Paige G. Wickner

Rising drug allergy alert overrides in electronic health records: an observational retrospective study of a decade of experience

OBJECTIVE There have been growing concerns about the impact of drug allergy alerts on patient safety and provider alert fatigue. The authors aimed to explore the common drug allergy alerts over the last 10 years and the reasons why providers tend to override these alerts. DESIGN Retrospective observational cross-sectional study (2004-2013). MATERIALS AND METHODS Drug allergy alert data (n = 611,192) were collected from two large academic hospitals in Boston, MA (USA). RESULTS Overall, the authors found an increase in the rate of drug allergy alert overrides, from 83.3% in 2004 to 87.6% in 2013 (P < .001). Alarmingly, alerts for immune mediated and life threatening reactions with definite allergen and prescribed medication matches were overridden 72.8% and 74.1% of the time, respectively. However, providers were less likely to override these alerts compared to possible (cross-sensitivity) or probable (allergen group) matches (P < .001). The most common drug allergy alerts were triggered by allergies to narcotics (48%) and other analgesics (6%), antibiotics (10%), and statins (2%). Only slightly more than one-third of the reactions (34.2%) were potentially immune mediated. Finally, more than half of the overrides reasons pointed to irrelevant alerts (i.e., patient has tolerated the medication before, 50.9%) and providers were significantly more likely to override repeated alerts (89.7%) rather than first time alerts (77.4%, P < .001). DISCUSSION AND CONCLUSIONS These findings underline the urgent need for more efforts to provide more accurate and relevant drug allergy alerts to help reduce alert override rates and improve alert fatigue.

Alcohol-induced Respiratory Symptoms Are Common in Patients With Aspirin Exacerbated Respiratory Disease

BACKGROUND A large percentage of patients with aspirin exacerbated respiratory disease (AERD) report the development of alcohol-induced respiratory reactions, but the true prevalence of respiratory reactions caused by alcoholic beverages in these patients was not known. OBJECTIVE We sought to evaluate the incidence and characteristics of alcohol-induced respiratory reactions in patients with AERD. METHODS A questionnaire designed to assess alcohol-induced respiratory symptoms was administered to patients at Brigham and Womens Hospital and Scripps Clinic. At least 50 patients were recruited into each of 4 clinical groups: (1) patients with aspirin challenge-confirmed AERD, (2) patients with aspirin-tolerant asthma (ATA), (3) patients with aspirin tolerance and with chronic rhinosinusitis, and (4) healthy controls. Two-tailed Fisher exact tests with Bonferroni corrections were used to compare the prevalence of respiratory symptoms among AERD and other groups, with P ≤ .017 considered significant. RESULTS The prevalence of alcohol-induced upper (rhinorrhea and/or nasal congestion) respiratory reactions in patients with AERD was 75% compared with 33% with aspirin-tolerant asthma, 30% with chronic rhinosinusitis, and 14% with healthy controls (P < .001 for all comparisons). The prevalence of alcohol-induced lower (wheezing and/or dyspnea) respiratory reactions in AERD was 51% compared with 20% in aspirin-tolerant asthma and with 0% in both chronic rhinosinusitis and healthy controls (P < .001 for all comparisons). These reactions were generally not specific to one type of alcohol and often occurred after ingestion of only a few sips of alcohol. CONCLUSION Alcohol ingestion causes respiratory reactions in the majority of patients with AERD, and clinicians should be aware that these alcohol-induced reactions are significantly more common in AERD than in controls who are aspirin tolerant.

Tackling inpatient penicillin allergies: Assessing tools for antimicrobial stewardship

Background Reported penicillin allergy rarely reflects penicillin intolerance. Failure to address inpatient penicillin allergies results in more broad‐spectrum antibiotic use, treatment failures, and adverse drug events. Objective We aimed to determine the optimal approach to penicillin allergies among medical inpatients. Methods We evaluated internal medicine inpatients reporting penicillin allergy in 3 periods: (1) standard of care (SOC), (2) penicillin skin testing (ST), and (3) computerized guideline application with decision support (APP). The primary outcome was use of a penicillin or cephalosporin, comparing interventions to SOC using multivariable logistic regression. Results There were 625 patients: SOC, 148; ST, 278; and APP, 199. Of 278 ST patients, 179 (64%) were skin test eligible; 43 (24%) received testing and none were allergic. In the APP period, there were 292 unique Web site views; 112 users (38%) completed clinical decision support. Although ST period patients did not have increased odds of penicillin or cephalosporin use overall (adjusted odds ratio [aOR] 1.3; 95% CI, 0.8‐2.0), we observed significant increased odds of penicillin or cephalosporin use overall in the APP period (aOR, 1.8; 95% CI, 1.1‐2.9) and in a per‐protocol analysis of the skin tested subset (aOR, 5.7; 95% CI, 2.6‐12.5). Conclusions Both APP and ST—when completed—increased the use of penicillin and cephalosporin antibiotics among inpatients reporting penicillin allergy. While the skin tested subset showed an almost 6‐fold impact, the computerized guideline significantly increased penicillin or cephalosporin use overall nearly 2‐fold and was readily implemented.

Association of maternal anemia with increased wheeze and asthma in children

BACKGROUND Increasing interest has focused on maternal nutrition and micronutrient status during pregnancy and respiratory disease development in the offspring. OBJECTIVE To examine the relationship between maternal anemia in pregnancy with wheeze and asthma in early childhood. METHODS The cohort included children of women followed through pregnancy and recontacted when the child was 6 years of age to evaluate respiratory health. Exposure was assessed using maternal anemia diagnosis and hemoglobin (Hgb) < 11 during delivery hospitalization. Study outcomes include wheezing in early childhood; patterns of wheeze from birth to age 6 (early-onset transient wheeze; late-onset wheeze; early-onset persistent wheeze); and diagnosis of childhood asthma. RESULTS Maternal anemia was reported by 11.9% of mothers and was associated with recurrent infant wheeze in the first year (adjusted odds ratio [ORa] = 2.17, 95% confidence interval [CI] 1.18, 4.00), wheezing before age 3 (Ora = 2.42, 95% CI 1.38, 4.23), and early-onset transient and early-onset persistent wheeze patterns (Ora = 2.81, 95%CI 1.38, 5.72, and Ora = 2.07, 95% CI 1.02, 4.22), respectively. Among children of mothers with asthma, maternal anemia was associated with recurrent wheeze in year 1 (Ora = 4.22, 95% CI 1.65, 10.80) and wheeze before age 3 (Ora = 2.73, 95% CI 1.17, 6.35). Offspring of mothers with asthma also had increased odds of asthma diagnosis (Ora = 2.53, 95% CI 1.04, 6.17) and current asthma (Ora = 3.46, 95% CI 1.45, 8.26). CONCLUSIONS Maternal anemia during pregnancy is associated with infant respiratory health outcomes. If this observation is replicated, maternal anemia may be a target for intervention and future research.

Adverse and Hypersensitivity Reactions to Prescription Nonsteroidal Anti-Inflammatory Agents in a Large Health Care System

BACKGROUND Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used medications in the United States. NSAID use can be limited by adverse drug reactions (ADRs), including hypersensitivity reactions (HSRs). OBJECTIVE We aimed to use electronic health record data to determine the incidence and predictors of HSRs to prescription NSAIDs. METHODS We performed a retrospective cohort study of all adult outpatients in a large health care system prescribed diclofenac, indomethacin, nabumetone, or piroxicam between January 1, 2004, and September 30, 2012. The primary outcome was an ADR or HSR attributed to the prescribed NSAID within 1 year of prescription, determined from a longitudinal allergy database. We used natural language processing to classify known ADRs as either HSRs or side effects. Multivariable logistic regression models were used to identify independent risk factors for NSAID HSRs. RESULTS Of 62,719 patients prescribed NSAIDs, 1,035 (1.7%) had an ADR, of which 189 (18.3%) were HSRs. Multivariable regression analysis identified that patients with prior drug HSR history (odds ratio [OR] 1.8 [95% CI 1.3, 2.5]), female sex (OR 1.8 [95% CI 1.3, 2.4]), autoimmune disease (OR 1.7 [95% CI 1.1, 2.7]), and those prescribed the maximum standing NSAID dose (OR 1.5 [95% CI 1.1, 2.0]) had increased odds of NSAID HSR. CONCLUSIONS NSAID therapeutic use can be limited by ADRs; about 1 in 5 NSAID ADRs is an HSR. Both patient and drug factors contribute to HSR risk and are important to guide patient counseling.

Addressing Inpatient Beta-Lactam Allergies: A Multihospital Implementation

Addressing inaccurate penicillin allergies is encouraged as part of antibiotic stewardship in the inpatient setting. However, implementing interventions targeted at the 10% to 15% of inpatients reporting a previous penicillin allergy can pose substantial logistic challenges. We implemented a computerized guideline for patients with reported beta-lactam allergy at 5 hospitals within a single health care system in the Boston area. In this article, we describe our implementation roadmap, including both successes achieved and challenges faced. We explain key implementation steps, including assembling a team, stakeholder engagement, developing or selecting an approach, spreading the change, establishing measures, and measuring impact. The objective was to detail the lessons learned while empowering others to be part of this important, multidisciplinary work to improve the care of patients with reported beta-lactam allergies.

Stevens-Johnson syndrome and toxic epidermal necrolysis: a cross-sectional analysis of patients in an integrated allergy repository of a large health care system.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions, carrying an associated mortality ranging from 5% to 40%. Known risk factors for SJS/TEN include HIV infection, female gender, and certain HLA genotypes. Various medications have been described to cause SJS/TEN, with strongest associations with allopurinol, antiepileptics, nonsteroidal antiinflammatory drugs (NSAIDs), sulfa-containing antibiotics, b-lactam antibiotics, quinolones, and nevirapine. SJS/TEN is rare, affecting about 2 persons per million per year, with SJS 3 times more common than TEN. However, much of the epidemiologic data on SJS/ TEN are limited to national and international reporting networks or cohorts after specialist referral or hospitalization. The largest US epidemiologic data identified cases on the basis of International Classification of Diseases, Ninth Revision, Clinical Modification codes. We aimed to determine the prevalence of SJS/TEN among patients in a large health system by searching an electronic allergy repository and to evaluate demographic, allergy, and allergen characteristics of this population.

Automated identification of an aspirin-exacerbated respiratory disease cohort

Background: Aspirin‐exacerbated respiratory disease (AERD) is characterized by 3 clinical features: asthma, nasal polyposis, and respiratory reactions to cyclooxygenase‐1 inhibitors (nonsteroidal anti‐inflammatory drugs). Electronic health records (EHRs) contain information on each feature of this triad. Objective: We sought to determine whether an informatics algorithm applied to the EHR could electronically identify patients with AERD. Methods: We developed an informatics algorithm to search the EHRs of patients aged 18 years and older from the Partners Healthcare system over a 10‐year period (2004‐2014). Charts with search terms for asthma, nasal polyps, and record of respiratory (cohort A) or unspecified (cohort B) reactions to nonsteroidal anti‐inflammatory drugs were identified as “possible AERD.” Two clinical experts reviewed all charts to confirm a diagnosis of “clinical AERD” and classify cases as “diagnosed AERD” or “undiagnosed AERD” on the basis of physician‐documented AERD‐specific terms in patient notes. Results: Our algorithm identified 731 “possible AERD” cases, of which 638 were not in our AERD patient registry. Chart review of cohorts A (n = 511) and B (n = 127) demonstrated a positive predictive value of 78.4% for “clinical AERD,” which rose to 88.7% when unspecified reactions were excluded. Of those with clinical AERD, 12.4% had no mention of AERD by any treating caregiver and were classified as “undiagnosed AERD.” “Undiagnosed AERD” cases were less likely than “diagnosed AERD” cases to have been seen by an allergist/immunologist (38.7% vs 93.2%; P < .0001). Conclusions: An informatics algorithm can successfully identify both known and previously undiagnosed cases of AERD with a high positive predictive value. Involvement of an allergist/immunologist significantly increases the likelihood of an AERD diagnosis.

Lenalidomide desensitization for delayed hypersensitivity reactions in 5 patients with multiple myeloma

Lenalidomide, an analogue of thalidomide, is an immunomodulatory agent that is approved for use in multiple myeloma (MM), myelodysplastic syndrome and mantle cell lymphoma. Lenalidomide is administered as a single agent or in conjunction with dexamethasone in relapsed and refractory MM (Richardson et al, 2009), as an induction therapy for newly diagnosed MM (Rajkumar et al, 2010) and as a single agent maintenance therapy following autologous stem cell transplantation (McCarthy et al, 2012). Although generally well tolerated, lenalidomide therapy is frequently associated with rashes, ranging from urticaria, purpura or morbiliform lesions and Stevens–Johnson Syndrome (SJS) or Toxic Epidermal necrolysis (TEN) (Sviggum et al, 2006). A recently published meta-analysis of lenalidomide-associated rash in cancer patients reported an incidence of all-grade and high-grade rash of 27 2% and 3 6% respectively (Nardone et al, 2013). Interestingly, individuals with HLA-DRB1*1501 and HLA-DQB1*0602 could present with more severe dermatological reactions during lenalidomide treatment (Penna et al, 2012). Desensitization remains an option in patients with lenalidomide-associated rash and three case reports of rapid, inpatient desensitization in patients with acute urticarial rash have previously been published (Table I) (Phillips et al, 2007; Ca~ namares Orbis et al, 2012; Seki et al, 2013). We report five MM patients with delayed adverse skin reactions to lenalidomide who were able to tolerate lenalidomide via an outpatient desensitization protocol and without subsequent adverse effects (Table II). None of these patients presented with fever, mucosal involvement, bullous-like lesions, and shortness of breath or syncope.

Immediate Drug Hypersensitivity

Drug allergy affects a large percentage of the general population. A listed drug allergy can also have broad implications for many aspects of patient care. Here, we will review recent advances in the arena of drug allergies with a focus on antibiotics, monoclonals, NSAIDs, and chemotherapeutics.