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

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          Abstract

          This cohort study assesses whether removal of a warning against use of cephalosporins in the electronic health record (EHR) of patients with penicillin allergy was associated with changes in the dispensing or administration of cephalosporins.

          Key Points

          Question

          Is removal of a warning to avoid cephalosporin use in patients with penicillin allergies associated with an increase in cephalosporin dispensing or administration?

          Findings

          In this cohort study of 4 398 792 patients who had received antibiotic treatment, after an alert in the electronic health record system to avoid prescribing of cephalosporins to patients with a penicillin allergy was removed at 1 of 2 health system sites, cephalosporin dispensing or administration increased significantly among patients with a penicillin allergy at that site compared with patients without a penicillin allergy at the same site and patients at the comparison site that retained the warning.

          Meaning

          In this study, removal of a warning in the electronic health record to avoid cephalosporin use in patients with penicillin allergies was associated with increased dispensing and administration of cephalosporin.

          Abstract

          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.

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          Most cited references30

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          The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.

          Much of biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalizability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September 2004, with methodologists, researchers, and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE Statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles. Eighteen items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies. A detailed Explanation and Elaboration document is published separately and is freely available on the web sites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE Statement will contribute to improving the quality of reporting of observational studies.
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            Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data.

            Implementation of the International Statistical Classification of Disease and Related Health Problems, 10th Revision (ICD-10) coding system presents challenges for using administrative data. Recognizing this, we conducted a multistep process to develop ICD-10 coding algorithms to define Charlson and Elixhauser comorbidities in administrative data and assess the performance of the resulting algorithms. ICD-10 coding algorithms were developed by "translation" of the ICD-9-CM codes constituting Deyo's (for Charlson comorbidities) and Elixhauser's coding algorithms and by physicians' assessment of the face-validity of selected ICD-10 codes. The process of carefully developing ICD-10 algorithms also produced modified and enhanced ICD-9-CM coding algorithms for the Charlson and Elixhauser comorbidities. We then used data on in-patients aged 18 years and older in ICD-9-CM and ICD-10 administrative hospital discharge data from a Canadian health region to assess the comorbidity frequencies and mortality prediction achieved by the original ICD-9-CM algorithms, the enhanced ICD-9-CM algorithms, and the new ICD-10 coding algorithms. Among 56,585 patients in the ICD-9-CM data and 58,805 patients in the ICD-10 data, frequencies of the 17 Charlson comorbidities and the 30 Elixhauser comorbidities remained generally similar across algorithms. The new ICD-10 and enhanced ICD-9-CM coding algorithms either matched or outperformed the original Deyo and Elixhauser ICD-9-CM coding algorithms in predicting in-hospital mortality. The C-statistic was 0.842 for Deyo's ICD-9-CM coding algorithm, 0.860 for the ICD-10 coding algorithm, and 0.859 for the enhanced ICD-9-CM coding algorithm, 0.868 for the original Elixhauser ICD-9-CM coding algorithm, 0.870 for the ICD-10 coding algorithm and 0.878 for the enhanced ICD-9-CM coding algorithm. These newly developed ICD-10 and ICD-9-CM comorbidity coding algorithms produce similar estimates of comorbidity prevalence in administrative data, and may outperform existing ICD-9-CM coding algorithms.
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              Methods for evaluating changes in health care policy: the difference-in-differences approach.

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                Author and article information

                Journal
                JAMA Netw Open
                JAMA Netw Open
                JAMA Netw Open
                JAMA Network Open
                American Medical Association
                2574-3805
                29 April 2021
                April 2021
                29 April 2021
                : 4
                : 4
                : e218367
                Affiliations
                [1 ]Department of Allergy and Clinical Immunology, Southern California Permanente Medical Group, San Diego Medical Center, San Diego
                [2 ]Kaiser Permanente Center for Effectiveness & Safety Research, Pasadena, California
                [3 ]Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, California
                [4 ]Department of Allergy and Clinical Immunology, Southern California Permanente Medical Group, South Bay Medical Center, Los Angeles
                [5 ]Department of Allergy and Clinical Immunology, The Permanente Medical Group, Oakland Medical Center, Oakland, California
                [6 ]Department of Pharmacy, Arrowhead Regional Medical Center, Colton, California
                [7 ]Department of Allergy and Immunology, Sansum Clinic, Santa Barbara, California
                [8 ]Kaiser Permanente Research, Pasadena, California
                Author notes
                Article Information
                Accepted for Publication: March 10, 2021.
                Published: April 29, 2021. doi:10.1001/jamanetworkopen.2021.8367
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Macy E et al. JAMA Network Open.
                Corresponding Author: Elizabeth A. McGlynn, PhD, Kaiser Permanente Research, 100 S Los Robles, 3rd Floor, Pasadena, CA 91101 ( elizabeth.a.mcglynn@ 123456kp.org ).
                Author Contributions: Drs McCormick and Adams had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: Macy, Adams, Crawford, Nguyen, Davis.
                Acquisition, analysis, or interpretation of data: Macy, McCormick, Adams, Crawford, Hoang, Eng, McGlynn.
                Drafting of the manuscript: Macy, McCormick, Adams, Nguyen, Davis, McGlynn.
                Critical revision of the manuscript for important intellectual content: Macy, Crawford, Hoang, Eng, McGlynn.
                Statistical analysis: McCormick, Adams, Hoang.
                Administrative, technical, or material support: Nguyen, Davis, McGlynn.
                Supervision: Macy, Adams, McGlynn.
                Conflict of Interest Disclosures: Dr Macy reported receiving grants from ALK-Abello A/S during the conduct of the study and serving as a panelist for the American Academy of Allergy, Asthma, and Immunology. No other disclosures were reported.
                Additional Contributions: Nicholas Emptage, MAE, assisted with exploratory literature review; Donna Woo, MA, assisted with project management; Lilia Grigoryan, MPH, assisted with manuscript formatting; and Liz Moisan, MS; Becky Gambatese, MPH; Jenny Staab, PhD; Richard Contreras, MS; Lie Chen, DrPH, MSPH; Akshay Manek, MD; and Dana Kliem, BS, provided data expertise and advice. All were employees of Kaiser Permanente during the time of the study and received no compensation beyond their salaries.
                Article
                zoi210265
                10.1001/jamanetworkopen.2021.8367
                8085727
                33914051
                98c39a46-5c14-4028-905a-31f5db08b45f
                Copyright 2021 Macy E et al. JAMA Network Open.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 19 October 2020
                : 10 March 2021
                Categories
                Research
                Original Investigation
                Online Only
                Allergy

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