Incidence and Economic Burden of Adverse Drug Reactions in Hospitalization: A Prospective Study in Korea

Background@#Adverse drug reactions (ADRs) are escalating, and their socioeconomic burden is increasing. However, large-scale prospective studies investigating ADRs during hospitalization are rare in Korea. We prospectively investigated the incidence, characteristics, and economic burden of ADRs in hospitalized patients based on electronic medical records (EMRs). @*Methods@#Among patients admitted to three hospitals from October 2016 to October 2017, 5,000 patients were randomly selected and prospectively observed during hospitalization.Research nurses monitored and detected patients who had symptoms, signs, or laboratory findings suspicious for ADRs using an EMR-based detection protocol. Next, allergy and ADR specialists reviewed the medical records to determine the relationship between adverse reactions and drugs. Cases in which a causal relationship was certain, probable/likely, or possible were included in the ADR cases. Clinically meaningful ADR cases or those leading to prolonged hospitalization were defined as significant ADRs. @*Results@#ADRs occurred in 510 (10.2%) patients. The mean length of hospital stay was approximately 5 days longer in patients with ADRs. Opioids accounted for the highest percentage of total ADRs. Significant ADRs were observed in 148 (3.0%) patients. Antibiotics accounted for the highest percentage of significant ADRs. Drug hypersensitivity reactions (DHRs) occurred in 88 (1.8%) patients. Antibiotics accounted for the highest percentage of DHRs. The average medical expenses for one day of hospitalization per patient were highest in significant ADRs, followed by non-significant ADRs, and non-ADRs. @*Conclusion@#ADRs in hospitalized patients are an important clinical issue, resulting in a substantial socioeconomic burden. EMR-based strategy could be a useful tool for ADR monitoring and early detection.

Expert opinion: The clinical usefulness of skin tests prior to the administration of beta-lactam antibiotics

An allergy skin test is used to diagnose certain allergies by identifying sensitized allergens. In other words, it is a test for patients who are already sensitized to certain allergens. Because of the prevailing perception that beta-lactam allergy can be dangerous and potentially lethal, the intradermal test has long been routinely performed before use to screen beta-lactam allergy in Korea. The prevalence of penicillin allergy is estimated to be 1% to 2%. However, only 14% of the subjects with perceived penicillin allergy is considered to have true penicillin allergy. Moreover, it is difficult to justify performing a skin test on subjects who are very unlikely to be sensitized to beta-lactam, such as those who never used beta-lactam or never experienced allergy after previous use of beta-lactam.Therefore, allergists recommend beta-lactam skin testing in those who have allergy after the use of beta-lactam. Nevertheless, many hospitals in Korea are conducting routine skin tests on patients regardless of a history of beta-lactam allergy, which are not clinically validated but consume considerable human and material resources. False-positive results can consequently result in inappropriate labeling of beta-lactam allergy, leading to the unnecessary restriction of medication prescriptions and the increase in medical expenses. Herein, the drug allergy working group affiliated with the Korean Academy of Asthma, Allergy, and Clinical Immunology announces an expert opinion on the preuse beta-lactam skin test for subjects without a history of beta-lactam allergy based on the objective evidence from the literature and clinical relevance.

Frequency and clinical characteristics of adverse transfusion reactions in hospitalized patients: A retrospective review of electronic medical records

Purpose@#Adverse transfusion reactions (ATRs) are unfavorable reactions to the transfused unit, and the severity may be different among individuals, depending upon the type of reactions and the patient’s susceptibility. It is necessary to operate and manage a systematic monitoring system to minimize these ATRs and increase the safety. This study was conducted to evaluate clinical features of transfusion-related adverse events and morbidities. @*Methods@#We retrospectively analyzed transfusion data from electronic medical records during the recent 3 years (April 2017 to April 2020) at Seoul National University Bundang Hospital. The electronic search strategy was applied to search for the type of blood products prescribed and identify symptoms that occurred during transfusion as recorded in the nursing chart which is based on the International Classification for Nursing Practice. @*Results@#A total of 18,772 people were transfused during the study period. A total of 524 people were reported as suspected ATRs, of whom 466 were finally confirmed. Red blood cell was the most frequent culprit blood product (59.9%), followed by apheresis platelet (25.1%), fresh frozen plasma (10.1%), and platelet (4.9%). Clinical symptoms included fever (54.9%), urticaria and itching (34.7%), chillness and shivering (21.9%), and chest discomfort (6.0%), dyspnea (5.3%), cold sweating (3.8%), hypotension (2.1%), and palpitations (1.9%). The severity of ATRs were mild (91.8%), moderate (7.1%), and severe (1.1%). @*Conclusion@#ATRs are mostly mild, but life-threatening reactions may occur. Physicians should be aware of various features of ATRs to appropriately recognize and treat such patients.

Current practice for diagnosing immediate drug hypersensitivity reactions in Korea

Background/Aims@#Skin (STs) and drug provocation (DPTs) tests are essential for identifying the culprit drugs causing drug hypersensitivity reactions (DHRs). Several protocols have been developed for the identification of some culprit drugs, but they are neither thoroughly validated nor standardized. Furthermore, language barriers may impede the exchange of information necessary for test standardization. @*Methods@#We searched the Korean literature for articles on drug hypersensitivity published from 1933 to 2016 using the KoreaMed search engine and archives of Korean journals. We reviewed and rated all articles according to the description of STs and DPTs. @*Results@#Of the 632 articles obtained in our initial search, 34 had adequate descriptions of 15 STs and 22 DPTs. Up to 27 healthy control subjects in STs were enrolled to determine non-irritating concentrations. The concentrations used for intradermal tests were commonly a 1/10 dilution of those used for skin prick tests. The interpretations of the STs were mostly similar among researchers. For DPTs, most procedures were single-arm open-label tests of various drugs. The initial dose ranged from a quarter dose to a single therapeutic dose, depending on the severity of the original hypersensitivity reaction. The interval between doses was usually 30 to 60 minutes, and a positive reaction usually occurred within twice the time of the original reaction. @*Conclusions@#Efforts to distribute information are necessary to standardize protocols and better understand DHRs.

Allergen-Specific Immunotherapy Against Allergic Respiratory Diseases / 대한내과학회지

Allergen-specific immunotherapy (AIT) can alter the natural course of an allergic disease. It is widely held that the efficacy of a given therapeutic modality should be proven by well-designed double-blind placebo-controlled randomized clinical trials and meta-analyses. In this article, the therapeutic efficacy of AIT for allergic respiratory diseases, such as allergic rhinitis and asthma, is reviewed. In addition, potential clinical and experimental predictors of the treatment response are reviewed for AITs requiring long-term treatment, and for some allergic rhinitis and asthma patients who show no response to AIT.

Evaluation of Drug-Induced Liver Injury Developed During Hospitalization Using Electronic Health Record (EHR)-Based Algorithm

PURPOSE: The incidence of drug-induced liver injury (DILI) has been increasing; however, few algorithms are available to identify DILI in electronic health records (EHRs). We aimed to identify and evaluate DILI with an appropriate screening algorithm.METHODS: We collected data from 3 university hospitals between June 2015 and May 2016 using our newly developed algorithm for identifying DILI. Among patients with alanine transferase (ALT) ≤ 120 IU/L and total bilirubin (TB) ≤ 2.4 mg/dL in blood test results within 48 hours of admission, those who either had 1) ALT > 120 IU/L and TB > 2.4 mg/dL or 2) ALT > 200 IU/L at least once during hospitalization were identified. After excluding patients with liver disease-related diagnosis at discharge, medical records were retrospectively reviewed to evaluate epidemiological characteristics of DILI.RESULTS: The total number of inpatients was 256,598, of whom 1,100 (0.43%) were selected by the algorithm as suspected DILI. Subsequently, 365 cases (0.14% of total inpatients, 95% confidence interval, 0.13–0.16) were identified as DILI, yielding a positive predictive value of 33.1%. Antibiotics (n = 214, 47.2%) were the major class of causative drug followed by chemotherapeutic agents (n = 87, 19.2%). The most common causative drug was piperacillin-tazobactam (n = 38, 8.4%); the incidence of DILI by individual agent was highest for methotrexate (19.4 cases/1,000 patients administered the drug). Common reasons for excluding suspected DILI cases were ischemic hepatitis and postoperative liver dysfunction.CONCLUSIONS: Using our EHR-based algorithm, we identified that approximately 0.14% of patients developed DILI during hospitalization. Further studies are needed to modify criteria for more accurate identification of DILI.

A Prospective Observation of Psychological Distress in Patients With Anaphylaxis

PURPOSE: Anaphylaxis is an immediate allergic reaction characterized by potentially life-threatening, severe, systemic manifestations. While studies have evaluated links between serious illness and posttraumatic stress disorder (PTSD), few have investigated PTSD after anaphylaxis in adults. We sought to investigate the psychosocial burden of recent anaphylaxis in Korean adults.METHODS: A total of 203 (mean age of 44 years, 120 females) patients with anaphylaxis were recruited from 15 university hospitals in Korea. Questionnaires, including the Impact of Event Scale-Revised-Korean version (IES-R-K), the Korean version of the Beck Anxiety Inventory (K-BAI), and the Korean version of the Beck Depression Inventory (K-BDI), were administered. Demographic characteristics, causes and clinical features of anaphylaxis, and serum inflammatory markers, including tryptase, platelet-activating factor, interleukin-6, tumor necrosis factor-α, and C-reactive protein, were evaluated.RESULTS: PTSD (IES-R-K ≥ 25) was noted in 84 (41.4%) patients with anaphylaxis. Of them, 56.0% had severe PTSD (IES-R-K ≥ 40). Additionally, 23.2% and 28.1% of the patients had anxiety (K-BAI ≥ 22) and depression (K-BDI ≥ 17), respectively. IES-R-K was significantly correlated with both K-BAI (r = 0.609, P < 0.0001) and K-BDI (r = 0.550, P < 0.0001). Among the inflammatory mediators, tryptase levels were lower in patients exhibiting PTSD; meanwhile, platelet-activating factor levels were lower in patients exhibiting anxiety and depression while recovering from anaphylaxis. In multivariate analysis, K-BAI and K-BDI were identified as major predictive variables of PTSD in patients with anaphylaxis.CONCLUSIONS: In patients with anaphylaxis, we found a remarkably high prevalence of PTSD and associated psychological distresses, including anxiety and depression. Physicians ought to be aware of the potential for psychological distress in anaphylactic patients and to consider psychological evaluation.

Allergen-Specific Immunotherapy Against Allergic Respiratory Diseases / 대한내과학회지

Allergen-specific immunotherapy (AIT) can alter the natural course of an allergic disease. It is widely held that the efficacy of a given therapeutic modality should be proven by well-designed double-blind placebo-controlled randomized clinical trials and meta-analyses. In this article, the therapeutic efficacy of AIT for allergic respiratory diseases, such as allergic rhinitis and asthma, is reviewed. In addition, potential clinical and experimental predictors of the treatment response are reviewed for AITs requiring long-term treatment, and for some allergic rhinitis and asthma patients who show no response to AIT.

Analysis of Individual Case Safety Reports of Severe Cutaneous Adverse Reactions in Korea

PURPOSE: Despite morbidities and fatalities, nationwide epidemiologic data for severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), are not widely available. We aimed to investigate SCAR epidemiology over the last two decades in Korea. MATERIALS AND METHODS: We analyzed individual case safety reports (ICSRs) of SCARs in the Korea Adverse Event Reporting System from 1988 to 2013. Administered drugs, demographic profiles, and causality assessment according to the World Health Organization-Uppsala Monitoring Center system were analyzed. RESULTS: A total of 755 SCAR cases (508 SJS/TEN, 247 DRESS) were reported. The number of SCAR ICSRs has been increasing with increasing ICSRs for overall adverse drug events. Since 2010, the number of SCAR ICSRs has increased up to 100 cases/year. Allopurinol was the most common causative drug (SJS/TEN: 10.2%; DRESS: 11.3%; SCAR ICSRs: 10.6%), followed by carbamazepine (SJS/TEN: 8.7%; DRESS: 9.7%; SCAR ICSRs: 8.6%). Regarding drug groups, antiepileptics (19.5%) and antibiotics for systemic use (12.7%) were common causative drug groups. Twenty SCAR-related deaths were recorded. Antibacterials were the most common causes of deaths (8 cases), followed by antiepileptics (5 cases). The potential risk of SCARs was not specified in the drug information leaflet for 40.2% of drugs causing SJS/TEN and 82.5% causing DRESS syndrome in Korea. CONCLUSION: The number of SCAR ICSRs has increased rapidly with recent active pharmacovigilance programs in Korea. Allopurinol and antiepileptics are the most common individual and categorical causative agents, respectively.

119 Rescue team's awareness of anaphylaxis and asthma exacerbation in Gyeonggi-do province of Korea: Before and after education

PURPOSE: Anaphylaxis and asthma exacerbation could be life-threatening medical emergencies. The 119 (911 in the United States) rescue teams are at the forefront of such emergency conditions. Early recognition and proper prehospital management by 119 rescuers are important. We evaluated the awareness of 119 rescuers of anaphylaxis and asthma exacerbation in Korea. METHODS: Between May 17 and June 28 of 2018, a total of 180 rescuers were recruited from Gyeonggi-do province, Korea. The 90-minute educational sessions on anaphylaxis and asthma exacerbation were provided by an allergy specialist, which included some lectures and a hands-on workshop on self-injectable epinephrine autoinjector. A questionnaire survey with the same content was performed before and after education to assess the improvement in awareness. It had 2 domains: anaphylaxis awareness and asthma awareness. RESULTS: After education, awareness score for anaphylaxis increased from an average of 3.1 (51.7%) to 5.5 (91.7%). Particularly, the effect of education on the use of epinephrine, the most crucial treatment for anaphylaxis, was greatest. The awareness score for asthma after education increased from an average of 21.3 (78.9%) to 25.1 (93%). The effect of education on treatment and management of asthma was greatest. CONCLUSION: The 119 rescuers could be the first medical personnel at the forefront of anaphylaxis and asthma exacerbation. Hence, it is important to increase their awareness of anaphylaxis and asthma exacerbation. A simple educational activity can dramatically change the level of awareness.

How to Apply the Concept of Cough Hypersensitivity in Clinical Practice?

No abstract available.

Severe Cutaneous Adverse Reactions to Antiepileptic Drugs: A Nationwide Registry-Based Study in Korea

PURPOSE: Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) to antiepileptic drug (AED), are rare, but result in significant morbidity and mortality. We investigated the major culprit drugs, clinical characteristics, and clinical course and outcomes of AED-induced SCARs using a nationwide registry in Korea. METHODS: A total of 161 patients with AED-induced SCARs from 28 referral hospitals were analyzed. The causative AEDs, clinical characteristics, organ involvements, details of treatment, and outcomes were evaluated. We compared the clinical and laboratory parameters between SJS/TEN and DRESS according to the leading causative drugs. We further determined risk factors for prolonged hospitalization in AED-induced SCARs. RESULTS: Carbamazepine and lamotrigine were the most common culprit drugs causing SCARs. Valproic acid and levetiracetam also emerged as the major causative agents. The disease duration and hospital stay in carbamazepine-induced SJS/TEN were shorter than those in other AEDs (P< 0.05, respectively). In younger patients, lamotrigine caused higher incidences of DRESS than other drugs (P= 0.045). Carbamazepine, the most common culprit drug for SCARs, was associated with a favorable outcome related with prolonged hospitalization in SJS (odds ratio, 0.12; 95% confidence interval, 0.02-0.63, P= 0.12), and thrombocytopenia was found to be a risk factor for prolonged hospitalization in DRESS. CONCLUSION: This was the first large-scale epidemiological study of AED-induced SCARs in Korea. Valproic acid and levetiracetam were the significant emerging AEDs causing SCARs in addition to the well-known offending AEDs such as carbamazepine and lamotrigine. Carbamazepine was associated with reduced hospitalization, but thrombocytopenia was a risk factor for prolonged hospitalization. Our results suggest that the clinical characteristics and clinical courses of AED-induced SCARs might vary according to the individual AEDs.

Results of Intradermal Skin Testing with Cefazolin according to a History of Hypersensitivity to Antibiotics

Direct costs of severe cutaneous adverse reactions in a tertiary hospital in Korea

BACKGROUND/AIMS: There are only a few reports on the direct costs of severe cutaneous adverse reactions (SCARs), including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), despite the tremendous negative impact these reactions can have on patients. We estimated the direct costs of treating SCARs. METHODS: Patients admitted to a tertiary teaching hospital for the treatment of SCARs from January 1, 2005 to December 31, 2010 were included. Patients who had experienced SCARs during their admission for other medical conditions were excluded. The direct costs of hospitalization and outpatient department visits were collected. Inpatient and outpatient care costs were calculated, and factors affecting inpatient care costs were analyzed. RESULTS: The total healthcare cost for the management of 73 SCAR patients (36 with DRESS, 21 with SJS, and 16 with TEN) was 752,067 US dollars (USD). Most of the costs were spent on inpatient care (703,832 USD). The median inpatient care cost per person was 3,720 (range, 1,133 to 107,490) USD for DRESS, 4,457 (range, 1,224 to 21,428) USD for SJS, and 8,061 (range, 1,127 to 52,220) USD for TEN. Longer hospitalization significantly increased the inpatient care costs of the patients with DRESS (by 428 USD [range, 395 to 461] per day). Longer hospitalization and death significantly increased the inpatient care costs of the patients with SJS/TEN (179 USD [range, 148 to 210] per day and an additional 14,425 USD [range, 9,513 to 19,337] for the deceased). CONCLUSIONS: The management of SCARs required considerable direct medical costs. SCARs are not only a health problem but also a significant financial burden for the affected individuals.

The KAAACI Standardization Committee Report on the procedure and application of the bronchial provocation tests

Bronchial provocation tests are of value in the evaluation of airway hyperresponsiveness. Nonspecific bronchial challenge (methacholine, mannitol, exercise, etc.) is used when the symptoms, physical examination, and measurements of pulmonary function are unremarkable in the diagnosis of asthma, when a patient is suspected of having occupational asthma or exercise-induced bronchoconstriction (EIB), and when a screening test for asthma or EIB is required for some occupational groups in whom bronchospasm would pose an unacceptable hazard. Methacholine inhalation challenge is most widely used pharmacologic challenge and highly sensitive. For appropriate interpretation of the results of methacholine provocation, it is important to perform the test with the standardized protocol and to recognize that inhalation methods significantly influence the sensitivity of the procedure. Indirect challenges (e.g., mannitol and exercise) correlate with airway inflammation and are more specific but less sensitive for asthma. Indirect provocation tests are used to confirm asthma, to differentiate asthma from other airway diseases, and to evaluate EIB.

Relief System for Adverse Drug Reactions in Korea / 대한내과학회지

The relief system for adverse drug reactions is a reimbursement system for non-fault injury from drugs that started with the intent of relieving victims of adverse drug reactions despite normal use of the medicines. In Korea, the relief system for adverse drug reactions started on December 19, 2014. To date, the deliberation process for 100 cases of adverse drug reactions has ended, of which 78 cases received relief reimbursement. As this is the early phase of system implementation, efforts to stabilize the system are needed. It is very important for clinicians to participate actively in mediating between the victims of adverse drug reactions and the Korea Institute of Drug Safety & Risk Management, to establish an effective relief system. It is also important to implement the most favorable relief system considering the socioeconomic and medical environment in Korea.

Erratum: Seasonal Cycle and Relationship of Seasonal Rhino- and Influenza Virus Epidemics With Episodes of Asthma Exacerbation in Different Age Groups

This erratum is being published to correct the printing error on page 517 of the article. Corrections for Fig. 1 and main text in page 519 are needed. The authors apologize for any inconvenience that this may have caused.

Dog and Cat Allergies and Allergen Avoidance Measures in Korean Adult Pet Owners Who Participated in a Pet Exhibition

PURPOSE: This study evaluated dog and cat allergies and their association with allergen avoidance measures in Korean adults. METHODS: The study population consisted of 537 adults who currently kept dogs or cats and participated in a pet exhibition in Korea. The subjects were asked to complete questionnaires regarding pet ownership, allergen avoidance, and allergy symptoms, and underwent skin prick tests. They were considered to have a dog or cat allergy if they suffered from one or more of allergy symptoms during contact with their pets. RESULTS: In total, 103 of 407 dog owners (25.3%) and 45 of 130 cat owners (34.6%) had a dog or cat allergy, respectively. Dog owners kept 1.3±1.5 dogs; this number did not differ according to the presence of dog allergy. Dog owners with a dog allergy had owned their dogs longer than those without (88.0±72.0 vs 67.5±72.7 months, P < 0.05). Cat owners kept 2.1±3.6 cats; this number did not differ according to the presence of cat allergy, nor did the duration of cat ownership. Cat owners with a cat allergy had facial contact and slept with their cats less frequently (8.6±11.9 vs 18.3±27.0 times/day, P < 0.01; 71.1% vs 81.2%, P < 0.05); however, they had their cats shaved and beds cleaned less frequently than those without (1.8±3.3 vs 3.2±4.4 times/year, P < 0.05; 1.5±1.5 vs 3.9±6.0 times/month, P < 0.01). CONCLUSIONS: Cat owners with a cat allergy tried to minimize contact with their cats, but efforts to avoid indoor cat allergens were lower than those without. In comparison, dog owners with a dog allergy had kept their dogs for longer time than those without; however, current contact with their dogs and allergen avoidance measures did not differ between the 2 groups.

Electronic Consultation Support System for Radiocontrast Media Hypersensitivity Changes Clinicians' Behavior

PURPOSE: Patients with a history of radiocontrast media (RCM) hypersensitivity can be overlooked, resulting in repeated reactions. Therefore, a consultation support system for RCM hypersensitivity has been in operation at Seoul National University Bundang Hospital since December 2011. We analyzed the effect of this system on physicians' practice. METHODS: A retrospective study was conducted on patients with previous RCM reactions (December 1, 2010 to November 30, 2012). The control period was December 2010 to November 2011, and the intervention period was December 2011 to November 2012. The primary outcome was the composite outcome of premedication and consultation. Premedication was defined as preventive medication prescribed by the physician who ordered RCM-enhanced computed tomography (CT) at the same time. The secondary outcome was the recurrence rate after using the consultation support system. RESULTS: A total of 189 clinicians prescribed 913 CT scans during the control period and 225 clinicians performed 1,153 examinations during the intervention period. The odds ratio (OR) of achieving the composite outcome increased significantly after use of the consultation support system (OR, 1.54; 95% confidence interval [CI], 1.15–2.05). Clinicians in both medical (OR, 1.48; 95% CI, 1.06–2.07) and surgical (OR, 2.07; 95% CI, 1.24–3.46) departments showed significant changes in their behavior, whereas those in the emergency department did not (OR, 1.07; 95% CI, 0.41–2.78). Professors (OR, 1.47; 95% CI, 1.06–2.04) and trainees (OR, 1.97, 95% CI, 1.22–3.18) showed significant changes in their behavior toward patients with previous RCM reactions. The behavior of 86 clinicians who ordered CT scans during both the control and intervention periods was unchanged. CONCLUSIONS: The consultation support system for those with previous RCM hypersensitivity reactions changed physicians' practice patterns and decreased recurrent RCM hypersensitivity reactions as well.

Relief System for Adverse Drug Reactions in Korea / 대한내과학회지

The relief system for adverse drug reactions is a reimbursement system for non-fault injury from drugs that started with the intent of relieving victims of adverse drug reactions despite normal use of the medicines. In Korea, the relief system for adverse drug reactions started on December 19, 2014. To date, the deliberation process for 100 cases of adverse drug reactions has ended, of which 78 cases received relief reimbursement. As this is the early phase of system implementation, efforts to stabilize the system are needed. It is very important for clinicians to participate actively in mediating between the victims of adverse drug reactions and the Korea Institute of Drug Safety & Risk Management, to establish an effective relief system. It is also important to implement the most favorable relief system considering the socioeconomic and medical environment in Korea.