24 research outputs found

    Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

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    The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

    Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

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    Data sharing: To download the data used in these analyses, please visit the Global Health Data Exchange at https://ghdx.healthdata.org/gbd–2017 .GBD 2017 DALYs and HALE Collaborators: Hmwe Hmwe Kyu, Degu Abate, Kalkidan Hassen Abate, Solomon M Abay, Cristiana Abbafati, Nooshin Abbasi, Hedayat Abbastabar, Foad Abd-Allah, Jemal Abdela, Ahmed Abdelalim, Ibrahim Abdollahpour, Rizwan Suliankatchi Abdulkader, Molla Abebe, Zegeye Abebe, Olifan Zewdie Abil, Victor Aboyans, Aklilu Roba Abrham, Laith Jamal Abu-Raddad, Niveen M E Abu-Rmeileh, Manfred Mario Kokou Accrombessi, Dilaram Acharya, Pawan Acharya, Ilana N Ackerman, Abdu A Adamu, Oladimeji M Adebayo, Victor Adekanmbi, Zanfina Ademi, Olatunji O Adetokunboh, Mina G Adib, Jose C Adsuar, Kossivi Agbelenko Afanvi, Mohsen Afarideh, Ashkan Afshin, Gina Agarwal, Kareha M Agesa, Rakesh Aggarwal, Sargis Aghasi Aghayan, Anurag Agrawal, Alireza Ahmadi, Mehdi Ahmadi, Hamid Ahmadieh, Muktar Beshir Ahmed, Sayem Ahmed, Amani Nidhal Aichour, Ibtihel Aichour, Miloud Taki Eddine Aichour, Tomi Akinyemiju, Nadia Akseer, Ziyad Al-Aly, Ayman Al-Eyadhy, Hesham M Al-Mekhlafi, Rajaa M Al-Raddadi, Fares Alahdab, Khurshid Alam, Tahiya Alam, Alaa Alashi, Seyed Moayed Alavian, Kefyalew Addis Alene, Mehran Alijanzadeh, Reza Alizadeh-Navaei, Syed Mohamed Aljunid, Ala'a Alkerwi, François Alla, Peter Allebeck, Jordi Alonso, Ubai Alsharif, Khalid Altirkawi, Nelson Alvis-Guzman, Leopold N Aminde, Erfan Amini, Mohammadreza Amiresmaili, Walid Ammar, Yaw Ampem Amoako, Nahla Hamed Anber, Catalina Liliana Andrei, Sofia Androudi, Megbaru Debalkie Animut, Mina Anjomshoa, Mustafa Geleto Ansha, Carl Abelardo T Antonio, Palwasha Anwari, Jalal Arabloo, Olatunde Aremu, Johan Ärnlöv, Amit Arora, Megha Arora, Al Artaman, Krishna K Aryal, Hamid Asayesh, Zerihun Ataro, Marcel Ausloos, Leticia Avila-Burgos, Euripide F G A Avokpaho, Ashish Awasthi, Beatriz Paulina Ayala Quintanilla, Rakesh Ayer, Peter S Azzopardi, Arefeh Babazadeh, Hamid Badali, Kalpana Balakrishnan, Ayele Geleto Bali, Maciej Banach, Joseph Adel Mattar Banoub, Aleksandra Barac, Miguel A Barboza, Suzanne Lyn Barker-Collo, Till Winfried Bärnighausen, Simon Barquera, Lope H Barrero, Shahrzad Bazargan-Hejazi, Neeraj Bedi, Ettore Beghi, Masoud Behzadifar, Meysam Behzadifar, Bayu Begashaw Bekele, Eyasu Tamru Bekru, Abate Bekele Belachew, Yihalem Abebe Belay, Michelle L Bell, Aminu K Bello, Derrick A Bennett, Isabela M Bensenor, Adugnaw Berhane, Eduardo Bernabe, Robert S Bernstein, Mircea Beuran, Tina Beyranvand, Neeraj Bhala, Samir Bhatt, Soumyadeep Bhaumik, Zulfiqar A Bhutta, Belete Biadgo, Molly H Biehl, Ali Bijani, Boris Bikbov, Ver Bilano, Nigus Bililign, Muhammad Shahdaat Bin Sayeed, Donal Bisanzio, Tone Bjørge, Archie Bleyer, Eshetu Mulisa Bobasa, Ibrahim R Bou-Orm, Soufiane Boufous, Rupert Bourne, Oliver J Brady, Luisa C Brant, Carol Brayne, Alexandra Brazinova, Nicholas J K Breitborde, Hermann Brenner, Paul Svitil Briant, Andrey Nikolaevich Briko, Gabrielle Britton, Traolach Brugha, Rachelle Buchbinder, Reinhard Busse, Zahid A Butt, Lucero Cahuana-Hurtado, Julio Cesar Campuzano Rincon, Jorge Cano, Rosario Cárdenas, Juan J Carrero, Austin Carter, Félix Carvalho, Carlos A Castañeda-Orjuela, Jacqueline Castillo Rivas, Franz Castro, Ferrán Catalá-López, Kelly M Cercy, Ester Cerin, Yazan Chaiah, Jung-Chen Chang, Fiona J Charlson, Vijay Kumar Chattu, Peggy Pei-Chia Chiang, Abdulaal Chitheer, Jee-Young J Choi, Hanne Christensen, Devasahayam J Christopher, Sheng-Chia Chung, Flavia M Cicuttini, Massimo Cirillo, Daniel Collado-Mateo, Cyrus Cooper, Paolo Angelo Cortesi, Monica Cortinovis, Ewerton Cousin, Michael H Criqui, Elizabeth A Cromwell, Marita Cross, John A Crump, Alemneh Kabeta Daba, Berihun Assefa Dachew, Abel Fekadu Dadi, Lalit Dandona, Rakhi Dandona, Paul I Dargan, Ahmad Daryani, Rajat Das Gupta, José Das Neves, Tamirat Tesfaye Dasa, Dragos Virgil Davitoiu, Fernando Pio De La Hoz, Diego De Leo, Jan-Walter De Neve, Hans De Steur, Meaza Girma Degefa, Louisa Degenhardt, Selina Deiparine, Gebre Teklemariam Demoz, Edgar Denova-Gutiérrez, Kebede Deribe, Nikolaos Dervenis, Don C Des Jarlais, Subhojit Dey, Samath D Dharmaratne, Meghnath Dhimal, Mesfin Tadese Dinberu, M Ashworth Dirac, Shirin Djalalinia, Linh Doan, Klara Dokova, David Teye Doku, E Ray Dorsey, Kerrie E Doyle, Tim Robert Driscoll, Manisha Dubey, Eleonora Dubljanin, Eyasu Ejeta Duken, Bruce B Duncan, Andre R Duraes, Hedyeh Ebrahimi, Soheil Ebrahimpour, Michelle M Echko, Dumessa Edessa, David Edvardsson, Andem Effiong, Anne Elise Eggen, Joshua R Ehrlich, Charbel El Bcheraoui, Ziad El-Khatib, Iqbal R F Elyazar, Ahmadali Enayati, Melese Linger Endalifer, Aman Yesuf Endries, Benjamin Er, Holly E Erskine, Sharareh Eskandarieh, Alireza Esteghamati, Sadaf Esteghamati, Hamed Fakhim, Mahbobeh Faramarzi, Mohammad Fareed, Farzaneh Farhadi, Talha A Farid, Carla Sofia E sá Farinha, Andrea Farioli, Andre Faro, Farshad Farzadfar, Ali Akbar Fazaeli, Valery L Feigin, Netsanet Fentahun, Seyed-Mohammad Fereshtehnejad, Eduarda Fernandes, Joao C Fernandes, Alize J Ferrari, Manuela L Ferreira, Irina Filip, Florian Fischer, Christina Fitzmaurice, Nataliya A Foigt, Kyle J Foreman, Tahvi D Frank, Takeshi Fukumoto, Nancy Fullman, Thomas Fürst, João M Furtado, Emmanuela Gakidou, Seana Gall, Silvano Gallus, Morsaleh Ganji, Alberto L Garcia-Basteiro, William M Gardner, Abadi Kahsu Gebre, Amanuel Tesfay Gebremedhin, Teklu Gebrehiwo Gebremichael, Tilayie Feto Gelano, Johanna M Geleijnse, Ricard Genova-Maleras, Yilma Chisha Dea Geramo, Peter W Gething, Kebede Embaye Gezae, Mohammad Rasoul Ghadami, Keyghobad Ghadiri, Maryam Ghasemi-Kasman, Mamata Ghimire, Aloke Gopal Ghoshal, Paramjit Singh Gill, Tiffany K Gill, Ibrahim Abdelmageed Ginawi, Giorgia Giussani, Elena V Gnedovskaya, Ellen M Goldberg, Srinivas Goli, Hector Gómez-Dantés, Philimon N Gona, Sameer Vali Gopalani, Taren M Gorman, Alessandra C Goulart, Bárbara Niegia Garcia Goulart, Ayman Grada, Giuseppe Grosso, Harish Chander Gugnani, Francis Guillemin, Yuming Guo, Prakash C Gupta, Rahul Gupta, Rajeev Gupta, Tanush Gupta, Reyna Alma Gutiérrez, Bishal Gyawali, Juanita A Haagsma, Vladimir Hachinski, Nima Hafezi-Nejad, Hassan Haghparast Bidgoli, Tekleberhan B Hagos, Tewodros Tesfa Hailegiyorgis, Arvin Haj-Mirzaian, Arya Haj-Mirzaian, Randah R Hamadeh, Samer Hamidi, Alexis J Handal, Graeme J Hankey, Yuantao Hao, Hilda L Harb, Sivadasanpillai Harikrishnan, Hamidreza Haririan, Josep Maria Haro, Hadi Hassankhani, Hamid Yimam Hassen, Rasmus Havmoeller, Roderick J Hay, Simon I Hay, Akbar Hedayatizadeh-Omran, Behzad Heibati, Delia Hendrie, Andualem Henok, Ileana Heredia-Pi, Claudiu Herteliu, Fatemeh Heydarpour, Pouria Heydarpour, Desalegn Tsegaw Hibstu, Hans W Hoek, Howard J Hoffman, Michael K Hole, Enayatollah Homaie Rad, Praveen Hoogar, H Dean Hosgood, Seyed Mostafa Hosseini, Mehdi Hosseinzadeh, Mihaela Hostiuc, Sorin Hostiuc, Peter J Hotez, Damian G Hoy, Mohamed Hsairi, Aung Soe Htet, John J Huang, Kim Moesgaard Iburg, Chad Thomas Ikeda, Olayinka Stephen Ilesanmi, Seyed Sina Naghibi Irvani, Caleb Mackay Salpeter Irvine, Sheikh Mohammed Shariful Islam, Farhad Islami, Kathryn H Jacobsen, Leila Jahangiry, Nader Jahanmehr, Sudhir Kumar Jain, Mihajlo Jakovljevic, Spencer L James, Achala Upendra Jayatilleke, Panniyammakal Jeemon, Ravi Prakash Jha, Vivekanand Jha, John S Ji, Catherine O Johnson, Jost B Jonas, Jitendra Jonnagaddala, Zahra Jorjoran Shushtari, Ankur Joshi, Jacek Jerzy Jozwiak, Suresh Banayya Jungari, Mikk Jürisson, Zubair Kabir, Rajendra Kadel, Amaha Kahsay, Rizwan Kalani, Tanuj Kanchan, Chittaranjan Kar, Manoochehr Karami, Behzad Karami Matin, André Karch, Corine Karema, Narges Karimi, Seyed M Karimi, Amir Kasaeian, Dessalegn H Kassa, Getachew Mullu Kassa, Tesfaye Dessale Kassa, Nicholas J Kassebaum, Srinivasa Vittal Katikireddi, Anil Kaul, Norito Kawakami, Zhila Kazemi, Ali Kazemi Karyani, Masoud Masoud Keighobadi, Peter Njenga Keiyoro, Laura Kemmer, Grant Rodgers Kemp, Andre Pascal Kengne, Andre Keren, Yousef Saleh Khader, Behzad Khafaei, Morteza Abdullatif Khafaie, Alireza Khajavi, Nauman Khalid, Ibrahim A Khalil, Ejaz Ahmad Khan, Muhammad Shahzeb Khan, Muhammad Ali Khan, Young-Ho Khang, Mona M Khater, Mohammad Khazaei, Abdullah T Khoja, Ardeshir Khosravi, Mohammad Hossein Khosravi, Aliasghar A Kiadaliri, Zelalem Teklemariam Kidanemariam, Daniel N Kiirithio, Cho-Il Kim, Daniel Kim, Young-Eun Kim, Yun Jin Kim, Ruth W Kimokoti, Yohannes Kinfu, Adnan Kisa, Katarzyna Kissimova-Skarbek, Ann Kristin Skrindo Knudsen, Jonathan M Kocarnik, Sonali Kochhar, Yoshihiro Kokubo, Tufa Kolola, Jacek A Kopec, Soewarta Kosen, Georgios A Kotsakis, Parvaiz A Koul, Ai Koyanagi, Kewal Krishan, Sanjay Krishnaswami, Kristopher J Krohn, Barthelemy Kuate Defo, Burcu Kucuk Bicer, G Anil Kumar, Manasi Kumar, Igor Kuzin, Deepesh P Lad, Sheetal D Lad, Alessandra Lafranconi, Ratilal Lalloo, Tea Lallukka, Faris Hasan Lami, Justin J Lang, Sinéad M Langan, Van C Lansingh, Arman Latifi, Kathryn Mei-Ming Lau, Jeffrey V Lazarus, Janet L Leasher, Jorge R Ledesma, Paul H Lee, James Leigh, Mostafa Leili, Cheru Tesema Leshargie, Janni Leung, Miriam Levi, Sonia Lewycka, Shanshan Li, Yichong Li, Xiaofeng Liang, Yu Liao, Misgan Legesse Liben, Lee-Ling Lim, Stephen S Lim, Miteku Andualem Limenih, Shai Linn, Shiwei Liu, Katharine J Looker, Alan D Lopez, Stefan Lorkowski, Paulo A Lotufo, Rafael Lozano, Tim C D Lucas, Raimundas Lunevicius, Ronan A Lyons, Stefan Ma, Erlyn Rachelle King Macarayan, Mark T Mackay, Emilie R Maddison, Fabiana Madotto, Dhaval P Maghavani, Hue Thi Mai, Marek Majdan, Reza Majdzadeh, Azeem Majeed, Reza Malekzadeh, Deborah Carvalho Malta, Abdullah A Mamun, Ana-Laura Manda, Helena Manguerra, Mohammad Ali Mansournia, Ana Maria Mantilla Herrera, Lorenzo Giovanni Mantovani, Joemer C Maravilla, Wagner Marcenes, Ashley Marks, Francisco Rogerlândio Martins-Melo, Ira Martopullo, Winfried März, Melvin B Marzan, João Massano, Benjamin Ballard Massenburg, Manu Raj Mathur, Pallab K Maulik, Mohsen Mazidi, Colm McAlinden, John J McGrath, Martin McKee, Brian J McMahon, Suresh Mehata, Ravi Mehrotra, Kala M Mehta, Varshil Mehta, Fabiola Mejia-Rodriguez, Tesfa Mekonen, Addisu Melese, Mulugeta Melku, Peter T N Memiah, Ziad A Memish, Walter Mendoza, Getnet Mengistu, George A Mensah, Seid Tiku Mereta, Atte Meretoja, Tuomo J Meretoja, Tomislav Mestrovic, Bartosz Miazgowski, Tomasz Miazgowski, Anoushka I Millear, Ted R Miller, G K Mini, Mojde Mirarefin, Andreea Mirica, Erkin M Mirrakhimov, Awoke Temesgen Misganaw, Philip B Mitchell, Habtamu Mitiku, Babak Moazen, Bahram Mohajer, Karzan Abdulmuhsin Mohammad, Moslem Mohammadi, Noushin Mohammadifard, Mousa Mohammadnia-Afrouzi, Mohammed A Mohammed, Shafiu Mohammed, Farnam Mohebi, Ali H Mokdad, Mariam Molokhia, Lorenzo Monasta, Julio Cesar Montañez, Mahmood Moosazadeh, Ghobad Moradi, Mahmoudreza Moradi, Maziar Moradi-Lakeh, Mehdi Moradinazar, Paula Moraga, Lidia Morawska, Ilais Moreno Velásquez, Joana Morgado-Da-Costa, Shane Douglas Morrison, Marilita M Moschos, Seyyed Meysam Mousavi, Kalayu Brhane Mruts, Achenef Asmamaw Muche, Kindie Fentahun Muchie, Ulrich Otto Mueller, Oumer Sada Muhammed, Satinath Mukhopadhyay, Kate Muller, John Everett Mumford, G V S Murthy, Kamarul Imran Musa, Ghulam Mustafa, Ashraf F Nabhan, Chie Nagata, Gabriele Nagel, Mohsen Naghavi, Aliya Naheed, Azin Nahvijou, Gurudatta Naik, Farid Najafi, Hae Sung Nam, Vinay Nangia, Jobert Richie Nansseu, Nahid Neamati, Ionut Negoi, Ruxandra Irina Negoi, Subas Neupane, Charles Richard James Newton, Josephine W Ngunjiri, Anh Quynh Nguyen, Grant Nguyen, Ha Thu Nguyen, Huong Lan Thi Nguyen, Huong Thanh Nguyen, Long Hoang Nguyen, Minh Nguyen, Nam Ba Nguyen, Son Hoang Nguyen, Emma Nichols, Dina Nur Anggraini Ningrum, Molly R Nixon, Shuhei Nomura, Mehdi Noroozi, Bo Norrving, Jean Jacques Noubiap, Hamid Reza Nouri, Malihe Nourollahpour Shiadeh, Mohammad Reza Nowroozi, Elaine O Nsoesie, Peter S Nyasulu, Christopher M Odell, Richard Ofori-Asenso, Felix Akpojene Ogbo, In-Hwan Oh, Olanrewaju Oladimeji, Andrew T Olagunju, Tinuke O Olagunju, Pedro R Olivares, Helen Elizabeth Olsen, Bolajoko Olubukunola Olusanya, Jacob Olusegun Olusanya, Kanyin L Ong, Sok King Ong, Eyal Oren, Alberto Ortiz, Erika Ota, Stanislav S Otstavnov, Simon Øverland, Mayowa Ojo Owolabi, Mahesh P A, Rosana Pacella, Abhijit P Pakhare, Amir H Pakpour, Adrian Pana, Songhomitra Panda-Jonas, Eun-Kee Park, James Park, Charles D H Parry, Hadi Parsian, Yahya Pasdar, Shanti Patel, Snehal T Patil, Ajay Patle, George C Patton, Vishnupriya Rao Paturi, Deepak Paudel, Katherine R Paulson, Neil Pearce, Alexandre Pereira, David M Pereira, Norberto Perico, Konrad Pesudovs, Max Petzold, Hai Quang Pham, Michael R Phillips, David M Pigott, Julian David Pillay, Michael A Piradov, Meghdad Pirsaheb, Farhad Pishgar, Oleguer Plana-Ripoll, Suzanne Polinder, Svetlana Popova, Maarten J Postma, Akram Pourshams, Hossein Poustchi, Dorairaj Prabhakaran, Swayam Prakash, V Prakash, Narayan Prasad, Caroline A Purcell, Mostafa Qorbani, D Alex Quistberg, Amir Radfar, Anwar Rafay, Alireza Rafiei, Fakher Rahim, Kazem Rahimi, Zohreh Rahimi, Afarin Rahimi-Movaghar, Vafa Rahimi-Movaghar, Mahfuzar Rahman, Mohammad Hifz Ur Rahman, Muhammad Aziz Rahman, Sajjad Ur Rahman, Rajesh Kumar Rai, Fatemeh Rajati, Prabhat Ranjan, Puja C Rao, Davide Rasella, David Laith Rawaf, Salman Rawaf, K Srinath Reddy, Robert C Reiner, Marissa Bettay Reitsma, Giuseppe Remuzzi, Andre M N Renzaho, Serge Resnikoff, Satar Rezaei, Mohammad Sadegh Rezai, Antonio Luiz P Ribeiro, Nicholas L S Roberts, Stephen R Robinson, Leonardo Roever, Luca Ronfani, Gholamreza Roshandel, Ali Rostami, Gregory A Roth, Dietrich Rothenbacher, Enrico Rubagotti, Perminder S Sachdev, Nafis Sadat, Ehsan Sadeghi, Sahar Saeedi Moghaddam, Hosein Safari, Yahya Safari, Roya Safari-Faramani, Mahdi Safdarian, Sare Safi, Saeid Safiri, Rajesh Sagar, Amirhossein Sahebkar, Mohammad Ali Sahraian, Haniye Sadat Sajadi, Nasir Salam, Joseph S Salama, Payman Salamati, Zikria Saleem, Yahya Salimi, Hamideh Salimzadeh, Joshua A Salomon, Sundeep Santosh Salvi, Inbal Salz, Abdallah M Samy, Juan Sanabria, Maria Dolores Sanchez-Niño, Damian Francesco Santomauro, Itamar S Santos, João Vasco Santos, Milena M Santric Milicevic, Bruno Piassi Sao Jose, Mayank Sardana, Abdur Razzaque Sarker, Rodrigo Sarmiento-Suárez, Nizal Sarrafzadegan, Benn Sartorius, Shahabeddin Sarvi, Brijesh Sathian, Maheswar Satpathy, Arundhati R Sawant, Monika Sawhney, Sonia Saxena, Elke Schaeffner, Maria Inês Schmidt, Ione J C Schneider, Aletta Elisabeth Schutte, David C Schwebel, Falk Schwendicke, James G Scott, Mario Sekerija, Sadaf G Sepanlou, Edson Serván-Mori, Seyedmojtaba Seyedmousavi, Hosein Shabaninejad, Azadeh Shafieesabet, Mehdi Shahbazi, Amira A Shaheen, Masood Ali Shaikh, Mehran Shams-Beyranvand, Mohammadbagher Shamsi, Heidar Sharafi, Kiomars Sharafi, Mehdi Sharif, Mahdi Sharif-Alhoseini, Jayendra Sharma, Rajesh Sharma, Jun She, Aziz Sheikh, Peilin Shi, Kenji Shibuya, Mekonnen Sisay Shiferaw, Mika Shigematsu, Rahman Shiri, Reza Shirkoohi, Ivy Shiue, Yalda Shokoohinia, Farhad Shokraneh, Haitham Shoman, Mark G Shrime, Si Si, Soraya Siabani, Abla Mehio Sibai, Tariq J Siddiqi, Inga Dora Sigfusdottir, Rannveig Sigurvinsdottir, Diego Augusto Santos Silva, João Pedro Silva, Dayane Gabriele Alves Silveira, Narayana Sarma Venkata Singam, Jasvinder A Singh, Narinder Pal Singh, Virendra Singh, Dhirendra Narain Sinha, Eirini Skiadaresi, Vegard Skirbekk, Karen Sliwa, David L Smith, Mari Smith, Adauto Martins Soares Filho, Badr Hasan Sobaih, Soheila Sobhani, Moslem Soofi, Reed J D Sorensen, Joan B Soriano, Ireneous N Soyiri, Luciano A Sposato, Chandrashekhar T Sreeramareddy, Vinay Srinivasan, Jeffrey D Stanaway, Vladimir I Starodubov, Dan J Stein, Caitlyn Steiner, Timothy J Steiner, Mark A Stokes, Lars Jacob Stovner, Michelle L Subart, Agus Sudaryanto, Mu'awiyyah Babale Sufiyan, Gerhard Sulo, Bruno F Sunguya, Patrick John Sur, Bryan L Sykes, P N Sylaja, Dillon O Sylte, Cassandra E I Szoeke, Rafael Tabarés-Seisdedos, Takahiro Tabuchi, Santosh Kumar Tadakamadla, Nikhil Tandon, Segen Gebremeskel Tassew, Mohammad Tavakkoli, Nuno Taveira, Hugh R Taylor, Arash Tehrani-Banihashemi, Tigist Gashaw Tekalign, Shishay Wahdey Tekelemedhin, Merhawi Gebremedhin Tekle, Mohamad-Hani Temsah, Omar Temsah, Abdullah Sulieman Terkawi, Belay Tessema, Mebrahtu Teweldemedhin, Kavumpurathu Raman Thankappan, Andrew Theis, Sathish Thirunavukkarasu, Nihal Thomas, Binyam Tilahun, Quyen G To, Marcello Tonelli, Roman Topor-Madry, Anna E Torre, Miguel Tortajada-Girbés, Mathilde Touvier, Marcos Roberto Tovani-Palone, Jeffrey A Towbin, Bach Xuan Tran, Khanh Bao Tran, Christopher E Troeger, Afewerki Gebremeskel Tsadik, Derrick Tsoi, Lorainne Tudor Car, Stefanos Tyrovolas, Kingsley Nnanna Ukwaja, Irfan Ullah, Eduardo A Undurraga, Rachel L Updike, Muhammad Shariq Usman, Olalekan A Uthman, Muthiah Vaduganathan, Afsane Vaezi, Pascual R Valdez, Elena Varavikova, Santosh Varughese, Tommi Juhani Vasankari, Narayanaswamy Venketasubramanian, Santos Villafaina, Francesco S Violante, Sergey Konstantinovitch Vladimirov, Vasily Vlassov, Stein Emil Vollset, Theo Vos, Kia Vosoughi, Isidora S Vujcic, Fasil Shiferaw Wagnew, Yasir Waheed, Yafeng Wang, Yuan-Pang Wang, Elisabete Weiderpass, Robert G Weintraub, Daniel J Weiss, Fitsum Weldegebreal, Kidu Gidey Weldegwergs, Andrea Werdecker, T Eoin West, Ronny Westerman, Harvey A Whiteford, Justyna Widecka, Tissa Wijeratne, Hywel C Williams, Lauren B Wilner, Shadrach Wilson, Andrea Sylvia Winkler, Alison B Wiyeh, Charles Shey Wiysonge, Charles D A Wolfe, Anthony D Woolf, Grant M A Wyper, Denis Xavier, Gelin Xu, Simon Yadgir, Seyed Hossein Yahyazadeh Jabbari, Tomohide Yamada, Lijing L Yan, Yuichiro Yano, Mehdi Yaseri, Yasin Jemal Yasin, Alex Yeshaneh, Ebrahim M Yimer, Paul Yip, Engida Yisma, Naohiro Yonemoto, Seok-Jun Yoon, Marcel Yotebieng, Mustafa Z Younis, Mahmoud Yousefifard, Chuanhua Yu, Vesna Zadnik, Zoubida Zaidi, Sojib Bin Zaman, Mohammad Zamani, Hamed Zandian, Heather J Zar, Zerihun Menlkalew Zenebe, Ben Zipkin, Maigeng Zhou, Sanjay Zodpey, Inbar Zucker, Liesl Joanna Zuhlke, Christopher J L Murray.Correction: Errata, June 20, 2019. Volume 393, Issue 10190e44June 22, 2019. GBD 2017 DALYs and HALE Collaborators. Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018; 392: 1859–922—In this Global Health Metrics paper, Joan B Soriano has been added to the collaborators list; affiliation details have been amended for Joseph Adel Mattar Banoub, Tanuj Kanchan, and Yasin Jemal Yasin; and the declaration of interests statement has been amended for Boris Bikbov. These corrections have been made to the online version as of June 20, 2019.Background: How long one lives, how many years of life are spent in good and poor health, and how the population's state of health and leading causes of disability change over time all have implications for policy, planning, and provision of services. We comparatively assessed the patterns and trends of healthy life expectancy (HALE), which quantifies the number of years of life expected to be lived in good health, and the complementary measure of disability-adjusted life-years (DALYs), a composite measure of disease burden capturing both premature mortality and prevalence and severity of ill health, for 359 diseases and injuries for 195 countries and territories over the past 28 years. Methods: We used data for age-specific mortality rates, years of life lost (YLLs) due to premature mortality, and years lived with disability (YLDs) from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to calculate HALE and DALYs from 1990 to 2017. We calculated HALE using age-specific mortality rates and YLDs per capita for each location, age, sex, and year. We calculated DALYs for 359 causes as the sum of YLLs and YLDs. We assessed how observed HALE and DALYs differed by country and sex from expected trends based on Socio-demographic Index (SDI). We also analysed HALE by decomposing years of life gained into years spent in good health and in poor health, between 1990 and 2017, and extra years lived by females compared with males. Findings: Globally, from 1990 to 2017, life expectancy at birth increased by 7·4 years (95% uncertainty interval 7·1–7·8), from 65·6 years (65·3–65·8) in 1990 to 73·0 years (72·7–73·3) in 2017. The increase in years of life varied from 5·1 years (5·0–5·3) in high SDI countries to 12·0 years (11·3–12·8) in low SDI countries. Of the additional years of life expected at birth, 26·3% (20·1–33·1) were expected to be spent in poor health in high SDI countries compared with 11·7% (8·8–15·1) in low-middle SDI countries. HALE at birth increased by 6·3 years (5·9–6·7), from 57·0 years (54·6–59·1) in 1990 to 63·3 years (60·5–65·7) in 2017. The increase varied from 3·8 years (3·4–4·1) in high SDI countries to 10·5 years (9·8–11·2) in low SDI countries. Even larger variations in HALE than these were observed between countries, ranging from 1·0 year (0·4–1·7) in Saint Vincent and the Grenadines (62·4 years [59·9–64·7] in 1990 to 63·5 years [60·9–65·8] in 2017) to 23·7 years (21·9–25·6) in Eritrea (30·7 years [28·9–32·2] in 1990 to 54·4 years [51·5–57·1] in 2017). In most countries, the increase in HALE was smaller than the increase in overall life expectancy, indicating more years lived in poor health. In 180 of 195 countries and territories, females were expected to live longer than males in 2017, with extra years lived varying from 1·4 years (0·6–2·3) in Algeria to 11·9 years (10·9–12·9) in Ukraine. Of the extra years gained, the proportion spent in poor

    Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016

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    Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of risk factor exposure and attributable burden of disease. By providing estimates over a long time series, this study can monitor risk exposure trends critical to health surveillance and inform policy debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2016. This study included 481 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk (RR) and exposure estimates from 22 717 randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources, according to the GBD 2016 source counting methods. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. Finally, we explored four drivers of trends in attributable burden: population growth, population ageing, trends in risk exposure, and all other factors combined. Findings Since 1990, exposure increased significantly for 30 risks, did not change significantly for four risks, and decreased significantly for 31 risks. Among risks that are leading causes of burden of disease, child growth failure and household air pollution showed the most significant declines, while metabolic risks, such as body-mass index and high fasting plasma glucose, showed significant increases. In 2016, at Level 3 of the hierarchy, the three leading risk factors in terms of attributable DALYs at the global level for men were smoking (124.1 million DALYs [95% UI 111.2 million to 137.0 million]), high systolic blood pressure (122.2 million DALYs [110.3 million to 133.3 million], and low birthweight and short gestation (83.0 million DALYs [78.3 million to 87.7 million]), and for women, were high systolic blood pressure (89.9 million DALYs [80.9 million to 98.2 million]), high body-mass index (64.8 million DALYs [44.4 million to 87.6 million]), and high fasting plasma glucose (63.8 million DALYs [53.2 million to 76.3 million]). In 2016 in 113 countries, the leading risk factor in terms of attributable DALYs was a metabolic risk factor. Smoking remained among the leading five risk factors for DALYs for 109 countries, while low birthweight and short gestation was the leading risk factor for DALYs in 38 countries, particularly in sub-Saharan Africa and South Asia. In terms of important drivers of change in trends of burden attributable to risk factors, between 2006 and 2016 exposure to risks explains an 9.3% (6.9-11.6) decline in deaths and a 10.8% (8.3-13.1) decrease in DALYs at the global level, while population ageing accounts for 14.9% (12.7-17.5) of deaths and 6.2% (3.9-8.7) of DALYs, and population growth for 12.4% (10.1-14.9) of deaths and 12.4% (10.1-14.9) of DALYs. The largest contribution of trends in risk exposure to disease burden is seen between ages 1 year and 4 years, where a decline of 27.3% (24.9-29.7) of the change in DALYs between 2006 and 2016 can be attributed to declines in exposure to risks. Interpretation Increasingly detailed understanding of the trends in risk exposure and the RRs for each risk-outcome pair provide insights into both the magnitude of health loss attributable to risks and how modification of risk exposure has contributed to health trends. Metabolic risks warrant particular policy attention, due to their large contribution to global disease burden, increasing trends, and variable patterns across countries at the same level of development. GBD 2016 findings show that, while it has huge potential to improve health, risk modification has played a relatively small part in the past decade. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

    Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations : a systematic analysis from the Global Burden of Disease Study 2016

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    Background: A key component of achieving universal health coverage is ensuring that all populations have access to quality health care. Examining where gains have occurred or progress has faltered across and within countries is crucial to guiding decisions and strategies for future improvement. We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) to assess personal health-care access and quality with the Healthcare Access and Quality (HAQ) Index for 195 countries and territories, as well as subnational locations in seven countries, from 1990 to 2016. Methods: Drawing from established methods and updated estimates from GBD 2016, we used 32 causes from which death should not occur in the presence of effective care to approximate personal health-care access and quality by location and over time. To better isolate potential effects of personal health-care access and quality from underlying risk factor patterns, we risk-standardised cause-specific deaths due to non-cancers by location-year, replacing the local joint exposure of environmental and behavioural risks with the global level of exposure. Supported by the expansion of cancer registry data in GBD 2016, we used mortality-to-incidence ratios for cancers instead of risk-standardised death rates to provide a stronger signal of the effects of personal health care and access on cancer survival. We transformed each cause to a scale of 0–100, with 0 as the first percentile (worst) observed between 1990 and 2016, and 100 as the 99th percentile (best); we set these thresholds at the country level, and then applied them to subnational locations. We applied a principal components analysis to construct the HAQ Index using all scaled cause values, providing an overall score of 0–100 of personal health-care access and quality by location over time. We then compared HAQ Index levels and trends by quintiles on the Socio-demographic Index (SDI), a summary measure of overall development. As derived from the broader GBD study and other data sources, we examined relationships between national HAQ Index scores and potential correlates of performance, such as total health spending per capita. Findings: In 2016, HAQ Index performance spanned from a high of 97·1 (95% UI 95·8–98·1) in Iceland, followed by 96·6 (94·9–97·9) in Norway and 96·1 (94·5–97·3) in the Netherlands, to values as low as 18·6 (13·1–24·4) in the Central African Republic, 19·0 (14·3–23·7) in Somalia, and 23·4 (20·2–26·8) in Guinea-Bissau. The pace of progress achieved between 1990 and 2016 varied, with markedly faster improvements occurring between 2000 and 2016 for many countries in sub-Saharan Africa and southeast Asia, whereas several countries in Latin America and elsewhere saw progress stagnate after experiencing considerable advances in the HAQ Index between 1990 and 2000. Striking subnational disparities emerged in personal health-care access and quality, with China and India having particularly large gaps between locations with the highest and lowest scores in 2016. In China, performance ranged from 91·5 (89·1–93·6) in Beijing to 48·0 (43·4–53·2) in Tibet (a 43·5-point difference), while India saw a 30·8-point disparity, from 64·8 (59·6–68·8) in Goa to 34·0 (30·3–38·1) in Assam. Japan recorded the smallest range in subnational HAQ performance in 2016 (a 4·8-point difference), whereas differences between subnational locations with the highest and lowest HAQ Index values were more than two times as high for the USA and three times as high for England. State-level gaps in the HAQ Index in Mexico somewhat narrowed from 1990 to 2016 (from a 20·9-point to 17·0-point difference), whereas in Brazil, disparities slightly increased across states during this time (a 17·2-point to 20·4-point difference). Performance on the HAQ Index showed strong linkages to overall development, with high and high-middle SDI countries generally having higher scores and faster gains for non-communicable diseases. Nonetheless, countries across the development spectrum saw substantial gains in some key health service areas from 2000 to 2016, most notably vaccine-preventable diseases. Overall, national performance on the HAQ Index was positively associated with higher levels of total health spending per capita, as well as health systems inputs, but these relationships were quite heterogeneous, particularly among low-to-middle SDI countries. Interpretation: GBD 2016 provides a more detailed understanding of past success and current challenges in improving personal health-care access and quality worldwide. Despite substantial gains since 2000, many low-SDI and middle-SDI countries face considerable challenges unless heightened policy action and investments focus on advancing access to and quality of health care across key health services, especially non-communicable diseases. Stagnating or minimal improvements experienced by several low-middle to high-middle SDI countries could reflect the complexities of re-orienting both primary and secondary health-care services beyond the more limited foci of the Millennium Development Goals. Alongside initiatives to strengthen public health programmes, the pursuit of universal health coverage hinges upon improving both access and quality worldwide, and thus requires adopting a more comprehensive view—and subsequent provision—of quality health care for all populations

    Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016

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    Background: Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI). Methods: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE differed from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate. Findings: The highest globally observed HALE at birth for both women and men was in Singapore, at 75.2 years (95% uncertainty interval 71.9-78.6) for females and 72.0 years (68.8-75.1) for males. The lowest for females was in the Central African Republic (45.6 years [42.0-49.5]) and for males was in Lesotho (41.5 years [39.0-44.0]). From 1990 to 2016, global HALE increased by an average of 6.24 years (5.97-6.48) for both sexes combined. Global HALE increased by 6.04 years (5.74-6.27) for males and 6.49 years (6.08-6.77) for females, whereas HALE at age 65 years increased by 1.78 years (1.61-1.93) for males and 1.96 years (1.69-2.13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2.3% [-5.9 to 0.9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the five lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16.1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally. Interpretation: At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs offset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention efforts, and development assistance for health, including financial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support

    Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries : an analysis from the Global Burden of Disease Study 2016

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    Background: The UN's Sustainable Development Goals (SDGs) are grounded in the global ambition of "leaving no one behind". Understanding today's gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990-2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030. Methods: We used standardised GBD 2016 methods to measure 37 health-related indicators from 1990 to 2016, an increase of four indicators since GBD 2015. We substantially revised the universal health coverage (UHC) measure, which focuses on coverage of essential health services, to also represent personal health-care access and quality for several non-communicable diseases. We transformed each indicator on a scale of 0-100, with 0 as the 2.5th percentile estimated between 1990 and 2030, and 100 as the 97.5th percentile during that time. An index representing all 37 health-related SDG indicators was constructed by taking the geometric mean of scaled indicators by target. On the basis of past trends, we produced projections of indicator values, using a weighted average of the indicator and country-specific annualised rates of change from 1990 to 2016 with weights for each annual rate of change based on out-of-sample validity. 24 of the currently measured health-related SDG indicators have defined SDG targets, against which we assessed attainment. Findings: Globally, the median health-related SDG index was 56.7 (IQR 31.9-66.8) in 2016 and country-level performance markedly varied, with Singapore (86.8, 95% uncertainty interval 84.6-88.9), Iceland (86.0, 84.1-87.6), and Sweden (85.6, 81.8-87.8) having the highest levels in 2016 and Afghanistan (10.9, 9.6-11.9), the Central African Republic (11.0, 8.8-13.8), and Somalia (11.3, 9.5-13.1) recording the lowest. Between 2000 and 2016, notable improvements in the UHC index were achieved by several countries, including Cambodia, Rwanda, Equatorial Guinea, Laos, Turkey, and China; however, a number of countries, such as Lesotho and the Central African Republic, but also high-income countries, such as the USA, showed minimal gains. Based on projections of past trends, the median number of SDG targets attained in 2030 was five (IQR 2-8) of the 24 defined targets currently measured. Globally, projected target attainment considerably varied by SDG indicator, ranging from more than 60% of countries projected to reach targets for under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria, to less than 5% of countries projected to achieve targets linked to 11 indicator targets, including those for childhood overweight, tuberculosis, and road injury mortality. For several of the health-related SDGs, meeting defined targets hinges upon substantially faster progress than what most countries have achieved in the past. Interpretation: GBD 2016 provides an updated and expanded evidence base on where the world currently stands in terms of the health-related SDGs. Our improved measure of UHC offers a basis to monitor the expansion of health services necessary to meet the SDGs. Based on past rates of progress, many places are facing challenges in meeting defined health-related SDG targets, particularly among countries that are the worst off. In view of the early stages of SDG implementation, however, opportunity remains to take actions to accelerate progress, as shown by the catalytic effects of adopting the Millennium Development Goals after 2000. With the SDGs' broader, bolder development agenda, multisectoral commitments and investments are vital to make the health-related SDGs within reach of all populations

    Global, regional, and national prevalence of adult overweight and obesity, 1990–2021, with forecasts to 2050: a forecasting study for the Global Burden of Disease Study 2021

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    BackgroundOverweight and obesity is a global epidemic. Forecasting future trajectories of the epidemic is crucial for providing an evidence base for policy change. In this study, we examine the historical trends of the global, regional, and national prevalence of adult overweight and obesity from 1990 to 2021 and forecast the future trajectories to 2050. MethodsLeveraging established methodology from the Global Burden of Diseases, Injuries, and Risk Factors Study, we estimated the prevalence of overweight and obesity among individuals aged 25 years and older by age and sex for 204 countries and territories from 1990 to 2050. Retrospective and current prevalence trends were derived based on both self-reported and measured anthropometric data extracted from 1350 unique sources, which include survey microdata and reports, as well as published literature. Specific adjustment was applied to correct for self-report bias. Spatiotemporal Gaussian process regression models were used to synthesise data, leveraging both spatial and temporal correlation in epidemiological trends, to optimise the comparability of results across time and geographies. To generate forecast estimates, we used forecasts of the Socio-demographic Index and temporal correlation patterns presented as annualised rate of change to inform future trajectories. We considered a reference scenario assuming the continuation of historical trends. FindingsRates of overweight and obesity increased at the global and regional levels, and in all nations, between 1990 and 2021. In 2021, an estimated 1·00 billion (95% uncertainty interval [UI] 0·989–1·01) adult males and 1·11 billion (1·10–1·12) adult females had overweight and obesity. China had the largest population of adults with overweight and obesity (402 million [397–407] individuals), followed by India (180 million [167–194]) and the USA (172 million [169–174]). The highest age-standardised prevalence of overweight and obesity was observed in countries in Oceania and north Africa and the Middle East, with many of these countries reporting prevalence of more than 80% in adults. Compared with 1990, the global prevalence of obesity had increased by 155·1% (149·8–160·3) in males and 104·9% (95% UI 100·9–108·8) in females. The most rapid rise in obesity prevalence was observed in the north Africa and the Middle East super-region, where age-standardised prevalence rates in males more than tripled and in females more than doubled. Assuming the continuation of historical trends, by 2050, we forecast that the total number of adults living with overweight and obesity will reach 3·80 billion (95% UI 3·39–4·04), over half of the likely global adult population at that time. While China, India, and the USA will continue to constitute a large proportion of the global population with overweight and obesity, the number in the sub-Saharan Africa super-region is forecasted to increase by 254·8% (234·4–269·5). In Nigeria specifically, the number of adults with overweight and obesity is forecasted to rise to 141 million (121–162) by 2050, making it the country with the fourth-largest population with overweight and obesity. InterpretationNo country to date has successfully curbed the rising rates of adult overweight and obesity. Without immediate and effective intervention, overweight and obesity will continue to increase globally. Particularly in Asia and Africa, driven by growing populations, the number of individuals with overweight and obesity is forecast to rise substantially. These regions will face a considerable increase in obesity-related disease burden. Merely acknowledging obesity as a global health issue would be negligent on the part of global health and public health practitioners; more aggressive and targeted measures are required to address this crisis, as obesity is one of the foremost avertible risks to health now and in the future and poses an unparalleled threat of premature disease and death at local, national, and global levels. FundingBill & Melinda Gates Foundation.This study was funded by the Bill & Melinda Gates Foundation (OPP1152504)

    Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

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    Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. Methods: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Findings: Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1–4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0–8·4) while the total sum of global YLDs increased from 562 million (421–723) to 853 million (642–1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6–9·2) for males and 6·5% (5·4–7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782–3252] per 100 000 in males vs s1400 [1279–1524] per 100 000 in females), transport injuries (3322 [3082–3583] vs 2336 [2154–2535]), and self-harm and interpersonal violence (3265 [2943–3630] vs 5643 [5057–6302]). Interpretation: Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury

    Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

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    Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk–outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk–outcome pairs, and new data on risk exposure levels and risk–outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk–outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings In 2017, 34·1 million (95% uncertainty interval [UI] 33·3–35·0) deaths and 1·21 billion (1·14–1·28) DALYs were attributable to GBD risk factors. Globally, 61·0% (59·6–62·4) of deaths and 48·3% (46·3–50·2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10·4 million (9·39–11·5) deaths and 218 million (198–237) DALYs, followed by smoking (7·10 million [6·83–7·37] deaths and 182 million [173–193] DALYs), high fasting plasma glucose (6·53 million [5·23–8·23] deaths and 171 million [144–201] DALYs), high body-mass index (BMI; 4·72 million [2·99–6·70] deaths and 148 million [98·6–202] DALYs), and short gestation for birthweight (1·43 million [1·36–1·51] deaths and 139 million [131–147] DALYs). In total, risk-attributable DALYs declined by 4·9% (3·3–6·5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23·5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18·6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

    Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

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    Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk–outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk–outcome pairs, and new data on risk exposure levels and risk–outcome associations. Methods: We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk–outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings: In 2017, 34·1 million (95% uncertainty interval [UI] 33·3–35·0) deaths and 1·21 billion (1·14–1·28) DALYs were attributable to GBD risk factors. Globally, 61·0% (59·6–62·4) of deaths and 48·3% (46·3–50·2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10·4 million (9·39–11·5) deaths and 218 million (198–237) DALYs, followed by smoking (7·10 million [6·83–7·37] deaths and 182 million [173–193] DALYs), high fasting plasma glucose (6·53 million [5·23–8·23] deaths and 171 million [144–201] DALYs), high body-mass index (BMI; 4·72 million [2·99–6·70] deaths and 148 million [98·6–202] DALYs), and short gestation for birthweight (1·43 million [1·36–1·51] deaths and 139 million [131–147] DALYs). In total, risk-attributable DALYs declined by 4·9% (3·3–6·5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23·5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18·6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning
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