Assessment of International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) Code Assignment Validity for Case Finding of Medication-related Hypoglycemia Acute Care Visits Among Medicare Beneficiaries.

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.

Trends in US Outpatient Antibiotic Prescriptions During the Coronavirus Disease 2019 Pandemic.

BACKGROUND: The objective of our study was to describe trends in US 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 from January 2017 through May 2020. We averaged estimates from 2017 through 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 because of seasonal trends alone, possibly related to the coronavirus disease 2019 pandemic and associated mitigation measures.

Outpatient insulin-related adverse events due to mix-up errors: Findings from two national surveillance systems, United States, 2012-2017.

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 US 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 5636 (95% CI, 4143-7128) 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, approximately 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.

US Emergency Department Visits Attributed to Medication Harms, 2017-2019.

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.

Electronic Measurement of a Clinical Quality Measure for Inpatient Hypoglycemic Events: A Multicenter Validation Study.

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.

Assessment of ICD-10-CM code assignment validity for case finding of outpatient anticoagulant-related bleeding among Medicare beneficiaries.

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.

Emergency Department Visits for Adverse Events Related to Dietary Supplements.

BACKGROUND: Dietary supplements, such as herbal or complementary nutritional products and micronutrients (vitamins and minerals), are commonly used in the United States, yet national data on adverse effects are limited. METHODS: We used nationally representative surveillance data from 63 emergency departments obtained from 2004 through 2013 to describe visits to U.S. emergency departments because of adverse events related to dietary supplements. RESULTS: On the basis of 3667 cases, we estimated that 23,005 (95% confidence interval [CI], 18,611 to 27,398) emergency department visits per year were attributed to adverse events related to dietary supplements. These visits resulted in an estimated 2154 hospitalizations (95% CI, 1342 to 2967) annually. Such visits frequently involved young adults between the ages of 20 and 34 years (28.0% of visits; 95% CI, 25.1 to 30.8) and unsupervised children (21.2% of visits; 95% CI, 18.4 to 24.0). After the exclusion of unsupervised ingestion of dietary supplements by children, 65.9% (95% CI, 63.2 to 68.5) of emergency department visits for single-supplement-related adverse events involved herbal or complementary nutritional products; 31.8% (95% CI, 29.2 to 34.3) involved micronutrients. Herbal or complementary nutritional products for weight loss (25.5%; 95% CI, 23.1 to 27.9) and increased energy (10.0%; 95% CI, 8.0 to 11.9) were commonly implicated. Weight-loss or energy products caused 71.8% (95% CI, 67.6 to 76.1) of supplement-related adverse events involving palpitations, chest pain, or tachycardia, and 58.0% (95% CI, 52.2 to 63.7) involved persons 20 to 34 years of age. Among adults 65 years of age or older, choking or pill-induced dysphagia or globus caused 37.6% (95% CI, 29.1 to 46.2) of all emergency department visits for supplement-related adverse events; micronutrients were implicated in 83.1% (95% CI, 73.3 to 92.9) of these visits. CONCLUSIONS: An estimated 23,000 emergency department visits in the United States every year are attributed to adverse events related to dietary supplements. Such visits commonly involve cardiovascular manifestations from weight-loss or energy products among young adults and swallowing problems, often associated with micronutrients, among older adults. (Funded by the Department of Health and Human Services.).

National Estimates of Emergency Department Visits for Antibiotic Adverse Events Among Adults-United States, 2011-2015.

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.

US Emergency Department Visits for Outpatient Adverse Drug Events, 2013-2014.

Importance: The Patient Protection and Affordable Care Act of 2010 brought attention to adverse drug events in national patient safety efforts. Updated, detailed, nationally representative data describing adverse drug events can help focus these efforts. Objective: To describe the characteristics of emergency department (ED) visits for adverse drug events in the United States in 2013-2014 and describe changes in ED visits for adverse drug events since 2005-2006. Design, Setting, and Participants: Active, nationally representative, public health surveillance in 58 EDs located in the United States and participating in the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project. Exposures: Drugs implicated in ED visits. Main Outcomes and Measures: National weighted estimates of ED visits and subsequent hospitalizations for adverse drug events. Results: Based on data from 42 585 cases, an estimated 4.0 (95% CI, 3.1-5.0) ED visits for adverse drug events occurred per 1000 individuals annually in 2013 and 2014 and 27.3% (95% CI, 22.2%-32.4%) of ED visits for adverse drug events resulted in hospitalization. An estimated 34.5% (95% CI, 30.3%-38.8%) of ED visits for adverse drug events occurred among adults aged 65 years or older in 2013-2014 compared with an estimated 25.6% (95% CI, 21.1%-30.0%) in 2005-2006; older adults experienced the highest hospitalization rates (43.6%; 95% CI, 36.6%-50.5%). Anticoagulants, antibiotics, and diabetes agents were implicated in an estimated 46.9% (95% CI, 44.2%-49.7%) of ED visits for adverse drug events, which included clinically significant adverse events, such as hemorrhage (anticoagulants), moderate to severe allergic reactions (antibiotics), and hypoglycemia with moderate to severe neurological effects (diabetes agents). Since 2005-2006, the proportions of ED visits for adverse drug events from anticoagulants and diabetes agents have increased, whereas the proportion from antibiotics has decreased. Among children aged 5 years or younger, antibiotics were the most common drug class implicated (56.4%; 95% CI, 51.8%-61.0%). Among children and adolescents aged 6 to 19 years, antibiotics also were the most common drug class implicated (31.8%; 95% CI, 28.7%-34.9%) in ED visits for adverse drug events, followed by antipsychotics (4.5%; 95% CI, 3.3%-5.6%). Among older adults (aged ≥65 years), 3 drug classes (anticoagulants, diabetes agents, and opioid analgesics) were implicated in an estimated 59.9% (95% CI, 56.8%-62.9%) of ED visits for adverse drug events; 4 anticoagulants (warfarin, rivaroxaban, dabigatran, and enoxaparin) and 5 diabetes agents (insulin and 4 oral agents) were among the 15 most common drugs implicated. Medications to always avoid in older adults according to Beers criteria were implicated in 1.8% (95% CI, 1.5%-2.1%) of ED visits for adverse drug events. Conclusions and Relevance: The prevalence of emergency department visits for adverse drug events in the United States was estimated to be 4 per 1000 individuals in 2013 and 2014. The most common drug classes implicated were anticoagulants, antibiotics, diabetes agents, and opioid analgesics.

Outbreak of Serratia marcescens bloodstream infections in patients receiving parenteral nutrition prepared by a compounding pharmacy.

BACKGROUND: Compounding pharmacies often prepare parenteral nutrition (PN) and must adhere to rigorous standards to avoid contamination of the sterile preparation. In March 2011, Serratia marcescens bloodstream infections (BSIs) were identified in 5 patients receiving PN from a single compounding pharmacy. An investigation was conducted to identify potential sources of contamination and prevent further infections. METHODS: Cases were defined as S. marcescens BSIs in patients receiving PN from the pharmacy between January and March 2011. We reviewed case patients' clinical records, evaluated pharmacy compounding practices, and obtained epidemiologically directed environmental cultures. Molecular relatedness of available Serratia isolates was determined by pulsed-field gel electrophoresis (PFGE). RESULTS: Nineteen case patients were identified; 9 died. The attack rate for patients receiving PN in March was 35%. No case patients were younger than 18 years. In October 2010, the pharmacy began compounding and filter-sterilizing amino acid solution for adult PN using nonsterile amino acids due to a national manufacturer shortage. Review of this process identified breaches in mixing, filtration, and sterility testing practices. S. marcescens was identified from a pharmacy water faucet, mixing container, and opened amino acid powder. These isolates were indistinguishable from the outbreak strain by PFGE. CONCLUSIONS: Compounding of nonsterile amino acid components of PN was initiated due to a manufacturer shortage. Failure to follow recommended compounding standards contributed to an outbreak of S. marcescens BSIs. Improved adherence to sterile compounding standards, critical examination of standards for sterile compounding from nonsterile ingredients, and more rigorous oversight of compounding pharmacies is needed to prevent future outbreaks.

Emergency hospitalizations for adverse drug events in older Americans.

BACKGROUND: Adverse drug events are important preventable causes of hospitalization in older adults. However, nationally representative data on adverse drug events that result in hospitalization in this population have been limited. METHODS: We used adverse-event data from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project (2007 through 2009) to estimate the frequency and rates of hospitalization after emergency department visits for adverse drug events in older adults and to assess the contribution of specific medications, including those identified as high-risk or potentially inappropriate by national quality measures. RESULTS: On the basis of 5077 cases identified in our sample, there were an estimated 99,628 emergency hospitalizations (95% confidence interval [CI], 55,531 to 143,724) for adverse drug events in U.S. adults 65 years of age or older each year from 2007 through 2009. Nearly half of these hospitalizations were among adults 80 years of age or older (48.1%; 95% CI, 44.6 to 51.6). Nearly two thirds of hospitalizations were due to unintentional overdoses (65.7%; 95% CI, 60.1 to 71.3). Four medications or medication classes were implicated alone or in combination in 67.0% (95% CI, 60.0 to 74.1) of hospitalizations: warfarin (33.3%), insulins (13.9%), oral antiplatelet agents (13.3%), and oral hypoglycemic agents (10.7%). High-risk medications were implicated in only 1.2% (95% CI, 0.7 to 1.7) of hospitalizations. CONCLUSIONS: Most emergency hospitalizations for recognized adverse drug events in older adults resulted from a few commonly used medications, and relatively few resulted from medications typically designated as high-risk or inappropriate. Improved management of antithrombotic and antidiabetic drugs has the potential to reduce hospitalizations for adverse drug events in older adults.

Vital signs: improving antibiotic use among hospitalized patients.

BACKGROUND: Antibiotics are essential to effectively treat many hospitalized patients. However, when antibiotics are prescribed incorrectly, they offer little benefit to patients and potentially expose them to risks for complications, including Clostridium difficile infection (CDI) and antibiotic-resistant infections. Information is needed on the frequency of incorrect prescribing in hospitals and how improved prescribing will benefit patients. METHODS: A national administrative database (MarketScan Hospital Drug Database) and CDC's Emerging Infections Program (EIP) data were analyzed to assess the potential for improvement of inpatient antibiotic prescribing. Variability in days of therapy for selected antibiotics reported to the National Healthcare Safety Network (NHSN) antimicrobial use option was computed. The impact of reducing inpatient antibiotic exposure on incidence of CDI was modeled using data from two U.S. hospitals. RESULTS: In 2010, 55.7% of patients discharged from 323 hospitals received antibiotics during their hospitalization. EIP reviewed patients' records from 183 hospitals to describe inpatient antibiotic use; antibiotic prescribing potentially could be improved in 37.2% of the most common prescription scenarios reviewed. There were threefold differences in usage rates among 26 medical/surgical wards reporting to NHSN. Models estimate that the total direct and indirect effects from a 30% reduction in use of broad-spectrum antibiotics will result in a 26% reduction in CDI. CONCLUSIONS: Antibiotic prescribing for inpatients is common, and there is ample opportunity to improve use and patient safety by reducing incorrect antibiotic prescribing. Implications for Public Health: Hospital administrators and health-care providers can reduce potential harm and risk for antibiotic resistance by implementing formal programs to improve antibiotic prescribing in hospitals.

The National Healthcare Safety Network's digital quality measures: CDC's automated measures for surveillance of patient safety.

OBJECTIVE: This article presents the National Healthcare Safety Network (NHSN)'s approach to automation for public health surveillance using digital quality measures (dQMs) via an open-source tool (NHSNLink) and piloting of this approach using real-world data in a newly established collaborative program (NHSNCoLab). The approach leverages Health Level Seven Fast Healthcare Interoperability Resources (FHIR) application programming interfaces to improve data collection and reporting for public health and patient safety beginning with common, clinically significant, and preventable patient harms, such as medication-related hypoglycemia, healthcare facility-onset Clostridioides difficile infection, and healthcare-associated venous thromboembolism. CONCLUSIONS: The NHSN's FHIR dQMs hold the promise of minimizing the burden of reporting, improving accuracy, quality, and validity of data collected by NHSN, and increasing speed and efficiency of public health surveillance.

Bleeding related to oral anticoagulants: Trends in US emergency department visits, 2016-2020.

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.

Outbreak of adverse reactions associated with contaminated heparin.

BACKGROUND: In January 2008, the Centers for Disease Control and Prevention began a nationwide investigation of severe adverse reactions that were first detected in a single hemodialysis facility. Preliminary findings suggested that heparin was a possible cause of the reactions. METHODS: Information on clinical manifestations and on exposure was collected for patients who had signs and symptoms that were consistent with an allergic-type reaction after November 1, 2007. Twenty-one dialysis facilities that reported reactions and 23 facilities that reported no reactions were included in a case-control study to identify facility-level risk factors. Unopened heparin vials from facilities that reported reactions were tested for contaminants. RESULTS: A total of 152 adverse reactions associated with heparin were identified in 113 patients from 13 states from November 19, 2007, through January 31, 2008. The use of heparin manufactured by Baxter Healthcare was the factor most strongly associated with reactions (present in 100.0% of case facilities vs. 4.3% of control facilities, P<0.001). Vials of heparin manufactured by Baxter from facilities that reported reactions contained a contaminant identified as oversulfated chondroitin sulfate (OSCS). Adverse reactions to the OSCS-contaminated heparin were often characterized by hypotension, nausea, and shortness of breath occurring within 30 minutes after administration. Of 130 reactions for which information on the heparin lot was available, 128 (98.5%) occurred in a facility that had OSCS-contaminated heparin on the premises. Of 54 reactions for which the lot number of administered heparin was known, 52 (96.3%) occurred after the administration of OSCS-contaminated heparin. CONCLUSIONS: Heparin contaminated with OSCS was epidemiologically linked to adverse reactions in this nationwide outbreak. The reported clinical features of many of the cases further support the conclusion that contamination of heparin with OSCS was the cause of the outbreak.

Emergency department visits for antiviral adverse events during the 2009 H1N1 influenza pandemic.

The 2009 pandemic influenza A (H1N1) outbreak was associated with an increased use of antiviral agents and highlighted the role of population-based monitoring for related adverse drug events (ADEs). An ongoing, nationally representative emergency department-based surveillance system was used to identify and characterize ADEs during the pandemic. Active surveillance for ADEs successfully provided timely, population-based data during the pandemic. Increases in antiviral ADEs paralleled increases in prescribing. Type and severity of ADEs were similar across all seasons.

Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates.

OBJECTIVE: To document neonatal exposures to the potentially harmful pharmaceutical excipients benzyl alcohol (BA) and propylene glycol (PG) present in parenteral medications routinely administered in the intensive care unit. DESIGN: Retrospective, observational study. SETTING: Neonatal and pediatric intensive care units of a tertiary care, university hospital. PATIENTS: Randomly selected sample of 170 episodes of exposure to parenteral medications containing BA (n = 88) or PG (n = 82). MEASUREMENTS: We identified all medication sources of BA or PG administered to study neonates during hospitalization, and calculated cumulative doses (mg/kg/day and mg/day) of BA or PG received as a result of exposure to those medications. MAIN RESULTS: We observed a wide range in the cumulative excipient dose received by neonates. Median (range) cumulative dose was 4.5 mg/kg/day (0.6-319.5 mg/kg/day) for BA, and 204.9 mg/kg/day (17.3-9472.7 mg/kg/day) for PG. Patients who received medications via continuous infusion received significantly higher excipient doses than patients who received medications intermittently (p < 0.0001). In this subset of patients, median cumulative excipient doses (BA, 106.3 mg/kg/day and PG, 4554.5 mg/kg/day) were approximately 21 and 180 times the acceptable daily intakes of BA and PG (5 and 25 mg/kg/day), respectively, and exceeded the doses above which toxicity has been reported in infants. No significant correlation between duration of medication administration and cumulative excipient exposure was identified for BA or PG. Midazolam and lorazepam were involved in over two-thirds of BA and PG exposures, respectively. CONCLUSIONS: Critically ill neonates, especially those receiving medications by continuous infusion, are at risk of being exposed to BA and PG at potentially toxic doses during routine medication administration. Given the serious adverse reactions known to be associated with BA and PG, future studies are warranted to determine the clinical consequences associated with this degree of excipient exposure.

US Emergency Department Visits for Adverse Drug Events From Antibiotics in Children, 2011-2015.

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.