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Background Angioedema with eosinophilia (AE) is a rare allergic disease classified as episodic or nonepisodic. AE is characterized by angioedema, urticaria, fever, weight gain, and eosinophilia, but its etiology and pathogenesis have not yet been clarified. Case presentations We present a 70-year-old woman presented with generalized edema and urticaria after Moderna COVID-19 vaccination. Peripheral blood eosinophil count was marked elevated and echocardiography and Doppler ultrasonography of both the upper and lower extremities were unremarkable. Her symptoms and peripheral blood eosinophil count were improved after systemic steroid therapy, but she failed to respond to steroid tapering. Reslizumab (anti-interluekin-5) was administered intravenously, and she remained symptom free with a normal eosinophil count during 8 months of reslizumab treatment without steroids. Conclusions We report a case of nonepisodic AE after COVID-19 vaccination that was successfully treated with reslizumab.

Introduction: Allergic rhinitis and asthma share a common inflammatory mechanism and are closely related, recognized as “one airway disease.” Thus, the guidelines recommend allergic rhinitis and asthma be treated together, and leukotriene antagonists and antihistamines have been administered simultaneously; however, there are few reports of the use of combination drugs so far. Methods: The aim of the study was to evaluate the treatment effects and adverse events of Monterizine® (a combination of montelukast and levocetirizine); a total of 2,254 patients with perennial allergic rhinitis and asthma were prospectively enrolled from 60 hospitals nationwide in Korea. They were followed up for 3 (Period 1) or 6 months (Period 2). Total nasal symptom score (TNSS), satisfaction, and safety data were collected and compared to baseline. Results: TNSS scores were analyzed for 2,254 subjects. At Period 1 (n = 2,024) and 2 (n = 1,861), the scores decreased significantly from baseline (−1.20 ± 2.49 and −1.63 ± 2.78, p < 0.001). The mean quality of life (QoL) was significantly improved at Period 1 and 2 relative to baseline (−3.75 ± 6.58, −4.83 ± 7.11, both p < 0.0001). There were no serious adverse drug reactions, but there were some minor reactions including nasopharyngitis (2.92%), rhinitis (0.37%), and somnolence (0.34%). Conclusions: TNSS score and QoL were significantly improved by 3–6 months’ treatment with Monterizine without significant adverse reactions. These results indicate that Monterizine, as a combination drug, is effective and safe for improving nasal symptoms and quality of life in patients with allergic rhinitis who also have asthma.

Background Lyme disease (LD) is the fifth most reported notifiable disease in the US, but the true disease burden remains unknown due to inconsistent reporting. Claims-based algorithms estimate a ≥10-fold higher incidence compared to notifiable-disease surveillance, but these algorithms are unvalidated. Methods We evaluated a claims-based LD algorithm based on ICD codes (ICD-9-CM 088.81 or ICD-10-CM A69.2X) and a ≥7-day course of an antibiotic used to treat LD dispensed ±30 days of diagnosis. We applied the LD algorithm to Harvard Pilgrim Health Care (HPHC) claims data for Massachusetts (MA) residents. We sought health records for patients who met the algorithm between Jan 2015 and June 2019 and received care within the Massachusetts General Brigham (MGB) system at diagnosis. Three clinicians received training on case classification and conducted chart abstractions and adjudications. Cases were classified as confirmed, probable, suspect, or ruled out using 2017 CDC case definitions. To assess inter-rater reliability, the clinicians abstracted and adjudicated the same 20 charts; we computed the mean of kappa for each clinician-pair. We calculated the positive predictive value (PPV) of the algorithm for identifying confirmed, probable, or suspect LD cases, all of which required at least erythema migrans (EM) or clinical diagnosis with confirmatory serology and antibiotics prescription. Results We identified 11,823 HPHC members who met the LD algorithm. Of these members, 171 cases occurred within the study period among MGB patients; we obtained 128 (75%) patients’ charts for review. The average weighted kappa statistic of adjudicator agreement was 0.94. Of the reviewed charts, 103 (80.5%) were adults ≥ 18 years old. 71 patients (55.5%) were clinically diagnosed with LD, among whom 62 (48.4%) presented with EM rash. 24 reviewed cases (18.8%) had laboratory-confirmed LD. LD was ruled out for 8 cases. The overall algorithm PPV was 93.8% (95% CI 89.6-97.9%). Limited to confirmed and probable cases only, the PPV was 66.4% (95% CI 57.5-74.5%). Conclusion A claims-based algorithm combining diagnosis codes and antibiotic prescriptions identified LD cases in MA with high PPV. This algorithm could be used to describe the incidence of LD in regions with similar diagnostic, treatment, and coding practices. Disclosures Sheryl A. Kluberg, PhD, SM, GlaxoSmithKline: Grant/Research Support|Pfizer, Inc.: Support for the project described in the abstract Sarah J. Willis, PhD, MPH, Pfizer: Employment|Pfizer: Conducted Pfizer funded research while employed by Harvard Pilgrim Health Care Institute Noelle M. Cocoros, DSc, MPH, Pfizer: PI on study Bradford J. Gessner, M.D., M.P.H., Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds Sarah J. Pugh, PhD, MPH, Pfizer, Inc: Employee|Pfizer, Inc: Stocks/Bonds James H. Stark, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Chanu Rhee, MD, MPH, Cytovale: Advisor/Consultant|Pfizer: Advisor/Consultant|UpToDate, Inc.: Royalties.

Hyo-In Rhyou,1 Young-Hee Nam2 1Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea; 2Department of Internal Medicine, College of Medicine, Dong-A University Hospital, Busan, KoreaCorrespondence: Young-Hee Nam, Department of Internal Medicine, College of Medicine, Dong-A University, 26 Daesingongwon-ro, Seo-Gu, Busan, Korea, Tel +8251-240-5860, Fax +82-51-242-5864, Email yhnam@dau.ac.krPurpose: Drug hypersensitivity is an adverse drug reaction mediated by immunological mechanisms and is accompanied by a significant socioeconomic burden. The drug provocation test (DPT) is the gold standard for drug allergy diagnosis; however, a standardized protocol does not exist. This study aimed to investigate the effects of psychological relief from DPT in patients with drug hypersensitivity.Patients and Methods: A total of 46 patients who had experienced drug hypersensitivity were administered DPT after admission to our clinic at Dong-A University Hospital and asked to complete the questionnaires before and after DPT. Anxiety and depressive symptom levels were assessed using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI)-II, respectively.Results: There was a significant decrease in the BAI and BDI-II scores after DPT than before DPT, respectively (BAI: 10.22 ± 10.75 vs 7.26 ± 6.95, P=0.025; BDI-II: 13.00 ± 7.92 vs 11.17 ± 7.80, P = 0.019). Twenty-two patients with non-anaphylactic drug hypersensitivity showed a significant decrease in the BDI-II scores after DPT (11.50 ± 7.60 vs 9.50 ± 5.98, P = 0.009), but not in the BAI scores (8.45 ± 7.41 vs 6.18 ± 4.58, P = 0.127). However, there were no statistically significant differences in the BDI-II and BAI scores before and after DPT (BAI: 11.83 ± 13.05 vs 8.25 ± 8.56, P = 0.664; BDI-II: 14.38 ± 8.11 vs 12.71 ± 9.01, P = 0.215) in 24 patients with anaphylaxis.Conclusion: DPT may reduce the psychological burden in patients with drug hypersensitivity, especially in those without anaphylaxis.Keywords: drug hypersensitivity, diagnostic test, anxiety, depression

The US Food and Drug Administration (FDA) created the Sentinel System in response to a requirement in the FDA Amendments Act of 2007 that the agency establish a system for monitoring risks associated with drug and biologic products using data from disparate sources. The Sentinel System has completed hundreds of analyses, including many that have directly informed regulatory decisions. The Sentinel System also was designed to support a national infrastructure for a learning health system. Sentinel governance and guiding principles were designed to facilitate Sentinel’s role as a national resource. The Sentinel System infrastructure now supports multiple non-FDA projects for stakeholders ranging from regulated industry to other federal agencies, international regulators, and academics. The Sentinel System is a working example of a learning health system that is expanding with the potential to create a global learning health system that can support medical product safety assessments and other research.

HLA-B*58:01 is a well-known risk factor for allopurinol-induced severe cutaneous adverse reactions (SCARs). However, only a minority of HLA-B*58:01 carriers suffer SCARs after taking allopurinol. The aim of this study was to investigate subsidiary genetic markers that could identify those at further increased risk of developing allopurinol-induced drug reaction with eosinophilia and systemic symptoms (DRESS) in subjects with HLA-B*58:01.Subjects with B*58:01 were enrolled (21 allopurinol-induced DRESS and 52 allopurinol-tolerant control). HLA-A, -B, -C and -DRB1 alleles were compared. Comparison of risk between HLAs and allopurinol-induced SCAR in separate populations was performed to support the results. Kruskal-Wallis test, Pearson's chi-square test, Fisher's exact test and binary logistic regression were used to analyze the risk of SCAR development.Frequencies of A*24:02 (71.4 vs. 17.3%,The additional secondary screening with A*24:02 and DRB1*13:02 alleles may identify those at further increased risk of allopurinol-induced DRESS in B*58:01 carriers.

Tiotropium, a long-acting muscarinic antagonist, is recommended for add-on therapy to inhaled corticosteroids (ICS)-long-acting beta 2 agonists (LABA) for severe asthma. However, real-world studies on the predictors of response to tiotropium are limited. We investigated the real-world use of tiotropium in asthmatic adult patients in Korea and we identified predictors of positive response to tiotropium add-on.We performed a multicenter, retrospective, cohort study using data from the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA). We enrolled asthmatic participants who took ICS-LABA with at least 2 consecutive lung function tests at 3-month intervals. We compared tiotropium users and non-users, as well as tiotropium responders and non-responders to predict positive responses to tiotropium, defined as 1) increase in forced expiratory volume in 1 s (FEV1) ≥ 10% or 100 mL; and 2) increase in asthma control test (ACT) score ≥3 after 3 months of treatment.The study included 413 tiotropium users and 1756 tiotropium non-users. Tiotropium users had low baseline lung function and high exacerbation rate, suggesting more severe asthma. Clinical predictors for positive response to tiotropium add-on were 1) positive bronchodilator response (BDR) [odds ratio (OR) = 6.8, 95% confidence interval (CI): 1.6-47.4, P = 0.021] for FEV1 responders; 2) doctor-diagnosed asthma-chronic obstructive pulmonary disease overlap (ACO) [OR = 12.6, 95% CI: 1.8-161.5,The results of this study suggest that tiotropium add-on for uncontrolled asthma with ICS-LABA would be more effective in patients with positive BDR or ACO. Additionally, an increase in FEV1 following tiotropium may predict a lower risk of asthma exacerbation.

IntroductionThis study aimed to assess data relevancy and data quality of the Innovation in Medical Evidence Development and Surveillance System Distributed Database (IMEDS-DD) for diabetes research and to evaluate comparability of its type 2 diabetes cohort to the general type 2 diabetes population.Research design and methodsA retrospective study was conducted using the IMEDS-DD. Eligible members were adults with a medical encounter between April 1, 2018 and March 31, 2019 (index period). Type 2 diabetes and co-existing conditions were determined using all data available from April 1, 2016 to the most recent encounter within the index period. Type 2 diabetes patient characteristics, comorbidities and hemoglobin A1c(HbA1c) values were summarized and compared with those reported in national benchmarks and literature.ResultsType 2 diabetes prevalence was 12.6% in the IMEDS-DD. Of 4 14 672 patients with type 2 diabetes, 52.8% were male, and the mean age was 65.0 (SD 13.3) years. Common comorbidities included hypertension (84.5%), hyperlipidemia (82.8%), obesity (45.3%), and cardiovascular disease (44.7%). Moderate-to-severe chronic kidney disease was observed in 20.2% patients. The most commonly used antihyperglycemic agents included metformin (35.7%), sulfonylureas (14.8%), and insulin (9.9%). Less than one-half (48.9%) had an HbA1cvalue recorded. These findings demonstrated the notable similarity in patient characteristics between type 2 diabetes populations identified within the IMEDS-DD and other large databases.ConclusionsDespite the limitations related to HbA1cdata, our findings indicate that the IMEDS-DD contains robust information on key data elements to conduct pharmacoepidemiological studies in diabetes, including member demographic and clinical characteristics and health services utilization.

Background Cefaclor, a second-generation oral cephalosporin, is widely prescribed to treat infectious diseases. Immediate hypersensitivity (HS) reactions to cefaclor have continuously been reported and are expected to increase with its greater use. This study aimed to investigate the clinical characteristics and risk factors of immediate HS to cefaclor over the most recent 5 years. Methods This retrospective study investigated 521 adverse drug reactions (ADRs) to cefaclor at pharmacovigilance centers at two tertiary hospitals from January 2014 to December 2018. In total, 459 patients with immediate HS to cefaclor were reviewed. Results A total of 459 cases of cefaclor immediate HS were included among 521 cefaclor ADRs, and anaphylaxis was recorded in 61.2%. Female sex (odds ratio 2.917, 95% confidence interval 2.397–3.550, P P P P = 0.010), asthma (8.075, 5.301–12.302, P P Conclusions Cefaclor was found to elicit high proportions of immediate HS and anaphylaxis. Physicians ought to be cautious with prescribing cefaclor to females, individuals with hypertension, liver diseases, or asthma, and patients taking nonsteroidal anti-inflammatory drugs. Trial registration This study was retrospectively registered.

Background/Aims Emotional distress is thought to cause or maintain chronic urticaria (CU). We aimed to investigate the presence of anxiety, depression, and stress in Korean adult CU patients and to explore their potential impact on treatment. Methods We enrolled 79 CU patients and a disease control group comprising 39 persistent asthma patients. The Hospital Anxiety and Depression Scale (HADS) was used to evaluate depression and anxiety. Stress and quality of life (QoL) were assessed by Stress Response Inventory and CU-QoL questionnaires. The sociodemographic and clinical data such as urticaria activity score (UAS-15, UAS-6) were obtained. Results The prevalence of depression and anxiety based on the HADS were 48.1% and 38.0%. Although the prevalence of anxiety didn’t differ between the CU and asthma patients, depression was significantly more prevalent in the CU patients (48.1% vs. 28.2%). Stress tended to be lower in CU patients. Anxiety, depression, and stress exhibited negative correlations with QoL. Anxiety showed significant correlation with UAS-6 and pruritus-visual analog scale (VAS; r = 0.256, r = 0.272, p < 0.05, respectively); depression correlated with sleep difficulty-VAS (r = 0.261, p < 0.05). Stress was associated with UAS-15, UAS-6, pruritus-VAS, and sleep difficulty-VAS (r = 0.251, r = 0.317, r = 0.302, r = 0.258, p < 0.05, respectively). Conclusions The current study first presented that Korean CU patients frequently have anxiety and depression, which affect their QoL and demonstrated that anxiety, depression, and stress had different effects on sleep difficulty, pruritus, and urticaria severity in Korean CU patients.

Background/Aims: Chronic spontaneous urticaria (CSU) poses a considerable burden both on the quality of life (QoL) of individual patients and on healthcare systems. Real‑world data evaluating the disease burden of CSU are limited in this country. This study evaluated the disease burden and healthcare resource utilization (HRU) among symptomatic CSU patients.Methods: This multicenter, noninterventional, retrospective, and cross-sectional study assessed CSU patients symptomatic for more than 6 months despite step-wise H1-antihistamine medications. Primary outcomes included Urticaria Activity Score over 7 days (UAS7) and Chronic Urticaria QoL scale (CU-QoL). Secondary outcomes included EuroQol 5-Dimension 5-Level (EQ-5D-5L), Dermatology Life Quality Index (DLQI), association of disease activity with QoL, medications used for the past 6 months, and HRU.Results: Five hundred patients with CSU were enrolled. Mean disease duration was 3.7 years. Based on UAS7, 22.2% of patients were in well-controlled status and 31.2%, 28.4%, and 18.2% of them had mild, moderate, and severe disease, respectively. Mean CU-QoL and DLQI scores were 57.5 ± 29.7 and 10.2 ± 7.6, respectively, while the EQ-5D-5L utility score was 0.8 ± 0.2. H1-antihistamines were prescribed to 95% of patients, while omalizumab was prescribed to 33% of patients. Most patients (98%) had outpatient visits in the past 6 months. Negative correlations were noted between UAS7 and CU-QoL, EQ-5D-5L, EQ-5D-5L visual analog scale scores, but a positive correlation was noted with DLQI score (p < 0.001 for all). The number of outpatient department visits increased with disease activity (p = 0.001).Conclusions: CSU affects QoL, leading to increased HRU, particularly in patients with severe disease.

Background Asthma is characterized by chronic airway inflammation, and inhaled corticosteroids (ICSs) have been recommended as first-line treatment. However, response to ICS treatment is various, and the prediction of response to ICSs is still difficult, especially in individuals with newly diagnosed asthma. Objective To assess the clinical factors and biomarkers associated with response to ICSs in newly diagnosed asthma. Methods A total of 150 ICS-naive patients with newly diagnosed asthma in the allergy clinic of a single tertiary hospital in Korea from January 2014 to January 2019 were included in this study. All patients initially received moderate-dose ICSs and were treated for more than 1 year. We compared the clinical characteristics and parameters between patients with and without acute exacerbation (AE) during the study period. Results In this study, 99 patients had no AE (stable asthma group), and 51 patients presented with more than 1 AE (unstable asthma group). The mean (SD) blood eosinophil count (635.7 [780.3] × 103/μL vs 373.4 [266.8] × 103/μL, P = .003) and sputum eosinophil count (15.2% [23.9%] vs 8.3% [15.4%], P = .051) were higher and the sputum neutrophil count (42.9% [35.1%] vs 61.3% [35.1%], P = .057) was lower in the stable asthma group than in the unstable asthma group. Conclusion High blood and sputum eosinophil counts can predict a good response to ICS treatment in terms of prevention of AE in individuals with newly diagnosed asthma. The sputum neutrophil count may be an effective predictor of response to ICSs, even though additional studies must be conducted.

Drug interactions between warfarin and sulfonylureas are suggested by pharmacokinetic information and prior studies. However, clinical evidence on the association of such interactions and the risk of bleeding is lacking. Using healthcare claims data from 5 US Medicaid programs from 1999-2011 and a self-controlled case series design with warfarin as an object drug, we calculated confounder-adjusted rate ratios (RRs) for concomitant use of sulfonylureas and metformin for 3 outcomes separately: (i) serious bleeding as a composite outcome of gastrointestinal bleeding (GIB) and nontraumatic intracranial hemorrhage (ICH); (ii) GIB; and (iii) ICH. In 6,463 warfarin users experiencing serious bleeding, an increased rate of serious bleeding was not associated with concomitant use of glimepiride (RR: 0.93; 95% confidence interval (CI) 0.75-1.15), glipizide (RR: 0.97; 95% CI 0.84-1.13), glyburide (RR: 0.89; 95% CI 0.76-1.06), or metformin (RR: 0.85; 95% CI 0.76-0.96), nor was the occurrence of the component outcomes of GIB or ICH. These results suggest that use of sulfonylureas or metformin was not associated with an increased rate of serious bleeding in warfarin users.

Background and objective Lyme disease (LD) is the fifth most commonly reported notifiable infectious disease in the United States (US) with approximately 35,000 cases reported in 2019 via public health surveillance. However, healthcare claims-based studies estimate that the number of LD cases is >10 times larger than reported through surveillance. To assess the burden of LD using healthcare claims data and the effectiveness of interventions for LD prevention and treatment, it is important to use validated well-performing LD case-finding algorithms (“LD algorithms”). We conducted a systematic literature review to identify LD algorithms used with US healthcare claims data and their validation status. Methods We searched PubMed and Embase for articles published in English since January 1, 2000 (search date: February 20, 2021), using the following search terms: (1) “Lyme disease”; and (2) “claim*” or “administrative* data”; and (3) “United States” or “the US*”. We then reviewed the titles, abstracts, full texts, and bibliographies of the articles to select eligible articles, i.e., those describing LD algorithms used with US healthcare claims data. Results We identified 15 eligible articles. Of these, seven studies used LD algorithms with LD diagnosis codes only, four studies used LD diagnosis codes and antibiotic dispensing records, and the remaining four studies used serologic test order codes in combination with LD diagnosis codes and antibiotics records. Only one of the studies that provided data on algorithm performance: sensitivity 50% and positive predictive value 5%, and this was based on Lyme disease diagnosis code only. Conclusions US claims-based LD case-finding algorithms have used diverse strategies. Only one algorithm was validated, and its performance was poor. Further studies are warranted to assess performance for different algorithm designs and inform efforts to better assess the true burden of LD.

This cohort study investigates whether serious hypoglycemia is reduced in a Medicaid population receiving calcium-channel blockers with insulin secretagogues.

Serious hypoglycemia is a major adverse event associated with insulin secretagogues. Previous studies have suggested a potential relationship between angiotensin-converting enzyme inhibitors (ACEIs) used with sulfonylureas and serious hypoglycemia, and widely used drug compendia warn of this potential drug-drug interaction. We investigated the association between serious hypoglycemia and concomitant use of ACEIs in patients receiving insulin secretagogues, using the self-controlled case series design and Medicaid claims data from 5 US states linked to Medicare claims from 1999-2011. The exposure of interest was active prescription for ACEIs during insulin secretagogue or metformin (negative control object drug) episodes. The outcome was hospital presentation for serious hypoglycemia, identified by discharge diagnosis codes in inpatient and emergency department claims (positive predictive value ~78-89%). We calculated confounder-adjusted rate ratios (RRs) and 95% confidence internals (CIs) of outcome occurrence during ACEI-exposed versus ACEI-unexposed time using conditional Poisson regression. The RRs for ACEIs were not statistically elevated during observation time of glipizide (RR, 1.06; CI, 0.98-1.15), glyburide (RR, 1.05; CI, 0.96-1.15), repaglinide (RR, 1.15; CI, 0.94-1.41), or metformin (RR, 1.02; CI, 0.97-1.06); but was modestly elevated with glimepiride (RR, 1.23; CI, 1.11-1.37) and modestly reduced with nateglinide (RR, 0.73; CI, 0.56-0.96). The overall pattern of results do not suggest that ACEIs used with insulin secretagogues were associated with increased rates of serious hypoglycemia, with the possible exception of glimepiride.

Background Beta-lactams (BLs) are commonly used antibiotics and leading causative agents of drug-induced anaphylaxis. Few studies on the culprit drugs and risk factors of BL-induced anaphylaxis are available. Our goal was to evaluate the culprit drugs and compare the risk factors in patients with BL-induced anaphylaxis to matched tolerant controls in a hospital setting. Methods We retrospectively enrolled all patients who developed anaphylaxis from intravenous BL during hospitalization from 9 Korean hospitals. We compared clinical parameters between patients with BL-induced anaphylaxis and 4-fold BL-tolerant controls matched by age, sex, BL use, and the purpose of BL administration. Results Seventy-four cases of BL-induced anaphylaxis and 296 BL-tolerant controls were enrolled. Cephalosporin accounted for 77% of total BL-induced anaphylaxis, and the top derivatives were ceftriaxone (23.0%), cefazedone (10.8%), and cefbuperazone (9.5%). Among penicillin derivatives, piperacillin (16.2%) was the most common, followed by ampicillin (2.7%). History of drug allergy (odds ratio [OR], 19.91; 95% confidence interval [CI] 5.33–74.44), previous exposure to the causative BL (OR, 7.71; 95% CI, 1.62–36.76), and concurrent administration of angiotensin-converting enzyme inhibitors (ACEIs) (OR, 5.97; 95% CI, 1.28–27.91) were independent risk factors associated with BL-induced anaphylaxis. Food allergy (OR, 13.93; 95% CI 1.31–148.9) and previous exposure to BL (OR, 6.59; 95% CI, 1.30–33.31) were identified as risk factors for cephalosporin-induced anaphylaxis. Conclusions To prevent BL-induced anaphylaxis, attention should be paid to histories of drug or food allergy, previous exposure to BLs, and ACEI use. The risk factors and clinical outcomes might vary according to the BL classes.

Introduction. This study sought to evaluate the association between obesity factors (food consumption and physical activity) and breast cancer incidence in Korean women. Material and methods. The study included breast cancer patients (250 women) and normal participants undergoing medical checkups (250 women) who visited a specialized cancer research hospital between August 1, 2016 and February 15, 2017. Nutrient intake was assessed using a validated food frequency questionnaire (FFQ) covering 112 dishes and foods that Koreans often eat. Physical activity was assessed according to the International Physical Activity Questionnaire (IPAQ) guidelines and was quantified as metabolic equivalent (MET) scores. Results. The results for nutrient intake obtained using the FFQ showed that the control group had a higher consumption of dietary fiber (p < 0.004) and a lower intake of animal fat (p < 0.02) than the breast cancer group. Among breast cancer patients, pre-menopausal women consumed more animal fat (18.6 g ± 11.9 vs. 14.7 g ± 8.5, p < 0.03) than post-menopausal ones. An analysis of the MET scores with logistic regression revealed that lower physical activity among cancer patients was associated with an increased risk of breast cancer, and this association was greater among post-menopausal (OR = 2.11, p < 0.001) than pre-menopausal women (OR = 0.85, p < 0.02). Conclusion. Having a high-fat diet and doing less exercise increases the risk of breast cancer, so it is important to prevent the accumulation of fat and maintain proper weight through regular physical activity to lower the incidence of breast cancer.

Few population-based studies have examined bleeding associated with clopidogrel drug-drug interactions (DDIs). We sought to identify precipitant drugs taken concomitantly with clopidogrel (an object drug) that increased serious bleeding rates. We screened 2000-2015 Optum commercial health insurance claims to identify DDI signals. We performed self-controlled case series studies for clopidogrel plus precipitant pairs, examining associations with gastrointestinal bleeding or intracranial hemorrhage. To distinguish native bleeding effects of a precipitant, we reexamined associations using pravastatin as a negative control object drug. Among 431 analyses, 28 clopidogrel plus precipitant pairs were statistically significantly positively associated with serious bleeding. Ratios of rate ratios ranged from 1.13-3.94. Among these pairs, 13 were expected given precipitant drugs alone increased and/or were harbingers of serious bleeding. The remaining 15 pairs constituted new DDI signals, none of which are currently listed in two major DDI knowledge bases.

Background Lyme disease (LD) is the fifth most common notifiable disease in the US with 30,000-40,000 LD cases reported annually via public health surveillance. Recent healthcare claims-based studies utilizing case-finding algorithms estimate national LD cases are >10-fold higher than reported by surveillance. The reliability of claims-based data depends on the accuracy of the case-finding algorithms using the information available in the claims primarily generated for the administrative purposes. To assess the true burden of LD, it is imperative to use validated well-performing LD case-finding algorithms (“LD algorithms”). We conducted a systematic literature review to identify LD algorithms based upon healthcare claims data in the US and their respective performance. Methods We searched PubMed and Embase for articles published in English from January 1, 2000 through the most recent date as of February 20, 2021. We selected articles including all of the following search terms: (1) “Lyme disease”; (2) “claim*” or “administrative* data”; and (3) “United States” or “the US*”. We then reviewed the titles, abstracts, and full texts to identify articles describing LD algorithms developed for claims data. Figure 1 shows the flow diagram following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Results We found 15 articles meeting the inclusion criteria. Of these, 7 study algorithms used only LD diagnosis codes (ICD-9, 088.81; ICD-10, A69.2 or A69.2x), 4 studies additionally used antibiotic dispensing records, and 4 studies additionally used serologic test order codes (CPT 86617, 86618). Three studies used different algorithms for inpatient and outpatient settings. Only one study (in Tennessee, a low-incidence state for LD) provided validation results for their algorithm, which only used a LD diagnosis code (ICD-9, 088.81), with reported sensitivity=50% and positive predictive value=5%. Conclusion Validation data on the LD algorithms developed for healthcare claims data are limited, and suggest algorithms using only LD diagnosis codes may not perform well. Further validation of high-performance claims-based LD algorithms is critical to inform the true burden of LD overall and within subgroups. Disclosures Bradford D. Gessner, MD, MPH, Pfizer Inc. (Employee) James Stark, PhD, Pfizer Inc. (Employee) Sarah Pugh, PhD, Pfizer Inc. (Employee)

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.