Last data update: Nov 11, 2024. (Total: 48109 publications since 2009)
Records 1-29 (of 29 Records) |
Query Trace: Shehab N[original query] |
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The National Healthcare Safety Network's digital quality measures: CDC's automated measures for surveillance of patient safety
Shehab N , Alschuler L , Mc ILvenna S , Gonzaga Z , Laing A , deRoode D , Dantes RB , Betz K , Zheng S , Abner S , Stutler E , Geimer R , Benin AL . J Am Med Inform Assoc 2024 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
Geller AI , Shehab N , Lovegrove MC , Weidle NJ , Budnitz DS . Thromb Res 2023 225 110-115 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. |
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
Yang TH , Ziemba R , Shehab N , Geller AI , Talreja K , Campbell KN , Budnitz DS . Med Care 2022 60 (3) 219-226 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. |
US emergency department visits attributed to medication harms, 2017-2019
Budnitz DS , Shehab N , Lovegrove MC , Geller AI , Lind JN , Pollock DA . JAMA 2021 326 (13) 1299-1309 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. |
Outpatient insulin-related adverse events due to mix-up errors: Findings from two national surveillance systems, United States, 2012-2017
Geller AI , Conrad AO , Weidle NJ , Mehta H , Budnitz DS , Shehab N . Pharmacoepidemiol Drug Saf 2021 30 (5) 573-581 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. |
Trends in U.S. outpatient antibiotic prescriptions during the COVID-19 pandemic.
King LM , Lovegrove MC , Shehab N , Tsay S , Budnitz DS , Geller AI , Lind JN , Roberts R , Hicks LA , Kabbani S . Clin Infect Dis 2020 73 (3) e652-e660 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. |
Electronic measurement of a clinical quality measure for inpatient hypoglycemic events: A multicenter validation study
Santos CAQ , Conover C , Shehab N , Geller AI , Guerra YS , Kramer H , Kosacz NM , Zhang H , Budnitz DS , Trick WE . Med Care 2020 58 (10) 927-933 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. |
US Hydroxychloroquine, Chloroquine, and Azithromycin Outpatient Prescription Trends, October 2019 Through March 2020.
Shehab N , Lovegrove M , Budnitz DS . JAMA Intern Med 2020 180 (10) 1384-1386 This study examines how the prescription of hydroxychloroquine and chloroquine to outpatients has changed in the United States during the coronavirus disease 2019 pandemic. |
Emergency visits for oral anticoagulant bleeding
Geller AI , Shehab N , Lovegrove MC , Rose KO , Weidle NJ , Goring SK , Budnitz DS . J Gen Intern Med 2019 35 (1) 371-373 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 |
Assessment of ICD-10-CM code assignment validity for case finding of outpatient anticoagulant-related bleeding among Medicare beneficiaries
Shehab N , Ziemba R , Campbell KN , Geller AI , Moro RN , Gage BF , Budnitz DS , Yang TH . Pharmacoepidemiol Drug Saf 2019 28 (7) 951-964 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. |
American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy
Witt DM , Nieuwlaat R , Clark NP , Ansell J , Holbrook A , Skov J , Shehab N , Mock J , Myers T , Dentali F , Crowther MA , Agarwal A , Bhatt M , Khatib R , Riva JJ , Zhang Y , Guyatt G . Blood Adv 2018 2 (22) 3257-3291 BACKGROUND: Clinicians confront numerous practical issues in optimizing the use of anticoagulants to treat venous thromboembolism (VTE). OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians and other health care professionals in their decisions about the use of anticoagulants in the management of VTE. These guidelines assume the choice of anticoagulant has already been made. METHODS: ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment. RESULTS: The panel agreed on 25 recommendations and 2 good practice statements to optimize management of patients receiving anticoagulants. CONCLUSIONS: Strong recommendations included using patient self-management of international normalized ratio (INR) with home point-of-care INR monitoring for vitamin K antagonist therapy and against using periprocedural low-molecular-weight heparin (LMWH) bridging therapy. Conditional recommendations included basing treatment dosing of LMWH on actual body weight, not using anti-factor Xa monitoring to guide LMWH dosing, using specialized anticoagulation management services, and resuming anticoagulation after episodes of life-threatening bleeding. |
Anticoagulation across care transitions: Identifying minimum data to maximize drug safety
Shehab N , Greenwald JL , Budnitz DS . Jt Comm J Qual Patient Saf 2018 44 (11) 627-629 Adverse drug events (ADEs) are one of the most common and costly causes of iatrogenic patient harm, and anticoagulants are the leading cause of acute, serious ADEs among hospitalized patients, long term care residents, and older outpatients.1–5 In the United States, hospitalization costs associated with anticoagulant ADEs have been estimated at more than $2.5 billion,6 and in 2016 more than $5 billion was spent on anticoagulants in Medicare Part D claims.7 Accordingly, reducing patient harm associated with anticoagulation has been a Joint Commission National Patient Safety Goal (NPSG.03.05.01) since 2008,8,9 is one of three main focus areas of the 2014 Department of Health and Human Services National Action Plan for Adverse Drug Event Prevention,10 and is a key component of the ongoing Centers for Medicare & Medicaid Services Quality Innovation Network and Hospital Improvement Innovation Network efforts to improve patient safety.11,12 An article, “Defining Minimum Necessary Anticoagulation-Related Communication at Discharge: Consensus of the Care Transitions Task Force of the New York State Anticoagulation Coalition,” in this issue of The Joint Commission Journal on Quality and Patient Safety, Triller and colleagues take another important step on the long road to achieving safer and more effective anticoagulation by proposing the core information that needs to be communicated among providers as patients treated with anticoagulants make the transition between health care settings.13 |
US emergency department visits for adverse drug events from antibiotics in children, 2011-2015
Lovegrove MC , Geller AI , Fleming-Dutra KE , Shehab N , Sapiano MRP , Budnitz DS . J Pediatric Infect Dis Soc 2018 8 (5) 384-391 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. |
National estimates of emergency department visits for antibiotic adverse events among adults - United States, 2011-2015
Geller AI , Lovegrove MC , Shehab N , Hicks LA , Sapiano MRP , Budnitz DS . J Gen Intern Med 2018 33 (7) 1060-1068 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
Shehab N , Lovegrove MC , Geller AI , Rose KO , Weidle NJ , Budnitz DS . JAMA 2016 316 (20) 2115-2125 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. 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. 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. Drugs implicated in ED visits. National weighted estimates of ED visits and subsequent hospitalizations for adverse drug events. Based on data from 42585 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. 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. |
Emergency department visits for adverse events related to dietary supplements
Geller AI , Shehab N , Weidle NJ , Lovegrove MC , Wolpert BJ , Timbo BB , Mozersky RP , Budnitz DS . N Engl J Med 2015 373 (16) 1531-40 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.). |
U.S. compounding pharmacy-related outbreaks, 2001-2013: public health and patient safety lessons learned
Shehab N , Brown MN , Kallen AJ , Perz JF . J Patient Saf 2015 14 (3) 164-173 OBJECTIVES: Pharmacy-compounded sterile preparations (P-CSPs) are frequently relied upon in U.S. health care but are increasingly being linked to outbreaks of infections. We provide an updated overview of outbreak burden and characteristics, identify drivers of P-CSP demand, and discuss public health and patient safety lessons learned to help inform prevention. METHODS: Outbreaks of infections linked to contaminated P-CSPs that occurred between January 1, 2001, and December 31, 2013, were identified from internal Centers for Disease Control and Prevention reports, Food and Drug Administration drug safety communications, and published literature. RESULTS: We identified 19 outbreaks linked to P-CSPs, resulting in at least 1000 cases, including deaths. Outbreaks were reported across two-thirds of states, with almost one-half (8/19) involving cases in more than 1 state. Almost one-half of outbreaks were linked to injectable steroids (5/19) and intraocular bevacizumab (3/19). Non-patient-specific compounding originating from nonsterile ingredients and repackaging of already sterile products were the most common practices associated with P-CSP contamination. Breaches in aseptic processing and deficiencies in sterilization procedures or in sterility/endotoxin testing were consistent findings. Hospital outsourcing, preference for variations of commercially available products, commercial drug shortages, and lower prices were drivers of P-CSP demand. CONCLUSIONS: Recognized outbreaks linked to P-CSPs have been most commonly associated with non-patient-specific repackaging and nonsterile to sterile compounding and linked to lack of adherence to sterile compounding standards. Recently enhanced regulatory oversight of compounding may improve adherence to such standards. Additional measures to limit and control these outbreaks include vigilance when outsourcing P-CSPs, scrutiny of drivers for P-CSP demand, as well as early recognition and notification of possible outbreaks. |
Outbreak of Serratia marcescens bloodstream infections in patients receiving parenteral nutrition prepared by a compounding pharmacy
Gupta N , Hocevar SN , Moulton-Meissner H , Stevens KM , McIntyre MG , Jensen B , Kuhar DT , Noble-Wang J , Schnatz RG , Becker SC , Kastango ES , Shehab N , Kallen AJ . Clin Infect Dis 2014 59 (1) 1-8 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 five 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-patient 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; nine 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 non-sterile amino acids due to a national manufacturer shortage. Review of this process identified breaches in mixing, filtration, and sterility testing practices. Serratia 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 non-sterile 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 non-sterile ingredients, and more rigorous oversight of compounding pharmacies is needed to prevent future outbreaks. |
National estimates of insulin-related hypoglycemia and errors leading to emergency department visits and hospitalizations
Geller AI , Shehab N , Lovegrove MC , Kegler SR , Weidenbach KN , Ryan GJ , Budnitz DS . JAMA Intern Med 2014 174 (5) 678-86 IMPORTANCE: Detailed, nationally representative data describing high-risk populations and circumstances involved in insulin-related hypoglycemia and errors (IHEs) can inform approaches to individualizing glycemic targets. OBJECTIVE: To describe the US burden, rates, and characteristics of emergency department (ED) visits and emergency hospitalizations for IHEs. DESIGN, SETTING, AND PARTICIPANTS: Nationally representative public health surveillance of adverse drug events among insulin-treated patients seeking ED care (National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project) and a national household survey of insulin use (the National Health Interview Survey) were used to obtain data from January 1, 2007, through December 31, 2011. MAIN OUTCOMES AND MEASURES: Estimated annual numbers and estimated annual rates of ED visits and hospitalizations for IHEs among insulin-treated patients with diabetes mellitus. RESULTS: Based on 8100 National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance cases, an estimated 97 648 (95% CI, 64 410-130 887) ED visits for IHEs occurred annually; almost one-third (29.3%; 95% CI, 21.8%-36.8%) resulted in hospitalization. Severe neurologic sequelae were documented in an estimated 60.6% (95% CI, 51.3%-69.9%) of ED visits for IHEs, and blood glucose levels of 50 mg/dL (to convert to millimoles per liter, multiply by 0.0555) or less were recorded in more than half of cases (53.4%). Insulin-treated patients 80 years or older were more than twice as likely to visit the ED (rate ratio, 2.5; 95% CI, 1.5-4.3) and nearly 5 times as likely to be subsequently hospitalized (rate ratio, 4.9; 95% CI, 2.6-9.1) for IHEs than those 45 to 64 years. The most commonly identified IHE precipitants were reduced food intake and administration of the wrong insulin product. CONCLUSIONS AND RELEVANCE: Rates of ED visits and subsequent hospitalizations for IHEs were highest in patients 80 years or older; the risks of hypoglycemic sequelae in this age group should be considered in decisions to prescribe and intensify insulin. Meal-planning misadventures and insulin product mix-ups are important targets for hypoglycemia prevention efforts. |
Vital signs: improving antibiotic use among hospitalized patients
Fridkin S , Baggs J , Fagan R , Magill S , Pollack LA , Malpiedi P , Slayton R , Khader K , Rubin MA , Jones M , Samore MH , Dumyati G , Dodds-Ashley E , Meek J , Yousey-Hindes K , Jernigan J , Shehab N , Herrera R , McDonald CL , Schneider A , Srinivasan A . MMWR Morb Mortal Wkly Rep 2014 63 (9) 194-200 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. |
Emergency department visits and hospitalizations for digoxin toxicity: United States, 2005-2010
See I , Shehab N , Kegler SR , Laskar SR , Budnitz DS . Circ Heart Fail 2013 7 (1) 28-34 BACKGROUND: Recent data on digoxin prescribing and adverse events are lacking but could help inform the management of digoxin in contemporary heart failure treatment. METHODS AND RESULTS: We determined nationally-representative numbers and rates of emergency department (ED) visits for digoxin toxicity in the United States using 2005-2010 reports from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project and the National Ambulatory (and Hospital Ambulatory) Medical Care Surveys. Based on 441 cases, an estimated 5,156 (95% confidence interval [CI], 2,663-7,648) ED visits for digoxin toxicity occurred annually in the United States; over three-fourths (78.8% [95% CI, 73.5%-84.1%]) resulted in hospitalization. Serum digoxin level was ≥2.0 ng/mL for 95.8% (95% CI, 93.2%-98.4%) of estimated ED visits with levels reported (n=251 cases). The rate of ED visits per 10,000 outpatient prescription visits among patients ≥85 years was twice that of patients 40-84 years (rate ratio, 2.4 [95% CI, 1.2-5.0]); among females, the rate was twice that of males (rate ratio, 2.3 [95% CI, 1.1-4.7]). Digoxin toxicity accounted for an estimated 1.0% (95% CI, 0.6%-1.4%) of ED visits for all adverse drug events (ADEs) among patients ≥40 years, but an estimated 3.3% (95% CI, 2.3%-4.4%) of ED visits and 5.9% (95% CI, 4.0%-7.9%) of hospitalizations for all ADEs among patients ≥85 years. Estimated annual ED visits and hospitalizations remained relatively constant from 2005-2010. CONCLUSIONS: Digoxin toxicity is not declining; more careful prescribing to high-risk groups and improved monitoring of serum levels might be needed to reduce morbidity from outpatient digoxin use. |
Emergency hospitalizations for adverse drug events in older Americans
Budnitz DS , Lovegrove MC , Shehab N , Richards CL . N Engl J Med 2011 365 (21) 2002-12 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. |
Deriving measures of intensive care unit antimicrobial use from computerized pharmacy data: methods, validation, and overcoming barriers
Schwartz DN , Scott Evans R , Camins BC , Khan YM , Lloyd JF , Shehab N , Stevenson K . Infect Control Hosp Epidemiol 2011 32 (5) 472-80 OBJECTIVE: To outline methods for deriving and validating intensive care unit (ICU) antimicrobial utilization (AU) measures from computerized data and to describe programming problems that emerged. DESIGN: Retrospective evaluation of computerized pharmacy and administrative data. SETTING: ICUs from 4 academic medical centers over 36 months. Interventions. Investigators separately developed and validated programming code to report AU measures in selected ICUs. Use of antibacterial and antifungal drugs for systemic administration was categorized and expressed as antimicrobial-days (each day that each antimicrobial drug was given to each patient) and patient-days receiving antimicrobials (each day that any antimicrobial drug was given to each patient). Monthly rates were compiled and analyzed centrally, with ICU patient-days as the denominator. Results were validated against data collected from manual review of medical records. Frequent discussion among investigators aided identification and correction of programming problems. RESULTS: AU data were successfully programmed though a reiterative process of computer code revision. After identifying and resolving major programming errors, comparison of computerized patient-level data with data collected by manual review of medical records revealed discrepancies in antimicrobial-days and patient-days receiving antimicrobials that ranged from less than 1% to 17.7%. The hospital from which numerator data were derived from electronic records of medication administration had the least discrepant results. CONCLUSIONS: Computerized AU measures can be derived feasibly, but threats to validity must be sought out and corrected. The magnitude of discrepancies between computerized AU data and a gold standard based on manual review of medical records varies, with electronic records of medication administration providing maximal accuracy. |
Emergency department visits for antiviral adverse events during the 2009 H1N1 influenza pandemic
Lovegrove MC , Shehab N , Hales CM , Poneleit K , Crane E , Budnitz DS . Public Health Rep 2011 126 (3) 312-7 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. |
Time to change the paradigm--from "potentially inappropriate" to real patient harms
Shehab N , Budnitz DS . Arch Intern Med 2011 171 (5) 473-4 The recent study by Mattison et al1 demonstrated a statistically significant reduction in potentially inappropriate (Beers criteria) medication (PIM) orders for hospitalized older patients after the introduction of a computerized provider order entry (CPOE) warning system; however, the authors provided no evidence that patient harms were reduced or outcomes were improved as a result of PIM warnings. Thus, we disagree with their conclusions that a reduction from 12 to 10 PIM orders per day is clinically significant, and we caution against overreliance on CPOE warnings of PIM use as a “tool for improving the safety of hospitalized older adults.”1(p1336) | Potentially inappropriate medication use is a poor metric for monitoring safe medication use and a weak trigger for patient safety interventions. Steinman et al2 demonstrated that algorithmic identification of PIM hospital orders failed to accurately identify problematic prescribing when compared with individualized clinical record review. Published evidence that PIM prescribing leads to poor patient outcomes is mixed at best. Page et al,3 after adjustment for covariates, found no significant correlation between PIMs and adverse events, length of stay, discharge to higher levels of care, or in-hospital mortality. Schamder et al4 reduced PIM use among hospitalized patients, but this reduction did not result in fewer adverse reactions. |
National estimates of emergency department visits for hemorrhage-related adverse events from clopidogrel plus aspirin and from warfarin
Shehab N , Sperling LS , Kegler SR , Budnitz DS . Arch Intern Med 2010 170 (21) 1926-33 BACKGROUND: Dual antiplatelet therapy (DAT) with clopidogrel plus aspirin is a well-established antithrombotic strategy, with hemorrhage being the chief adverse event (AE) of concern. Outside of clinical trials, few published data describe the magnitude and nature of hemorrhage-related AEs from DAT. METHODS: To estimate the numbers and rates of emergency department (ED) visits for hemorrhage-related AEs (hemorrhage or evaluation for potential hemorrhage) from DAT in the United States and put them in the context of those from warfarin, we analyzed AEs from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project, 2006-2008, and outpatient prescribing from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey, 2006-2007. RESULTS: Based on 384 cases, there were an estimated 7654 (95% confidence interval [CI], 3325-11 983) ED visits annually for hemorrhage-related AEs from DAT compared with 2926 cases and an estimated 60,575 (36,117-85,033) ED visits from warfarin. Approximately 60% of ED visits for DAT consisted of epistaxis or other minor hemorrhages (eg, bleeding from small cuts). The risk of hospitalization for ED visits involving acute hemorrhages was not significantly different between DAT and warfarin (risk ratio, 0.73; 95% CI, 0.38-1.08). The estimated rate of ED visits involving acute hemorrhages from DAT was 1.2 per 1000 outpatient prescription visits vs 2.5 per 1000 outpatient prescription visits for warfarin (risk ratio, 0.49; 95% CI, 0.15-0.83). CONCLUSIONS: These findings indicate that the acute hemorrhagic risk with DAT is clinically significant and reinforce the importance of practitioners and patients recognizing and anticipating this risk. |
Calling it 'multidose' doesn't make it so: inappropriate sharing and contamination of parenteral medication vials
Schaefer MK , Shehab N , Perz JF . Am J Infect Control 2010 38 (7) 580-1 Motamedifar and Askarian reported the results of a study evaluating aerobic bacterial contamination of medication vials present on multiple wards at a large, teaching hospital in Iran.1 The authors identified bacterial contamination in 5.6% of the 637 medication vials that were sampled. In the United States, contamination of parenteral medication vials has served as an underappreciated source of health care-associated infections including bloodstream infections, epidural abscesses, and viral hepatitis.2, 3, 4, 5 This study highlighted the general risk of extrinsic contamination of medication vials and prompts us to comment on several important factors that contribute to the potential for contamination and spread of infections. | The investigators described all of the medication vials tested as “multidose” based on a functional definition: “a vial that was used more than once.” However, only 1 of the contaminated vials contained antimicrobial preservative. In the United States, these preservative-free parenteral medications would likely have been labeled as single-dose or single-use vials, not intended for use in more than 1 patient. Unfortunately, the distinction between true multidose vials, which are labeled as such and generally contain an antimicrobial preservative, and other types of medication is often not understood by health care providers. There have been repeated instances in which parenteral medications labeled as single-use or single-dose were mistakenly referred to by health care personnel as “multidose” and used for multiple patients because they appeared to contain quantities in excess of those needed for a single patient. When used properly, vials that are labeled by manufacturers as multidose can be safely accessed multiple times. This stands in contrast to other injectable medications labeled as single-use or single-dose, which should only be used for a single patient. |
Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates
Shehab N , Lewis CL , Streetman DD , Donn SM . Pediatr Crit Care Med 2009 10 (2) 256-9 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. |
CDC and FDA response to risk of confusion in dosing Tamiflu oral suspension
Budnitz DS , Lewis LL , Shehab N , Birnkrant D . N Engl J Med 2009 361 (19) 1913-4 On September 23, Parker et al.1 described a case in which Tamiflu (oseltamivir) for oral suspension was dispensed with pharmacy instructions to administer the drug in volume units (teaspoons), whereas the manufacturer's dosing syringe accompanying the product is calibrated in milligrams. Interest in the use of oseltamivir for young children has risen since the emergence of 2009 pandemic influenza A (H1N1) virus. We recognize that dosing instructions with units different from those given on the device included with the product create risks of confusion and dosing errors. | Together, the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA) have acted promptly to provide information that emphasizes appropriate dosing and dispensing of Tamiflu for oral suspension. Communications regarding potential dosing errors were posted on the CDC and FDA Web sites, and Roche has published a “Dear Healthcare Professional” letter.2 All communications recommend that, when dispensing commercially manufactured Tamiflu for oral suspension, pharmacists should ensure that the units of measure on the dosing instructions match those on the device provided. If the dosing instructions specify volumetric measures (teaspoons or milliliters), the manufacturer's syringe should be removed and replaced with an appropriate device with matching units. When dispensing this suspension for children younger than 1 year of age, according to the Emergency Use Authorization, the syringe in the package should always be replaced with an appropriate measuring device, because doses for children younger than 1 year of age cannot be measured with the manufacturer's syringe.3 |
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