Cardiovascular and mortality benefits of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists as third-step glucose-lowering medicine in patients with type 2 diabetes: a retrospective cohort analysis.

INTRODUCTION: Studies have found that sodium-glucose cotransporter 2 inhibitors (SGLT2) and glucagon-like peptide 1 receptor agonists (GLP1) have cardiovascular benefits for patients with type 2 diabetes (DM2) and atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), or heart failure (HF). The literature does not provide evidence specifically for patients with these conditions who are adding one of these medicines to two glucose-lowering medications (ie, as "third-step" therapy). We explored the effects of different third-step medications on cardiovascular outcomes in patients with diabetes and these comorbid conditions. Specifically, we compared third-step SGLT2 or GLP1 to third-step dipeptidyl peptidase-4 inhibitors (DPP4), insulin, or thiazolidinediones (TZD). RESEARCH DESIGN AND METHODS: We assembled a retrospective cohort of adults at five Kaiser Permanente sites with DM2 and ASCVD, CKD, or HF, initiating third-step treatment between 2016 and 2020. Propensity score weighted Poisson models were used to calculate adjusted rate ratios (ARRs) for all-cause mortality, incident major adverse cardiovascular event (MACE), and incident HF hospitalization in patients initiating SGLT2 or GLP1 compared with DPP4, insulin, or TZD. RESULTS: We identified 27 542 patients initiating third-step treatment with one or more of these conditions (19 958 with ASCVD, 14 577 with CKD, and 3919 with HF). ARRs for GLP1 and SGLT2 versus DPP4, insulin, and TZD in the patient subgroups ranged between 0.22 and 0.55 for all-cause mortality, 0.38 and 0.81 for MACE, and 0.46 and 1.05 for HF hospitalization. Many ARRs were statistically significant, and all significant ARRs showed a benefit (ARR <1) for GLP1 or SGLT2 when compared with DPP4, insulin, or TZD. CONCLUSIONS: Third-step SGLT2 and GLP1 are generally associated with a benefit for these outcomes in these patient groups when compared with third-step DPP4, insulin, or TZD. Our results add to evidence of a cardiovascular benefit of SGLT2 and GLP1 and could inform clinical guidelines for choosing third-step diabetes treatment.

Hospital Readmissions by Variation in Engagement in the Health Care Hotspotting Trial: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Variability in intervention participation within care management programs can complicate standard analysis strategies. Objective: To evaluate whether care management was associated with reduced hospital readmissions among individuals with higher participation probabilities. Design, Setting, and Participants: A total of 800 hospitalized patients aged 18 years and older were randomized as part of the Health Care Hotspotting randomized clinical trial, which was conducted in Camden, New Jersey, from June 2014 to September 2017. Data were collected through October 2018. In this new analysis performed between April 6, 2022, and April 23, 2023, the distillation method was applied to account for variable intervention participation. A gradient-boosting machine learning model produced predicted probabilities of engaged participation using baseline covariates only. Predicted probabilities were used to trim both intervention and control populations in an equivalent manner, and intervention effects were reevaluated within study population subsets that were increasingly concentrated with patients having higher participation probabilities. Patients had 2 or more hospitalizations in the 6-month preenrollment period and documented evidence of chronic illness and social complexity. Intervention: Multidisciplinary teams provided services to patients in the intervention arm for a mean 120 days after hospital discharge. Patients in the control group received usual postdischarge care. Main Outcomes and Measures: Hospital readmission rates and counts 30, 90, and 180 days postdischarge. Results: Of 800 eligible patients, 782 had complete discharge information and were included in this analysis (mean [SD] age, 56.6 [12.7] years; 395 [50.5%] female). In the intent-to-treat analysis, the unadjusted 180-day readmission rate for treatment and control groups was 60.1% vs 61.7% (adjusted odds ratio, 0.95; 95% CI, 0.71-1.28; P = .73) and the mean (SD) number of 180-day readmissions was 1.45 (1.89) vs 1.48 (1.94) (adjusted incidence rate ratio, 0.99, 95% CI, 0.88-1.12; P = .86). Among the population with the highest participation probabilities, the mean (SD) 180-day readmission count was 1.22 (1.74) vs 1.57 (1.74) and the incidence rate ratio attained statistical significance (adjusted incidence rate ratio, 0.74; 95% CI, 0.56-0.99; P = .045). Adjusted odds ratios and adjusted incidence rate ratios for 30- and 90-day outcomes reached statistical significance after population distillation. Conclusions and Relevance: This secondary analysis of a randomized clinical trial found that care management was associated with reduced readmissions among patients with higher participation probabilities, suggesting that program operation could be improved by addressing barriers to participation and refining inclusion criteria to identify patients most likely to benefit. Trial Registration: ClinicalTrials.gov Identifier: NCT02090426.

Comparing Kaiser Permanente Members to the General Population: Implications for Generalizability of Research.

Introduction Insight into the characteristics of populations from which research samples are drawn is essential to understanding the generalizability of research findings. This study characterizes the membership of Kaiser Permanente and compares members to the population of the communities in which they live. Methods This study is a descriptive comparison of population distributions for Kaiser Permanente members vs the general population within counties in which Kaiser Permanente operates. Kaiser Permanente data on demographics, membership, geographically linked census data, and chronic condition prevalence were compared with community data drawn from the US Census and the Behavioral Risk Factor Surveillance System. Results Overall, Kaiser Permanente members were older (50% aged 40 or older compared to 45.8% of the general population) and more likely to be female (51.8% vs 50.5% of the general population). Distribution by race and ethnicity was similar for all Regions combined but varied somewhat within Regions. Distribution by neighborhood-linked income, education, and social vulnerability was similar between Kaiser Permanente and the community. Prevalence of 6 of 7 chronic conditions was higher in the community than in Kaiser Permanente, with differences ranging from 0.5% for depression to 7.7% for hyperlipidemia. Conclusion The demographic characteristics of Kaiser Permanente members are similar to the general population within each of the Kaiser Permanente Regions. Overall, the size and diversity of the Kaiser Permanente membership offers an effective platform for research. This approach to comparing health system members with the larger community provides valuable context for interpreting real-world evidence, including understanding the generalizability of research and of measures of system performance.

Anakinra or high-dose corticosteroids in COVID-19 pneumonia patients who deteriorate on low-dose dexamethasone: an observational study of comparative effectiveness.

OBJECTIVES: To assess whether escalating to high-dose corticosteroids or anakinra compared with continuing low-dose corticosteroids reduced mortality in patients with severe COVID-19 whose respiratory function deteriorated while receiving dexamethasone 6 mg daily. METHODS: We conducted a retrospective cohort study between March 1 to December 31, 2020, of hospitalized patients with confirmed COVID-19 pneumonia. In-hospital death was analyzed using logistic regression with inverse probability of treatment weighting of receiving anakinra, high-dose corticosteroid (dexamethasone >10 mg daily), or remaining on low-dose corticosteroids on the day of first respiratory deterioration. RESULTS: We analyzed 6671 patients whose respiratory status deteriorated while receiving dexamethasone 6 mg daily for COVID-19 pneumonia, of whom 6265 stayed on low-dose corticosteroids, 232 were escalated to high-dose corticosteroids, and 174 to anakinra in addition to corticosteroids. The propensity score-adjusted odds of death were higher in the anakinra (odds ratio [OR] 1.76; 95% CI 1.13-2.72) and high-dose corticosteroid groups (OR 1.53; 95% CI 1.14-2.07) compared with those who continued low-dose corticosteroids on the day of respiratory deterioration. The odds of hospital-acquired infections were also higher in the anakinra (OR 2.00; 95% CI 1.28-3.11) and high-dose corticosteroid groups (OR 1.43; 95% CI 1.00-2.04) compared with low-dose corticosteroid group. CONCLUSION: Our findings do not support escalating patients with COVID-19 pneumonia who deteriorate on low-dose corticosteroids to high-dose corticosteroids or anakinra.

Addressing unmeasured confounding bias with a prior knowledge guided approach: coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in patients with stable ischemic heart disease.

Unmeasured confounding undermines the validity of observational studies. Although randomized clinical trials (RCTs) are considered the "gold standard" of study types, we often observe divergent findings between RCTs and empirical settings. We present the "L-table", a simulation-based, prior knowledge (e.g., RCTs) guided approach that estimates the true effect adjusting for the potential influence of unmeasured confounders when using observational data. Using electronic health record data from Kaiser Permanente Southern California, we compare the effectiveness of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) on endpoints at 1, 3, 5, and 10 years for patients with stable ischemic heart disease. We applied the L-table approach to the propensity score adjusted cohort to derive the omitted-confounder-adjusted estimated effects. After the L-table adjustment, CABG patients are 57.6% less likely to encounter major adverse cardiac and cerebrovascular event (MACCE) at 1 year (OR [95% CI] 0.424 [0.396, 0.517]), 56.4% less likely at 3 years (OR [95% CI] 0.436 [0.369, 0.527]), and 48.9% less likely at 5 years (OR [95% CI] 0.511 [0.451, 0.538]). CABG patients are also 49.5% less likely to die by the end of 10 years than PCI patients (OR [95% CI] 0.505 [0.446, 0.582]). We found the estimated true effects all shifted towards CABG as a more effective procedure that led to better health outcomes compared to PCI. Unlike existing sensitivity tools, the L-table approach explicitly lays out probable values and can therefore better support clinical decision-making. We recommend using L-table as a supplement to available techniques of sensitivity analysis. Supplementary Information: The online version contains supplementary material available at 10.1007/s10742-022-00282-y.

The intensity of anticoagulant dosing in hospitalized patients with COVID-19: An observational, comparative effectiveness study.

BACKGROUND: The question of anticoagulant dosing in hospitalized patients with coronavirus disease-2019 (COVID-19) is unresolved, with randomized trials showing mixed results and heterogeneity of treatment effects for in-hospital death. OBJECTIVE: To examine the association between the intensity of anticoagulation and clinical outcomes in hospitalized patients with COVID-19. DESIGN, SETTING AND PARTICIPANTS: Retrospective cohort study of patients with COVID-19 and respiratory impairment who were hospitalized between 3/1/2020-12/31/2020 in two Kaiser Permanente regions. EXPOSURE AND MAIN OUTCOME: We fit propensity score models using categorical regression to estimate the probability of receiving standard prophylactic, intermediate, or full-dose anticoagulation beginning on the day of admission or on the day of first respiratory deterioration. Exposure was defined by the highest dose on the day of admission or within 24 hours after deterioration. The primary outcome was in-hospital death. RESULTS: We included 17,130 patients in the day of admission analysis and 4,924 patients who experienced respiratory deterioration. There were no differences in propensity score-adjusted odds of in-hospital death for patients who received either intermediate (odds ratio [OR]: 1.00, 95% confidence intervals [CI] 0.89-1.12) or full anticoagulation (OR: 1.00, 95% CI: 0.85-1.17) compared with standard prophylaxis beginning on the day of admission. Similarly, there were no differences in in-hospital death for either intermediate (OR: 1.22, 95% CI: 0.82-1.82) or full anticoagulation (OR: 1.50, 95% CI: 0.90-2.51) compared with standard prophylaxis on the day of deterioration. CONCLUSION: Results of this real-world, comparative effectiveness study showed no differences in in-hospital death among newly admitted or deteriorating patients with COVID-19 who received intermediate-dose or full anticoagulation compared with standard prophylaxis.

High-dose corticosteroids in patients hospitalized for COVID-19 pneumonia: an observational study of comparative effectiveness.

OBJECTIVES: To assess whether high- compared with low-dose corticosteroids started upon hospitalization reduce mortality in patients with severe COVID-19 pneumonia or in subgroups stratified by severity of respiratory impairment on admission. METHODS: We conducted a retrospective cohort study of patients with confirmed SARS-CoV-2 infection who required oxygen supplementation upon hospitalization between March 1 and December 31, 2020. In-hospital death was analyzed using logistic regression with inverse probability of treatment weighting of receiving low- or high-dose corticosteroid (dexamethasone 6-10 mg daily or >10-20 mg daily or other corticosteroid equivalents). RESULTS: We analyzed 13,366 patients who received low-dose and 948 who received high-dose corticosteroids, of whom 31.3% and 40.4% had severe respiratory impairment (>15 l/min of oxygen or mechanical ventilation) upon admission, respectively. There were no differences in the propensity score-adjusted odds of death (odds ratio 1.17, 95% CI 0.72-1.90) or infections (odds ratio 0.70, 95% CI 0.44-1.11) for patients who received high-dose compared with low-dose corticosteroids, beginning on the day of admission. No significant differences in subgroups stratified by severity of respiratory impairment were found. CONCLUSION: Initiating high-dose compared with low-dose corticosteroids among newly hospitalized patients with COVID-19 pneumonia did not improve survival. However, benefit of high-dose corticosteroids in specific subgroups cannot be excluded.

The Contribution of First-name Information to the Accuracy of Racial-and-Ethnic Imputations Varies by Sex and Race-and-Ethnicity Among Medicare Beneficiaries.

BACKGROUND: Data on race-and-ethnicity that are needed to measure health equity are often limited or missing. The importance of first name and sex in predicting race-and-ethnicity is not well understood. OBJECTIVE: The objective of this study was to compare the contribution of first-name information to the accuracy of basic and more complex racial-and-ethnic imputations that incorporate surname information. RESEARCH DESIGN: We imputed race-and-ethnicity in a sample of Medicare beneficiaries under 2 scenarios: (1) with only sparse predictors (name, address, sex) and (2) with a rich set (adding limited administrative race-and-ethnicity, demographics, and insurance). SUBJECTS: A total of 284,627 Medicare beneficiaries who completed the 2014 Medicare Consumer Assessment of Healthcare Providers and Systems survey and reported race-and-ethnicity were included. RESULTS: Hispanic, non-Hispanic Asian/Pacific Islander, and non-Hispanic White racial-and-ethnic imputations are more accurate for males than females under both sparse-predictor and rich-predictor scenarios; adding first-name information increases accuracy more for females than males. In contrast, imputations of non-Hispanic Black race-and-ethnicity are similarly accurate for females and males, and first names increase accuracy equally for each sex in both sparse-predictor and rich-predictor scenarios. For all 4 racial-and-ethnic groups, incorporating first-name information improves prediction accuracy more under the sparse-predictor scenario than under the rich-predictor scenario. CONCLUSION: First-name information contributes more to the accuracy of racial-and-ethnic imputations in a sparse-predictor scenario than in a rich-predictor scenario and generally narrows sex gaps in accuracy of imputations.

The distillation method: A novel approach for analyzing randomized trials when exposure to the intervention is diluted.

OBJECTIVE: To introduce a novel analytical approach for randomized controlled trials that are underpowered because of low participant enrollment or engagement. DATA SOURCES: Reanalysis of data for 805 patients randomized as part of a pilot complex care intervention in 2015-2016 in a large delivery system. In the pilot randomized trial, only 64.6% of patients assigned to the intervention group participated. STUDY DESIGN: A case study and simulation. The "Distillation Method" capitalizes on the frequently observed correlation between the probability of subjects' participation or engagement in the intervention and the magnitude of benefit they experience. The novel method involves three stages: first, it uses baseline covariates to generate predicted probabilities of participation. Next, these are used to produce nested subsamples of the randomized intervention and control groups that are more concentrated with subjects who were likely to participate/engage. Finally, for the outcomes of interest, standard statistical methods are used to re-evaluate intervention effectiveness in these concentrated subsets. DATA EXTRACTION METHODS: We assembled secondary data on patients who were randomized to the pilot intervention for one year prior to randomization and two follow-up years. Data included program enrollment status, membership data, demographics, utilization, costs, and clinical data. PRINCIPAL FINDINGS: Using baseline covariates only, Generalized Boosted Regression Models predicting program enrollment performed well (AUC 0.884). We then distilled the full randomized sample to increasing levels of concentration and reanalyzed program outcomes. We found statistically significant differences in outpatient utilization and emergency department utilization (both follow-up years), and in total costs (follow-up year two only) at select levels of population concentration. CONCLUSIONS: By offering an internally valid analytic framework, the Distillation Method can increase the power to detect effects by redefining the estimand to subpopulations with higher enrollment probabilities and stronger average treatment effects while maintaining the original randomization.

Disparities In The Quality Of Clinical Care Delivered To American Indian/Alaska Native Medicare Advantage Enrollees.

This study used data from the 2019 Healthcare Effectiveness Data and Information Set (HEDIS) to examine differences in the quality of care received by American Indian/Alaska Native beneficiaries versus care received by non-Hispanic White beneficiaries enrolled in Medicare Advantage (managed care) plans. American Indian/Alaska Native beneficiaries were more likely than White beneficiaries to receive care that meets clinical standards for eight of twenty-six HEDIS measures and were less likely than White beneficiaries to receive care that meets clinical standards for five of twenty-six measures. Measures for which American Indian/Alaska Native beneficiaries were less likely to receive care meeting clinical standards were mainly ones pertaining to appropriate treatment of diagnosed conditions. In all cases, differences in care for American Indian/Alaska Native and White beneficiaries were largely within-plan differences. These findings indicate the need for improved clinical care for all beneficiaries. For American Indian/Alaska Native beneficiaries, there is a particular need for improvement in the treatment of diagnosed conditions, including diabetes, chronic obstructive pulmonary disease, and alcohol and other forms of substance abuse.

Opioid and Naloxone Prescribing Following Insertion of Prompts in the Electronic Health Record to Encourage Compliance With California State Opioid Law.

Importance: Opioid addiction or dependency is a serious crisis in the US that affects public health as well as social and economic welfare. The State of California passed Assembly Bill (AB) 2760 in 2018 that mandates the coprescription of naloxone and opioids for patients with a high overdose risk. Objective: To assess whether the AB 2760-based electronic prompts were associated with increased naloxone orders for opioid users and reduced opioid prescribing when integrated into the practitioner workflow. Design, Setting, and Participants: This cohort study used interrupted time series mixed models to evaluate data obtained from the regional integrated health care system Kaiser Permanente Southern California (KPSC) from January 1, 2018, to December 31, 2019. Clinician participants were continuously employed at KPSC during the study period and ordered an opioid analgesic for eligible patients in 2018. Patient participants were KPSC members aged 18 years or older who received an opioid analgesic prescription during the study period. A series of AB 2760-based electronic prompts were integrated into the KPSC electronic health record system on December 27, 2018. The prompts are triggered or activated when 1 or more opioid prescribing conditions, defined in the AB 2760, are met at outpatient visits. Data were analyzed from January 8, 2021, to September 15, 2021. Exposures: Assembly Bill 2760-based electronic prompts for outpatient opioid prescriptions in the electronic health record system. Main Outcomes and Measures: Primary outcomes were changes in outpatient naloxone order rates among patients who were prescribed opioids and changes in outpatient opioid prescribing rates. Secondary outcomes were total morphine milligram equivalents (MMEs) ordered per prescriber-month, prompts-targeted objectives, and unintended consequences. Risk for opioid abuse among 3 types of patients was also assessed. Results: The 6515 eligible clinicians (mean [SD] age, 45.9 [9.43] years; 3604 men [55.3%]) included in the study served 500 711 unique patients in 1 903 289 outpatient encounters (mean [SD] age, 60.4 [15.67] years; 1 121 004 women [58.9%]) in which an opioid analgesic was prescribed. Naloxone order rate increased from 2.0% in December 2018 to 13.2% in January 2019 and then continued to increase to 27.1% in December 2019. Outpatient opioid prescribing rates decreased by 15.1% (rate ratio [RR], 0.85; 95% CI, 0.83-0.87) per prescriber-month when the electronic prompts were implemented. The postimplementation trend increased by 0.7% per prescriber-month (RR, 1.01; 95% CI, 1.01-1.01); the overall trend was still decreasing. The total MMEs per prescriber-month decreased by 7.8% (RR, 0.92; 95% CI, 0.89-0.96) after implementation of the prompts. The postimplementation trend tapered off. Other safe opioid prescribing measures also improved after implementation (decreases in concomitant muscle relaxants orders [RR, 0.94; 95% CI, 0.89-1.00], initial [RR, 0.86; 0.83-0.89] and renewal [RR, 0.65; 95% CI, 0.62-0.69] opioid orders, and long-term high-dose orders [RR, 0.96; 95% CI, 0.94-0.98]). Conclusions and Relevance: This study found an association between implementation of AB 2760-based prompts and increased naloxone order rate; improved opioid prescribing measures (ie, decreased concomitant muscle relaxants orders, initial and renewal opioid orders, and long-term high-dose orders), except monthly median MMEs; and reduced opioid prescribing. The findings suggest that opioid overdose risks can be mitigated by encouraging safe prescribing habits.

The natural history of large abdominal aortic aneurysms in patients without timely repair.

OBJECTIVE: Contemporary data on the natural history of large abdominal aortic aneurysms (AAAs) in patients undergoing delayed or no repair are lacking. In this study, we examine the impact of large AAA size on the incidence of rupture and mortality. METHODS: From a prospectively maintained aneurysm surveillance registry, patients with an unrepaired, large AAA (≥5.5 cm in men and ≥5.0 cm in women) at baseline (ie, index imaging) or who progressed to a large size from 2003 to 2017 were included, with follow-up through March 2020. Outcomes of interest obtained by manual chart review included rupture (confirmed by imaging/autopsy), probable rupture (timing/findings consistent with rupture without more likely cause of death), repair, reasons for either no or delayed (>1 year after diagnosis of large AAA) repair and total mortality. Cumulative incidence of rupture was calculated using a nonparametric cumulative incidence function, accounting for the competing events of death and aneurysm repair and was stratified by patient sex. RESULTS: Of the 3248 eligible patients (mean age, 83.6 ± 9.1 years; 71.2% male; 78.1% white; and 32.0% current smokers), 1423 (43.8%) had large AAAs at index imaging, and 1825 progressed to large AAAs during the follow-up period, with a mean time to qualifying size of 4.3 ± 3.4 years. In total, 2215 (68%) patients underwent repair, of which 332 were delayed >1 year; 1033 (32%) did not undergo repair. The most common reasons for delayed repair were discrepancy in AAA measurement between surgeon and radiologist (34%) and comorbidity (20%), whereas the most common reasons for no repair were patient preference (48%) and comorbidity (30%). Among patients with delayed repair (mean time to repair, 2.6 ± 1.8 years), nine (2.7%) developed symptomatic aneurysms, and an additional 11 (3.3%) ruptured. Of patients with no repair, 94 (9.1%) ruptured. The 3-year cumulative incidence of rupture was 3.4% for initial AAA size 5.0 to 5.4 cm (women only), 2.2% for 5.5 to 6.0 cm, 6.0% for 6.1 to 7.0 cm, and 18.4% for >7.0 cm. Women with AAA size 6.1 to 7.0 cm had a 3-year cumulative incidence of rupture of 12.8% (95% confidence interval, 7.5%-19.6%) compared with 4.5% (95% confidence interval, 3.0%-6.5%) in men (P = .002). CONCLUSIONS: In this large cohort of AAA registry patients over 17 years, annual rupture rates for large AAAs were lower than previously reported, with possible increased risk in women. Further analyses are ongoing to identify those at increased risk for aneurysm rupture and may provide targeted surveillance regimens and improve patient counseling.

Population-Based Incidence of New Ampicillin, Cephalexin, Cefaclor, and Sulfonamide Antibiotic "Allergies" in Exposed Individuals with and without Preexisting Ampicillin, Cephalexin, or Cefaclor "Allergies".

BACKGROUND: There is a theoretical concern, unconfirmed by population-based challenge data, that clinically significant, immunologically mediated hypersensitivity occurs among ß-lactams sharing side chains. OBJECTIVE: To determine the population-based allergy incidence associated with the use of ß-lactams sharing exact R1 side chains (ampicillin, cephalexin, and cefaclor [ACC]), with or without a current ACC allergy or a sulfonamide antibiotic allergy for comparison. METHODS: All courses of ACC and trimethoprim-sulfamethoxazole used by any Kaiser Permanente California members in 2017 and 2018, with follow-up through January 2019, were identified along with their preexisting antibiotic allergy status and all new antibiotic-specific allergies reported within 30 days of course initiation. RESULTS: A total of 1,167,713 courses of ACC were administered to individuals with no sulfonamide antibiotic or ACC allergy and 4,771 new ACC allergies (0.41%) were reported. Moreover, 130,032 courses of ACC were administered to individuals with a sulfonamide antibiotic allergy and no ACC allergy, and 904 new ACC allergies (0.70%) were reported. There were 5,958 courses of ACC administered to individuals with an ACC allergy, 2,341 who also had sulfonamide antibiotic allergy, and 52 new ACC allergies (0.87%) were reported. CONCLUSIONS: The incidence of new ACC allergy reports is minimally and non-specifically increased among individuals with a preexisting ACC or sulfonamide antibiotic allergy compared to the baseline incidence in the population. This argues against clinically significant, immunologically mediated cross-reactivity among ß-lactams sharing exact side chains in individuals with preexisting but unconfirmed ß-lactam allergy. Any previously reported, even unrelated antibiotic allergy appears to be a risk factor for reporting a new antibiotic allergy.

Patient-Reported Care Coordination is Associated with Better Performance on Clinical Care Measures.

BACKGROUND: Prior studies using aggregated data suggest that better care coordination is associated with higher performance on measures of clinical care process; it is unclear whether this relationship reflects care coordination activities of health plans or physician practices. OBJECTIVE: Estimate within-plan relationships between beneficiary-reported care coordination measures and HEDIS measures of clinical process for the same individuals. DESIGN: Mixed-effect regression models in cross-sectional data. PARTICIPANTS: 2013 Medicare Advantage CAHPS respondents (n=152,069) with care coordination items linked to independently collected HEDIS data on clinical processes. MAIN MEASURES: Care coordination measures assessed follow-up, whether doctors had medical records during visits, whether doctors discussed medicines being taken, how informed doctors seemed about specialist care, and help received with managing care among different providers. HEDIS measures included mammography, colorectal cancer screening, cardiovascular LDL-C screening, controlling blood pressure, 5 diabetes care measures (LDL-C screening, retinal eye exam, nephropathy, blood sugar/HbA1c <9%, LCL-C<100 mg/dL), glaucoma screening in older adults, BMI assessment, osteoporosis management for women with a fracture, and rheumatoid arthritis therapy. KEY RESULTS: For 9 of the 13 HEDIS measures, within health plans, beneficiaries who reported better care coordination also received better clinical care (p<0.05) and none of the associations went in the opposite direction; HEDIS differences between those with excellent and poor coordination exceeded 5 percentage points for 7 measures. Nine measures had positive associations (breast cancer screening, colorectal cancer screening, cardiovascular care LDL-C screening, 4 of 5 diabetes care measures, osteoporosis management, and rheumatoid arthritis therapy). CONCLUSIONS: Within health plans, beneficiaries who report better care coordination also received higher-quality clinical care, particularly for care processes that entail organizing patient care activities and sharing information among different healthcare providers. These results extend prior research showing that health plans with better beneficiary-reported care coordination achieved higher HEDIS performance scores.

Association Between Removal of a Warning Against Cephalosporin Use in Patients With Penicillin Allergy and Antibiotic Prescribing.

Importance: Electronic health records (EHRs) often include default alerts that can influence physician selection of antibiotics, which in turn may be associated with a suboptimal choice of agents and increased antibiotic resistance. Objective: To examine whether removal of a default alert in the EHR to avoid cephalosporin use in patients with penicillin allergies is associated with changes in cephalosporin dispensing or administration in these patients. Design, Setting, and Participants: This retrospective cohort study of a natural experiment included data on patients who had received antibiotic treatment in the hospital or outpatient setting in 2 regions of a large, integrated health system in California from January 1, 2017, to December 31, 2018. Of 4 398 792 patients, 4 206 480 met the eligibility criteria: enrollment in the health system during antibiotic use, availability of complete demographic data, and use of antibiotics outside of the washout period. Interventions or Exposures: Oral or parenteral antibiotics dispensed or administered after removal of an EHR alert to avoid cephalosporin use in patients with a recorded penicillin allergy. Main Outcomes and Measures: Probability that an antibiotic course was a cephalosporin. A multinomial logistic regression model was used to examine the change in rates of cephalosporin use before and after an EHR penicillin allergy alert was removed in 1 of the study regions. Temporal changes in use rates were controlled for by comparing changes in cephalosporin use among patients with or without a penicillin allergy at the site that removed the warning and among patients at a comparison site that retained the warning. Regression models were used to examine adverse events. Results: Of the 4 206 480 patients who met all inclusion criteria, 2 465 849 (58.6%) were women; the mean (SD) age was 40.5 (23.2) years. A total of 10 652 014 antibiotic courses were administered or dispensed, divided approximately evenly between the period before and after removal of the warning. Before removal of an alert in the electronic health record system to avoid prescribing of cephalosporins to patients with a penicillin allergy at 1 of the 2 sites, 58 228 courses of cephalosporins (accounting for 17.9% of all antibiotic use at the site) were used among patients with a penicillin allergy; after removal of the alert, administration or dispensing of cephalosporins increased by 47% compared with cephalosporin administration or dispensing among patients without a penicillin allergy at the same site and patients at the comparison site that retained the warning (ratio of ratios of odds ratios [RROR], 1.47; 95% CI, 1.38-1.56) . No significant differences in anaphylaxis (9 total cases), new allergies (RROR, 1.02; 95% CI, 0.93-1.12), or treatment failures (RROR, 1.02; 95% CI, 0.99-1.05) were found at the course level. No significant differences were found in all-cause mortality (ratio of ratios of rate ratios [RRRR], 1.03; 95% CI, 0.94-1.13), hospital days (RRRR, 1.04; 95% CI, 0.99-1.10), and new infections (Clostridioides difficile: RRRR, 1.02; 95% CI, 0.84-1.22; methicillin-resistant Staphylococcus aureus: RRRR, 0.87; 95% CI, 0.75-1.00; and vancomycin-resistant Enterococcus: RRRR, 0.82; 95% CI, 0.55-1.22) at the patient level. Conclusions and Relevance: In this cohort study, removal of a warning in the electronic health record to avoid cephalosporin use in patients with penicillin allergies was associated with increased administration and dispensing of cephalosporin. This simple and rapidly implementable system-level intervention may be useful for improvement in antibiotic stewardship.

Comparison of Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation and Bioprosthetic Heart Valves.

There are limited data regarding direct oral anticoagulants (DOACs) for stroke prevention in patients with bioprosthetic heart valves (BHVs) and atrial fibrillation (AF). The objectives of this study were to evaluate the ambulatory utilization of DOACs and to compare the effectiveness and safety of DOACs versus warfarin in patients with AF and BHVs. We conducted a retrospective cohort study at a large integrated health care delivery system in California. Patients with BHVs and AF treated with warfarin, dabigatran, rivaroxaban, or apixaban between September 12, 2011 and June 18, 2020 were identified. Inverse probability of treatment-weighted comparative effectiveness and safety of DOACs compared with warfarin were determined. Use of DOACs gradually increased since 2011, with a significant upward in trend after a stay-at-home order related to COVID-19. Among 2,672 adults with BHVs and AF who met the inclusion criteria, 439 were exposed to a DOAC and 2233 were exposed to warfarin. For the primary effectiveness outcome of ischemic stroke, systemic embolism and transient ischemic attack, no significant association was observed between use of DOACs compared with warfarin (HR 1.19, 95% CI 0.96 to 1.48, p = 0.11). Use of DOACs was associated with lower risk of the primary safety outcome of intracranial hemorrhage, gastrointestinal bleeding, and other bleed (HR 0.69, 95% CI 0.56 to 0.85, p < 0.001). Results were consistent across multiple subgroups in the sensitivity analyses. These findings support the use of DOACs for AF in patients with BHVs.

Validation of natural language processing to determine the presence and size of abdominal aortic aneurysms in a large integrated health system.

OBJECTIVE: Previous studies of the natural history of abdominal aortic aneurysms (AAAs) have been limited by small cohort sizes or heterogeneous analyses of pooled data. By quickly and efficiently extracting imaging data from the health records, natural language processing (NLP) has the potential to substantially improve how we study and care for patients with AAAs. The aim of the present study was to test the ability of an NLP tool to accurately identify the presence or absence of AAAs and detect the maximal abdominal aortic diameter in a large dataset of imaging study reports. METHODS: Relevant imaging study reports (n = 230,660) from 2003 to 2017 were obtained for 32,778 patients followed up in a prospective aneurysm surveillance registry within a large, diverse, integrated healthcare system. A commercially available NLP algorithm was used to assess the presence of AAAs, confirm the absence of AAAs, and extract the maximal diameter of the abdominal aorta, if stated. A blinded expert manual review of 18,000 randomly selected imaging reports was used as the reference standard. The positive predictive value (PPV or precision), sensitivity (recall), and the kappa statistics were calculated. RESULTS: Of the randomly selected 18,000 studies that underwent expert manual review, 48.7% were positive for AAAs. In confirming the presence of an AAA, the interrater reliability of the NLP compared with the expert review showed a kappa value of 0.84 (95% confidence interval [CI], 0.83-0.85), with a PPV of 95% and sensitivity of 88.5%. The NLP algorithm showed similar results for confirming the absence of an AAA, with a kappa of 0.79 (95% CI, 0.799-0.80), PPV of 77.7%, and sensitivity of 91.9%. The kappa, PPV, and sensitivity of the NLP for correctly identifying the maximal aortic diameter was 0.88 (95% CI, 0.87-0.89), 88.8%, and 88.2% respectively. CONCLUSIONS: The use of NLP software can accurately analyze large volumes of radiology report data to detect AAA disease and assemble a contemporary aortic diameter-based cohort of patients for longitudinal analysis to guide surveillance, medical management, and operative decision making. It can also potentially be used to identify from the electronic medical records pre- and postoperative AAA patients "lost to follow-up," leverage human resources engaged in the ongoing surveillance of patients with AAAs, and facilitate the construction and implementation of AAA screening programs.

Predictors of Hyperkalemia and Hypokalemia in Individuals with Diabetes: a Classification and Regression Tree Analysis.

BACKGROUND: Both hyperkalemia and hypokalemia can lead to cardiac arrhythmias and are associated with increased mortality. Information on the predictors of potassium in individuals with diabetes in routine clinical practice is lacking. OBJECTIVE: To identify predictors of hyperkalemia and hypokalemia in adults with diabetes. DESIGN: Retrospective cohort study, with classification and regression tree (CART) analysis. PARTICIPANTS: 321,856 individuals with diabetes enrolled in four large integrated health care systems from 2012 to 2013. MAIN MEASURES: We used a single serum potassium result collected in 2012 or 2013. Hyperkalemia was defined as a serum potassium ≥ 5.5 mEq/L and hypokalemia as < 3.5 mEq/L. Predictors included demographic factors, laboratory measurements, comorbidities, medication use, and health care utilization. KEY RESULTS: There were 2556 hypokalemia events (0.8%) and 1517 hyperkalemia events (0.5%). In univariate analyses, we identified concordant predictors (associated with increased probability of both hyperkalemia and hypokalemia), discordant predictors, and predictors of only hyperkalemia or hypokalemia. In CART models, the hyperkalemia "tree" had 5 nodes and a c-statistic of 0.76. The nodes were defined by prior potassium results and eGFRs, and the 5 terminal "leaves" had hyperkalemia probabilities of 0.2 to 7.2%. The hypokalemia tree had 4 nodes and a c-statistic of 0.76. The hypokalemia tree included nodes defined by prior potassium results, and the 4 terminal leaves had hypokalemia probabilities of 0.3 to 17.6%. Individuals with a recent potassium between 4.0 and 5.0 mEq/L, eGFR ≥ 45 mL/min/1.73m2, and no hypokalemia in the previous year had a < 1% rate of either hypokalemia or hyperkalemia. CONCLUSIONS: The yield of routine serum potassium testing may be low in individuals with a recent serum potassium between 4.0 and 5.0 mEq/L, eGFR ≥ 45 mL/min/1.73m2, and no recent history of hypokalemia. We did not examine the effect of recent changes in clinical condition or medications on acute potassium changes.

Age-Dependent Hemoglobin A1c Therapeutic Targets Reduce Diabetic Medication Changes in the Elderly.

OBJECTIVE: To assess whether implementation of age-dependent therapeutic targets for high hemoglobin A1c (HbA1c) changed clinicians' ordering of diabetes medications for older adults. BACKGROUND: In 2016, Kaiser Permanente Southern California (KPSC) changed the therapeutic targets for alerting clinicians about high HbA1c results in the electronic health record, KP HealthConnect (KPHC). Previously, all HbA1c results ≥7.0 percent were flagged as high in adult patients with diabetes. Starting in 2016, HbA1c therapeutic targets were relaxed to <7.5 percent for patients age 65 to 75, and to <8.0 percent for patients over age 75 to reduce treatment intensity and adverse events. METHODS: This retrospective analysis used logistic regression models to calculate the change in odds of a medication change following an HbA1c result after age-dependent HbA1c flags were introduced. RESULTS: The odds of medication change decreased among patients whose HbA1c targets were relaxed: Odds Ratio (OR) 0.72 (95 percent CI 0.67-0.76) for patients age 65-75 and HbA1c 7.0 percent-7.5 percent; OR 0.72 (95 percent CI 0.65-0.80) for patients over age 75 and HbA1c 7.0 percent-7.5 percent; and OR 0.67 (95 percent CI 0.61-0.75) for patients over age 75 and HbA1c 7.5 percent-8.0 percent. In the age and HbA1c ranges for which the alerts did not change, the odds of medication change generally increased or stayed the same. There was little evidence of medication de-intensification in any group. CONCLUSIONS: These findings suggest that the change in therapeutic targets was associated with a reduction in medication intensification among older adults with diabetes.