Treatment of asthma and eosinophilic allergic diseases using biological products

Asthma and other eosinophilic allergic diseases are heterogeneous syndromes encompassing various endotypes and phenotypic characteristics. The recent development of several targeted biological products has enabled the personalized treatment for heterogeneous pathophysiology in these diseases.Current Concepts: Biological products approved by the US Food and Drug Administration for such diseases primarily comprise monoclonal antibodies that block the pathway of type 2 inflammation, such as immunoglobulin E, interleukin (IL)-5, IL-5 receptor, IL-4α receptor, and thymic stromal lymphopoietin. A practical strategy for selecting the optimal biological products for patients with severe eosinophilic allergic diseases is a shared decision-making process between the patient and physician on the basis of measurable biomarkers, co-morbidity, and patient preferences considering drug characteristics and costs.Discussion and Conclusion: The emergence of biological products in chronic eosinophilic allergic diseases has not only heralded an era of precise treatment but has also improved our understanding of the endogenous types through various treatment responses for each patient. The development of new biological products that affect various pathways and the discovery of novel biomarkers will facilitate the provision of optimized precision medicine to patients with severe uncontrolled diseases.

A case of anaphylactic shock to ethylenediaminetetraacetic acid as a drug excipient

If drug excipients hypersensitivity is not accurately recognized, the patient is at risk of experiencing repeated hypersensitivity to various drugs. Ethylenediaminetetraacetic acid (edetic acid, EDTA), often found as an excipient in injectable drugs and topical agents.Herein, we report a patient who developed anaphylactic shock to an injection containing EDTA and subsequently experienced both immediate and delayed hypersensitivity reactions to EDTA. A 51-year-old female was referred due to perioperative anaphylaxis. It took the patient 2 hours to return to the ward after receiving general anesthesia. Immediately after returning to the ward, the patient received injections of Mucosten (Medica), Traumeel (Saehan), and Botropase (Han Lim), and within 1 minute she experienced an anaphylactic shock. The patient had drug allergy histories to computed tomography contrast agents and injectable drugs as well as repeated contact dermatitis histories to topical agents. A month later, the patient came to the outpatient clinic. As a result, intradermal test for perioperative drugs, Mucosten, and Dexamethasone (Daewon Pharm) were positive. In addition, the 48-hour delay test for Mucosten and Dexamethasone was also positive. Under the suspicion of additive hypersensitivity, skin prick test was performed for disodium acetate, an additive containing Mucosten and Dexamethasone, which showed a positive result. However, skin prick test for N-Acetyl-L-cysteine, a main compound of Mucosten, was negative. This case is a hypersensitivity reaction to EDTA, which was confirmed by drug skin tests. In addition, this case is meaningful in that immediate and delayed hypersensitivity reactions to a single excipient appeared independently in the same patient.

Association Between Clinical Burden and Blood Eosinophil Counts in Asthma: Findings From a Korean Adult Asthma Cohort

Background@#Some reports have suggested that the clinical and economic burdens of asthma are associated with blood eosinophil levels. The association between clinical burden and blood eosinophil counts were evaluated in a Korean adult asthma cohort. @*Methods@#Clinical information including blood eosinophil counts that were not affected by systemic corticosteroids were extracted from the Cohort for Reality and Evolution of Adult Asthma in Korea database. Clinical burden was defined as 1) asthma control status, 2) medication demand and 3) acute exacerbation (AE) events during 1 consecutive year after enrollment. All patients were divided into atopic and non-atopic asthmatics. The associations between asthma outcomes and the blood eosinophil count were evaluated. @*Results@#In total, 302 patients (124 atopic and 178 non-atopic asthmatics) were enrolled. In all asthmatics, the risk of severe AE was higher in patients with blood eosinophil levels < 100 cells/µL than in patients with levels ≥ 100 cells/µL (odds ratio [OR], 5.406; 95% confidence interval [CI], 1.266–23.078; adjusted P = 0.023). Among atopic asthmatics, the risk of moderate AE was higher in patients with blood eosinophil levels ≥ 300 cells/µL than in patients with levels < 300 cells/µL (OR, 3.558; 95% CI, 1.083–11.686; adjusted P = 0.036). Among non-atopic asthmatics, the risk of medication of Global Initiative for Asthma (GINA) steps 4 or 5 was higher in patients with high blood eosinophil levels than in patients with low blood eosinophil levels at cutoffs of 100, 200, 300, 400, and 500 cells/µL. @*Conclusion@#The baseline blood eosinophil count may predict the future clinical burden of asthma.

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.

Nurses’ Perceived Needs and Barriers Regarding Pediatric Palliative Care: A Mixed-Methods Study / 한국호스피스완화의료학회지

Purpose@#This study aimed to describe nurses’ perceived needs and barriers to pediatric palliative care (PPC). @*Methods@#Mixed methods with an embedded design were applied. An online survey was conducted for nurses who participated in the End-of-Life Nursing Education Consortium- Pediatric Palliative Care (ELNEC-PPC) train-the-trainer program, of whom 63 responded. Quantitative data were collected with a survey questionnaire developed through the Delphi method. The 47 items for needs and 15 items for barriers to PPC were analyzed with descriptive statistics. Qualitative data were collected through openended questions and analyzed with topic modeling techniques. @*Results@#The mean scores of most subdomains of the PPC needs were 3.5 or higher out of 4, and those of PPC barriers ranged from 3.22 to 3.56, indicating the items in the questionnaire developed in this study properly reflect each factor. The needs for PPC were divided into 4 categories: “children and adolescents,” “families,” “PPC management system,” and “community-based PPC.” Meanwhile, PPC barriers were divided into 3 categories: “healthcare delivery system,” “healthcare provider,” and “client.” The keywords derived from the topic modeling were perception, palliative, children, and education for necessities and lack, perception, medical care, professional care providers, service, and system for barriers to PPC. @*Conclusion@#In this study, by using mixed-methods, items of nurses’ perceived needs and barriers to PPC were identified, categorized, and weighted, and their meanings were explored. For the stable establishment of PPC, the priority should be given to improving perceptions of PPC, establishing an appropriate system, and training professional care providers.

Analysis of Pediatric Surgery Using the National Healthcare Insurance Service Database in Korea: How Many Pediatric Surgeons Do We Need in Korea?

Background@#In the past, general surgeons (GSs) without a pediatric surgical subspecialty often performed surgery on children and, even now, GSs are performing many pediatric surgeries. We aimed to investigate the involvement of pediatric surgeons (PSs) and GSs in pediatric surgery, compare the outcomes of surgery in the neonatal intensive care unit (NICU), and estimate the appropriate PS workforce in Korea. @*Methods@#We used surgical data from the National Health Insurance Service database that was collected from patients under the age of 19 years in hospitals nationwide from January 2002 to December 2017. In this database, we found 37 hospitals where PSs worked by using the index operation (congenital diaphragmatic hernia, esophageal atresia, hypertrophic pyloric stenosis, Hirschsprung's disease, abdominal wall defect, jejunoileal atresia, malrotation, anorectal malformation, and biliary atresia). It was assumed that the surgery in the 37 hospitals was performed by PS and that the surgery in other hospitals was performed by GS. Mortality was analyzed to compare the outcomes of acute abdominal surgery in the NICU. We estimated the number of PS currently needed in Korea for each situation under the assumption that PS would perform all operations for the index operation, main pediatric diseases (index operation + gastroesophageal reflux disease, choledochal cyst, inguinal hernia, and appendicitis), acute abdominal surgery in the NICU, and all pediatric surgeries.Additionally, we estimated the appropriate number of PS required for more advanced pediatric surgery in the future. @*Results@#The number of pediatric surgeries from 2002 to 2017 increased by 124%.Approximately 10.25% of the total pediatric surgeries were performed by PSs, and the percentage of the surgery performed by PSs increased from 8.32% in 2002 to 15.92% in 2017. The percentage of index operations performed by PSs annually was 62.44% in average. It was only 47.81% in 2002, and increased to 88.79% in 2017. During the last 5 years of the study period, the average annual number of surgeries for main pediatric diseases was approximately 33,228. The ratio of the number of surgeries performed by PS vs. GS steadily increased in main pediatric diseases, however, the ratio of the number of surgery performed by PS for inguinal hernia and appendicitis remained low in the most recent years. The percentage of the number of acute abdominal surgery performed by PS in the NICU was 44% in 2002, but it had recently risen to 89.7%. After 30 days of birth, mortality was significantly lower in all groups that were operated on by PS, rather than GS, during the last 5 years. In 2019, 49 PSs who were under the age of 65 years were actively working in Korea. Assuming that all pediatric surgeries of the patients under the age of 19 years should be performed by PS, the minimum number of PS currently required was about 63 if they perform all of the index operations, the main pediatric surgery was about 209, the NICU operation was about 63, and the all pediatric surgeries was about 366. Additionally, it was determined that approximately 165 to 206 PS will be appropriate for Korea to implement more advanced pediatric surgery in the future. @*Conclusion@#The proportion of the pediatric surgery performed by PS rather than GS is increasing in Korea, but it is still widely performed by GS. PSs have better operative outcomes for acute abdominal surgery in the NICU than GSs. We believe that at least the index operation or the NICU operation should be performed by PS for better outcome, and that a minimum of 63 PSs are needed in Korea to do so. In addition, approximately 200 PSs will be required in Korea in order to manage main pediatric diseases and to achieve more advanced pediatric surgery in the future.

Analysis of Pediatric Surgery Using the National Healthcare Insurance Service Database in Korea: How Many Pediatric Surgeons Do We Need in Korea?

Background@#In the past, general surgeons (GSs) without a pediatric surgical subspecialty often performed surgery on children and, even now, GSs are performing many pediatric surgeries. We aimed to investigate the involvement of pediatric surgeons (PSs) and GSs in pediatric surgery, compare the outcomes of surgery in the neonatal intensive care unit (NICU), and estimate the appropriate PS workforce in Korea. @*Methods@#We used surgical data from the National Health Insurance Service database that was collected from patients under the age of 19 years in hospitals nationwide from January 2002 to December 2017. In this database, we found 37 hospitals where PSs worked by using the index operation (congenital diaphragmatic hernia, esophageal atresia, hypertrophic pyloric stenosis, Hirschsprung's disease, abdominal wall defect, jejunoileal atresia, malrotation, anorectal malformation, and biliary atresia). It was assumed that the surgery in the 37 hospitals was performed by PS and that the surgery in other hospitals was performed by GS. Mortality was analyzed to compare the outcomes of acute abdominal surgery in the NICU. We estimated the number of PS currently needed in Korea for each situation under the assumption that PS would perform all operations for the index operation, main pediatric diseases (index operation + gastroesophageal reflux disease, choledochal cyst, inguinal hernia, and appendicitis), acute abdominal surgery in the NICU, and all pediatric surgeries.Additionally, we estimated the appropriate number of PS required for more advanced pediatric surgery in the future. @*Results@#The number of pediatric surgeries from 2002 to 2017 increased by 124%.Approximately 10.25% of the total pediatric surgeries were performed by PSs, and the percentage of the surgery performed by PSs increased from 8.32% in 2002 to 15.92% in 2017. The percentage of index operations performed by PSs annually was 62.44% in average. It was only 47.81% in 2002, and increased to 88.79% in 2017. During the last 5 years of the study period, the average annual number of surgeries for main pediatric diseases was approximately 33,228. The ratio of the number of surgeries performed by PS vs. GS steadily increased in main pediatric diseases, however, the ratio of the number of surgery performed by PS for inguinal hernia and appendicitis remained low in the most recent years. The percentage of the number of acute abdominal surgery performed by PS in the NICU was 44% in 2002, but it had recently risen to 89.7%. After 30 days of birth, mortality was significantly lower in all groups that were operated on by PS, rather than GS, during the last 5 years. In 2019, 49 PSs who were under the age of 65 years were actively working in Korea. Assuming that all pediatric surgeries of the patients under the age of 19 years should be performed by PS, the minimum number of PS currently required was about 63 if they perform all of the index operations, the main pediatric surgery was about 209, the NICU operation was about 63, and the all pediatric surgeries was about 366. Additionally, it was determined that approximately 165 to 206 PS will be appropriate for Korea to implement more advanced pediatric surgery in the future. @*Conclusion@#The proportion of the pediatric surgery performed by PS rather than GS is increasing in Korea, but it is still widely performed by GS. PSs have better operative outcomes for acute abdominal surgery in the NICU than GSs. We believe that at least the index operation or the NICU operation should be performed by PS for better outcome, and that a minimum of 63 PSs are needed in Korea to do so. In addition, approximately 200 PSs will be required in Korea in order to manage main pediatric diseases and to achieve more advanced pediatric surgery in the future.

The KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children: Part 1. Definition, Methodology and First-line Management

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

The KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children: Part 1. Definition, Methodology and First-line Management

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

Drug-induced anaphylaxis: Analysis of the Pharmacovigilance Database

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.

Phenotypes of Severe Cutaneous Adverse Reactions Caused by Nonsteroidal Anti-inflammatory Drugs

PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are common cause of severe cutaneous adverse reactions (SCARs). The present study aimed to investigate the characteristics of SCARs induced by NSAIDs in the Korean SCAR registry. METHODS: A retrospective survey of NSAID-induced SCARs recorded between 2010 and 2015 at 27 university hospitals in Korea was conducted. Clinical phenotypes of SCARs were classified into Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Causative NSAIDs were classified into 7 groups according to their chemical properties: acetaminophen, and propionic, acetic, salicylic, fenamic and enolic acids. RESULTS: A total of 170 SCARs, consisting of 85 SJS, 32 TEN, 17 SJS-TEN overlap syndrome and 36 DRESS reactions, were induced by NSAIDs: propionic acids (n=68), acetaminophen (n=38), acetic acids (n=23), salicylic acids (n=16), coxibs (n=8), fenamic acids (n=7), enolic acids (n=5) and unclassified (n=5). Acetic acids (22%) and coxibs (14%) accounted for higher portions of DRESS than other SCARs. The phenotypes of SCARs induced by both propionic and salicylic acids were similar (SJS, TEN and DRESS, in order). Acetaminophen was primarily associated with SJS (27%) and was less involved in TEN (10%). DRESS occurred more readily among subjects experiencing coxib-induced SCARs than other NSAID-induced SCARs (62.5% vs. 19.7%, P = 0.013). The mean time to symptom onset was longer in DRESS than in SJS or TEN (19.1 ± 4.1 vs. 6.8 ±1.5 vs. 12.1 ± 3.8 days). SCARs caused by propionic salicylic acids showed longer latency, whereas acetaminophen- and acetic acid-induced SCARs appeared within shorter intervals. CONCLUSIONS: The present study indicates that the phenotypes of SCARs may differ according to the chemical classifications of NSAIDs. To establish the mechanisms and incidences of NSAID-induced SCARs, further prospective studies are needed.

Severe Cutaneous Adverse Reactions in Korean Pediatric Patients: A Study From the Korea SCAR Registry

PURPOSE: Although severe cutaneous adverse drug reactions (SCARs) are rare, they are associated with high morbidity and mortality, and thus early diagnosis and treatment are critical for improving prognoses. However, few studies have reported the characteristics of SCARs in children. Thus, we aimed to evaluate the clinical characteristics, current management and prognosis of pediatric SCARs. METHODS: We analyzed pediatric data in the Korean SCARs registry, which was built retrospectively in 2016 with SCAR cases treated in 34 tertiary referral university hospitals during 2010–2015. Using these cases, we descriptively analyzed detailed data regarding etiology, clinical and laboratory features, treatment strategies, and prognosis. RESULTS: Forty-seven pediatric SCAR cases from 15 tertiary referral hospitals were included. The median patient age was 10 (interquartile range, 3-15.5) years and 68.1% (n = 32) were males. The culprit drug was identified in 95.7% (n = 45) of the patients; antibiotics (44.7%) and antiepileptic drugs (19.1%) were the most common and second most common culprits, respectively. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) cases presented with the largest area of skin involvement without permanent sequelae. Stevens-Johnson syndrome (SJS) cases involved relatively small areas of skin but serious sequelae in two children. Of 4 patients with toxic epidermal necrolysis (TEN), 1 died. Of all patients assessed, 36 (76.6%) received systemic steroids and 21 (44.7%) received intravenous immunoglobulin (IVIG). Thirteen (27.7%) received both systemic steroids and IVIG. Cyclosporine was administered to only 1 patient along with a systemic steroid. CONCLUSIONS: In patients with pediatric SCARs, including those with DRESS, SJS and TEN, clinical presentations were variable. Thus, there was no clear continuous disease spectrum. Although the mortality rate was low (2.1%), clinical suspicion may be the best tool for proactive SCAR management.

Neutrophil oxidative burst as a diagnostic indicator of IgG-mediated anaphylaxis

BACKGROUND: IgG-mediated anaphylaxis occurs after infusion of certain monoclonal antibody-based therapeutics. New in vitro tests are urgently needed to diagnose such reactions. We investigated whether allergens trigger neutrophil oxidative burst (OB) and if neutrophil OB occurs due to allergen-specific IgG (sIgG). METHODS: Neutrophil OB was measured by dihydrorhodamine 123 flow cytometry using a leukocyte suspension spiked with a very small patch of the allergen crude extract, Dermatophagoides farinae (Der f). The mean fluorescence intensity ratio of stimulated to unstimulated samples was calculated as the neutrophil oxidative index (NOI). RESULTS: The Der f-specific NOI (Der f-sNOI) showed a time-dependent increase after Der f extract addition. At 15 min activation, higher Der f-sIgG levels were associated with lower Der f-sNOI values in 31 subjects (P < 0.05). This inverse relationship occurs due to the initial blocking effect of free Der f-sIgG. Additionally, neutrophil OB was nearly absent (Der f-sNOI of −1) in two cases: a subject with undetectable Der f-sIgG levels and washed leukocyte suspensions deprived of Der f-sIgG. CONCLUSION: Allergens can trigger neutrophil OB via preexisting allergen-sIgG. Neutrophil OB can be easily measured in a leukocyte suspension spiked with the allergen. This assay can be used to diagnose IgG-mediated anaphylaxis.

A New Scoring System for the Differential Diagnosis between Tuberculous Meningitis and Viral Meningitis

BACKGROUND: Tuberculous meningitis (TBM) is associated with high mortality and morbidity despite administering anti-tuberculous chemotherapy to the patients. Differential diagnosis between TBM and viral meningitis (VM) is difficult in some clinical situations. METHODS: We reviewed and analyzed records of adult patients who were admitted and diagnosed with TBM or VM at a tertiary hospital in Korea, between January 2006 and December 2015. Diagnostic criteria for TBM were categorized into three groups: definite, probable, and possible TBM. The VM group included patients with no evidence of other meningitis who achieved complete recovery with only conservative treatments. Clinical, laboratory and radiological findings, as well as outcomes, were compared between the TBM and VM groups. RESULTS: Ninety-eight patients were enrolled. Among the study patients, 47 had TBM and 51 had VM. Based on univariate analysis and multivariate logistic regression, sodium 70 (U/L) in cerebrospinal fluid (CSF), protein > 160 (mg/dL) in CSF, voiding difficulty, and symptoms of cranial nerve palsy were significant predictive factors for TBM in the final model. We constructed a weighted scoring system with predictive factors from multiple regression analyses. Receiver operating characteristic curve analyses and decision tree analyses were plotted to reveal an optimum cutoff point as 4 with this scoring system (range: 0–13). CONCLUSION: For differential diagnosis between TBM and VM, we created a new weighted scoring system. This scoring system and decision tree analysis are simple and easy to apply in clinical practice to differentiate TBM from VM.

Effectiveness, Safety, and Tolerability of a Switch to Dual Therapy with Dolutegravir Plus Cobicistat-Boosted Darunavir in Treatment-Experienced Patients with Human Immunodeficiency Virus

BACKGROUND: Dual regimen with dolutegravir plus cobicistat-boosted darunavir (DTG/DRV/c) is reasonable alternative option for patients with existing resistance and/or intolerance to nucleoside reverse transcriptase inhibitors (NRTIs). MATERIAL AND METHODS: All patients who switched to DTG/DRV/c among treatment-experienced patients with human immunodeficiency virus (HIV) in a tertiary university hospital were selected. We analyzed the effectiveness, safety, and tolerability based on serial laboratory data and clinical findings. The primary endpoint was defined as the proportion of patients with plasma HIV RNA below 50 copies/mL at week 48 after switch. Secondary endpoints included evaluation of safety and tolerability. RESULTS: Thirty-one patients were retrospectively analyzed. The main reasons for the change to DTG/DRV/c were treatment failure in 13 patients (41.9%), simplification in 12 patients (38.7%), and adverse drug reaction in 6 patients (19.4%). Among the 13 patients who switched owing to treatment failure, the proportion of patients in whom the viral loads were suppressed to less than 50 copies/mL increased from 0% at baseline to 45% at 4 weeks, 50% at 12 weeks, 50% at 24 weeks, and 66.7% at 48 weeks. HIV virus levels decreased and CD4⁺ T cell counts increased during the follow-up period. In non-treatment failure patients (18 patients), the levels of viral suppression and CD4⁺ T cells were maintained. There were no significant differences in renal function, liver function, glucose levels, and lipid profile before and after regimen changes. The tolerability was very good: 30 patients (96.8%) tolerated the drugs well and only 1 patient discontinued owing to no improvement in renal insufficiency. Two patients (6.4%) in treatment failure group failed to reach viral suppression. CONCLUSION: The use of DTG/DRV/c in HIV treatment-experienced patients appears to be a very good regimen for switch therapy that is effective and well tolerated, without significant adverse drug reaction.

Effectiveness, Safety, and Tolerability of a Switch to Dual Therapy with Dolutegravir Plus Cobicistat-Boosted Darunavir in Treatment-Experienced Patients with Human Immunodeficiency Virus

BACKGROUND: Dual regimen with dolutegravir plus cobicistat-boosted darunavir (DTG/DRV/c) is reasonable alternative option for patients with existing resistance and/or intolerance to nucleoside reverse transcriptase inhibitors (NRTIs). MATERIAL AND METHODS: All patients who switched to DTG/DRV/c among treatment-experienced patients with human immunodeficiency virus (HIV) in a tertiary university hospital were selected. We analyzed the effectiveness, safety, and tolerability based on serial laboratory data and clinical findings. The primary endpoint was defined as the proportion of patients with plasma HIV RNA below 50 copies/mL at week 48 after switch. Secondary endpoints included evaluation of safety and tolerability. RESULTS: Thirty-one patients were retrospectively analyzed. The main reasons for the change to DTG/DRV/c were treatment failure in 13 patients (41.9%), simplification in 12 patients (38.7%), and adverse drug reaction in 6 patients (19.4%). Among the 13 patients who switched owing to treatment failure, the proportion of patients in whom the viral loads were suppressed to less than 50 copies/mL increased from 0% at baseline to 45% at 4 weeks, 50% at 12 weeks, 50% at 24 weeks, and 66.7% at 48 weeks. HIV virus levels decreased and CD4⁺ T cell counts increased during the follow-up period. In non-treatment failure patients (18 patients), the levels of viral suppression and CD4⁺ T cells were maintained. There were no significant differences in renal function, liver function, glucose levels, and lipid profile before and after regimen changes. The tolerability was very good: 30 patients (96.8%) tolerated the drugs well and only 1 patient discontinued owing to no improvement in renal insufficiency. Two patients (6.4%) in treatment failure group failed to reach viral suppression. CONCLUSION: The use of DTG/DRV/c in HIV treatment-experienced patients appears to be a very good regimen for switch therapy that is effective and well tolerated, without significant adverse drug reaction.

Awareness and Acceptance of HIV Pre-exposure Prophylaxis among Medical Personnel and Men Who Have Sex with Men in Korea

BACKGROUND: We aimed to investigate the awareness of human immunodeficiency virus (HIV) infection among high-risk individuals, including men who have sex with men (MSM) and medical personnel (MP) in Korea through a cross-sectional survey, identify possible obstacles hindering their access to pre-exposure prophylaxis (PrEP). METHODS: In 2016, the first questionnaire survey was sent to randomly selected MSM and MP. To compare the changes in attitudes and knowledge of MSM, a second questionnaire survey was conducted in August 2017. RESULTS: More than half of MSM (61.3% in 2016, 88.6% in 2017) were aware of PrEP. However, MP who offered PrEP had less knowledge regarding PrEP (23.4%). The background knowledge and experience with PrEP among MSM and MP in this survey was low (3.4% in 2016 and 5.7% in 2017, 1.9% in MP). The major obstacles that MSM reported were lack of insurance coverage (29% in 2016 and 32% in 2017), concern regarding adverse effects of PrEP (19% and 21%), and risk of exposing HIV-positive status to other people (15% and 18%). Among MP, lack of knowledge regarding the efficacy of PrEP was the most common obstacle (30%), followed by lack of insurance coverage (22%), and concern regarding adverse effects (20%). CONCLUSION: Our study showed that PrEP is required among MSM in Korea; however, most MP were not aware of PrEP. Lack of insurance coverage and knowledge regarding PrEP were major hindrances in the access to PrEP; therefore, further studies on how to make PrEP information more accessible are needed to help prevent HIV infection.

Rhabdomyolysis and diabetic ketoacidosis after bee sting: A case report

Bee stings result in diverse clinical manifestations from localized pain, rash to life-threatening systemic allergic reactions or toxic reactions. Toxic reactions include skin necrosis, pancreatitis, acute renal failure, hemolysis or coagulopathy, while systemic allergic reactions present with IgE-mediated anaphylaxis. We experienced a 63-year-old woman who developed rhabdomyolysis and diabetic ketoacidosis after bee sting. The patient was accompanied by pulmonary edema due to acute kidney injury, which was recovered by intensive hemodialysis treatment. Here, we report a rare and serious case induced by bee sting with a review of the literature.

Perceptions of Severe Asthma and Asthma-COPD Overlap Syndrome Among Specialists: A Questionnaire Survey

PURPOSE: Severe asthma and asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) are difficult to control and are often associated with poor clinical outcomes. However, much is not understood regarding the diagnosis and treatment of severe asthma and ACOS. To evaluate the current perceptions of severe asthma and COPD among asthma and COPD specialists, we designed an e-mail and internet-based questionnaire survey. METHODS: Subjects were selected based on clinical specialty from among the members of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Academy of Tuberculosis and Respiratory Diseases. Of 432 subjects who received an e-mail invitation to the survey, 95 subjects, including 58 allergists and 37 pulmonologists, responded and submitted their answers online. RESULTS: The specialists estimated that the percentage of severe cases among total asthma patients in their practice was 13.9%±11.0%. Asthma aggravation by stepping down treatment was the most common subtype, followed by frequent exacerbation, uncontrolled asthma despite higher treatment steps, and serious exacerbation. ACOS was estimated to account for 20.7% of asthma, 38.0% of severe asthma, and 30.1% of COPD cases. A history of smoking, persistently low forced expiratory volume in 1 second (FEV1), and low FEV1 variation were most frequently classified as the major criteria for the diagnosis of ACOS among asthma patients. Among COPD patients, the highly selected major criteria for ACOS were high FEV1 variation, positive bronchodilator response, a personal history of allergies and positive airway hyperresponsiveness. Allergists and pulmonologists showed different assessments and opinions on asthma phenotyping, percentage, and diagnostic criteria for ACOS. CONCLUSIONS: Specialists had diverse perceptions and clinical practices regarding severe asthma and ACOS patients. This heterogeneity must be considered in future studies and strategy development for severe asthma and ACOS.