Integrating the STOP-BANG Score and Clinical Data to Predict Cardiovascular Events After Infarction A Machine Learning Study

BACKGROUND: OSA conveys worse clinical outcomes in patients with coronary artery disease. The STOP-BANG score is a simple tool that evaluates the risk of OSA and can be added to the large number of clinical variables and scores that are obtained during the management of patients with myocardial infarction (MI). Currently, machine learning (ML) is able to select and integrate numerous variables to optimize prediction tasks. RESEARCH QUESTION: Can the integration of STOP-BANG score with clinical data and scores through ML better identify patients who experienced an in-hospital cardiovascular event after acute MI? STUDY DESIGN AND METHOD: This is a prospective observational cohort study of 124 patients with acute MI of whom the STOP-BANG score classified 34 as low (27.4%), 30 as intermediate (24.2%), and 60 as high (48.4%) OSA-risk patients who were followed during hospitalization. ML implemented feature selection and integration across 47 variables (including STOP-BANG score, Killip class, GRACE score, and left ventricular ejection fraction) to identify those patients who experienced an in-hospital cardiovascular event (ie, death, ventricular arrhythmias, atrial fibrillation, recurrent angina, reinfarction, stroke, worsening heart failure, or cardiogenic shock) after definitive MI treatment. Receiver operating characteristic curves were used to compare ML performance against STOP-BANG score, Killip class, GRACE score, and left ventricular ejection fraction, independently. RESULTS: There were an increasing proportion of cardiovascular events across the low, intermediate, and high OSA risk groups (P = .005). ML selected 7 accessible variables (ie, Killip class, leukocytes, GRACE score, c reactive protein, oxygen saturation, STOP-BANG score, and N-terminal prohormone of B-type natriuretic peptide); their integration outperformed all comparators (area under the curve, 0.83 [95% CI, 0.74-0.90]; P <.01). INTERPRETATION: The integration of the STOP-BANG score into clinical evaluation (considering Killip class, GRACE score, and simple laboratory values) of subjects who were admitted for an acute MI because of ML can significantly optimize the identification of patients who will experience an in-hospital cardiovascular event

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Ethnic group inequalities in coverage with reproductive, maternal and child health interventions: cross-sectional analyses of national surveys in 16 Latin American and Caribbean countries

Summary: Background: Latin American and Caribbean populations include three main ethnic groups: indigenous people, people of African descent, and people of European descent. We investigated ethnic inequalities among these groups in population coverage with reproductive, maternal, newborn, and child health interventions. Methods: We analysed 16 standardised, nationally representative surveys carried out from 2004 to 2015 in Latin America and the Caribbean that provided information on ethnicity or a proxy indicator (household language or skin colour) and on coverage of reproductive, maternal, newborn, and child health interventions. We selected four outcomes: coverage with modern contraception, antenatal care coverage (defined as four or more antenatal visits), and skilled attendants at birth for women aged 15–49 years; and coverage with three doses of diphtheria-pertussis-tetanus (DPT3) vaccine among children aged 12–23 months. We classified women and children as indigenous, of African descent, or other ancestry (reference group) on the basis of their self-reported ethnicity or language. Mediating variables included wealth quintiles (based on household asset indices), woman's education, and urban-rural residence. We calculated crude and adjusted coverage ratios using Poisson regression. Findings: Ethnic gaps in coverage varied substantially from country to country. In most countries, coverage with modern contraception (median coverage ratio 0·82, IQR 0·66–0·92), antenatal care (0·86, 0·75–0·94), and skilled birth attendants (0·75, 0·68–0·92) was lower among indigenous women than in the reference group. Only three countries (Nicaragua, Panama, and Paraguay) showed significant gaps in DPT3 coverage between the indigenous and the reference groups. The differences were attenuated but persisted after adjustment for wealth, education, and residence. Women and children of African descent showed similar coverage to the reference group in most countries. Interpretation: The lower coverage levels for indigenous women are pervasive, and cannot be explained solely by differences in wealth, education, or residence. Interventions delivered at community level—such as vaccines—show less inequality than those requiring access to services, such as birth attendance. Regular monitoring of ethnic inequalities is essential to evaluate existing initiatives aimed at the inclusion of minorities and to plan effective multisectoral policies and programmes. Funding: The Bill & Melinda Gates Foundation (through the Countdown to 2030 initiative) and the Wellcome Trust

Efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate in ten countries in Europe and Latin America (HERALD): a randomised, observer-blinded, placebo-controlled, phase 2b/3 trial

Background: Additional safe and efficacious vaccines are needed to control the COVID-19 pandemic. We aimed to analyse the efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate. Methods: HERALD is a randomised, observer-blinded, placebo-controlled, phase 2b/3 clinical trial conducted in 47 centres in ten countries in Europe and Latin America. By use of an interactive web response system and stratification by country and age group (18–60 years and ≥61 years), adults with no history of virologically confirmed COVID-19 were randomly assigned (1:1) to receive intramuscularly either two 0·6 mL doses of CVnCoV containing 12 μg of mRNA or two 0·6 mL doses of 0·9% NaCl (placebo) on days 1 and 29. The primary efficacy endpoint was the occurrence of a first episode of virologically confirmed symptomatic COVID-19 of any severity and caused by any strain from 15 days after the second dose. For the primary endpoint, the trial was considered successful if the lower limit of the CI was greater than 30%. Key secondary endpoints were the occurrence of a first episode of virologically confirmed moderate-to-severe COVID-19, severe COVID-19, and COVID-19 of any severity by age group. Primary safety outcomes were solicited local and systemic adverse events within 7 days after each dose and unsolicited adverse events within 28 days after each dose in phase 2b participants, and serious adverse events and adverse events of special interest up to 1 year after the second dose in phase 2b and phase 3 participants. Here, we report data up to June 18, 2021. The study is registered at ClinicalTrials.gov, NCT04652102, and EudraCT, 2020–003998–22, and is ongoing. Findings: Between Dec 11, 2020, and April 12, 2021, 39 680 participants were enrolled and randomly assigned to receive either CVnCoV (n=19 846) or placebo (n=19 834), of whom 19 783 received at least one dose of CVnCoV and 19 746 received at least one dose of placebo. After a mean observation period of 48·2 days (SE 0·2), 83 cases of COVID-19 occurred in the CVnCoV group (n=12 851) in 1735·29 person-years and 145 cases occurred in the placebo group (n=12 211) in 1569·87 person-years, resulting in an overall vaccine efficacy against symptomatic COVID-19 of 48·2% (95·826% CI 31·0–61·4; p=0·016). Vaccine efficacy against moderate-to-severe COVID-19 was 70·7% (95% CI 42·5–86·1; CVnCoV 12 cases in 1735·29 person-years, placebo 37 cases in 1569·87 person-years). In participants aged 18–60 years, vaccine efficacy against symptomatic disease was 52·5% (95% CI 36·2–64·8; CVnCoV 71 cases in 1591·47 person-years, placebo, 136 cases in 1449·23 person-years). Too few cases occurred in participants aged 61 years or older (CVnCoV 12, placebo nine) to allow meaningful assessment of vaccine efficacy. Solicited adverse events, which were mostly systemic, were more common in CVnCoV recipients (1933 [96·5%] of 2003) than in placebo recipients (1344 [67·9%] of 1978), with 542 (27·1%) CVnCoV recipients and 61 (3·1%) placebo recipients reporting grade 3 solicited adverse events. The most frequently reported local reaction after any dose in the CVnCoV group was injection-site pain (1678 [83·6%] of 2007), with 22 grade 3 reactions, and the most frequently reported systematic reactions were fatigue (1603 [80·0%] of 2003) and headache (1541 [76·9%] of 2003). 82 (0·4%) of 19 783 CVnCoV recipients reported 100 serious adverse events and 66 (0·3%) of 19 746 placebo recipients reported 76 serious adverse events. Eight serious adverse events in five CVnCoV recipients and two serious adverse events in two placebo recipients were considered vaccination-related. None of the fatal serious adverse events reported (eight in the CVnCoV group and six in the placebo group) were considered to be related to study vaccination. Adverse events of special interest were reported for 38 (0·2%) participants in the CVnCoV group and 31 (0·2%) participants in the placebo group. These events were considered to be related to the trial vaccine for 14 (<0·1%) participants in the CVnCoV group and for five (<0·1%) participants in the placebo group. Interpretation: CVnCoV was efficacious in the prevention of COVID-19 of any severity and had an acceptable safety profile. Taking into account the changing environment, including the emergence of SARS-CoV-2 variants, and timelines for further development, the decision has been made to cease activities on the CVnCoV candidate and to focus efforts on the development of next-generation vaccine candidates. Funding: German Federal Ministry of Education and Research and CureVac

7th Drug hypersensitivity meeting: part two

Table of contents Poster walk 11: miscellaneous drug hypersensitivity 2 (P92–P94, P96–P101) P92 16 years of experience with proton pump inhibitors (PPIs) Javier Dionicio Elera, Cosmin Boteanu, Maria Aranzazu Jimenez Blanco, Rosario Gonzalez-Mendiola, Irene Carrasco García, Antonio Alvarez, Jose Julio Laguna Martinez P93 Allergy evaluation of quinolone induced adverse reactions Jaume Martí Garrido, Carla Torán Barona, Carolina Perales Chorda, Ramón López Salgueiro, Miguel Díaz Palacios, Dolores Hernández Fernández De Rojas P94 Bupropion-induced acute urticaria and angioedema, a case report Emre Ali Acar, Ayse Aktas, Aylin Türel Ermertcan, Peyker Temiz P96 Delayed type hypersensitivity and study of cross-reactivity between proton-pump inhibitors Chien-Yio Lin, Chung-Yee Rosaline Hui, Ya-Ching Chang, Chih-Hsun Yang, Wen-Hung Chung P97 Diagnostic work-up in suspected hypersensitivity to proton-pump inhibitors: looking at cross-reactivity Fabrícia Carolino, Diana Silva, Eunice Dias De Castro, Josefina R. Cernadas P98 Management of infusion-related hypersensitivity reactions to enzyme replacement therapy for lysosomal diseases Luis Felipe Ensina, Carolina Aranda, Ines Camelo Nunes, Alex Lacerda, Ana Maria Martins, Ekaterini Goudouris, Marcia Ribeiro, José Francisco Da Silva Franco, Leandra Queiroz, Dirceu Solé P99 Management of insulin allergy with continuous subcutaneous insulin infusion Ceyda Tunakan Dalgiç, Aytül Zerrin Sin, Fatma Düsünür Günsen, Gökten Bulut, Fatma Ömür Ardeniz, Okan Gülbahar, Emine Nihal Mete Gökmen, Ali Kokuludag P100 Off-label use of icatibant for management of serious angioedema associated with angiotensin inhibitors Ana M. Montoro De Francisco, Talía Mª De Vicente Jiménez, Adriana M. Mendoza Parra, Angella M. Burgos Pimentel, Amelia García Luque P101 Thiocolchicoside anaphylaxis: an unusual suspect? Luis Amaral, Fabricia Carolino, Leonor Carneiro Leão, Eunice Castro, Josefina Cernadas Poster walk 12: betalactam hypersensitivity (P102–P111) P102 A curious delayed reading: a case report of a β-lactam allergy in a child Nicole Pinto, Joana Belo, João Marques, Pedro Carreiro-Martins, Paula Leiria-Pinto P103 Betalactam-induced hypersensitivity: a 10-years’ experience Amel Chaabane, Haifa Ben Romdhane, Nadia Ben Fredj, Zohra Chadly, Naceur A. Boughattas, Karim Aouam P104 Cefazolin hypersensitivity: towards optimized diagnosis Astrid P. Uyttebroek, Chris H. Bridts, Antonino Romano, Didier G. Ebo, Vito Sabato P105 Clavulanic acid allergy: two cases report Anabela Lopes, Joana Cosme, Rita Aguiar, Tatiana Lourenço, Maria-João Paes, Amélia Spínola-Santos, Manuel Pereira-Barbosa P106 Diagnosis of betalactam allergy in an allergy department Cíntia Rito Cruz, Rute Pereira Dos Reis, Elza Tomaz, Ana Paula Pires, Filipe Inácio P107 Diagnostic work-up of 410 patients with suspicion of betalactam antibiotic hypersensitivity Filipe Benito-Garcia, Inês Mota, Magna Correia, Ângela Gaspar, Marta Chambel, Susana Piedade, Mário Morais-Almeida P108 Immediate selective hypersensitivity reactions to clavulanic acid Alla Nakonechna, Yurij Antipkin, Tetiana Umanets, Fernando Pineda, Francisca Arribas, Volodymyr Lapshyn P109 Prevalence and incidence of penicillin hypersensitivity reactions in Colombia Pablo Andrés Miranda, Bautista De La Cruz Hoyos P110 Selective sensitization to amoxicilin and clavulanic acid Jose Julio Laguna Martinez, Aranzazu Jimenez Blanco, Javier Dionicio Elera, Cosmin Boteanu, Rosario Gonzalez-Mendiola, Marta Del Pozo P111 Infliximab-specific T cells are detectable also in treated patients who have not developed anti-drug antibodies Alessandra Vultaggio, Francesca Nencini, Sara Pratesi, Andrea Matucci, Enrico Maggi Poster walk 13: biologicals, local anesthetics, others (P112–P118) P112 A case report of allergic immediate systemic reaction to adalimumab and certolizumab Ceyda Tunakan Dalgiç, Fatma Düsünür Günsen, Gökten Bulut, Fatma Ömür Ardeniz, Okan Gülbahar, Emine Nihal Mete Gökmen, Aytül Zerrin Sin, Ali Kokuludag P113 Allergy to local anesthetics: negative predictive value of skin tests Ivana Cegec, Danica Juricic Nahal, Viktorija Erdeljic Turk, Matea Radacic Aumiler, Ksenija Makar Ausperger, Iva Kraljickovic, Iveta Simic P114 Cutaneous adverse reactions of molecular targeted agents: a retrospective analysis in 150 patients in our department Yukie Yamaguchi, Tomoya Watanabe, Megumi Satoh, Tomohiko Tanegashima, Kayoko Oda, Hidefumi Wada, Michiko Aihara P115 Generalized paralysis induced by local lidocaine injection Jaechun Jason Lee, Jay Chol Choi, Hwa Young Lee P116 Hypersensitivity to local anaesthetics: a 10 year review Rosa-Anita Rodrigues Fernandes, Emília Faria, Joana Pita, Nuno Sousa, Carmelita Ribeiro, Isabel Carrapatoso, Ana Todo Bom P117 Local anaesthetics: a rare culprit in hypersensitivity reactions Ana Rodolfo, Eunice Dias-Castro, Josefina Cernadas P118 Stevens–Johnson syndrome in clinical practice: a variant of clinical course Marina Voronova Poster walk 14: RCM (P119–P128) P119 13 cases of severe anaphylactic reactions due to radiocontrast media Jaume Martí Garrido, Ramon Lopez Salgueiro, Diana Kury Valle, Verónica Pacheco Coronel, Carolina Perales Chordá, Dolores Hernandez Fernandez De Rojas P120 Anaphylactic shock after administration of iodinated contrast medium during cardiac catheterization Roselle Catherine Yu Madamba, Marta Ferrer, Maria Jose Goikoetxea, Carmen D’Amelio, Amalia Bernad, Olga Vega, Gabriel Gastaminza P121 Anaphylactic shock and cardiac arrest induced by gadolinium-based contrast agents Beatriz Pola Bibián, Marina Lluncor Salazar, Gemma Vilà Nadal, Ana María Fiandor Roman, Javier Dominguez Ortega, Miguel Gonzalez Muñoz, Santiago Quirce Gancedo, Maria Rosario Cabañas Moreno P122 Anaphylaxis to gadobenate and cross-reactivity to other gadolinium-based contrast agents in two patients Kathrin Scherer Hofmeier P123 Anaphylaxis to glatiramer acetate in a patient with multiple sclerosis Fabrícia Carolino, Vladyslava Barzylovych, Josefina R. Cernadas P124 Delayed hypersensitivity reaction to radiocontrast media Fabrícia Carolino, Diana Silva, Leonor Leão, Josefina R. Cernadas P125 Drug reaction with eosinophilia and systemic symptoms induced by iodixanol Gemma Vilà-Nadal, Beatriz Pola, Marina Lluncor, Ana Fiandor, Teresa Bellón, Javier Domínguez, Santiago Quirce P126 Electronic consultation support system for radiocontrast media hypersensitivity changes clinician’s behavior Min-Suk Yang, Sun-Sin Kim, Sae-Hoon Kim, Hye-Ryun Kang, Heung-Woo Park, Sang-Heon Cho, Kyung-Up Min, Yoon-Seok Chang P127 Hypersensitivity reactions to iodinated contrast media: skin testing and follow-up Danica Juricic Nahal, Ivana Cegec, Viktorija Erdeljic Turk, Iva Kraljickovic, Matea Radacic Aumiler, Ksenija Makar Ausperger, Iveta Simic P128 Would iodine allergy exist? Clémence Delahaye, Jenny Flabbee, Julie Waton, Olivia Bauvin, Annick Barbaud Poster walk 15: MPE/type 4 (P129–P137) P129 Delayed hypersensitivity cutaneous reactions: a case/control study from a tunisian database Karim Aouam, Najah Ben Fadhel, Zohra Chadly, Nadia Ben Fredj, Naceur A. Boughattas, Amel Chaabane P130 Delayed hypersensitivity reactions to cephalosporins: a review of seven cases Joana Cosme, Anabela Lopes, Amélia Spínola-Santos, Manuel Pereira-Barbosa P131 Diclofenac induced allergic contact dermatitis: case series of four patients Sandra Jerkovic Gulin, Anca Chiriac P132 Late-onset maculopapular rash to irbesartan Bárbara Kong Cardoso, Elza Tomaz, Regina Viseu, Filipe Inácio P133 Nonimmediate hypersensitivity reactions to betalactams: a retrospective analysis Ana Moreira, Susana Cadinha, Ana Castro Neves, Patricia Barreira, Daniela Malheiro, J. P. Moreira Da Silva P134 Occupational airborne contact dermatitis to omeprazole Ružica Jurakic-Toncic, Suzana Ljubojevic, Petra Turcic P135 Ornidazole-induced fixed drug eruption confirmed by positive patch test on a residual pigmented lesion Liesbeth Gilissen, Sara Huygens, An Goossens P136 Repeated delayed reaction induced by amoxicillin and amoxicillin clavulanate Inmaculada Andreu, Ramon Lopez-Salgueiro, Alicia Martinez Romero, Pau Gomez Cabezas P137 Systemic photosensitivity from fenofibrate in a patient photo-sensitized to ketoprofen Liesbeth Gilissen, An Goossens Poster walk 16: HLA genetics (P138–P146) P138 A copy number variation in ALOX5 and PTGER1 is associated with nonsteroidal anti-inflammatory drugs induced urticaria and/or angioedema Pedro Ayuso Parejo, Maria Del Carmen Plaza-Serón, Inmaculada Doña, Natalia Blanca López, Carlos Flores, Luisa Galindo, Ana Molina, James Richard Perkins, Jose Antonio Cornejo-García, José Augusto García-Agúndez, Elena García-Martín, Paloma Campo, María Gabriela Canto, Miguel Blanca P139 Association of galectin-3 (LGALS3) single nucleotide polymorphisms with non-steroidal anti-inflammatory drugs-induced urticaria/angioedema José Antonio Cornejo-Garcia, Inmaculada Doña, Rosa María Guéant-Rodríguez, Natalia Blanca-López, María Carmen Plaza-Serón, Raquel Jurado-Escobar, Esther Barrionuevo, María Salas, María Luisa Galindo, Gabriela Canto, Miguel Blanca, Jean-Louis Guéant P140 Detection of T cell responses to ticlopidine using peripheral blood mononuclear cells from HLA-A*33:03+ healthy donors Toru Usui, Arun Tailor, Lee Faulkner, John Farrell, Ana Alfirevic, B. Kevin Park, Dean J. Naisbitt P141 Epistasis approaches to identify novel genes potentially involved in NSAIDs hypersensitivity James Richard Perkins, Jose Antonio Cornejo García, Oswaldo Trelles, Inmaculada Doña, Esther Barrionuevo, María Salas, María Auxiliadora Guerrero, Miguel Blanca, Alex Upton P142 Genetic predisposition of cold medicine related SJS/TEN with severe ocular complications Mayumi Ueta, Hiromi Sawai, Chie Sotozono, Katushi Tokunaga, Shigeru Kinoshita P143 HLA-B*13:01 and dapsone induced hypersensitivity in Thai population Chonlaphat Chonlaphat Sukasem, Patompong Satapornpong, Therdpong Tempark, Pawinee Rerknimitr, Kulprapat Pairayayutakul, Jettanong Klaewsongkram P144 HLA-B*15:02 alleles and lamotrigine-induced cutaneous adverse drug reactions in Thai Chonlaphat Sukasem, N. Koomdee, T. Jantararoungtong, S. Santon, A. Puangpetch, U. Intusoma, W. Tassaneeyakul, V. Theeramoke P145 HLA-B*38:01 and HLA-A*24:02 allele frequencies in Spanish patients with lamotrigine-induced SCARs Teresa Bellón, Elena Ramirez, Alberto Manuel Borobia, Hoi Tong, Jose Luis Castañer, Francisco José De Abajo P146 Overrepresentation of a class II HLA haplotype in severe hypersensitivity type I reactions to carboplatin Violeta Régnier Galvao, Rebecca Pavlos, Elizabeth Mckinnon, Kristina Williams, Alicia Beeghly-Fadiel, Alec Redwood, Elizabeth Phillips, Mariana Castells Poster walk 17: in vivo diagnosis + sIgE (P147–P154) P147 Absence of specific Ig-e against beta-lactams 9 months after an allergic reaction to amoxicillin-clavulanic acid Elisa Boni, Marina Russello, Marina Mauro P148 Drug provocation tests in suspected opioid allergy Kok Loong Ue, Krzysztof Rutkowski P149 Improvement to the specific IgE cut-off in the assess of β-lactamic allergy Victor Soriano Gomis, Jorge Frances Ferre, Angel Esteban Rodriguez, Vicente Cantó Reig, Javier Fernandez Sanchez P150 Initial false negative specific IgE to gelatin in a patient with gelatin-induced anaphylaxis Christine Breynaert, Erna Van Hoeyveld, Rik Schrijvers P151 Inmediate reactions to beta-lactam antibiotics: pattern of skin test response over the time Jose Julio Laguna Martinez, Rosario Gonzalez Mendiola, Javier Dionicio Elera, Cosmin Boteanu, Aranzazu Jimenez Blanco, Marta Del Pozo, Raquel Fuentes Irigoyen P152 New fluorescent dendrimeric antigens for the evaluation of dendritic cell maturation as a test to detect allergy reactions to amoxicillin Daniel Collado, Yolanda Vida, Francisco Najera, Ezequiel Perez-Inestrosa, Pablo Mesa-Antunez, Cristobalina Mayorga, María José Torres, Miguel Blanca P153 Positive skin test or positive specific IgE to penicillin does not predict penicillin allergy Line K. Tannert, Charlotte G. Mortz, Per Stahl Skov, Carsten Bindslev-Jensen P154 Significance of skin testing and in vitro-analysis of neuromuscular blocking agents in diagnosis of perioperative drug hypersensitivity: evaluation of a negative control population Wolfgang Pfützner, Hannah Dörnbach, Johanna Visse, Michele Rauber, Christian Möbs Poster walk 18: in vitro/ex vivo (P155–P158, P160–P164) P155 Diagnostic value of the lymphocyte toxicity assay (LTA) and the in vitro platelet toxicity assay (IPTA) for β-lactam allergy Abdelbaset A. Elzagallaai, Lindsey Chow, Awatif M. Abuzgaia, Michael J. Rieder P156 Enzyme linked immunospot assay used in the diagnosis of severe cutaneous adverse reactions to antimicrobials Alec Redwood, Jason Trubiano, Rebecca Pavlos, Emily Woolnough, Kaija Stautins, Christina Cheng, Elizabeth Phillips P157 Evaluation of in vitro diagnostic methods for identifying the culprit drugs in drug hypersensitivity Kenichi Kato, Hiroaki Azukizawa, Takaaki Hanafusa, Ichiro Katayama P158 Ex-vivo expanded skin-infiltrating T cells from severe drug eruptions are reactive with causative drugs: a possible novel method for determination of causative drugs Toshiharu Fujiyama, Hideo Hashizume, Takatsune Umayahara, Taisuke Ito, Yoshiki Tokura P160 In vitro release of IL-2, IL-5 and IL-13 in diagnosis of patients with delayed-type nickel hypersensitivity Mira Silar, Mihaela Zidarn, Helena Rupnik, Peter Korosec P161 Single cell analysis of drug responsive T cells; identification of candidate drug reactive T cell receptors in abacavir and carbamazepine hypersensitivity Alec James Redwood, Kaija Strautins, Katie White, Abha Chopra, Katherine Konvinse, Shay Leary, Rebecca Pavlos, Simon Mallal, Elizabeth Phillips P162 Specificity and sensitivity of LTT in DRESS: analysis of agreement with the Spanish pharmacovigilance system probability algorithm Rosario Cabañas, Elena Ramirez, Ana María Fiandor, Teresa Bellón P163 The role of interleukin-22 in β-lactam hypersensitivity Andrew Sullivan, Paul Whitaker, Daniel Peckham, B. Kevin Park, Dean J. Naisbitt P164 Vancomycin-specific T cell responses and teicoplanin cross-reactivity Wei Yann Haw, Marta E. Polak, Carolann Mcguire, Michael R. Ardern-Jones Poster walk 19: BAT and biomarkers (P165–P173) P165 A combination of early biomarkers useful for the prediction of severe ADRs Yumi Aoyama, Tetsuo Shiohara P166 Basophil activation test in the diagnostic approach of reactions during general anaesthesia Ana Moreira, Susana Cadinha, Patrícia Barreira, Ana Castro Neves, Daniela Malheiro, Sara Correia, J. P. Moreira Da Silva P167 IL-10 can be related to successful desensitization Asli Gelincik, Semra Demir, Fatma Sen, Hamza Ugur Bozbey, Muge Olgac, Derya Unal, Raif Coskun, Bahauddin Colakoglu, Suna Buyuozturk, Esin Çatin-Aktas, Gunnur Deniz P168 Immediate reactions to proton pump inhibitors: value of basophil activation test Maria Salas, Jose Julio Laguna, Esther Barrionuevo, J. Dionicio, Tahia Fernandez, R. Gonzalez-Mendiola, I. Olazabal, Maria Dolores Ruiz, Miguel Blanca, Cristobalina Mayorga, Maria José Torres P169 Improvement of the elevated tryptase criterion to discriminate IgE from non-IgE mediated allergic reactions Gabriel Gastaminza, Alberto Lafuente, Carmen D’Amelio, Amalia Bernad, Olga Vega, Roselle Catherine Madamba, M. Jose Goikoetxea, Marta Ferrer, Jorge Núñez P170 Low expression of Tim-3 could serve as a biomarker for control and diagnose maculopapular exanthema induced by drugs Tahia Diana Fernández, Inmaculada Doña, Francisca Palomares, Rubén Fernández, Maria Salas, Esther Barrionuevo, Maria Isabel Sanchez, Miguel Blanca, Maria José Torres, Cristobalina Mayorga P171 Role of basophil activation test using two different activation markers for the diagnosis of allergy to fluoroquinolones Esther Barrionuevo, Tahía Fernandez, Arturo Ruiz, Adriana Ariza, Maria Salas, Inmaculada Doña, Ana Molina, Miguel Blanca, Maria Jose Torres, Cristobalina Mayorga P172 The importance of basophil activation test in anaphylaxis due to celecoxib Amalia Bernad Alonso, Carmen D’Amelio Garófalo, Olga Vega Matute, Marta Ferrer Puga, María José Goikoetxea Lapresa, Roselle Catherine Yu Madamba, Gabriel Gastaminza Lasarte P173 The role of basophil activation test in the diagnosis of immediate type drug hypersensitivity to betalactam antibiotics Antonia Thinnes, Hans F. Merk, Jens Malte Baron, Martin Leverkus, Galina Balakirski Poster walk 20: TCR recognition, cellular (P174–P183) P174 Characterisation of the effect of co-inhibitory signalling on the activation of drug-derived antigen-specific T-cells Andrew Gibson, Monday Ogese, Lee Faulkner, B. Kevin Park, Dean J. Naisbitt P175 Characterization of drug hapten-specific T cell responses in piperacillin hypersensitive patients Zaid Al-Attar, Fiazia Yaseen, Xiaoli Meng, Rozalind Jenkins, Paul Whitaker, Daniel Peckham, Lee Faulkner, John Farrel, Kevin Park, Dean Naisbitt P176 Characterization of the response of T-cells to telaprevir and its metabolite in normal volunteers Zaid Al-Attar, Khetam Alhilali, Yanni Xue, John Farrell, Lee Faulkner, Kevin Park, Dean Naisbitt P177 Characterization of the T cell receptor signatures of drug-responsive T cells Patricia Illing, Nicole Mifsud, Heidi Fettke, Jeffrey Lai, Rebecca Ho, Patrick Kwan, Anthony Purcell P178 Defining the signals between hepatocytes and immune cells in idiosyncratic drug-induced liver injury (DILI) Monday O. Ogese, Lee Faulkner, B. Kevin Park, Catherine Betts, Dean J. Naisbitt P179 Development of novel chemicals that do not bind to HLA-B*57:01 or activate CD8 + T-cells through modification of the 6-amino cyclopropyl group of abacavir Paul Thomson, John Farrell, Mohammad Alhaidari, Neill Berry, Paul M. O’Neill, B. Kevin Park, Dean J. Naisbitt P180 Generation and characterization of dapsone- and nitroso-dapsone-specific T-cell clones using lymphocytes from healthy volunteers Abdulaziz Alzahrani, Monday O. Ogese, John Farrell, Lee Faulkner, Andrew Gibson, Arun Tailor, B. Kevin Park, Dean J. Naisbitt P181 Identification of benzylpenicillin-hapten peptides responsible for naïve T-cell activation and immunization of allergic patients to penicillin Marie Eliane Azoury, Lucia Fili, Rami Bechara, Noémie Scornet, Cathy Nhim, Richard Weaver, Nancy Claude, Delphine Joseph, Bernard Maillere, Paola Parronchi, Marc Pallardy P182 Massive expansion of clonotypic and polycytotoxic CD8+ T cells in toxic epidermal necrolysis Axel Patrice Villani, Aurore Rozières, Benoît Bensaïd, Mathilde Tardieu, Floriane Albert, Virginie Mutez, Tugba Baysal, Marc Pallardy, Janet Maryanski, Jean-François Nicolas, Osami Kanagawa, Marc Vocanson P183 Pharmaco-immunological synapse of HLA-drug-TCR in SCAR Shuen-Iu Hung Poster walk 21: new in vitro methods, haptens, etc. (P184–P194) P184 Amoxicillin-clavulanate forms distinct multiple haptenic structures on human serum albumin in patients Xiaoli Meng, Arun Tailor, Caroline J. Harrison, Rosalind E. Jenkins, Paul Whitaker, Neil S. French, Dean J. Naisbitt, B. Kevin Park P185 Dendrimeric antigens for studying the influence of penicillin determinants orientation on IgE recognition Maria Isabel Montañez, Cristobalina Mayorga, Francisco Najera, Adriana Ariza, Tahia D. Fernandez, Maria Salas, Angela Martin-Serrano, Miguel Blanca, Ezequiel Perez-Inestrosa, Maria Jose Torres P186 Dendrimeric antigens on solid supports: designed materials for IgE quantification Yolanda Vida, Maria Isabel Montañez, Noemi Molina, Daniel Collado, Francisco Najera, Adriana Ariza, Maria Jose Torres, Cristobalina Mayorga, Ezequiel Perez-Inestrosa P187 Development of a screening assay for drug hypersensitivity using naïve T cells from donors with seven different HLA class I risk alleles Lee Faulkner, Sally Wood, Ana Alfirevic, Munir Pirmohamed, Dean J. Naisbitt, B. Kevin Park P188 Different patterns of recognition of structures derived from amoxicillin by IgE antibodies from patients with immediate hypersensitivity reactions to betalactams Adriana Ariza, Cristobalina Mayorga, María Isabel Montañez, María Salas, Inmaculada Doña, Ángela Martín-Serrano, Ezequiel Pérez-Inestrosa, Dolores Pérez-Sala, Miguel Blanca, Antonio E. Guzmán, María José Torres P189 High-resolution typing of HLA polymorphism and T-cell receptor repertoire for severe adverse drug reactions based on the cost-effective next-generation sequencing approaches Tai-Ming Ko, Yuan-Tsong Chen, Jer-Yuarn Wu P190 Identification and fate of intracellular proteins haptenated by amoxicillin Francisco J. Sánchez-Gómez, Juan M. González-Morena, Yolanda Vida, Ezequiel Pérez-Inestrosa, Miguel Blanca, María J. Torres, Dolores Pérez-Sala P191 In vitro detection of terbinafine protein adducts Arun Tailor, Toru Usui, Yanni Xue, Xiaoli Meng, Dean J. Naisbitt, B. Kevin Park P192 MicroRNAs dysregulation in PBMCs from drug hypersensitivity patients during drug challenge in vitro Alejandra Monroy Arreola, Jesus Agustin Badillo Corona, Silvia Mendez Flores, Judith Dominguez Cherit, Dean J. Naisbitt, Noe Valentin Duran Figueroa, Jose Luis Castrejon Flores P193 NSAIDs-exacerbated cutaneous disease: high throughput gene expression profiling José Antonio Cornejo-García, James Perkins, Natalia Blanca-López, Diana Pérez-Alzate, Raquel Jurado-Escobar, Inmaculada Doña, Gador Bogas, María J. Torres, Gabriela Canto, Miguel Blanca P194 Utility of skin tests in non-immediate reactions to amoxicillin Luis Mario Tubella Marti, Fernando Pineda De La Losa, Francisca Arribas Poves, Jaime Tubella Lopez, Teodora Lopez Santiag

Direct observation of the dead-cone effect in quantum chromodynamics

The direct measurement of the QCD dead cone in charm quark fragmentation is reported, using iterative declustering of jets tagged with a fully reconstructed charmed hadron

International Nosocomial Infection Control Consortiu (INICC) report, data summary of 43 countries for 2007-2012. Device-associated module

We report the results of an International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2007-December 2012 in 503 intensive care units (ICUs) in Latin America, Asia, Africa, and Europe. During the 6-year study using the Centers for Disease Control and Prevention's (CDC) U.S. National Healthcare Safety Network (NHSN) definitions for device-associated health care–associated infection (DA-HAI), we collected prospective data from 605,310 patients hospitalized in the INICC's ICUs for an aggregate of 3,338,396 days. Although device utilization in the INICC's ICUs was similar to that reported from ICUs in the U.S. in the CDC's NHSN, rates of device-associated nosocomial infection were higher in the ICUs of the INICC hospitals: the pooled rate of central line–associated bloodstream infection in the INICC's ICUs, 4.9 per 1,000 central line days, is nearly 5-fold higher than the 0.9 per 1,000 central line days reported from comparable U.S. ICUs. The overall rate of ventilator-associated pneumonia was also higher (16.8 vs 1.1 per 1,000 ventilator days) as was the rate of catheter-associated urinary tract infection (5.5 vs 1.3 per 1,000 catheter days). Frequencies of resistance of Pseudomonas isolates to amikacin (42.8% vs 10%) and imipenem (42.4% vs 26.1%) and Klebsiella pneumoniae isolates to ceftazidime (71.2% vs 28.8%) and imipenem (19.6% vs 12.8%) were also higher in the INICC's ICUs compared with the ICUs of the CDC's NHSN

Direct observation of the dead-cone effect in quantum chromodynamics

At particle collider experiments, elementary particle interactions with large momentum transfer produce quarks and gluons (known as partons) whose evolution is governed by the strong force, as described by the theory of quantum chromodynamics (QCD) [1]. The vacuum is not transparent to the partons and induces gluon radiation and quark pair production in a process that can be described as a parton shower [2]. Studying the pattern of the parton shower is one of the key experimental tools in understanding the properties of QCD. This pattern is expected to depend on the mass of the initiating parton, through a phenomenon known as the dead-cone effect, which predicts a suppression of the gluon spectrum emitted by a heavy quark of mass m and energy E, within a cone of angular size m/E around the emitter [3]. A direct observation of the dead-cone effect in QCD has not been possible until now, due to the challenge of reconstructing the cascading quarks and gluons from the experimentally accessible bound hadronic states. Here we show the first direct observation of the QCD dead-cone by using new iterative declustering techniques [4, 5] to reconstruct the parton shower of charm quarks. This result confirms a fundamental feature of QCD, which is derived more generally from its origin as a gauge quantum field theory. Furthermore, the measurement of a dead-cone angle constitutes the first direct experimental observation of the non-zero mass of the charm quark, which is a fundamental constant in the standard model of particle physics.The direct measurement of the QCD dead cone in charm quark fragmentation is reported, using iterative declustering of jets tagged with a fully reconstructed charmed hadron.In particle collider experiments, elementary particle interactions with large momentum transfer produce quarks and gluons (known as partons) whose evolution is governed by the strong force, as described by the theory of quantum chromodynamics (QCD). These partons subsequently emit further partons in a process that can be described as a parton shower which culminates in the formation of detectable hadrons. Studying the pattern of the parton shower is one of the key experimental tools for testing QCD. This pattern is expected to depend on the mass of the initiating parton, through a phenomenon known as the dead-cone effect, which predicts a suppression of the gluon spectrum emitted by a heavy quark of mass $m_{\rm{Q}}$ and energy $E$, within a cone of angular size $m_{\rm{Q}}$/$E$ around the emitter. Previously, a direct observation of the dead-cone effect in QCD had not been possible, owing to the challenge of reconstructing the cascading quarks and gluons from the experimentally accessible hadrons. We report the direct observation of the QCD dead cone by using new iterative declustering techniques to reconstruct the parton shower of charm quarks. This result confirms a fundamental feature of QCD. Furthermore, the measurement of a dead-cone angle constitutes a direct experimental observation of the non-zero mass of the charm quark, which is a fundamental constant in the standard model of particle physics