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

Identification and complete sequencing of novel human transcripts through the use of mouse orthologs and testis cDNA sequences

The correct identification of all human genes, and their derived transcripts, has not yet been achieved, and it remains one of the major aims of the worldwide genomics community. Computational programs suggest the existence of 30,000 to 40,000 human genes. However, definitive gene identification can only be achieved by experimental approaches. We used two distinct methodologies, one based on the alignment of mouse orthologous sequences to the human genome, and another based on the construction of a high-quality human testis cDNA library, in an attempt to identify new human transcripts within the human genome sequence. We generated 47 complete human transcript sequences, comprising 27 unannotated and 20 annotated sequences. Eight of these transcripts are variants of previously known genes. These transcripts were characterized according to size, number of exons, and chromosomal localization, and a search for protein domains was undertaken based on their putative open reading frames. In silico expression analysis suggests that some of these transcripts are expressed at low levels and in a restricted set of tissues

Contributions of the international plant science community to the fight against human infectious diseases - part 1: epidemic and pandemic diseases.

Infectious diseases, also known as transmissible or communicable diseases, are caused by pathogens or parasites that spread in communities by direct contact with infected individuals or contaminated materials, through droplets and aerosols, or via vectors such as insects. Such diseases cause ˜17% of all human deaths and their management and control places an immense burden on healthcare systems worldwide. Traditional approaches for the prevention and control of infectious diseases include vaccination programmes, hygiene measures and drugs that suppress the pathogen, treat the disease symptoms or attenuate aggressive reactions of the host immune system. The provision of vaccines and biologic drugs such as antibodies is hampered by the high cost and limited scalability of traditional manufacturing platforms based on microbial and animal cells, particularly in developing countries where infectious diseases are prevalent and poorly controlled. Molecular farming, which uses plants for protein expression, is a promising strategy to address the drawbacks of current manufacturing platforms. In this review article, we consider the potential of molecular farming to address healthcare demands for the most prevalent and important epidemic and pandemic diseases, focussing on recent outbreaks of high-mortality coronavirus infections and diseases that disproportionately affect the developing world

Gathering and exploring scientific knowledge in pharmacovigilance

Pharmacovigilance plays a key role in the healthcare domain through the assessment, monitoring and discovery of interactions amongst drugs and their effects in the human organism. However, technological advances in this field have been slowing down over the last decade due to miscellaneous legal, ethical and methodological constraints. Pharmaceutical companies started to realize that collaborative and integrative approaches boost current drug research and development processes. Hence, new strategies are required to connect researchers, datasets, biomedical knowledge and analysis algorithms, allowing them to fully exploit the true value behind state-of-the-art pharmacovigilance efforts. This manuscript introduces a new platform directed towards pharmacovigilance knowledge providers. This system, based on a service-oriented architecture, adopts a plugin-based approach to solve fundamental pharmacovigilance software challenges. With the wealth of collected clinical and pharmaceutical data, it is now possible to connect knowledge providers’ analysis and exploration algorithms with real data. As a result, new strategies allow a faster identification of high-risk interactions between marketed drugs and adverse events, and enable the automated uncovering of scientific evidence behind them. With this architecture, the pharmacovigilance field has a new platform to coordinate large-scale drug evaluation efforts in a unique ecosystem, publicly available at http://bioinformatics.ua.pt/euadr/.This work was supported by the European Commission (EU-ADR, ICT‐215847), FCT (PTDC/EIA‐CCO/100541/2008), and Instituto de Salud Carlos III FEDER (CP10/00524). The Research Programme on Biomedical Informatics (GRIB) is a node of the Spanish National Institute of Bioinformatics (INB

7th drug hypersensitivity meeting: part one

Table of contents Oral Abstracts O1 Functionally distinct HMGB1 isoforms correlate with physiological processes in drug-induced SJS/TEN Daniel F. Carr, Wen-Hung Chung, Rosalind E. Jenkiins, Mas Chaponda, Gospel Nwikue, Elena M. Cornejo Castro, Daniel J. Antoine, Munir Pirmohamed O2 Hypersensitivity reactions to beta-lactams, does the t cell recognition pattern influence the clinical picture? Natascha Wuillemin, Dolores Dina, Klara K. Eriksson, Daniel Yerly O3 Specific binding characteristics of HLA alleles associated with nevirapine hypersensitivity Rebecca Pavlos, Elizabeth Mckinnin, David Ostrov, Bjoern Peters, Soren Buus, David Koelle, Abha Chopra, Craig Rive, Alec Redwood, Susana Restrepo, Austin Bracey, Jing Yuan, Silvana Gaudieri, Mary Carrington, David Haas, Simon Mallal, Elizabeth Phillips O4 Do we need to measure total ige for the interpretation of analytical results of ImmunoCAP dnd 3gAllergy specific IgE? Douwe De Boer, Paul Menheere, Chris Nieuwhof, Judith Bons O5 Neutrophil activation in systemic anaphylaxis: results from the multicentric NASA study Friederike Jonsson, Luc De Chaisemartin, Vanessa Granger, Caitlin Gillis, Aurelie Gouel, Catherine Neukirch, Fadia Dib, Pascale Roland Nicaise, Dan Longrois, Florence Tubach, Sylvie Martin, Pierre Bruhns, NASA Study Group O6 Purpuric drug eruptions due to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for non-small-cell lung cancer (NSCLC): a clinic-pathological study of 32 cases Kai-Lung Chen, Shu-Ling Liao, Yi-Shuan Sheen, Yung-Tsu Cho, Che-Wen Yang, Jau-Yu Liau, Chia-Yu Chu Poster presentations: Poster Walk 1—Anaphylaxis (P01–P09) P1 Anaphylactic reactions during anaesthesia and the perioperative period Rita Aguiar, Anabela Lopes, Natália Fernandes, Leonor Viegas, M. A. Pereira-Barbosa P2 Anaphylaxis to chlorhexidine: is there a cross-reactivity to alexidine? Antonia Bünter, Nisha Gupta, Tatjana Pecaric Petkovic, Nicole Wirth, Werner J. Pichler, Oliver Hausmann P3 Cefotaxime-induced severe anaphylaxis in a neonate Mehtap Yazicioglu, Pinar G. Ozdemir, Gokce Ciplak, Ozkan Kaya P4 Clinical features and diagnosis of anaphylaxis resulting from exposure to chlorhexidine Peter John Cooke P5 Drug-induced anaphylaxis: five-year single-center survey Inês Mota, Ângela Gaspar, Filipe Benito-Garcia, Marta Chambel, Mário Morais-Almeida P6 Intraoperative severe anaphylactic reaction due to patent blue v dye Luis Marques, Eva Alcoceba, Silvia Lara P7 Kounis syndrome in the setting of anaphylaxis to diclofenac Leonor Carneiro-Leão, Carmen Botelho, Eunice Dias-Castro, Josefina Cernadas P8 Perioperative anaphylaxis audit: Royal Melbourne Hospital Katherine Nicholls, William Lay, Olivia Smith, Christine Collins, Gary Unglik, Kymble Spriggs, Priscilla Auyeung, Jeremy McComish, Jo A. Douglass P9 Recurrent peri-operative anaphylaxis: a perfect storm Jonny G. Peter, Paul Potter Poster Walk 2: DH regions and patient groups (P10–P19) P10 A rare presentation of amoxicillin allergy in a young child Fabrícia Carolino, Eunice Dias De Castro, Josefina R. Cernadas P11 Adverse drug reactions in children: antibiotics or virus? Ana Sofia Moreira, Carmo Abreu, Eva Gomes P12 Allergic reactions in invasive medical procedures Bárbara Kong Cardoso, Elza Tomaz, Sara Correia, Filipe Inácio P13 Antibiotic allergy in children: room for improvement Annabelle Arnold, Natasha Bear, Kristina Rueter, Grace Gong, Michael O’Sullivan, Saravanan Muthusamy, Valerie Noble, Michaela Lucas P14 Drug hypersensitivity reactions in children and results of diagnostic evaluation Neringa Buterleviciute, Odilija Rudzeviciene P15 Nonimmediate cutaneous drug reactions in children: are skin tests required? Ana Sofia Moreira, Carmo Abreu, Eva Gomes P16 Pediatric patients with a history of penicillin allergy and a positive penicillin skin test may not be at an increased risk for multiple drug allergies Sara May, Thanai Pongdee, Miguel Park P17 Proved hypersensitivity to drugs according data of Vilnius University Hospital Santariskiu Klinikos Linas Griguola, Arturas Vinikovas, Simona Kašinskaite, Violeta Kvedariene P18 Self-reported prevalence of drug hypersensitivity reactions among students in Celal Bayar University, Turkey Ayse Aktas, Suheyla Rahman, Huseyin Elbi, Beyhan Cengiz Ozyurt P19 Severe drug hypersensitivity reactions in pediatric age Ozlem Cavkaytar, Betul Karaatmaca, Pinar Gur Cetinkaya, Saliha Esenboga, Umit M. Sahiner, Bulent E. Sekerel, Ozge Soyer Poster Walk 3: Desensitisation (P20–P28) P20 A protocol for desensitisation to valaciclovir Celia Zubrinich, Bianca Tong, Mittal Patel, Michelle Giles, Robyn O’Hehir, Robert Puy P21 A rare case of desensitization to modafinil Josefina Cernadas, Luís Amaral, Fabrícia Carolino P22 A sixteen-day desensitization protocol in delayed type hypersensitivity reactions to oral drugs Semra Demir, Asli Gelincik, Muge Olgac, Raif Caskun, Derya Unal, Bahauddin Colakoglu, Suna Buyukozturk P23 Desensitization to intravenous etoposide using a 12 and a 13-step protocol. Two cases report Olga Vega Matute, Amalia Bernad, Gabriel Gastaminza, Roselle Madamba, Carlos Lacasa, M. J. Goikoetxea, Carmen D’Amelio, Jose Rifón, Nicolas Martínez, Marta Ferrer P24 Drug desensitisation in oncology: the experience of an immunoallergology department for 5 years Carmelita Ribeiro, Emília Faria, Cristina Frutuoso, Anabela Barros, Rosário Lebre, Alice Pego, Ana Todo Bom P25 Filgrastim anaphylaxis: a successful desensitization protocol Luis Amaral, Josefina Cernadas P26 Galsulfase hypersensitivity and desensitization of a mucopolysaccharidosis VI patient Luis Felipe Ensina, Carolina Aranda, Ines Camelo Nunes, Ana Maria Martins, Dirceu Solé P27 Rapid drug desensitization with biologicals: one-center experience with four biologicals Sevim Bavbek, Resat Kendirlinan, Pamir Çerçi, Seda Tutluer, Sadan Soyyigit, Zeynep Çelebi Sözener, Ömür Aydin, Reyhan Gümüsburun P28 Successful desensitization to a high dose of methotrexate in a delayed type hypersensitivity reaction Josefina Cernadas, Leonor Carneiro-Leão, Fabrícia Carolino, Marta Almeida Poster Walk 4: SJS (P29–P38) P29 Assessment of impact of infection on drug-induced severe cutaneous adverse reactions and rhabdomyolysis using the Japanese adverse drug event report database Kimie Sai, Takuya Imatoh, Ryosuke Nakamura, Chisato Fukazawa, Yasushi Hinomura, Yoshiro Saito P30 Characterization of erythema multiforme and severe cutaneous adverse reactions hospitalizations Bernardo Sousa-Pinto, Cláudia Correia, Lídia Gomes, Sara Gil-Mata, Luís Araújo, Luís Delgado P31 Effects of infection on incidence/severity of SJS/TEN and myopathy in Japanese cases analyzed by voluntary case reports Ryosuke Nakamura, Kimie Sai, Takuya Imatoh, Yoshimi Okamoto-Uchida, Koji Kajinami, Kayoko Matsunaga, Michiko Aihara, Yoshiro Saito P32 Efficacy of tumor necrosis factor—a antagonists in Stevens–Johnson syndrome and toxic epidermal necrolysis: a randomized controlled trial and immunosuppressive effects evaluation Chuang-Wei Wang, Shih-Chi Su, Shuen-Iu Hung, Hsin-Chun Ho, Chih-Hsun Yang, Wen-Hung Chung P33 Evolution of drug causality in Stevens–Johnson syndrome and toxic epidermal necrolysis in Europe: analysis of 10 years RegiSCAR-Study Maren Paulmann, Ariane Dunant, Maja Mockenhaupt, Peggy Sekula, Martin Schumacher, Sylvia Kardaun, Luigi Naldi, Teresa Bellón, Daniel Creamer, Cynthia Haddad, Bruno Sassolas, Bénédicte Lebrun-Vignes, Laurence Valeyrie-Allanore, Jean-Claude Roujeau P34 Long-term sequelae in patients with Stevens–Johnson syndrome and toxic epidermal necrolysis: a 5-year analysis Maren Paulmann, Carmen Kremmler, Peggy Sekula, Laurence Valeyrie-Allanore, Luigi Naldi, Sylvia Kardaun, Maja Mockenhaupt P35 Major emotional complications and decreased health related quality of life among survivors of Stevens–Johnson syndrome and toxic epidermal necrolysis Roni P. Dodiuk-Gad, Cristina Olteanu, Anthony Feinstein, Rena Hashimoto, Raed Alhusayen, Sonia Whyte-Croasdaile, Yaron Finkelstein, Marjorie Burnett, Shachar Sade, Robert Cartotto, Marc Jeschke, Neil H. Shear P36 Retrospective analysis of Stevens–Johnson syndrome and toxic epidermal necrolysis in Japanese patients: treatment and outcome Naoko Takamura, Yumiko Yamane, Setsuko Matsukura, Kazuko Nakamura, Yuko Watanabe, Yukie Yamaguchi, Takeshi Kambara, Zenro Ikezawa, Michiko Aihara P37 Severe physical complications among survivors of Stevens–Johnson syndrome and toxic epidermal necrolysis Roni P. Dodiuk-Gad, Cristina Olteanu, Rena Hashimoto, Hall Chew, Raed Alhusayen, Sonia Whyte-Croasdaile, Yaron Finkelstein, Marjorie Burnett, Shachar Sade, Robert Cartotto, Marc Jeschke, Neil H. Shear P38 Stevens–Johnson syndrome/toxic epidermal necrolysis combined with haemophagocytic lymphohistiocytosis: a case report Brittany Knezevic, Una Nic Ionmhain, Allison Barraclough, Michaela Lucas, Matthew Anstey Poster Walk 5: Other organs/unexpected immune reactions (P39–P47) P39 A case report of patient with anti-tuberculosis drug-related severe liver failure Toru Usui, Xiaoli Meng, John Farrell, Paul Whitaker, John Watson, Neil French, Kevin Park, Dean Naisbitt P40 Acute interstitial nephritis induced by ibuprofen Ana Castro Neves, Susana Cadinha, Ana Moreira, J. P. Moreira Da Silva P41 Cetuximab induced acneiform rash—two case reports Daniela Ledic Drvar, Sandra Jerkovic Gulin, Suzana Ljubojevic Hadzavdic, Romana Ceovic P42 Enteropathy associated with losartan Ana Montoro De Francisco, Talía De Vicente Jiménez, Amelia García Luque, Natalia Rosado David, José Mª Mateos Galván P43 Granuloma annulare after therapy with canakinumab Razvigor Darlenski P44 Hypersensitivity eosinophilic myocarditis or acute coronary syndrome? Case report Dario Gulin, Jozica Sikic, Jasna Cerkez Habek, Sandra Jerkovic Gulin, Edvard Galic P45 Piperacillin-induced immune haemolytic anaemia: a severe and frequent complication of antibiotic treatment in patients with cystic fibrosis Philip Specht, Doris Staab, Beate Mayer, Jobst Roehmel P46 Progesterone triggered pemphigus foliaceus: case report Sandra Jerkovic Gulin, Caius Solovan, Anca Chiriac P47 Ramipril: triggered generalized pustular psoriasis Paola Djurinec, Kresimir Kostovic, Mirna Bradamante, Sandra Jerkovic Gulin, Romana Ceovic Poster Walk 6: NSAIDs (P48–P56) P48 Aspirin desensitization in cardiovascular disease—Portuguese experience Jose Pedro Almeida, Joana Caiado, Elisa Pedro, Pedro Canas Da Silva, Manuel Pereira Barbosa P49 Asthma and/or rhinitis to NSAIDs with good tolerance to ASA Gador Bogas, Natalia Blanca-López, Diana Pérez-Alzate, Inmaculada Doña, José Augusto Agúndez, Elena García-Martín, José Antonio Cornejo-García, Cristobalina Mayorga, María José Torres, Gabriela Canto, Miguel Blanca P50 Clinical characteristics of 196 patients with non-steroidal anti-inflammatory drug (NSAIDs) hypersensitivity Sengül Aksakal, Aytül Zerrin Sin, Zeynep Peker Koç, Fatma Düsünür Günsen, Ömür Ardeniz, Emine Nihal Mete Gökmen, Okan Gülbahar, Ali Kokuludag P51 Development of immediate hypersensitivity to several NSAIDs maintaining good tolerance to ASA Natalia Pérez-Sánchez, Natalia Blanca-López, Diana Pérez-Alzate, Gador Bogas, Inmaculada Doña, María Salas, María José Torres, Miguel Blanca, Gabriela Canto P52 Diagnosis of hypersensitivity reactions to paracetamol in a large series of cases Inmaculada Doña, Maria Salas, Francisca Gomez, Natalia Blanca-Lopez, Diana Perez-Alzate, Gador Bogas, Esther Barrionuevo, Maria Jose Torres, Inmaculada Andreu, Miguel Ángel Miranda, Gabriela Canto, Miguel Blanca P53 Hypersensitivity to paracetamol according to the new classification of hypersensitivity to NSAIDs Gabija Didžiokaite, Olesia Gaidej, Simona Kašinskaite, Violeta Kvedariene P54 Ibuprofen and other aryl propionic derivates can induce immediate selective hypersensitivity responses Diana Perez-Alzate, Natalia Blanca-López, Maria Isabel Garcimartin, Inmaculada Doña, Maria Luisa Somoza, Cristobalina Mayorga, Maria Jose Torres, Gador Bojas, Jose Antonio Cornejo-Garcia, Maria Gabriela Canto, Miguel Blanca P55 Subjects developing immediate responses to several NSAIDs can be selective with good tolerance to ASA Natalia Blanca-Lopez, Diana Pérez-Alzate, Francisco Javier Ruano Perez, Inmaculada Doña, Maria Luisa Somoza, Inmaculada Andreu, Miguel Angel Miranda, Cristobalina Mayorga, Maria Jose Torres, Jose Antonio Cornejo-Garcia, Miguel Blanca, Maria Gabriela Canto P56 Utility of low-dose oral aspirin challenges for diagnosis of aspirin exacerbated respiratory disease Elina Jerschow, Teresa Pelletier, Zhen Ren, Golda Hudes, Marek Sanak, Esperanza Morales, Victor Schuster, Simon D. Spivack, David Rosenstreich Poster Walk 7: NSAID 2 (P57–P65) P57 Alternate regulation of cyclooxygenase-2 (COX-2) MRNA expression may predispose patients to aspirin-induced exacerbations Renato Erzen, Mira Silar, Nissera Bajrovic, Matija Rijavec, Mihaela Zidarn, Peter Korosec P58 Anaphylaxis to diclofenac: what about the underlying mechanism? Leonor Carneiro-Leão, Fabrícia Carolino, Luís Amaral, Carmen Botelho, Eunice Dias-Castro, Josefina Cernadas P59 COX-2 inhibitors: are they always a safe alternative in hypersensitivity to nonsteroidal anti-inflammatory drugs? Luis Amaral, Fabricia Carolino, Eunice Castro, Josefina Cernadas P60 Management of patients with history of NSAIDs reactions prior to coronary angioplasty Mona Al-Ahmad, Tito Rodriguez P61 Oral drug challenge with non-steroidal anti-inflammatory drug under spirometric control: clinical series of 110 patients João Pedro Azevedo, Emília Faria, Beatriz Tavares, Frederico Regateiro, Ana Todo-Bom P62 Prevalence and incidence of analgesic hypersensitivity reactions in Colombia Pablo Andrés Miranda, Bautista De La Cruz Hoyos P63 Recent endoscopic sinus surgery lessens reactions during aspirin challenge in patients with aspirin exacerbated respiratory disease Teresa Pelletier, Waleed Abuzeid, Nadeem Akbar, Marc Gibber, Marvin Fried, Weiguo Han, Taha Keskin, Robert Tamayev, Golda Hudes, Simon D. Spivack, David Rosenstreich, Elina Jerschow P64 Safe use of imidazole salycilate in a case of multiple NSAIDs induced urticaria-angioedema Elisa Boni, Marina Russello, Marina Mauro P65 Selective hypersensitivity reactions to ibuprofen—seven years experience Marta Ferreira Neto Poster Walk 8: Epidemiological methods (P66–P72) P66 Allopurinol hypersensitivity: a 7-year review Lise Brosseron, Daniela Malheiro, Susana Cadinha, Patrícia Barreira, J. P. Moreira Da Silva P67 Antibiotic allergy labelling is associated with increased hospital readmission rates in Australia Brittany Knezevic, Dustin Sprigg, Michelle Trevenen, Jason Seet, Jason Trubiano, William Smith, Yogesh Jeelall, Sandra Vale, Richard Loh, Andrew Mclean-Tooke, Michaela Lucas P68 Experts’ opinions on severe cutaneous adverse drug reactions-report of a survey from the 9th international congress on cutaneous adverse drug reactions 2015 Roni P. Dodiuk-Gad, Cristina Olteanu, Wen-Hung Chung, Neil H. Shear P69 HLA-A*31-positive AGEP with carbamazepine use and other severe cutaneous adverse drug reactions (SCARs) detected by electronic medical records screening Sabine Müller, Ursula Amstutz, Lukas Jörg, Nikhil Yawalkar, Stephan Krähenbühl P70 Patients with suspected drug allergy: a specific psychological profile? Eunice Dias-Castro, Ana Leblanc, Laura Ribeiro, Josefina R. Cernadas P71 Use of an electronic device and a computerized mathematic algorithm to detect the allergic drug reactions through the analysis of heart rate variability Arantza Vega, Raquel Gutierrez Rivas, Ana Alonso, Juan Maria Beitia, Belén Mateo, Remedios Cárdenas, Juan Jesus Garcia-Dominguez P72 Variation in ERAP influences risk for HLA-B*57:01 positive abacavir hypersensitivity Rebecca Pavlos, Kaija Strautins, Ian James, Simon Mallal, Alec Redwood, Elizabeth Phillips Poster Walk 9: DRESS/AGEP (P73–P81) P73 A clinical case of DRESS syndrome in a child after administration of amoxicillin-clavulanic acid Rita Aguiar, Anabela Lopes, Ana Neves, Maria Do Céu Machado, M. A. Pereira-Barbosa P74 Acute generalized exanthematous pustulosis (AGEP) induced by mesalazine, reliable and oftenly used drug to treat inflammatory bowel disease Ceyda Tunakan Dalgiç, Emine Nihal Mete Gökmen, Fatma Düsünür Günsen, Gökten Bulut, Fatma Ömür Ardeniz, Okan Gülbahar, Ali Kokuludag, Aytül Zerrin Sin P75 Changes of blood plasmacytoid dendritic cells, myeloid dendritic cells, and basophils during the acute stage of drug reaction with eosinophilia and systemic symptoms (DRESS) and other drug eruptions Shao-Hsuan Hsu, Yung-Tsu Cho, Che-Wen Yang, Kai-Lung Chen, Chia-Yu Chu P76 Characterization of isoniazid/rifampicin-specific t-cell responses in patients with DRESS syndrome Young-Min Ye, Gyu-Young Hur, Hae-Sim Park, Seung-Hyun Kim P77 DRESS syndrome secondary to sulfasalazine with delayed TEN: a case presentation Syed Ali, Michaela Lucas, Peter N. Hollingsworth, Andrew P. C. Mclean-Tooke P78 Drug rash with eosinophilia and systemic symptoms (DRESS) features according to the culprit drug Zohra Chadly, Nadia Ben Fredj, Karim Aouam, Haifa Ben Romdhane, Naceur A. Boughattas, Amel Chaabane P79 Drug reaction with eosinophilia and systemic symptoms induced by allopurinol: not always easy to diagnose Marina Lluncor Salazar, Beatriz Pola, Ana Fiandor, Teresa Bellón, Elena Ramírez, Javier Domínguez Ortega, Santiago Quirce, Rosario Cabañas P80 Drug reaction with eosinophilia and systemic symptoms syndrome induced by two drugs simultaneously: a case report Krasimira Baynova, Marina Labella, Manuel Prados P81 The drug reaction with eosinophilia and systemic symptoms (DRESS) induced by the second-line antituberculosis drugs and Epstein–Barr virus infection Agne Ramonaite, Ieva Bajoriuniene, Brigita Sitkauskiene, Raimundas Sakalauskas Poster Walk 10: Miscellaneous drug hypersensitivity (P82–P91) P82 A case of cycloserine-induced lichenoid drug eruption confirmed with a lymphocatye transformation test Jae-Woo Kwon, Shinyoung Park P83 Allergic reaction to topical eye drops: 5 years’ retrospective study in a drug allergy unit Diana Silva, Leonor Carneiro Leão, Fabricia Carolino, Eunice Castro, Josefina Cernadas P84 Allergy to heparins Diana Perez-Alzate, Natalia Blanca-López, Maria Luisa Somoza Alvarez, Maria Garcimartin, Maria Vazquez De La Torre, Francisco Javier Ruano Pérez, Elisa Haroun, Gabriela Canto Diez P85 Allopurinol-induced adverse drug reactions Katinka Ónodi-Nagy, Ágnes Kinyó, Lajos Kemény, Zsuzsanna Bata-Csörgo P86 Analysis of a population with immediate hypersensitivity to corticosteroids: an 11 year review Joana Sofia Pita, Emília Faria, Rosa Anita Fernandes, Ana Moura, Nuno Sousa, Carmelita Ribeiro, Carlos Loureiro, Ana Todo Bom P87 Anaphylaxis against mivacurium in a 12-months old boy at first-time exposure Wolfgang Pfützner P88 Antihistamine-exacerbated chronic spontaneous urticaria: a paradox? Nadine Marrouche, Clive Grattan P89 Anti-osteoporotic agents-induced cutaneous adverse drug reactions in Asians Yu-En Chen, Chun-Bing Chen, Wen-Hung Chung, Yu-

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

BackgroundRegular, 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.MethodsThe 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.FindingsThe 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.InterpretationLong-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

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

BackgroundEstimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period.Methods22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution.FindingsGlobal all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations.InterpretationGlobal adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic