergies).Materials and methodsEligible patients who enrolled received an after-visit patient-reported outcomes survey through the patient portal. No additional recruitment/messaging efforts were made.ResultsA total of 386 of 843 patients completed preCheck-in, 308 of whom signed the HAF and enrolled in the study (37% enrollment rate). Of 93 patients who were eligible to receive the after-visit survey, 45 completed it (48% completion rate).ConclusionEnrollment and survey completion rates were higher than what is typically seen with recruitment by patient portal messaging, suggesting that preCheck-in recruitment can enhance research study recruitment and warrants further investigation.

ImportanceAmong patients with type 2 diabetes (T2D), Hispanic individuals are more likely than non-Hispanic White individuals to develop diabetes-related complications.ObjectiveTo examine the association of a pharmacist-led intervention (UCMyRx) with hemoglobin A1c (HbA1c) and systolic blood pressure (SBP) among Hispanic patients with T2D.Design, setting, and participantsThis quality improvement study used electronic health record data and a difference-in-differences study design to evaluate the association of UCMyRx exposure with changes in HbA1c concentration and SBP among Hispanic patients with T2D, relative to usual care, at University of California, Los Angeles primary care clinics between February and April of 2023. The study population included patients with an International Classification of Diseases, Ninth Revision/International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis of T2D, self-reporting Hispanic ethnicity, age 18 years or older, with 1 or more visits with a UCMyRx pharmacist (treatment) or 2 or more visits, 2 or more years apart, during the study window (comparison). Additionally, patients had to have the following observations during the study window (March 2, 2013-December 31, 2018): (1) a HbA1c 8% or higher, anywhere between 365 days before and 14 days after the index date (date of the first UCMyRx visit or a randomly generated index date) and a follow-up HbA1c measure within 120 to 365 days after the index date (n = 396) and/or (2) a SBP 140 mm Hg or higher between 365 days before and 14 days after the index date, and a follow-up SBP measure within 120 to 450 days after the index date (n = 795).ExposurePharmacists review laboratory results/vital signs, perform medication reconciliation, and develop personally tailored interventions to address adherence barriers and increase guideline-concordant care.Main outcomes and measuresPre- to post-index date changes in HbA1c and SBP.ResultsOf the 931 unique patients with T2D analyzed, the mean (SD) age was 64 (14.1) years, and 552 (59.3%) were female. In adjusted analyses, having 1 or more UCMyRx visits was associated with a reduction in HbA1c concentration (β = -0.46%; 95% CI, -0.84% to -0.07%) but no change in SBP (β = -1.71 mm Hg; 95% CI, -4.00 to 0.58 mm Hg).Conclusions and relevanceIn this quality improvement study of UCMyRx among Hispanic patients with T2D, a negative association was observed between UCMyRx exposure and HbA1c concentration but not SBP. Pharmacist-led intervention may be a strategy for improving outcomes among Hispanic patients with T2D.

ObjectivesTertiary and quaternary (TQ) care refers to complex cases requiring highly specialized health services. Our study aimed to compare the ability of a natural language processing (NLP) model to an existing human workflow in predictively identifying TQ cases for transfer requests to an academic health center.Materials and methodsData on interhospital transfers were queried from the electronic health record for the 6-month period from July 1, 2020 to December 31, 2020. The NLP model was allowed to generate predictions on the same cases as the human predictive workflow during the study period. These predictions were then retrospectively compared to the true TQ outcomes.ResultsThere were 1895 transfer cases labeled by both the human predictive workflow and the NLP model, all of which had retrospective confirmation of the true TQ label. The NLP model receiver operating characteristic curve had an area under the curve of 0.91. Using a model probability threshold of ≥0.3 to be considered TQ positive, accuracy was 81.5% for the NLP model versus 80.3% for the human predictions (P = .198) while sensitivity was 83.6% versus 67.7% (P

ObjectiveWe aimed to develop a distributed, immutable, and highly available cross-cloud blockchain system to facilitate federated data analysis activities among multiple institutions.Materials and methodsWe preprocessed 9166 COVID-19 Structured Query Language (SQL) code, summary statistics, and user activity logs, from the GitHub repository of the Reliable Response Data Discovery for COVID-19 (R2D2) Consortium. The repository collected local summary statistics from participating institutions and aggregated the global result to a COVID-19-related clinical query, previously posted by clinicians on a website. We developed both on-chain and off-chain components to store/query these activity logs and their associated queries/results on a blockchain for immutability, transparency, and high availability of research communication. We measured run-time efficiency of contract deployment, network transactions, and confirmed the accuracy of recorded logs compared to a centralized baseline solution.ResultsThe smart contract deployment took 4.5 s on an average. The time to record an activity log on blockchain was slightly over 2 s, versus 5-9 s for baseline. For querying, each query took on an average less than 0.4 s on blockchain, versus around 2.1 s for baseline.DiscussionThe low deployment, recording, and querying times confirm the feasibility of our cross-cloud, blockchain-based federated data analysis system. We have yet to evaluate the system on a larger network with multiple nodes per cloud, to consider how to accommodate a surge in activities, and to investigate methods to lower querying time as the blockchain grows.ConclusionBlockchain technology can be used to support federated data analysis among multiple institutions.

BackgroundFluoride is vital in the prevention of dental caries in children. In 2014, the U.S. Preventive Services Task Force deemed fluoride varnish a recommended preventive service (grade B). Electronic health record-based clinical decision support (CDS) tools have shown variable ability to alter physicians' ordering behaviors.ObjectivesThis study aimed to increase the application of fluoride varnish in children while analyzing the effect of two passive CDS tools-an order set and a note template.MethodsData on outpatient pediatric visits over an 18-month period before and after CDS implementation (October 15, 2020-April 15, 2022) were queried, while trends in application rate of fluoride were examined. We constructed a multiple logistic regression model with a primary outcome of whether a patient received fluoride at his/her visit. The primary predictor was a "phase" variable representing the CDS implemented. Physician interaction with CDS as well as the financial effects of the resulting service use were also examined.ResultsThere were 3,049 well-child visits of children aged 12 months to 5 years. The addition of a fluoride order to a "Well Child Check" order set led to a 10.6% increase in ordering over physician education alone (25.4 vs. 14.8%, p = 0.001), while the insertion of fluoride-specific text to drop-down lists in clinical notes led to a 6.2% increase (31.5 vs. 25.4%, p = 0.005). Whether a patient received topical fluoride was positively associated with order set implementation (odds ratio [OR] = 5.87, 95% confidence interval [CI]: 4.20-8.21) and fluoride-specific drop-down lists (OR = 7.81, 95% CI: 5.41-11.28). Female providers were more likely to use order sets when ordering fluoride (56.2 vs. 40.9% for males, p ≤ 0.0001). Added revenue totaled $15,084.ConclusionThe targeted use of order sets and note templates was positively associated with the ordering of topical fluoride by physicians.

ObjectiveClinical decision support (CDS) alerts may improve health care quality but "alert fatigue" can reduce provider responsiveness. We analyzed how the introduction of competing alerts affected provider adherence to a single depression screening alert.Materials and methodsWe analyzed the audit data from all occurrences of a CDS alert at a large academic health system. For patients who screen positive for depression during ambulatory visits, a noninterruptive alert was presented, offering a number of relevant documentation actions. Alert adherence was defined as the selection of any option offered within the alert. We assessed the effect of competing clinical guidance alerts presented during the same encounter and the total of all CDS alerts that the same provider had seen in the prior 90 days, on the probability of depression screen alert adherence, adjusting for physician and patient characteristics.ResultsThe depression alert fired during 55 649 office visits involving 418 physicians and 40 474 patients over 41 months. After adjustment, physicians who had seen the most alerts in the prior 90 days were much less likely to respond (adjusted OR highest-lowest quartile, 0.38; 95% CI 0.35-0.42; P

ObjectivesReduction in unnecessary services is one strategy for increasing the value of health care. Reference laboratory, or send-out, tests are associated with considerable costs. We investigated whether displaying cost and turnaround time (TAT), or time-to-result, for reference laboratory tests at the time of order entry in the electronic health record (EHR) system would impact provider ordering practices.MethodsReference laboratory test cost and TAT data were randomized prior to the study and only displayed for the intervention group. A 24-month dataset composed of 12 months each for baseline and study periods was extracted from the clinical data mart. A difference-in-differences (DID) analysis was conducted using a linear mixed-effects model to estimate the association between the intervention and changes in test-ordering patterns.ResultsIn the inpatient setting, the DIDs of aggregate test-order costs and volume were not different among the control and intervention groups (p = 0.31 and p = 0.26, respectively). In the ambulatory setting, the DIDs of aggregate test-order costs and volume were not different among the control and intervention groups (p = 0.82 and p = 0.51, respectively). For both inpatient and ambulatory settings, no significant difference was observed in the DID of aggregate test-order costs and volumes calculated in respect to stratified relative cost and TAT groups (p > 0.05).ConclusionLack of alternative tests, test orders placed at a late step in patient management, and orders facilitated by trainees or mid-level providers may have limited the efficacy of the intervention. Our randomized study demonstrated no significant association between the display of cost or TAT display and ordering frequency.

In a prior survey, we found that applicants for 2017 ACGME-accredited clinical informatics fellowship positions were only 24% female and only 3% were members of underrepresented minorities (URM, consisting of American Indian or Alaska Native, Black or African American, Hispanic, Latino, or Spanish Origin, or Native Hawaiian or Other Pacific Islander). Since 2018, applications for clinical informatics fellowships have been accepted through the AAMC's Electronic Residency Application Service (ERAS). We analyzed national data from ERAS on applicants to clinical informatics fellowship programs for 2018 to 2020 positions. We also obtained applicants' subsequent success in starting clinical informatics fellowship training from the AAMC's GME Track survey. Over these 3 years, we found that the fellowship applicant pool grew from 63 to 74 (17%) and the number of positions offered grew from 34 to 41 (17%). The proportion of women applicants grew to 34% by 2020 and the proportion of underrepresented minorities grew to 12% by 2020. By comparison, medical students 7 years earlier (2013) were 47% female (P=.01) and 16% URM (P>.20), and applicants to many other subspecialties were similar. Applicants' sex and URM membership were not associated with success in starting fellowship training. We conclude that the underrepresentation of women and URM members in clinical informatics fellowships has improved but not resolved. Urgent efforts are needed to increase the both the numbers and the diversity of clinical informatics applicants by promoting the field among medical students and residents, particularly among women and URM members.

BackgroundApproximately 3.8% of adults worldwide have used cannabis in the past year. Understanding how cannabis use is associated with other health conditions is crucial for healthcare providers seeking to understand the needs of their patients, and for health policymakers. This paper analyzes the relationship between documented cannabis use disorders (CUD), cannabis use (CU) and other health diagnoses among primary care patients during a time when medical use of marijuana was permitted by state law in California, United States of America.MethodsThe study utilized primary care electronic health record (EHR) data from an academic health system, using a case-control design to compare diagnoses among individuals with CUD/CU to those of matched controls, and those of individuals with CUD diagnoses with individuals who had CU otherwise documented. Associations of documented CU and CUD with general medical conditions and health conditions associated with cannabis use (both medical and behavioral) were analyzed using conditional logistic regression.ResultsOf 1,047,463 patients with ambulatory encounters from 2013-2017, 729 (0.06%) had CUD diagnoses and 3,731 (0.36%) had CU documented in their EHR. Patients with documented CUD and CU patients had significantly (p

Given the growing number of prediction algorithms developed to predict COVID-19 mortality, we evaluated the transportability of a mortality prediction algorithm using a multi-national network of healthcare systems. We predicted COVID-19 mortality using baseline commonly measured laboratory values and standard demographic and clinical covariates across healthcare systems, countries, and continents. Specifically, we trained a Cox regression model with nine measured laboratory test values, standard demographics at admission, and comorbidity burden pre-admission. These models were compared at site, country, and continent level. Of the 39,969 hospitalized patients with COVID-19 (68.6% male), 5717 (14.3%) died. In the Cox model, age, albumin, AST, creatine, CRP, and white blood cell count are most predictive of mortality. The baseline covariates are more predictive of mortality during the early days of COVID-19 hospitalization. Models trained at healthcare systems with larger cohort size largely retain good transportability performance when porting to different sites. The combination of routine laboratory test values at admission along with basic demographic features can predict mortality in patients hospitalized with COVID-19. Importantly, this potentially deployable model differs from prior work by demonstrating not only consistent performance but also reliable transportability across healthcare systems in the US and Europe, highlighting the generalizability of this model and the overall approach.

ObjectiveImplementation of residency duty hour standards has led to adoption of different staffing models, such as the "holdover" model, whereby nighttime teams admit patients and transfer their care to daytime teams who provide ongoing care. In contrast, nonholdover teams at our institution are responsible for both admitting patients and providing ongoing care. We sought to determine whether patients admitted by holdover teams experience worse outcomes than those admitted by nonholdover teams.MethodsThis is a retrospective cohort study of patients admitted to the internal medicine hospital service at a quaternary care hospital from July 2013 to June 2015. Primary outcomes included hospital length of stay (LOS) and transfer to an intensive care unit within 72 hours of admission. Secondary outcomes were any transfer to an intensive care unit, in-hospital mortality, discharge to home (versus discharge to postacute care facility), and readmission to the health system within 30 days of discharge.ResultsWe analyzed 5518 encounters, 64% of which were admitted by a holdover team. Outcomes were similar between study groups, except the LOS, which was 5.5 hours longer for holdover encounters in unadjusted analyses (5.18 versus 4.95 days, P = 0.04) but not significantly different in adjusted analyses. The mean discharge time was 4:00 p.m. for both groups, whereas the mean admission times were 12:00 a.m. and 4:00 p.m. for holdover and nonholdover encounters, respectively.ConclusionsHoldover encounters at our institution were not associated with worse patient safety outcomes. A small increase in LOS may have been attributable to holdover patients having earlier admission and identical discharge times.

Background: The risks of osteoporosis and breast cancer are increasing in elderly women. Bisphosphonates and denosumab are recommended for treatment of osteoporosis. They have different and overlapping pharmacodynamics and previous studies have shown conflicting results regarding their risk association with breast cancer. We intend to further look into this issue through a comparative study. Methods: Electronic health records of 91,626 women older than 50 years with no previous history of malignancy and no nonbreast cancer during follow-up were retrieved from southern California and retrospectively analyzed using univariate, bivariate, and log-rank tests. Medication use, breast cancer risk, and associated demographic and clinical history were assessed. Results: Over an average of 3.6 years follow-up, the breast cancer relative risks (RRs) counted after 365 days of latency are 1.12 (95% confidence interval [CI]: 0.64-1.97) for denosumab ever users and 0.37 (95% CI: 0.21-0.66) for bisphosphonates ever users, when covariates are comparable. The significant difference is supported by the Log-rank test (p = 0.0004). Excluding statins coprescribers, the breast cancer RR is 1.31 (0.71, 2.43) in denosumab group and 0.26 (0.11, 0.62) in bisphosphonates group. There is a reduced RR in statins ever users (0.47, 95% CI: 0.38-0.58), and the breast cancer risk difference is not significant between concomitant denosumab/statins and bisphosphonates/statins ever users with RR 0.65 (0.16, 2.58) versus 0.55 (0.26, 1.16), p = 0.692. Conclusions: Our data support an association of lower breast cancer risk with bisphosphonates use in elderly women. We did not observe a lower breast cancer risk in denosumab group; however, our data revealed a potential lower breast cancer risk in denosumab users with concurrent statins use and this requires further study.

ObjectiveTo utilize, in an individual and institutional privacy-preserving manner, electronic health record (EHR) data from 202 hospitals by analyzing answers to COVID-19-related questions and posting these answers online.Materials and methodsWe developed a distributed, federated network of 12 health systems that harmonized their EHRs and submitted aggregate answers to consortia questions posted at https://www.covid19questions.org. Our consortium developed processes and implemented distributed algorithms to produce answers to a variety of questions. We were able to generate counts, descriptive statistics, and build a multivariate, iterative regression model without centralizing individual-level data.ResultsOur public website contains answers to various clinical questions, a web form for users to ask questions in natural language, and a list of items that are currently pending responses. The results show, for example, that patients who were taking angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, within the year before admission, had lower unadjusted in-hospital mortality rates. We also showed that, when adjusted for, age, sex, and ethnicity were not significantly associated with mortality. We demonstrated that it is possible to answer questions about COVID-19 using EHR data from systems that have different policies and must follow various regulations, without moving data out of their health systems.Discussion and conclusionsWe present an alternative or a complement to centralized COVID-19 registries of EHR data. We can use multivariate distributed logistic regression on observations recorded in the process of care to generate results without transferring individual-level data outside the health systems.

ObjectiveThe Consortium for Clinical Characterization of COVID-19 by EHR (4CE) is an international collaboration addressing coronavirus disease 2019 (COVID-19) with federated analyses of electronic health record (EHR) data. We sought to develop and validate a computable phenotype for COVID-19 severity.Materials and methodsTwelve 4CE sites participated. First, we developed an EHR-based severity phenotype consisting of 6 code classes, and we validated it on patient hospitalization data from the 12 4CE clinical sites against the outcomes of intensive care unit (ICU) admission and/or death. We also piloted an alternative machine learning approach and compared selected predictors of severity with the 4CE phenotype at 1 site.ResultsThe full 4CE severity phenotype had pooled sensitivity of 0.73 and specificity 0.83 for the combined outcome of ICU admission and/or death. The sensitivity of individual code categories for acuity had high variability-up to 0.65 across sites. At one pilot site, the expert-derived phenotype had mean area under the curve of 0.903 (95% confidence interval, 0.886-0.921), compared with an area under the curve of 0.956 (95% confidence interval, 0.952-0.959) for the machine learning approach. Billing codes were poor proxies of ICU admission, with as low as 49% precision and recall compared with chart review.DiscussionWe developed a severity phenotype using 6 code classes that proved resilient to coding variability across international institutions. In contrast, machine learning approaches may overfit hospital-specific orders. Manual chart review revealed discrepancies even in the gold-standard outcomes, possibly owing to heterogeneous pandemic conditions.ConclusionsWe developed an EHR-based severity phenotype for COVID-19 in hospitalized patients and validated it at 12 international sites.

Statin medications reduce cardiovascular events, but many patients never start taking their prescribed statin (primary nonadherence). Limited knowledge exists about the attitudes and beliefs of those with primary nonadherence. In this study, patients with primary nonadherence to statin medications (n = 173) completed a self-administered cross-sectional survey that assessed their attitudes and beliefs related to primary nonadherence and to potential motivators for statin use. Patients were recruited in 2019 from two academic health systems and nationwide internet advertisements. Only 49 of 173 (28.3%) patients with primary nonadherence reported having cardiovascular disease (CVD). Ninety-nine patients (57.2%) never filled their prescription, and 74 (42.8%) filled but never took any statin. Over half failed to initially inform their prescriber they might not take the statin. Patients strongly or somewhat agreed that they desired alternate treatment plans such as diet and/or exercise (n = 134; 77.4%) or natural remedies/dietary supplements (n = 125; 72.3%). Ninety-eight (56.6%) stronglyor somewhat worried about the possibility of statin dependence or addiction. Twenty-seven (15.6%) patients noted that they would not take a statin based solely on CVD risk estimates; 50 (28.9%) selected a CVD risk threshold of >20%; and 23 (13.3%) a threshold of >50% as motivating factors to take statins. Patients with primary nonadherence have attitudes about taking statins based on CVD risk that differ from scientific recommendations, may not tell providers about their hesitation to take statins, and likely prefer alternative initial approaches to cholesterol lowering. Early shared decision-making and assessment of patient attitudes about statins could potentially better align initial approaches for CVD risk reduction.

BackgroundThe appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy.MethodsUsing an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis.ResultsA total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]).ConclusionsIn this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily. (Funded by the Patient-Centered Outcomes Research Institute; ADAPTABLE ClinicalTrials.gov number, NCT02697916.).

BackgroundPharmacists are effective at improving control of cardiovascular risk factors, but it less clear whether these improvements translate into less emergency department (ED) use and fewer hospitalizations. The UCMyRx program embed pharmacists in primary care.ObjectiveThe objective of this study was to examine if the integration of pharmacists into primary care was associated with lower ED and hospital use for patients with diabetes.DesignThis was a quasi-experimental study with a comparator group.SubjectsThe analytic sample included patients with diabetes with uncontrolled cardiovascular risk factors (A1C >9%, blood pressure >140/90 mm Hg, low-density lipoprotein-cholesterol >130 mg/dL) who had 1 or more visits in either a UCMyRx (648 patients, 14 practices) or usual care practice (1944 patients, 14 practices).MeasuresOur outcomes were ED and hospitalization rates as measured before and after the consultations between UCMyRx and usual care. Our predictor variable was the pharmacist consultation. Poisson generalized estimating equations model was used to estimate the adjusted predicted change in utilization before and after the pharmacist consultation. The Average Treatment Effect on the Treated was estimated.ResultsIn models adjusted, the adjusted mean predicted number of emergency department visits/month during the year before the consultation was 0.09 among UCMyRx patients. During the year after initiating the care with the pharmacists, this rate decreased to an adjusted mean monthly rate of 0.07, with an Average Treatment Effect on the Treated=0.021 (P=0.035), a predicted reduction of 21% in emergency department visits associated with the clinical pharmacist consults. There was a nonsignificant predicted 3.2% reduction in hospitalizations over time for patients in the UCMyRx program.ConclusionClinical pharmacists are an important addition to clinical care teams in primary care practices and significantly decreased utilization of the ED among patients with poorly controlled diabetes.

Insights into oncogenesis derived from cancer susceptibility loci (SNP) hold the potential to facilitate better cancer management and treatment through precision oncology. However, therapeutic insights have thus far been limited by our current lack of understanding regarding both interactions of these loci with somatic cancer driver mutations and their influence on tumorigenesis. For example, although both germline and somatic genetic variation to the p53 tumor suppressor pathway are known to promote tumorigenesis, little is known about the extent to which such variants cooperate to alter pathway activity. Here we hypothesize that cancer risk-associated germline variants interact with somatic TP53 mutational status to modify cancer risk, progression, and response to therapy. Focusing on a cancer risk SNP (rs78378222) with a well-documented ability to directly influence p53 activity as well as integration of germline datasets relating to cancer susceptibility with tumor data capturing somatically-acquired genetic variation provided supportive evidence for this hypothesis. Integration of germline and somatic genetic data enabled identification of a novel entry point for therapeutic manipulation of p53 activities. A cluster of cancer risk SNPs resulted in increased expression of prosurvival p53 target gene KITLG and attenuation of p53-mediated responses to genotoxic therapies, which were reversed by pharmacologic inhibition of the prosurvival c-KIT signal. Together, our results offer evidence of how cancer susceptibility SNPs can interact with cancer driver genes to affect cancer progression and identify novel combinatorial therapies. SIGNIFICANCE: These results offer evidence of how cancer susceptibility SNPs can interact with cancer driver genes to affect cancer progression and present novel therapeutic targets.

BackgroundPatients often seek medical treatment among different health care organizations, which can lead to redundant tests and treatments. One electronic health record (EHR) platform, Epic Systems, uses a patient linkage tool called Care Everywhere (CE), to match patients across institutions. To the extent that such linkages accurately identify shared patients across organizations, they would hold potential for improving care.ObjectiveThis study aimed to understand how accurate the CE tool with default settings is to identify identical patients between two neighboring academic health care systems in Southern California, The University of California Los Angeles (UCLA) and Cedars-Sinai Medical Center.MethodsWe studied CE patient linkage queries received at UCLA from Cedars-Sinai between November 1, 2016, and April 30, 2017. We constructed datasets comprised of linkages ("successful" queries), as well as nonlinkages ("unsuccessful" queries) during this time period. To identify false positive linkages, we screened the "successful" linkages for potential errors and then manually reviewed all that screened positive. To identify false-negative linkages, we applied our own patient matching algorithm to the "unsuccessful" queries and then manually reviewed a sample to identify missed patient linkages.ResultsDuring the 6-month study period, Cedars-Sinai attempted to link 181,567 unique patient identities to records at UCLA. CE made 22,923 "successful" linkages and returned 158,644 "unsuccessful" queries among these patients. Manual review of the screened "successful" linkages between the two institutions determined there were no false positives. Manual review of a sample of the "unsuccessful" queries (n = 623), demonstrated an extrapolated false-negative rate of 2.97% (95% confidence interval [CI]: 1.6-4.4%).ConclusionWe found that CE provided very reliable patient matching across institutions. The system missed a few linkages, but the false-negative rate was low and there were no false-positive matches over 6 months of use between two nearby institutions.

BackgroundBlack individuals with type 2 diabetes suffer disproportionate morbidity and mortality relative to whites with type 2 diabetes, irrespective of health insurance coverage.ObjectiveExamine the impact of a primary care-embedded clinical pharmacist-led intervention (UCMyRx) on cardiovascular risk factor control among blacks with type 2 diabetes in a large healthcare system.DesignWe used data extracted from the electronic health records (EHR) system and a difference-in-differences study design with a propensity-matched comparison group to evaluate the impact of UCMyRx on HbA1c and systolic blood pressure (SBP) among black patients with type 2 diabetes, relative to usual care.ParticipantsIndividuals with type 2 diabetes identified as either black or African American in the EHR that were ≥ 18 years of age that had the following observations during the study window (03/02/2013-12/31/18: (1) HbA1C ≥ 8%, at least once, anywhere between 365 days before and 14 days after the UCMyRx visit and a follow-up HbA1c measure within 120 to 365 days after the visit and/or (2) SBP ≥ 140 mmHg at least once between 365 days before and 14 days after the UCMyRx visit that had a follow-up SBP measure within 120 to 450 days after the visit.InterventionUCMyRx pharmacists review labs and vital signs, perform medication reconciliation, use a standardized survey to assess barriers to medication adherence, and develop tailored interventions to improve medication adherence.Main measuresChange in HbA1c and change in SBP from before to after the first UCMyRx visit.Key resultsHaving at least one visit with a UCMyRx clinical pharmacist was associated with a significant reduction in HbA1c (- 0.4%, p value = .01); however, there was no significant impact on SBP (- .051 mmHg, p value = 0.74).ConclusionsThe UCMyRx intervention is a useful strategy for improving HbA1c control among blacks with type 2 diabetes.

We leveraged the largely untapped resource of electronic health record data to address critical clinical and epidemiological questions about Coronavirus Disease 2019 (COVID-19). To do this, we formed an international consortium (4CE) of 96 hospitals across five countries (www.covidclinical.net). Contributors utilized the Informatics for Integrating Biology and the Bedside (i2b2) or Observational Medical Outcomes Partnership (OMOP) platforms to map to a common data model. The group focused on temporal changes in key laboratory test values. Harmonized data were analyzed locally and converted to a shared aggregate form for rapid analysis and visualization of regional differences and global commonalities. Data covered 27,584 COVID-19 cases with 187,802 laboratory tests. Case counts and laboratory trajectories were concordant with existing literature. Laboratory tests at the time of diagnosis showed hospital-level differences equivalent to country-level variation across the consortium partners. Despite the limitations of decentralized data generation, we established a framework to capture the trajectory of COVID-19 disease in patients and their response to interventions.

BackgroundSepsis is the leading cause of in-hospital death. The SEP-1 sepsis bundle is a protocol for early sepsis care that requires providers to diagnose and treat sepsis quickly. Limited evidence suggests that adherence to the sepsis bundle is lower in cases of hospital-onset sepsis.ObjectiveTo compare sepsis bundle adherence in hospital-onset vs. community-onset sepsis.DesignRetrospective cohort study using multivariable analysis of clinical data.ParticipantsA total of 4658 inpatients age 18 or older were identified by diagnosis codes consistent with sepsis or disseminated infection.SettingFour university hospitals in California between 2014 and 2016.Main outcomes and measuresThe primary outcome was adherence to key components of the sepsis bundle defined by the Centers for Medicare and Medicaid Services in their core measure, SEP-1. Covariates included clinical characteristics related to the patient, infection, and pathogen.Key resultsCompared with community-onset, cases of hospital-onset sepsis were less likely to receive SEP-1 adherent care (relative risk 0.33, 95% confidence interval 0.29-0.38, p

ObjectiveA growing body of evidence suggests that testing for influenza virus alone is more appropriate than multiplex respiratory viral panel (RVP) testing for general populations of patients with respiratory tract infections. We aimed to decrease the proportion of RVPs out of total respiratory viral testing ordered during influenza season.MethodsWe implemented two consecutive interventions: reflex testing for RVPs only after a negative influenza test, and noninterruptive clinical decision support (CDS) including modifications of the computerized physician order entry search behavior and cost display. We conducted an interrupted time series of RVPs and influenza polymerase chain reaction tests pre- and postintervention, and performed a mixed-effects logistic regression analysis with a primary outcome of proportion of RVPs out of total respiratory viral tests. The primary predictor was the intervention period, and covariates included the provider, clinical setting, associated diagnoses, and influenza incidence.ResultsFrom March 2013 to April 2019, there were 24,294 RVPs and 26,012 influenza tests (n = 50,306). Odds of ordering an RVP decreased during the reflex testing period (odds ratio: 0.432, 95% confidence interval: 0.397-0.469), and decreased more dramatically during the noninterruptive CDS period (odds ratio: 0.291, 95% confidence interval: 0.259-0.327).DiscussionThe odds of ordering an RVP were 71% less with the noninterruptive CDS intervention, which projected 4,773 fewer RVPs compared with baseline. Assuming a cost equal to Medicare reimbursement rates for RVPs and influenza tests, this would generate an estimated averted cost of $1,259,474 per year.ConclusionNoninterruptive CDS interventions are effective in reducing unnecessary and expensive testing, and avoid typical pitfalls such as alert fatigue.

Observation is a useful tool, even in infant and toddler classrooms. Applied correctly, observation and assessment can help lay a foundation for a successful education throughout life. As appropriate practices are researched and policies change, teachers and caregivers of the youngest children (referred to as careteachers for this article) find themselves in the middle of the assessment challenge. Many early childhood programs and teachers struggle with implementing observation and assessment practices. With increasing demands of families and administration, the careteacher's plate can be very full. However, appropriate practices suggest that an ongoing assessment system should be implemented for all children in-group care settings. Accreditation criteria from the National Association for the Education of Young Children or NAEYC (2006) require a systematic and authentic assessment program be implemented for all children. This system should include observation, screening, and criterion based strategies. Many schools are implementing these practices for their preschool programs but infant and toddler programs can benefit from them as well. This article will briefly address the why, what, and how of observation as assessment with infants and toddlers.

ImportanceChronic kidney disease (CKD) is serious and common, yet recognition and public health responses are limited.ObjectiveTo describe clinical features of, prevalence of, major risk factors for, and care for CKD among patients treated in 2 large US health care systems.Design, setting, and participantsThis cohort study collected data from the Center for Kidney Disease Research, Education, and Hope (CURE-CKD) registry, an electronic health record-based registry jointly curated and sponsored by Providence St Joseph Health and the University of California, Los Angeles. Patients were adults and children with CKD (excluding end-stage kidney disease) and adults at risk of CKD (ie, with diabetes, hypertension, or prediabetes) identified by laboratory values, vital signs, prescriptions, and administrative codes. Data were collected from January 2006 through December 2017, with analyses performed from March 2019 through November 2019.ExposuresDiabetes, hypertension, and prediabetes.Main outcomes and measuresClinical and demographic characteristics, prevalence, and prescribed medications.ResultsOf 2 625 963 adults and children in the sample, 606 064 adults (23.1%) with CKD had a median (interquartile range [IQR]) age of 70 (59-81) years, with 338 785 women (55.9%) and 434 474 non-Latino white individuals (71.7%). A total of 12 591 children (0.4%) with CKD had a median (IQR) age of 6 (1-13) years, with 7079 girls (56.2%) and 6653 non-Latino white children (52.8%). Median (IQR) estimated glomerular filtration rate was 53 (41-61) mL/min/1.73 m2 among adults and 70 (50-95) mL/min/1.73 m2 in children. Prevalence rates for CKD in adults were 4.8% overall (606 064 of 12 669 700) with 1.6% (93 644 of 6 011 129) during 2006 to 2009, 5.7% (393 455 of 6 903 084) during 2010 to 2013, and 8.4% (683 574 of 8 179 860) during 2014 to 2017 (P

BackgroundChronic kidney disease (CKD) is a global public health problem, exhibiting sharp increases in incidence, prevalence, and attributable morbidity and mortality. There is a critical need to better understand the demographics, clinical characteristics, and key risk factors for CKD; and to develop platforms for testing novel interventions to improve modifiable risk factors, particularly for the CKD patients with a rapid decline in kidney function.MethodsWe describe a novel collaboration between two large healthcare systems (Providence St. Joseph Health and University of California, Los Angeles Health) supported by leadership from both institutions, which was created to develop harmonized cohorts of patients with CKD or those at increased risk for CKD (hypertension/HTN, diabetes/DM, pre-diabetes) from electronic health record data.ResultsThe combined repository of candidate records included more than 3.3 million patients with at least a single qualifying measure for CKD and/or at-risk for CKD. The CURE-CKD registry includes over 2.6 million patients with and/or at-risk for CKD identified by stricter guide-line based criteria using a combination of administrative encounter codes, physical examinations, laboratory values and medication use. Notably, data based on race/ethnicity and geography in part, will enable robust analyses to study traditionally disadvantaged or marginalized patients not typically included in clinical trials.DiscussionCURE-CKD project is a unique multidisciplinary collaboration between nephrologists, endocrinologists, primary care physicians with health services research skills, health economists, and those with expertise in statistics, bio-informatics and machine learning. The CURE-CKD registry uses curated observations from real-world settings across two large healthcare systems and has great potential to provide important contributions for healthcare and for improving clinical outcomes in patients with and at-risk for CKD.

BACKGROUND University of California at Los Angeles Health implemented a Best Practice Advisory (BPA) alert for the initiation of an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB) for individuals with diabetes. The BPA alert was configured with a “chart closure” hard stop, which demanded a response before closing the chart. OBJECTIVE The aim of the study was to evaluate whether the implementation of the BPA was associated with changes in ACEI and ARB prescribing during primary care encounters for patients with diabetes. METHODS We defined ACEI and ARB prescribing opportunities as primary care encounters in which the patient had a diabetes diagnosis, elevated blood pressure in recent encounters, no active ACEI or ARB prescription, and no contraindications. We used a multivariate logistic regression model to compare the change in the probability of an ACEI or ARB prescription during opportunity encounters before and after BPA implementation in primary care sites that did (n=30) and did not (n=31) implement the BPA. In an additional subgroup analysis, we compared ACEI and ARB prescribing in BPA implementation sites that had also implemented a pharmacist-led medication management program. RESULTS We identified a total of 2438 opportunity encounters across 61 primary care sites. The predicted probability of an ACEI or ARB prescription increased significantly from 11.46% to 22.17% during opportunity encounters in BPA implementation sites after BPA implementation. However, in the subgroup analysis, we only observed a significant improvement in ACEI and ARB prescribing in BPA implementation sites that had also implemented the pharmacist-led program. Overall, the change in the predicted probability of an ACEI or ARB prescription from before to after BPA implementation was significantly greater in BPA implementation sites compared with nonimplementation sites (difference-in-differences of 11.82; P

BackgroundInfections due to carbapenem-resistant Gram-negative rods (CR-GNR) are increasing in frequency and result in high morbidity and mortality. Appropriate initial antibiotic therapy is necessary to reduce adverse consequences and shorten length of stay.MethodsTo determine risk factors for recovery on culture of CR-GNR, cases were retrospectively analyzed at a major academic hospital system from 2011 to 2016. Ertapenem resistance (ER-GNR) and antipseudomonal (nonertapenem) carbapenem resistance (ACR-GNR) patterns were analyzed separately. A total of 30951 GNR isolates from 12370 patients were analyzed, 563 of which were ER and 1307 of which were ACR.ResultsIn multivariate analysis, risk factors for ER-GNR were renal disease, admission from another health care facility, ventilation at any point before culture during the index hospitalization, receipt of any carbapenem in the prior 30 days, and receipt of any anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) agent in the prior 30 days (c-statistic, 0.74). Risk factors for ACR-GNR were male sex, admission from another health care facility, ventilation at any point before culture during the index hospitalization, receipt of any carbapenem in the prior 30 days, and receipt of any anti-MRSA agent in the prior 30 days (c-statistic, 0.76).ConclusionsA straightforward scoring system derived from these models can be applied by providers to guide empiric antimicrobial therapy; it outperformed use of a standard hospital antibiogram in predicting infections with ER-GNR and ACR-GNR.