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.

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.

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.

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.

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.

Impact of Social Needs Navigation on Utilization Among High Utilizers in a Large Integrated Health System: a Quasi-experimental Study.

BACKGROUND: Programs addressing social determinants of health for high-utilizing patients are gaining interest among health systems as an avenue to promote health and decrease utilization. OBJECTIVE: To evaluate impacts of a social needs screening and navigation program for adult predicted high utilizers on total medical visit utilization. DESIGN: A prospective, quasi-experimental study using an intent-to-treat propensity-weighted difference-in-differences approach. Stratified analyses assessed intervention effects among three low-socioeconomic status sub-samples: patients in low-income areas, in low-education areas, and with Medicaid insurance. PARTICIPANTS: Predicted high utilizers-patients predicted to be in the highest 1% for total utilization in a large integrated health system. INTERVENTION: A telephonic social needs screening and navigation program. MAIN MEASURES: Primary difference-in-difference analyses compared total visit count utilization, including outpatient, emergency department (ED), and inpatient utilization, between the intervention and control groups at both in-network and out-of-network facilities. Prevalence of social needs among sample patients and their connection rates to social needs resources are also described. KEY RESULTS: The study included 34,225 patients (7107 intervention, 27,118 control). Most (53%) patients screened reported social needs, but only a minority (10%) of those with a need were able to connect with resources to address these needs. Primary analysis found total utilization visits decreased 2.2% (95% CI - 4.5%, 0.1%; p = 0.058) in the intervention group. Stratified analyses showed decreases in total utilization for all low-socioeconomic status subgroups receiving the intervention compared with controls: - 7.0% (95% CI - 11.9%, - 1.9%; p = 0.008) in the low-income area group, - 11.5% (- 17.6%, 5.0%; p < 0.001) in the low-education area group, and - 12.1% (- 18.1%, - 5.6%; p < 0.001) in the Medicaid group. CONCLUSIONS: Social needs navigation programs for high-utilizing patients may have modest effects on utilization for the population overall. However, significant decreases in utilization were found among low-socioeconomic status patients more likely to experience social needs.

Bisphosphonate Drug Holiday and Fracture Risk: A Population-Based Cohort Study.

Holidays from bisphosphonates (BPs) may help to prevent rare adverse events such as atypical femoral fractures, but may be appropriate only if risk of osteoporosis-related fractures does not increase. Our objective was to compare the incidence of osteoporosis-related fractures among women who had a BP holiday to those who continued to use BPs. This retrospective cohort study, conducted within four Kaiser Permanente integrated health system regions, included 39,502 women aged ≥45 years with ≥3 years exposure to BP. Participants with a BP holiday (≥12 months with no use) were compared to persistent (use with ≥50% adherence) and nonpersistent (use with <50% adherence) users for incident osteoporosis-related fractures. The BP holiday (n = 11,497), nonpersistent user (n = 10,882), and persistent user groups (n = 17,123) were observed for 156,657 person-years. A total of 5199 osteoporosis-related fractures (including 1515 hip fractures and 2147 vertebral fractures) were observed. Compared to the persistent use group, there was a slight difference in overall osteoporosis-related fracture risk (HR 0.92; 95% CI, 0.84 to 0.99)and no difference in hip fracture risk (HR 0.95; 95% CI, 0.83 to 1.10) for the BP holiday group. A slight reduction in risk of vertebral fracture was observed (HR 0.83; 95% CI, 0.74 to 0.95). Compared to the nonpersistent user group, the BP holiday group was at decreased risk for osteoporosis-related fractures (HR 0.71; 95% CI, 0.65 to 0.79), vertebral fractures (HR 0.68; 95% CI, 0.59 to 0.78), and hip fractures (HR 0.59; 95% CI, 0.50 to 0.70). Women who undertake a BP holiday from BP of ≥12 months duration for any reason after ≥3 years of BP use do not appear to be at greater risk of osteoporosis-related fragility fracture, hip, or vertebral fractures compared to ongoing BP users. In our cohort, BP holiday remains a viable strategy for balancing the benefits and potential harms associated with long-term BP use. © 2018 American Society for Bone and Mineral Research.

Is Self-Referral Associated with Higher Quality Care?

OBJECTIVE: To assess the extent to which patients self-refer to cancer specialists and whether self-referral is associated with better experiences and quality of care. DATA SOURCES: Data from surveys and medical record abstraction collected through the Cancer Care Outcomes Research and Surveillance Consortium. STUDY DESIGN: Observational study of patients with lung and colorectal cancer diagnosed from 2003 through 2005 in five geographically defined regions and five integrated health care delivery systems. METHODS: Multivariable logistic regression models used to assess factors associated with self-referral and propensity score-weighted doubly robust models to test the association between self-referral and experiences/quality of care. PRINCIPAL FINDINGS: Among 5,882 patients, 9.7 percent of lung cancer patients and 14.9 percent of colorectal cancer patients self-referred to at least one cancer specialist. Black patients were less likely to self-refer than white patients (odds ratio: 0.48, 95 percent confidence interval: 0.35, 0.64); patients with high incomes (vs. low) and with a college degree (vs. non-high school graduates) were significantly more likely to self-refer. Self-referral was associated with lower ratings of overall physician communication for patients with lung cancer but, conversely, higher odds of curative surgery among patients with stage I/II lung cancer. CONCLUSIONS: A small but significant proportion of patients self-referred to their cancer specialists; rates varied by patient race and socioeconomic status. To the extent that self-referral is associated with quality, it may reinforce disparities in care.

Adjuvant chemotherapy use and adverse events among older patients with stage III colon cancer.

CONTEXT: Randomized trials suggest adjuvant chemotherapy is effective for older patients with stage III colon cancer. However, older patients are less likely to receive this therapy than younger patients, perhaps because of concern about adverse effects. OBJECTIVE: To evaluate adjuvant chemotherapy use and outcomes for older patients with stage III colon cancer from well-defined population-based settings and health care systems. DESIGN: Observational study of adjuvant chemotherapy use and outcomes by age using Poisson regression to estimate the number of adverse events adjusted for demographic and clinical factors, including comorbid illness and specific elements of chemotherapy regimens documented with clinically detailed medical record reviews and patient and surrogate surveys. SETTING: Five geographically defined regions (Alabama, Iowa, Los Angeles County, northern California, and North Carolina), 5 integrated health care delivery systems, and 15 Veterans Affairs hospitals. PATIENTS: Six hundred seventy-five patients diagnosed with stage III colon cancer from 2003 through 2005 who underwent surgical resection and were followed up for as long as 15 months postdiagnosis. MAIN OUTCOME MEASURES: Chemotherapy regimen, dose, duration, and annualized mean number of adverse events stratified by age. RESULTS: Of 202 patients aged 75 years and older, 101 (50%) received adjuvant chemotherapy compared with 87% of 473 younger patients (difference, 37%; 95% confidence interval [CI], 30%-45%). Among patients who received adjuvant chemotherapy, 14 patients (14%) aged 75 years and older and 178 younger patients (44%) received a regimen containing oxaliplatin (difference, 30%; 95% CI, 21%-38%). Older patients were less likely to continue treatment, such that by 150 days, 99 patients (40%) aged 65 years and older and 68 younger patients (25%) had discontinued chemotherapy (difference, 15%; 95% CI, 7%-23%). Overall, 162 patients (24%) had at least 1 adverse clinical event, with more events among patients treated with vs without adjuvant chemotherapy (mean, 0.39 vs 0.16; difference, 0.23; 95% CI, 0.11-0.36; P < .001). Among patients receiving adjuvant chemotherapy, adjusted rates of late clinical adverse events were lower for patients 75 years and older (mean, 0.28) vs for younger patients (0.35 for ages 18-54 years, 0.52 for ages 55-64 years, and 0.45 for ages 65-74 years; P = .008 for any age effect). CONCLUSION: Among patients with stage III colon cancer who underwent surgical resection and received adjuvant chemotherapy, older patients in the community received less-toxic and shorter chemotherapy regimens, and those treated had fewer adverse events than younger patients.