Monitoring COVID-19 vaccination coverage among nursing home (NH) residents and staff is important to ensure high coverage and guide patient-safety policies. With the termination of the federal Pharmacy Partnership for Long-Term Care Program, another source of facility-based vaccination data is needed. We compared numbers of COVID-19 vaccinations administered to NH residents and staff reported by pharmacies participating in the temporary federal Pharmacy Partnership for Long-Term Care Program with those reported by NHs participating in new COVID-19 vaccination modules of CDC’s National Healthcare Safety Network (NHSN). Pearson correlation coefficients comparing the number vaccinated between the two approaches were 0.89, 0.96, and 0.97 for residents and 0.74, 0.90, and 0.90 for staff, in the weeks ending January 3, 10, and 17, respectively. Based on subsequent NHSN reporting, vaccination coverage with ≥1 vaccine dose reached 77% for residents and 50% for staff the week ending January 31 and plateaued through April 2021.Three-question summary boxWhat is the current understanding of the subject?Because of high risk of disease, nursing home residents and staff were prioritized for COVID-19 vaccination when doses were limited.What does this report add to the literature?National monitoring of nursing home residents and staff vaccination coverage through the CDC National Healthcare Safety Network (NHSN) correlated with vaccination administration reports from the federal Pharmacy Partnership for Long-Term Care Program in January 2021. NHSN-reported vaccination coverage rates plateaued from February through April 2021.What are the implications for public health practice?NHSN can track COVID-19 vaccination in nursing homes and help guide efforts to increase vaccine uptake in residents and staff.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThe authors received no financial support for the research, authorship, and/or publication of this article.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy (See e.g., 45 C.F.R. part 46, 21 C.F.R. part 56; 42 U.S.C. section 241(d); 5 U.S.C. section 552a; 44 U.S.C. section 3501 et seq.).All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData supporting the findings of the study are found in the manuscript and/or supplementary files. Any other data can be furnished upon request.

Background: Thrombosis with thrombocytopenia syndrome (TTS) is a potentially life-threatening condition associated with adenoviral-vectored COVID-19 vaccination. TTS presents similarly to autoimmune heparin-induced thrombocytopenia. Twelve cases of cerebral venous sinus thrombosis following Janssen/Johnson & Johnson (Ad26.COV2.S) COVID-19 vaccination have been described. Objective(s): Describe surveillance data and reporting rates of TTS cases following COVID-19 vaccination. Design(s): Case series. Setting(s): United States Patients: Case-patients reported to the Vaccine Adverse Event Reporting System (VAERS) receiving COVID-19 vaccine from December 14, 2020 through August 31, 2021, with thrombocytopenia and thrombosis (excluding isolated ischemic stroke or myocardial infarction). If thrombosis was only in an extremity vein or pulmonary embolism, a positive enzyme-linked immunosorbent assay for anti-platelet factor 4 antibody was required. Measurements: Reporting rates (cases/million vaccine doses) and descriptive epidemiology. Result(s): 52 TTS cases were confirmed following Ad26.COV2.S (n=50) or mRNA-based COVID-19 (n=2) vaccination. TTS reporting rates were 3.55 per million (Ad26.COV2.S) and 0.0057 per million (mRNA-based COVID-19 vaccines). Median age of patients with TTS following Ad26.COV2.S vaccination was 43.5 years (range: 18-70); 70% were female. Both TTS cases following mRNA-based COVID-19 vaccination occurred in males aged >50 years. All cases following Ad26.COV2.S vaccination involved hospitalization including 32 (64%) with intensive care unit admission. Outcomes of hospitalizations following Ad26.COV2.S vaccination included death (12%), discharge to post-acute care (16%), and discharge home (72%). Limitation(s): Under-reporting and incomplete case follow-up. Conclusion(s): TTS is a rare but serious adverse event associated with Ad26.COV2.S vaccination. The different demographic characteristics of the two cases reported after mRNA-based COVID-19 vaccines and the much lower reporting rate suggest that these cases represent a background rate. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Introduction: Emergency department visits and hospitalizations for unsupervised medication exposures among young children increased in the early 2000s. Prevention efforts were initiated in response. Methods: Nationally representative data from the National Electronic Injury Surveillance System–Cooperative Adverse Drug Event Surveillance project collected from 2009 to 2020 were analyzed in 2022 to assess overall and medication-specific trends in emergency department visits for unsupervised exposures among children aged ≤5 years. Results: From 2009 to 2020, there were an estimated 677,968 (95% CI=550,089, 805,846) emergency department visits for unsupervised medication exposures among children aged ≤5 years in the U.S. Most visits involved children aged 1–2 years (2009–2012 [70.3%], 2017–2020 [67.4%]), and nearly one half involved prescription solid medications (2009–2012 [49.4%], 2017–2020 [48.1%]). The largest declines in estimated numbers of annual visits from 2009–2012 to 2017–2020 were for exposures involving prescription solid benzodiazepines (–2,636 visits, –72.0%) and opioids (–2,596 visits, –53.6%) and over-the-counter liquid cough and cold medications (–1,954 visits, –71.6%) and acetaminophen (–1,418 visits, –53.4%). The estimated number of annual visits increased for exposures involving over-the-counter solid herbal/alternative remedies (+1,028 visits, +65.6%), with the largest increase for melatonin exposures (+1,440 visits, +421.1%). Overall, the estimated number of visits for unsupervised medication exposures decreased from 66,416 in 2009 to 36,564 in 2020 (annual percentage change= –6.0%). Emergent hospitalizations for unsupervised exposures also declined (annual percentage change= –4.5%). Conclusions: Declines in estimated emergency department visits and hospitalizations for unsupervised medication exposures from 2009 to 2020 coincided with renewed prevention efforts. Targeted approaches may be needed to achieve continued declines in unsupervised medication exposures among young children. © 2023

BACKGROUND: Clinical trials suggest lower rates of major bleeding with direct-acting oral anticoagulants (DOACs) than with warfarin, but anticoagulant-related bleeding remains one of the most common outpatient adverse drug events. METHODS: We estimated the number of emergency department (ED) visits and subsequent hospitalizations for oral anticoagulant-related bleeding in 2016-2020 based on active surveillance in a nationally representative, size-stratified probability sample of 60 U.S. hospitals. We estimated rates of ED visits using a nationally-projected retail prescription dispensing database. RESULTS: Based on 19,557 cases, oral anticoagulant-related bleeding resulted in an estimated 1,270,259 (95 % Confidence Interval [CI], 644,686-1,895,832) ED visits for the five years 2016-2020, of which 47.8 % (95 % CI, 40.6 %-55.0 %) resulted in hospitalization. Oral anticoagulant-related bleeding resulted in an estimated 230,163 (95% CI, 109,598-350,728) ED visits in 2016 and 301,433 (95% CI, 138,363-464,503) in 2020. During 2016-2020, ED visits for DOAC-related bleeding increased by an average of 27.9 % (95 % CI, 24.0 %-32.0 %; p < .001) per year, while ED visits for warfarin-related bleeding decreased by an average of 8.8 % (95 % CI, -10.7 % to -7.0 %; p = .001) per year. The estimated rate of bleeding visits per 100 patients dispensed oral anticoagulants at least once in 2016-2020 was highest for patients aged ≥ 80 years (13.1; 95 % CI, 6.2-20.0) and lowest for those aged <45 years (4.0; 95 % CI, 2.6-5.5); it was 5.9 visits per 100 patients dispensed DOACs [95 % CI, 2.5-9.2] and 13.0 visits per 100 patients dispensed warfarin [95 % CI, 7.4-18.7]. CONCLUSIONS: Although the rates of ED visits for anticoagulant-related bleeding may be lower for DOACs than for warfarin, persistently large numbers of patients requiring ED visits for anticoagulant-related bleeding despite increased use of DOACs and declining use of warfarin suggest that efforts to improve appropriate prescribing and monitoring of anticoagulants remain important.

BACKGROUND: Medication poisoning is a common form of self-harm injury, and increases in injuries due to self-harm, including suicide attempts, have been reported over the last two decades. METHODS: Cross-sectional (2016-2019) data from 60 emergency departments (EDs) participating in an active, nationally representative public health surveillance system were analysed and US national estimates of ED visits for medication-related self-harm injuries were calculated. RESULTS: Based on 18 074 surveillance cases, there were an estimated 269 198 (95% CI 222 059 to 316 337) ED visits for medication-related self-harm injuries annually in 2016-2019 compared with 1 404 090 visits annually from therapeutic use of medications. Population rates of medication-related self-harm ED visits were highest among persons aged 11-19 years (58.5 (95% CI 45.0 to 72.0) per 10 000) and lowest among those aged ≥65 years (6.6 (95% CI 4.4 to 8.8) per 10 000). Among persons aged 11-19 years, the ED visit rate for females was four times that for males (95.4 (95% CI 74.2 to 116.7) vs 23.0 (95% CI 16.4 to 29.6) per 10 000). Medical or psychiatric admission was required for three-quarters (75.1%; 95% CI 70.0% to 80.2%) of visits. Concurrent use of alcohol or illicit substances was documented in 40.2% (95% CI 36.8% to 43.7%) of visits, and multiple medication products were implicated in 38.6% (95% CI 36.8% to 40.4%). The most frequently implicated medication categories varied by patient age. CONCLUSIONS: Medication-related self-harm injuries are an important contributor to the overall burden of ED visits and hospitalisations for medication-related harm, with the highest rates among adolescent and young adult females. These findings support continued prevention efforts targeting patients at risk of self-harm.

Monitoring COVID-19 vaccination coverage among nursing home residents and staff is important to ensure high coverage rates and guide patient-safety policies. With the termination of the federal Pharmacy Partnership for Long-Term Care Program, another source of facility-based vaccination data is needed. We compared numbers of COVID-19 vaccinations administered to nursing home residents and staff reported by pharmacies participating in the temporary federal Pharmacy Partnership for Long-Term Care Program with the numbers of COVID-19 vaccinations reported by nursing homes participating in new COVID-19 vaccination modules of the Centers for Disease Control and Prevention's National Healthcare Safety Network (NHSN). Pearson correlation coefficients comparing the number vaccinated between the 2 approaches were 0.89, 0.96, and 0.97 for residents and 0.74, 0.90, and 0.90 for staff, in the weeks ending January 3, 10, and 17, 2021, respectively. Based on subsequent NHSN reporting, vaccination coverage with ≥1 vaccine dose reached 73.7% for residents and 47.6% for staff the week ending January 31 and increased incrementally through July 2021. Continued monitoring of COVID-19 vaccination coverage is important as new nursing home residents are admitted, new staff are hired, and additional doses of vaccine are recommended.

OBJECTIVE: Administrative claims are commonly relied upon to identify hypoglycemia. We assessed validity of 14 International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis code assignments to identify medication-related hypoglycemia leading to acute care encounters. RESEARCH DESIGN AND METHODS: A multisite, retrospective medical record review study was conducted in a sample of Medicare beneficiaries prescribed outpatient diabetes medications and who received hospital care between January 1, 2016 and September 30, 2017. Diagnosis codes were validated with structured medical record review using prespecified criteria (clinical presentation, blood glucose values, and treatments for hypoglycemia). Sensitivity, specificity, and positive and negative predictive value (PPV, NPV) were calculated and adjusted using sampling weights to correct for partial verification bias. RESULTS: Among 990 encounters (496 cases, 494 controls), hypoglycemia codes demonstrated moderate PPV (69.2%; 95% confidence interval: 65.0-73.0) and moderate sensitivity (83.9%; 95% confidence interval: 70.0-95.5). Codes performed better at identifying hypoglycemic events among emergency department/observation encounters compared with hospitalizations (PPV 92.9%, sensitivity 100.0% vs. PPV 53.7%, sensitivity 71.0%). Accuracy varied by diagnosis position, especially for hospitalizations, with PPV of 95.6% versus 46.5% with hypoglycemia in primary versus secondary positions. Use of adverse event/poisoning codes did not improve accuracy; reliance on these codes alone would have missed 97% of true hypoglycemic events. CONCLUSIONS: Accuracy of International Classification of Diseases, Tenth Revision codes in administrative claims to identify medication-related hypoglycemia varied substantially by encounter type and diagnosis position. Consideration should be given to the trade-off between PPV and sensitivity when selecting codes, encounter types, and diagnosis positions to identify hypoglycemia.

BACKGROUND: Thrombosis with thrombocytopenia syndrome (TTS) is a potentially life-threatening condition associated with adenoviral-vectored COVID-19 vaccination. It presents similarly to spontaneous heparin-induced thrombocytopenia. Twelve cases of cerebral venous sinus thrombosis after vaccination with the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson) have previously been described. OBJECTIVE: To describe surveillance data and reporting rates of all reported TTS cases after COVID-19 vaccination in the United States. DESIGN: Case series. SETTING: United States. PATIENTS: Case patients receiving a COVID-19 vaccine from 14 December 2020 through 31 August 2021 with thrombocytopenia and thrombosis (excluding isolated ischemic stroke or myocardial infarction) reported to the Vaccine Adverse Event Reporting System. If thrombosis was only in an extremity vein or pulmonary embolism, a positive enzyme-linked immunosorbent assay for antiplatelet factor 4 antibodies or functional heparin-induced thrombocytopenia platelet test result was required. MEASUREMENTS: Reporting rates (cases per million vaccine doses) and descriptive epidemiology. RESULTS: A total of 57 TTS cases were confirmed after vaccination with Ad26.COV2.S (n= 54) or a messenger RNA (mRNA)-based COVID-19 vaccine (n= 3). Reporting rates for TTS were 3.83 per million vaccine doses (Ad26.COV2.S) and 0.00855 per million vaccine doses (mRNA-based COVID-19 vaccines). The median age of patients with TTS after Ad26.COV2.S vaccination was 44.5 years (range, 18 to 70 years), and 69% of patients were women. Of the TTS cases after mRNA-based COVID-19 vaccination, 2 occurred in men older than 50 years and 1 in a woman aged 50 to 59 years. All cases after Ad26.COV2.S vaccination involved hospitalization, including 36 (67%) with intensive care unit admission. Outcomes of hospitalizations after Ad26.COV2.S vaccination included death (15%), discharge to postacute care (17%), and discharge home (68%). LIMITATIONS: Underreporting and incomplete case follow-up. CONCLUSION: Thrombosis with thrombocytopenia syndrome is a rare but serious adverse event associated with Ad26.COV2.S vaccination. The different demographic characteristics of the 3 cases reported after mRNA-based COVID-19 vaccines and the much lower reporting rate suggest that these cases represent a background rate. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

BACKGROUND AND PURPOSE: Characterization of emergency department (ED) visits for acute harms related to use of over-the-counter cough and cold medications (CCMs) by patient demographics, intent of CCM use, concurrent substance use, and clinical manifestations can help guide prevention of medication harms. METHODS: Public health surveillance data from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project were used to estimate numbers and population rates of ED visits from 2017-2019. RESULTS: Based on 1,396 surveillance cases, there were an estimated 26,735 (95% CI, 21,679-31,791) US ED visits for CCM-related harms annually, accounting for 1.3% (95% CI, 1.2%-1.5%) of all ED visits for medication adverse events. Three fifths (61.4%, 95% CI, 55.6%-67.2%) of these visits were attributed to non-therapeutic CCM use (nonmedical use, self-harm, unsupervised pediatric exposures). Most visits by children aged <4 years (74.0%, 95% CI, 59.7%-88.3%) were for unsupervised CCM exposures. Proportion hospitalized was higher for visits for self-harm (76.5%, 95% CI, 68.9%-84.2%) than for visits for nonmedical use (30.3%, 95% CI, 21.1%-39.6%) and therapeutic use (8.8%, 95% CI, 5.9%-11.8%). Overall, estimated population rates of ED visits for CCM-related harms were higher for patients aged 12-34 years (16.5 per 100,000, 95% CI, 13.0-20.0) compared with patients aged <12 years (5.1 per 100,000, 95% CI, 3.6-6.5) and ≥35 years (4.3 per 100,000, 95% CI, 3.4-5.1). Concurrent use of other medications, illicit drugs, or alcohol was frequent in ED visits for nonmedical use (61.3%) and self-harm (75.9%). CONCLUSIONS: Continued national surveillance of CCM-related harms can assess progress toward safer use.

IMPORTANCE: Assessing the scope of acute medication harms to patients should include both therapeutic and nontherapeutic medication use. OBJECTIVE: To describe the characteristics of emergency department (ED) visits for acute harms from both therapeutic and nontherapeutic medication use in the US. DESIGN, SETTING, AND PARTICIPANTS: Active, nationally representative, public health surveillance based on patient visits to 60 EDs in the US participating in the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance Project from 2017 through 2019. EXPOSURES: Medications implicated in ED visits, with visits attributed to medication harms (adverse events) based on the clinicians' diagnoses and supporting data documented in the medical record. MAIN OUTCOMES AND MEASURES: Nationally weighted estimates of ED visits and subsequent hospitalizations for medication harms. RESULTS: Based on 96 925 cases (mean patient age, 49 years; 55% female), there were an estimated 6.1 (95% CI, 4.8-7.5) ED visits for medication harms per 1000 population annually and 38.6% (95% CI, 35.2%-41.9%) resulted in hospitalization. Population rates of ED visits for medication harms were higher for patients aged 65 years or older than for those younger than 65 years (12.1 vs 5.0 [95% CI, 7.4-16.8 vs 4.1-5.8] per 1000 population). Overall, an estimated 69.1% (95% CI, 63.6%-74.7%) of ED visits for medication harms involved therapeutic medication use, but among patients younger than 45 years, an estimated 52.5% (95% CI, 48.1%-56.8%) of visits for medication harms involved nontherapeutic use. The proportions of ED visits for medication harms involving therapeutic use were lowest for barbiturates (6.3%), benzodiazepines (11.1%), nonopioid analgesics (15.7%), and antihistamines (21.8%). By age group, the most frequent medication types and intents of use associated with ED visits for medication harms were therapeutic use of anticoagulants (4.5 [95% CI, 2.3-6.7] per 1000 population) and diabetes agents (1.8 [95% CI, 1.3-2.3] per 1000 population) for patients aged 65 years and older; therapeutic use of diabetes agents (0.8 [95% CI, 0.5-1.0] per 1000 population) for patients aged 45 to 64 years; nontherapeutic use of benzodiazepines (1.0 [95% CI, 0.7-1.3] per 1000 population) for patients aged 25 to 44 years; and unsupervised medication exposures (2.2 [95% CI, 1.8-2.7] per 1000 population) and therapeutic use of antibiotics (1.4 [95% CI, 1.0-1.8] per 1000 population) for children younger than 5 years. CONCLUSIONS AND RELEVANCE: According to data from 60 nationally representative US emergency departments, visits attributed to medication harms in 2017-2019 were frequent, with variation in products and intent of use by age.

Residents of long-term care facilities (LTCFs) and health care personnel (HCP) working in these facilities are at high risk for COVID-19-associated mortality. As of March 2021, deaths among LTCF residents and HCP have accounted for almost one third (approximately 182,000) of COVID-19-associated deaths in the United States (1). Accordingly, LTCF residents and HCP were prioritized for early receipt of COVID-19 vaccination and were targeted for on-site vaccination through the federal Pharmacy Partnership for Long-Term Care Program (2). In December 2020, CDC's National Healthcare Safety Network (NHSN) launched COVID-19 vaccination modules, which allow U.S. LTCFs to voluntarily submit weekly facility-level COVID-19 vaccination data.* CDC analyzed data submitted during March 1-April 4, 2021, to describe COVID-19 vaccination coverage among a convenience sample of HCP working in LTCFs, by job category, and compare HCP vaccination coverage rates with social vulnerability metrics of the surrounding community using zip code tabulation area (zip code area) estimates. Through April 4, 2021, a total of 300 LTCFs nationwide, representing approximately 1.8% of LTCFs enrolled in NHSN, reported that 22,825 (56.8%) of 40,212 HCP completed COVID-19 vaccination.(†) Vaccination coverage was highest among physicians and advanced practice providers (75.1%) and lowest among nurses (56.7%) and aides (45.6%). Among aides (including certified nursing assistants, nurse aides, medication aides, and medication assistants), coverage was lower in facilities located in zip code areas with higher social vulnerability (social and structural factors associated with adverse health outcomes), corresponding to vaccination disparities present in the wider community (3). Additional efforts are needed to improve LTCF immunization policies and practices, build confidence in COVID-19 vaccines, and promote COVID-19 vaccination. CDC and partners have prepared education and training resources to help educate HCP and promote COVID-19 vaccination coverage among LTCF staff members.(§).

Ivermectin is an antiparasitic medication approved by the US Food and Drug Administration (FDA) for use in humans. Ivermectin oral tablets are used worldwide for treatment of certain parasitic infections. An in vitro study has shown that ivermectin inhibits the replication of SARS-CoV-2 in tissue cell cultures.1 Some observational studies and clinical trials have evaluated ivermectin for the treatment and prevention of COVID-19 in humans; however, most had incomplete information and methodological limitations.2 Human data from well-designed and well-conducted clinical trials with robust sample sizes are needed to provide more specific, evidence-based guidance on the role of ivermectin for the treatment or prevention of COVID-19.

BACKGROUND: Trends in prescribing for nursing home (NH) residents, which may have been influenced by the COVID-19 pandemic, have not been characterized. METHODS: Long-term care pharmacy data from 1,944 U.S. NHs were used to evaluate trends in prescribing of antibiotics and drugs that were investigated for COVID-19 treatment, including hydroxychloroquine, famotidine, and dexamethasone. To account for seasonal variability in antibiotic prescribing and decreased NH occupancy during the pandemic, monthly prevalence of residents with a prescription dispensed per 1,000 residents serviced was calculated from January - October and compared as relative percent change from 2019 to 2020. RESULTS: In April 2020, prescribing was significantly higher in NHs for drugs investigated for COVID-19 treatment than 2019; including hydroxychloroquine (+563%, 95% confidence interval (CI) 5.87, 7.48) and azithromycin (+150%, 95% CI 2.37, 2.63). Ceftriaxone prescribing also increased (+43%, 95% CI 1.34, 1.54). Prescribing of dexamethasone was 36% lower in April (95% CI 0.55, 0.73) and 303% higher in July (95% CI 3.66, 4.45). Although azithromycin and ceftriaxone prescribing increased, total antibiotic prescribing among residents was lower from May (-5%, 95% CI 0.94, 0.97) through October (-4%, 95% CI 0.94, 0.97) in 2020 compared to 2019. CONCLUSIONS: During the pandemic, large numbers of residents were prescribed drugs investigated for COVID-19 treatment, and an increase in prescribing of antibiotics commonly used for respiratory infections was observed. Prescribing of these drugs may increase the risk of adverse events, without providing clear benefits. Surveillance of NH prescribing practices is critical to evaluate concordance with guideline-recommended therapy and improve resident safety.

PURPOSE: We used data from two public health surveillance systems for national estimates and detailed descriptions of insulin mix-up errors resulting in emergency department (ED) visits and other serious adverse events to help inform prevention efforts. METHODS: ED visits involving patients seeking care for insulin medication errors collected by the NEISS-CADES project in 2012-2017 and voluntary reports of serious insulin medication errors submitted to the U.S. Food and Drug Administration (FDA) in 2016-2017 were analyzed. National estimates of insulin product prescriptions dispensed from retail pharmacies were obtained from IQVIA National Prescription Audit. RESULTS: Between 2012 and 2017, based on 514 NEISS-CADES cases, there were an estimated 5,636 (95% CI, 4,143-7,128) ED visits annually for insulin mix-up errors; overall, over three-quarters (77.5%; 95% CI, 71.6%-83.3%) involved taking rapid-acting instead of long-acting insulin. Between 2012 and 2017, the proportion of mix-up errors among all estimated ED visits for all insulin errors decreased by 60%; concurrently, the proportion of pens among all insulin package types dispensed increased by 50%. Among 58 voluntary reports submitted to FAERS, over one-half (56.9%) of cases involved taking rapid- instead of long-acting insulin. Among 27 cases with documented contributing factors, approximatley one-half involved patients having difficulty differentiating products. CONCLUSIONS: Among all ED visits for insulin errors collected by NEISS-CADES in 2012-2017, the proportion involving mix-up errors has declined. Continued reductions may require additional prevention strategies, including improving insulin distinctiveness, particularly for rapid- vs. long-acting insulins. Ongoing national surveillance is important for identifying the impact of interventions. This article is protected by copyright. All rights reserved.

This cross-sectional study examines changes in the outpatient retail dispensing frequency of proposed treatments for coronavirus disease 2019 after the March 13, 2020, declaration of a national emergency due to the pandemic.

BACKGROUND: The objective of our study was to describe trends in U.S. outpatient antibiotic prescriptions from January through May 2020 and compare with trends in previous years (2017-2019). METHODS: We used data from the IQVIA Total Patient Tracker to estimate the monthly number of patients dispensed antibiotic prescriptions from retail pharmacies in January 2017-May 2020. We averaged estimates from 2017-2019 and defined expected seasonal change as the average percent change from January to May 2017-2019. We calculated percentage point and volume changes in the number of patients dispensed antibiotics from January to May 2020 exceeding expected seasonal changes. We also calculated average percent change in number of patients dispensed antibiotics per month in 2017- 2019 versus 2020. Data were analyzed overall and by agent, class, patient age, state, and prescriber specialty. RESULTS: From January to May 2020, the number of patients dispensed antibiotic prescriptions decreased from 20.3 to 9.9 million, exceeding seasonally expected decreases by 33 percentage points and 6.6 million patients. The largest changes in 2017-2019 versus 2020 were observed in April (-39%) and May (-42%). The number of patients dispensed azithromycin increased from February to March 2020 then decreased. Overall, beyond-expected decreases were greatest among children (≤19 years) and agents used for respiratory infections, dentistry, and surgical prophylaxis. CONCLUSIONS: From January 2020 to May 2020, the number of outpatients with antibiotic prescriptions decreased substantially more than would be expected due to seasonal trends alone, possibly related to the COVID-19 pandemic and associated mitigation measures.

Using a coronavirus disease 2019 (COVID-19)-associated hospitalization surveillance network, we found that 42.5% of hospitalized COVID-19 cases with available data from March 1-June 30, 2020, received ≥1 COVID-19 investigational treatment. Hydroxychloroquine, azithromycin, and remdesivir were used frequently; however, hydroxychloroquine and azithromycin use declined over time, while use of remdesivir increased.

BACKGROUND: Hypoglycemia related to antidiabetic drugs (ADDs) is important iatrogenic harm in hospitalized patients. Electronic identification of ADD-related hypoglycemia may be an efficient, reliable method to inform quality improvement. OBJECTIVE: Develop electronic queries of electronic health records for facility-wide and unit-specific inpatient hypoglycemia event rates and validate query findings with manual chart review. METHODS: Electronic queries were created to associate blood glucose (BG) values with ADD administration and inpatient location in 3 tertiary care hospitals with Patient-Centered Outcomes Research Network (PCORnet) databases. Queries were based on National Quality Forum criteria with hypoglycemia thresholds <40 and <54 mg/dL, and validated using a stratified random sample of 321 BG events. Sensitivity and specificity were calculated with manual chart review as the reference standard. RESULTS: The sensitivity and specificity of queries for hypoglycemia events were 97.3% [95% confidence interval (CI), 90.5%-99.7%] and 100.0% (95% CI, 92.6%-100.0%), respectively for BG <40 mg/dL, and 97.7% (95% CI, 93.3%-99.5%) and 100.0% (95% CI, 95.3%-100.0%), respectively for <54 mg/dL. The sensitivity and specificity of the query for identifying ADD days were 91.8% (95% CI, 89.2%-94.0%) and 99.0% (95% CI, 97.5%-99.7%). Of 48 events missed by the queries, 37 (77.1%) were due to incomplete identification of insulin administered by infusion. Facility-wide hypoglycemia rates were 0.4%-0.8% (BG <40 mg/dL) and 1.9%-3.0% (BG <54 mg/dL); rates varied by patient care unit. CONCLUSIONS: Electronic queries can accurately identify inpatient hypoglycemia. Implementation in non-PCORnet-participating facilities should be assessed, with particular attention to patient location and insulin infusions.

The opioid partial agonist buprenorphine is a critical component of medication-assisted treatment for opioid use disorder and is associated with improved treatment adherence and decreased illicit opioid use (1). Combination buprenorphine/naloxone transmucosal products are designed to deter injection owing to the opioid-antagonist actions of naloxone and can reduce the desired effects and precipitate rapid withdrawal when these products are administered intravenously; nonetheless, injection of transmucosal buprenorphine/naloxone has been reported (2,3). During 2016–2017, 14.6% of approximately 127,000 emergency department (ED) visits for nonmedical use* of prescription opioids involved buprenorphine products, commonly for injection-related complications (4). ED visits for nonmedical use of buprenorphine involved less severe overdose morbidity (e.g., unresponsiveness or cardiorespiratory failure) than did those involving other opioids (4). Complications of injecting transmucosal buprenorphine products represent a potentially preventable source of morbidity from nonmedical use of buprenorphine. Further description of complications related to buprenorphine injection can help prevent these complications while preserving access to this effective therapy for opioid use disorder.

INTRODUCTION: Characterization of emergency department visits attributed to adverse events involving benzodiazepines can be used to guide preventive interventions. This study describes U.S. emergency department visits attributed to adverse events involving benzodiazepines by intent, patient characteristics, and clinical manifestations. METHODS: Data from the 2016-2017 National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project were analyzed in 2019 to calculate estimated annual numbers and rates of emergency department visits attributed to adverse events involving benzodiazepines, by intent of benzodiazepine use. RESULTS: Based on 6,148 cases, there were an estimated 212,770 (95% CI=167,163, 258,377) emergency department visits annually attributed to adverse events involving benzodiazepines. More than half were visits involving nonmedical use of benzodiazepines (119,008; 55.9%, 95% CI=50.0%, 61.9%), one third were visits involving self-harm with benzodiazepines (64,721; 30.4%, 95% CI=25.6%, 35.2%), and a smaller proportion of visits involved therapeutic use of benzodiazepines (29,041; 13.6%, 95% CI=11.4%, 15.9%). The estimated population rate of visits was highest for nonmedical use of benzodiazepines by patients aged 15-34 years (7.4 visits per 10,000 people). Among visits involving nonmedical use of benzodiazepines, 54.8% (95% CI=49.8%, 59.8%) were made by patients aged 15-34 years, 82.7% (95% CI=80.1%, 85.4%) involved concurrent use of other substances (illicit drugs, alcohol, prescription opioids, and/or other pharmaceuticals), and 24.2% (95% CI=17.7%, 30.6%) involved cardiorespiratory arrest or unresponsiveness. CONCLUSIONS: These findings support recommendations to assess for and address substance use disorder before initiating or continuing benzodiazepines and reinforce the need for validated self-harm risk assessment tools for clinicians.

Purpose: To identify possible changes in the U.S. emergency department (ED) visits from zolpidem-attributed adverse drug reactions (ADRs) after 2013 Food and Drug Administration (FDA) Drug Safety Communications (DSCs), which notified the public about FDA's new dosing recommendations for zolpidem. Method(s): We estimated the occurrence of ED visits from zolpidem-attributed ADRs using nationally representative, public health surveillance of medication harms (National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project, 2010-2017). We estimated the number of zolpidem prescriptions using IQVIA National Prescription Audit, 2010-2017. We calculated rates of ED visits for zolpidem-attributed ADRs per 10 000 dispensed zolpidem prescriptions and identified time trends and potential inflection points using the joinpoint regression. For comparison, we repeated these analyses for sedating antidepressants commonly used to treat disordered sleep (trazodone, doxepin, and mirtazapine). Result(s): The best-fit regression model for rates of ED visits for zolpidem-attributed ADRs by 6-month intervals identified a single inflection point in the second half of 2014 (P =.024) with a 6.7% biannual decrease from 2010 to 2014 ([-13.1%, 0.3%], P =.059) and a 13.9% biannual increase from the second half of 2014 through 2017 ([-1.1%, 31.3%], P =.068). No change or inflection points were identified for rates of ED visits for sedating antidepressant-attributed ADRs. Conclusion(s): While there was a nominal decline in the rate of ED visits for ADRs in the time period before and for 18 months after FDA's 2013 zolpidem DSCs, the decrease was not sustained, and thus questions remain concerning the long-term impact of the zolpidem DSCs on ADRs. Copyright Published 2020. This article is a U.S. Government work and is in the public domain in the USA.

Warfarin was the mainstay of outpatient antithrombotic management for decades, but in 2010, direct-acting oral anticoagulants (DOACs) were introduced with fixed dosing and without requirements for laboratory monitoring.1 Clinical trials suggested lower rates of major bleeding with DOACs than with warfarin.2, 3 The number of patients prescribed DOACs has been increasing, yet the number treated for emergent DOAC-related bleeding in the USA is unknown.4

To facilitate ease of swallowing and promote patient adherence, the U.S. Food and Drug Administration (FDA) has provided voluntary guidance for the size of generic drug tablets and capsules (1). This guidance recommends that generic products should not exceed 17 millimeters (mm) in a single dimension. If a branded product already exceeds 17 mm, then the generic product should be no larger. No tablets or capsules should exceed 22 mm. Currently, no similar guidance for dietary supplements exists; however, supplements are implicated in swallowing problems, particularly among adults aged 65 years or older (2).

OBJECTIVE: The use of emergency medical services (EMS) for diabetes-related events is believed to be substantial but has not been quantified nationally despite the diverse acute complications associated with diabetes. We describe diabetes-related EMS activations in 2015 among people of all ages from 23 U.S. states. METHODS: We used data from 23 states that reported >/=95% of their EMS activations to the U.S. National Emergency Medical Services Information System (NEMSIS) in 2015. A diabetes-related EMS activation was defined using coded EMS provider impressions of "diabetes symptoms" and coded complaints recorded by dispatch of "diabetic problem." We described activations by type of location, urbanicity, U.S. Census Division, season, and time of day; and patient-events by age category, race/ethnicity, disposition, and treatment with glucose. Crude and age-adjusted diabetes-related EMS patient-level event rates were calculated for adults >/=18 years of age with diagnosed diabetes using the Behavioral Risk Factor Surveillance System to estimate the population denominator. RESULTS: Of 10,324,031 relevant EMS records, 241,495 (2.3%) were diabetes-related activations, which involved over 235,000 hours of service. Most activations occurred in urban or suburban environ- ments (86.4%), in the home setting (73.5%), and were slightly more frequent in the summer months. Most patients (72.6%) were >/=45 years of age and over one-half (55.4%) were transported to the emergency department. The overall age-adjusted diabetes-related EMS event rate was 33.9 per 1,000 persons with diagnosed diabetes; rates were highest in patients 18-44 years of age, males, and non-Hispanic blacks and varied by U.S. Census Division. CONCLUSIONS: Diabetes results in a substantial burden on EMS resources. Collection of more detailed diabetes complication information in NEMSIS may help facilitate EMS resource planning and prevention strategies.

PURPOSE: To assess performance of International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code assignments for identifying bleeding events resulting in emergency department visits and hospitalizations among outpatient Medicare beneficiaries prescribed anticoagulants. METHODS: Performance of 206 ICD-10-CM code assignments indicative of bleeding, five anticoagulant adverse effect/poisoning codes, and five coagulopathy codes (according to Medicare Parts A and B claims) as assessed among Medicare fee-for-service beneficiaries prescribed anticoagulants between October 1, 2015 and September 30, 2016 (according to Part D claims). Structured medical record review was the gold standard for validating the presence of anticoagulant-related bleeding. Sensitivity was adjusted to correct for partial verification bias due to sampling design. RESULTS: Based on the study sample of 1166 records (583 cases, 583 controls), 57 of 206 codes yielded the optimal performance for anticoagulant-related bleeding (diagnostic odds ratio, 51; positive predictive value (PPV), 75.7% [95% CI, 72.0%-79.1%]; adjusted sensitivity, 70.0% [95% CI, 63.2%-77.7%]). Codes for intracranial bleeding demonstrated the highest PPV (85.0%) and adjusted sensitivity (91.0%). Bleeding codes in the primary position demonstrated high PPV (86.9%), but low adjusted sensitivity (36.0%). The adjusted sensitivity improved to 69.5% when codes in a secondary position were added. Only one adverse effect/poisoning code was used, appearing in 7.8% of cases and controls (PPV, 71.4% and adjusted sensitivity, 6.8%). CONCLUSIONS: Performance of ICD-10-CM code assignments for bleeding among patients prescribed anticoagulants varied by bleed type and code position. Adverse effect/poisoning codes were not commonly used and would have missed over 90% of anticoagulant-related bleeding cases.

OBJECTIVES: To estimate the number of US emergency department visits for prescription opioid harms by patient characteristics, intent, clinical manifestations, and active ingredient. METHODS: We used data from medical record-based surveillance from a nationally representative 60-hospital sample. RESULTS: Based on 7769 cases, there were 267 020 estimated emergency department visits annually (95% confidence interval [CI] = 209 833, 324 206) for prescription opioid harms from 2016 to 2017. Nearly half of visits (47.6%; 95% CI = 40.8%, 54.4%) were attributable to nonmedical opioid use, 38.9% (95% CI = 32.9%, 44.8%) to therapeutic use, and 13.5% (95% CI = 11.0%, 16.0%) to self-harm. Co-implication with other pharmaceuticals and concurrent illicit drug and alcohol use were common; prescription opioids alone were implicated in 31.5% (95% CI = 27.2%, 35.8%) of nonmedical use visits and 19.7% (95% CI = 15.7%, 23.7%) of self-harm visits. Unresponsiveness or cardiorespiratory failure (30.0%) and altered mental status (35.7%) were common in nonmedical use visits. Gastrointestinal effects (30.4%) were common in therapeutic use visits. Oxycodone was implicated in more than one third of visits across intents. CONCLUSIONS: Morbidity data can help target interventions, such as dispensing naloxone to family and friends of those with serious overdose, and screening and treatment of substance use disorder when opioids are prescribed long-term. (Am J Public Health. Published online ahead of print March 21, 2019: e1-e8. doi:10.2105/AJPH.2019.305007).

INTRODUCTION: National data on morbidity from nonmedical use of pharmaceuticals are limited. This study used nationally representative, public health surveillance data to characterize U.S. emergency department visits for acute harms from nonmedical use of pharmaceuticals and to guide prevention efforts. METHODS: Data collected in 2016 from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project were analyzed in 2018 to calculate national estimates of emergency department visits for harms from nonmedical use of pharmaceuticals. RESULTS: Based on 5,130 surveillance cases, there were an estimated 358,247 emergency department visits (95% CI=280,675, 435,819) in 2016 for harms from nonmedical use of pharmaceuticals and 41.1% resulted in hospitalization (95% CI=32.3%, 49.8%). One half (50.9%, 95% CI=46.6%, 55.3%) of estimated visits involved patients aged </=34 years; more than one half of estimated visits also involved non-pharmaceutical substances (52.9%, 95% CI=49.7%, 56.1%), including illicit drugs in 34.1% (95% CI=30.9%, 37.2%) and alcohol in 21.8% (95% CI=19.8%, 23.9%). Overall, benzodiazepines were implicated in 46.9% (95% CI=42.5%, 51.2%) of estimated emergency department visits for nonmedical use of pharmaceuticals but were the only substance implicated in just 6.5% (95% CI=5.1%, 7.9%). Prescription opioids were implicated in 36.2% (95% CI=30.8%, 41.7%) of estimated emergency department visits and were the only substance implicated in 11.3% (95% CI=8.6%, 14.0%). CONCLUSIONS: Although prescription opioids or benzodiazepines are frequently implicated in emergency department visits for nonmedical use, because other substances and additional pharmaceuticals are most often involved, prescribing clinicians should consider implementing specific screening to address polysubstance use and, when warranted, treatment interventions.

Background: Antibiotics are among the most commonly prescribed medications for children; however, at least one-third of pediatric antibiotic prescriptions are unnecessary. National data on short-term antibiotic-related harms could inform efforts to reduce overprescribing and to supplement interventions that focus on the long-term benefits of reducing antibiotic resistance. Methods: Frequencies and rates of emergency department (ED) visits for antibiotic adverse drug events (ADEs) in children were estimated using adverse event data from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project and retail pharmacy dispensing data from QuintilesIMS (2011-2015). Results: On the basis of 6542 surveillance cases, an estimated 69464 ED visits (95% confidence interval, 53488-85441) were made annually for antibiotic ADEs among children aged </=19 years from 2011 to 2015, which accounts for 46.2% of ED visits for ADEs that results from systemic medication. Two-fifths (40.7%) of ED visits for antibiotic ADEs involved a child aged </=2 years, and 86.1% involved an allergic reaction. Amoxicillin was the most commonly implicated antibiotic among children aged </=9 years. When we accounted for dispensed prescriptions, the rates of ED visits for antibiotic ADEs declined with increasing age for all antibiotics except sulfamethoxazole-trimethoprim. Amoxicillin had the highest rate of ED visits for antibiotic ADEs among children aged </=2 years, whereas sulfamethoxazole-trimethoprim resulted in the highest rate among children aged 10 to 19 years (29.9 and 24.2 ED visits per 10000 dispensed prescriptions, respectively). Conclusions: Antibiotic ADEs lead to many ED visits, particularly among young children. Communicating the risks of antibiotic ADEs could help reduce unnecessary prescribing. Prevention efforts could target pediatric patients who are at the greatest risk of harm.

BACKGROUND: Detailed, nationally representative data describing high-risk populations and circumstances involved in antibiotic adverse events (AEs) can inform approaches to prevention. OBJECTIVE: Describe US burden, rates, and characteristics of emergency department (ED) visits by adults for antibiotic AEs. DESIGN: Nationally representative, public health surveillance of adverse drug events (National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance [NEISS-CADES]) and a nationally projected database of dispensed prescriptions (QuintilesIMS), 2011-2015. PATIENTS: Antibiotic-treated adults (>/= 20 years) seeking ED care. MAIN MEASURES: Estimated annual numbers and rates of ED visits for antibiotic AEs among outpatients treated with systemically administered antibiotics. KEY RESULTS: Based on 10,225 cases, US adults aged >/= 20 years made an estimated 145,490 (95% confidence interval, 115,279-175,701) ED visits for antibiotic AEs each year in 2011-2015. Antibiotics were implicated in 13.7% (12.3-15.2%) of all estimated adult ED visits for adverse drug events. Most (56.6%; 54.8-58.4%) antibiotic AE visits involved adults aged < 50 years, and 71.8% (70.4-73.1%) involved females. Accounting for prescriptions dispensed from retail and long-term care pharmacies, adults aged 20-34 years had twice the estimated rate of ED visits for oral antibiotic AEs compared with those aged >/= 65 years (9.7 [7.6-11.8] versus 4.6 [3.6-5.7] visits per 10,000 dispensed prescriptions, respectively). Allergic reactions accounted for three quarters (74.3%; 70.0-78.6%) of estimated ED visits for antibiotic AEs. The three most frequently implicated antibiotic classes in ED visits for antibiotic AEs were oral sulfonamides (23.2%; 20.6-25.8%), penicillins (20.8%; 19.3-22.4%), and quinolones (15.7%; 14.2-17.1%). Per-prescription rates declined with increasing age group. CONCLUSIONS: Antibiotics are a common cause of ED visits by adults for adverse drug events and represent an important safety issue. Quantifying risks of AEs from specific antibiotics for specific patient populations, such as younger adults, provides additional information to help clinicians assess risks versus benefits when making the decision to prescribe or not prescribe an antibiotic. AE rates may also facilitate communication with patients about antibiotic risks.