15 research outputs found

    Recent Advancements in Reducing the Off-Target Effect of CRISPR-Cas9 Genome Editing

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    Misganaw Asmamaw Mengstie,1 Muluken Teshome Azezew,2 Tadesse Asmamaw Dejenie,3 Assefa Agegnehu Teshome,4 Fitalew Tadele Admasu,1 Awgichew Behaile Teklemariam,1 Anemut Tilahun Mulu,1 Melaku Mekonnen Agidew,1 Dagnew Getnet Adugna,5 Habtamu Geremew,6 Endeshaw Chekol Abebe1 1Department of Biochemistry, College of Medicine and Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia; 2Department of Physiology, College of Medicine and Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia; 3Department of Medical Biochemistry, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia; 4Department of Anatomy, College of Medicine and Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia; 5Department of Anatomy, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia; 6College of Health Sciences, Oda Bultum University, Chiro, EthiopiaCorrespondence: Misganaw Asmamaw Mengstie, Department of Biochemistry, College of Medicine and Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia, Tel +25196715350, Email [email protected]: The CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)) and the associated protein (Cas9) system, a young but well-studied genome-editing tool, holds plausible solutions to a wide range of genetic disorders. The single-guide RNA (sgRNA) with a 20-base user-defined spacer sequence and the Cas9 endonuclease form the core of the CRISPR-Cas9 system. This sgRNA can direct the Cas9 nuclease to any genomic region that includes a protospacer adjacent motif (PAM) just downstream and matches the spacer sequence. The current challenge in the clinical applications of CRISPR-Cas9 genome-editing technology is the potential off-target effects that can cause DNA cleavage at the incorrect sites. Off-target genome editing confuses and diminishes the therapeutic potential of CRISPR-Cas9 in addition to potentially casting doubt on scientific findings regarding the activities of genes. In this review, we summarize the recent technological advancements in reducing the off-target effect of CRISPR-Cas9 genome editing.Keywords: CRISPR-Cas9, genome editing, off-target effect, recent advancements, revie

    Poor treatment outcomes of acute exacerbations of chronic obstructive pulmonary disease and their associated factors among admitted patients in East Gojjam, 2023

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    BackgroundAcute exacerbation of chronic obstructive pulmonary disease (COPD) poses a significant public health challenge globally, resulting in considerable health and economic burden. To date, there has been insufficient research in Ethiopia regarding poor treatment outcomes associated with these acute exacerbations.ObjectiveThis study aims to assess the poor treatment outcomes of acute exacerbations of chronic obstructive pulmonary disease and identify the associated factors among admitted patients in East Gojjam in 2023.DesignAn institutional-based cross-sectional study design was employed.MethodsThe institutional-based cross-sectional study was conducted from 7 April 2023 to 7 May 2023, involving 384 participants selected through simple random sampling. Data were extracted from patient charts and registers. Data entry was performed using EpiData, and the analysis was conducted using IBM SPSS Statistics version 26 software. Binary logistic regression analysis was used to identify the association between dependent and independent variables. Variables with a p-value of <0.25 in the bivariable logistic regression analysis were considered candidates for multivariable logistic regression. Variables with a p-value of <0.05 were considered statistically significant.ResultsOut of a total of 346 patients, 99 (28.6%) (95% CI, 23.9–33.3) developed poor treatment outcomes following exacerbations of chronic obstructive pulmonary diseases. Poor treatment outcomes were significantly associated with the following variables: age 65 or older (AOR = 3.9; 95% CI: 1.57–9.71), presence of comorbidities (AOR = 2.6; 95% CI: 1.287–5.20), a hospital stay longer than 7 days (AOR = 3.9; 95% CI: 1.97–7.70), and low oxygen saturation (<88%) (AOR = 9.0; 95% CI: 4.43–18.34).ConclusionApproximately one-third of the patients treated for acute exacerbations of chronic obstructive pulmonary disease at the Debre Markos Comprehensive Specialized Hospital experienced poor treatment outcomes. There is a significant association between poor treatment outcomes of acute exacerbation of chronic obstructive pulmonary disease and age ≥ 65 years, having comorbidities, prolonged hospital stay, and low oxygen saturation

    Progress in health among regions of Ethiopia, 1990-2019 : a subnational country analysis for the Global Burden of Disease Study 2019

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    Abstract: Background Previous Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) studies have reported national health estimates for Ethiopia. Substantial regional variations in socioeconomic status, population, demography, and access to health care within Ethiopia require comparable estimates at the subnational level. The GBD 2019 Ethiopia subnational analysis aimed to measure the progress and disparities in health across nine regions and two chartered cities. Methods We gathered 1057 distinct data sources for Ethiopia and all regions and cities that included census, demographic surveillance, household surveys, disease registry, health service use, disease notifications, and other data for this analysis. Using all available data sources, we estimated the Socio-demographic Index (SDI), total fertility rate (TFR), life expectancy, years of life lost, years lived with disability, disability-adjusted life-years, and risk-factor-attributable health loss with 95% uncertainty intervals (UIs) for Ethiopia's nine regions and two chartered cities from 1990 to 2019. Spatiotemporal Gaussian process regression, cause of death ensemble model, Bayesian meta-regression tool, DisMod-MR 2.1, and other models were used to generate fertility, mortality, cause of death, and disability rates. The risk factor attribution estimations followed the general framework established for comparative risk assessment. Findings The SDI steadily improved in all regions and cities from 1990 to 2019, yet the disparity between the highest and lowest SDI increased by 54% during that period. The TFR declined from 6.91 (95% UI 6.59-7.20) in 1990 to 4.43 (4.01-4.92) in 2019, but the magnitude of decline also varied substantially among regions and cities. In 2019, TFR ranged from 6.41 (5.96-6.86) in Somali to 1.50 (1.26-1.80) in Addis Ababa. Life expectancy improved in Ethiopia by 21.93 years (21.79-22.07), from 46.91 years (45.71-48.11) in 1990 to 68.84 years (67.51-70.18) in 2019. Addis Ababa had the highest life expectancy at 70.86 years (68.91-72.65) in 2019; Afar and Benishangul-Gumuz had the lowest at 63.74 years (61.53-66.01) for Afar and 64.28 (61.99-66.63) for Benishangul-Gumuz. The overall increases in life expectancy were driven by declines in under-5 mortality and mortality from common infectious diseases, nutritional deficiency, and war and conflict. In 2019, the age-standardised all-cause death rate was the highest in Afar at 1353.38 per 100 000 population (1195.69-1526.19). The leading causes of premature mortality for all sexes in Ethiopia in 2019 were neonatal disorders, diarrhoeal diseases, lower respiratory infections, tuberculosis, stroke, HIV/AIDS, ischaemic heart disease, cirrhosis, congenital defects, and diabetes. With high SDIs and life expectancy for all sexes, Addis Ababa, Dire Dawa, and Harari had low rates of premature mortality from the five leading causes, whereas regions with low SDIs and life expectancy for all sexes (Afar and Somali) had high rates of premature mortality from the leading causes. In 2019, child and maternal malnutrition; unsafe water, sanitation, and handwashing; air pollution; high systolic blood pressure; alcohol use; and high fasting plasma glucose were the leading risk factors for health loss across regions and cities. Interpretation There were substantial improvements in health over the past three decades across regions and chartered cities in Ethiopia. However, the progress, measured in SDI, life expectancy, TFR, premature mortality, disability, and risk factors, was not uniform. Federal and regional health policy makers should match strategies, resources, and interventions to disease burden and risk factors across regions and cities to achieve national and regional plans, Sustainable Development Goals, and universal health coverage targets. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd

    Global fertility in 204 countries and territories, 1950–2021, with forecasts to 2100 : a comprehensive demographic analysis for the Global Burden of Disease Study 2021

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    Natalia V Bhattacharjee, Austin E Schumacher, Amirali Aali, Yohannes Habtegiorgis Abate, Rouzbeh Abbasgholizadeh, Mohammadreza Abbasian, Mohsen Abbasi-Kangevari, Hedayat Abbastabar, Samar Abd ElHafeez, Sherief Abd-Elsalam, Mohammad Abdollahi, Mohammad-Amin Abdollahifar, Meriem Abdoun, Auwal Abdullahi, Mesfin Abebe, Samrawit Shawel Abebe, Olumide Abiodun, Hassan Abolhassani, Meysam Abolmaali, Mohamed Abouzid, Girma Beressa Aboye, Lucas Guimarães Abreu, Woldu Aberhe Abrha, Michael R M Abrigo, Dariush Abtahi, Hasan Abualruz, Bilyaminu Abubakar, Eman Abu-Gharbieh, Niveen ME Abu-Rmeileh, Tadele Girum Girum Adal, Mesafint Molla Adane, Oluwafemi Atanda Adeagbo Adeagbo, Rufus Adesoji Adedoyin, Victor Adekanmbi, Bashir Aden, Abiola Victor Adepoju, Olatunji O Adetokunboh, Juliana Bunmi Adetunji, Daniel Adedayo Adeyinka, Olorunsola Israel Adeyomoye, Qorinah Estiningtyas Sakilah Adnani, Saryia Adra, Rotimi Felix Afolabi, Shadi Afyouni, Muhammad Sohail Afzal, Saira Afzal, Shahin Aghamiri, Antonella Agodi, Williams Agyemang-Duah, Bright Opoku Ahinkorah, Austin J Ahlstrom, Aqeel Ahmad, Danish Ahmad, Firdos Ahmad, Muayyad M Ahmad, Sajjad Ahmad, Tauseef Ahmad, Ali Ahmed, Ayman Ahmed, Haroon Ahmed, Luai A Ahmed, Meqdad Saleh Ahmed, Syed Anees Ahmed, Marjan Ajami, Budi Aji, Gizachew Taddesse Akalu, Hossein Akbarialiabad, Rufus Olusola Akinyemi, Mohammed Ahmed Akkaif, Sreelatha Akkala, Hanadi Al Hamad, Syed Mahfuz Al Hasan, Mohammad Al Qadire, Tareq Mohammed Ali AL-Ahdal, Samer O Alalalmeh, Tariq A Alalwan, Ziyad Al-Aly, Khurshid Alam, Rasmieh Mustafa Al-amer, Fahad Mashhour Alanezi, Turki M Alanzi, Almaza Albakri, Mohammed Albashtawy, Mohammad T AlBataineh, Hediyeh Alemi, Sharifullah Alemi, Yihun Mulugeta Alemu, Ayman Al-Eyadhy, Adel Ali Saeed Al-Gheethi, Khalid F Alhabib, Noora Alhajri, Fadwa Alhalaiqa Naji Alhalaiqa, Robert Kaba Alhassan, Abid Ali, Beriwan Abdulqadir Ali, Liaqat Ali, Mohammed Usman Ali, Rafat Ali, Syed Shujait Shujait Ali, Sheikh Mohammad Alif, Mohammad Aligol, Mehran Alijanzadeh, Mohammad A M Aljasir, Syed Mohamed Aljunid, Sabah Al-Marwani, Joseph Uy Almazan, Hesham M Al-Mekhlafi, Omar Almidani, Mahmoud A Alomari, Basem Al-Omari, Jaber S Alqahtani, Ahmed Yaseen Alqutaibi, Rajaa M Al-Raddadi, Salman Khalifah Al-Sabah, Awais Altaf, Jaffar A Al-Tawfiq, Khalid A Altirkawi, Deborah Oyine Aluh, Farrukh Jawad Alvi, Nelson Alvis-Guzman, Hassan Alwafi, Yaser Mohammed Al-Worafi, Hany Aly, Safwat Aly, Karem H Alzoubi, Edward Kwabena Ameyaw, Tarek Tawfik Amin, Alireza Amindarolzarbi, Mostafa Amini-Rarani, Sohrab Amiri, Irene Gyamfuah Ampomah, Dickson A Amugsi, Ganiyu Adeniyi Amusa, Robert Ancuceanu, Deanna Anderlini, Pedro Prata Andrade, Catalina Liliana Andrei, Tudorel Andrei, Abhishek Anil, Sneha Anil, Adnan Ansar, Alireza Ansari-Moghaddam, Catherine M Antony, Ernoiz Antriyandarti, Saeid Anvari, SALEHA ANWAR, Razique Anwer, Anayochukwu Edward Anyasodor, Jalal Arabloo, Razman Arabzadeh Bahri, Elshaimaa A Arafa, Mosab Arafat, Ana Margarida Araújo, Aleksandr Y Aravkin, Abdulfatai Aremu, Timur Aripov, Mesay Arkew, Benedetta Armocida, Johan Ärnlöv, Mahwish Arooj, Anton A Artamonov, Judie Arulappan, Raphael Taiwo Aruleba, Ashokan Arumugam, Mohsen Asadi-Lari, Zatollah Asemi, Saeed Asgary, Mona Asghariahmadabad, Mohammad Asghari-Jafarabadi, Mubarek Yesse Ashemo, Muhammad Ashraf, Tahira Ashraf, Marvellous O Asika, Seyyed Shamsadin Athari, Maha Moh'd Wahbi Atout, Alok Atreya, Avinash Aujayeb, Marcel Ausloos, Abolfazl Avan, Amlaku Mulat Aweke, Getnet Melaku Ayele, Seyed Mohammad Ayyoubzadeh, Sina Azadnajafabad, Rui M S Azevedo, Ahmed Y Azzam, Muhammad Badar, Ashish D Badiye, Soroush Baghdadi, Nasser Bagheri, Sara Bagherieh, Najmeh Bahmanziari, Ruhai Bai, Atif Amin Baig, Jennifer L Baker, Abdulaziz T Bako, Ravleen Kaur Bakshi, Madhan Balasubramanian, Ovidiu Constantin Baltatu, Kiran Bam, Maciej Banach, Soham Bandyopadhyay, Biswajit Banik, Palash Chandra Banik, Hansi Bansal, Mehmet Firat Baran, Martina Barchitta, Mainak Bardhan, Erfan Bardideh, Suzanne Lyn Barker-Collo, Till Winfried Bärnighausen, Francesco Barone-Adesi, Hiba Jawdat Barqawi, Amadou Barrow, Sandra Barteit, Zarrin Basharat, Asma'u I J Bashir, Hameed Akande Bashiru, Afisu Basiru, João Diogo Basso, Sanjay Basu, Abdul-Monim Mohammad Batiha, Kavita Batra, Bernhard T Baune, Mohsen Bayati, Tahmina Begum, Emad Behboudi, Amir Hossein Behnoush, Maryam Beiranvand, Diana Fernanda Bejarano Ramirez, Alehegn Bekele, Sefealem Assefa Belay, Uzma Iqbal Belgaumi, Michelle L Bell, Olorunjuwon Omolaja Bello, Apostolos Beloukas, Isabela M Bensenor, Zombor Berezvai, Alemshet Yirga Berhie, Amiel Nazer C Bermudez, Paulo J G Bettencourt, Akshaya Srikanth Bhagavathula, Nikha Bhardwaj, Pankaj Bhardwaj, Prarthna V Bhardwaj, Sonu Bhaskar, Vivek Bhat, Gurjit Kaur Bhatti, Jasvinder Singh Bhatti, Manpreet S Bhatti, Rajbir Bhatti, Antonio Biondi, Catherine Bisignano, Atanu Biswas, Raaj Kishore Biswas, Veera R Bitra, Tone Bjørge, Elye Bliss, Micheal Kofi Boachie, Anca Vasilica Bobirca, Virginia Bodolica, Aadam Olalekan Bodunrin, Eyob Ketema Bogale, Kassawmar Angaw Bogale, Milad Bonakdar Hashemi, Berrak Bora Basara, Souad Bouaoud, Dejana Braithwaite, Michael Brauer, Nicholas J K Breitborde, Dana Bryazka, Norma B Bulamu, Danilo Buonsenso, Katrin Burkart, Richard A Burns, Yasser Bustanji, Nadeem Shafique Butt, Zahid A Butt, Florentino Luciano Caetano dos Santos, Daniela Calina, Ismael R Campos-Nonato, Fan Cao, Shujin Cao, Angelo Capodici, Giulia Carreras, Andrea Carugno, Carlos A Castañeda-Orjuela, Giulio Castelpietra, Maria Sofia Cattaruzza, Arthur Caye, Luca Cegolon, Francieli Cembranel, Ester Cerin, Joshua Chadwick, Yaacoub Chahine, Chiranjib Chakraborty, Julian Chalek, Jeffrey Shi Kai Chan, Periklis Charalampous, Vijay Kumar Chattu, Sarika Chaturvedi, Malizgani Paul Chavula, An-Tian Chen, Haowei Chen, Simiao Chen, Gerald Chi, Fatemeh Chichagi, Ju-Huei Chien, Patrick R Ching, William C S Cho, Sungchul Choi, Bryan Chong, Hitesh Chopra, Sonali Gajanan Choudhari, Devasahayam J Christopher, Dinh-Toi Chu, Isaac Sunday Chukwu, Eric Chung, Sheng-Chia Chung, Zinhle Cindi, Iolanda Cioffi, Raffaela Ciuffreda, Rafael M Claro, Kaleb Coberly, Alyssa Columbus, Haley Comfort, Joao Conde, Michael H Criqui, Natália Cruz-Martins, Silvia Magali Cuadra-Hernández, Sriharsha Dadana, Omid Dadras, Tukur Dahiru, Zhaoli Dai, Bronte Dalton, Giovanni Damiani, Aso Mohammad Darwesh, Jai K Das, Saswati Das, Mohsen Dashti, Anna Dastiridou, Claudio Alberto Dávila-Cervantes, Kairat Davletov, Aklilu Tamire Debele, Shayom Debopadhaya, Somayeh Delavari, Ivan Delgado-Enciso, Dessalegn Demeke, Berecha Hundessa Demessa, Xinlei Deng, Edgar Denova-Gutiérrez, Kebede Deribe, Nikolaos Dervenis, Hardik Dineshbhai Desai, Rupak Desai, Vinoth Gnana Chellaiyan Devanbu, Arkadeep Dhali, Kuldeep Dhama, Meghnath Dhimal, Vishal R Dhulipala, Diana Dias da Silva, Daniel Diaz, Michael J Diaz, Adriana Dima, Delaney D Ding, M Ashworth Dirac, Thanh Chi Do, Thao Huynh Phuong Do, Camila Bruneli do Prado, Sushil Dohare, Wanyue Dong, Mario D'Oria, Wendel Mombaque dos Santos, Leila Doshmangir, Robert Kokou Dowou, Ashel Chelsea Dsouza, Haneil Larson Dsouza, Viola Dsouza, John Dube, Joe Duprey, Andre Rodrigues Duraes, Senbagam Duraisamy, Oyewole Christopher Durojaiye, Sulagna Dutta, Laura Dwyer-Lindgren, Paulina Agnieszka Dzianach, Arkadiusz Marian Dziedzic, Alireza Ebrahimi, Hisham Atan Edinur, Kristina Edvardsson, Ferry Efendi, Terje Andreas Eikemo, Michael Ekholuenetale, Maha El Tantawi, Noha Mousaad Elemam, Ghada Metwally Tawfik ElGohary, Muhammed Elhadi, Legesse Tesfaye Elilo, Omar Abdelsadek Abdou Elmeligy, Mohamed A Elmonem, Mohammed Elshaer, Ibrahim Elsohaby, Amir Emami Zeydi, Luchuo Engelbert Bain, Sharareh Eskandarieh, Francesco Esposito, Kara Estep, Farshid Etaee, Natalia Fabin, Adeniyi Francis Fagbamigbe, Saman Fahimi, Aliasghar Fakhri-Demeshghieh, Luca Falzone, Ali Faramarzi, MoezAlIslam Ezzat Mahmoud Faris, Sam Farmer, Andre Faro, Abidemi Omolara Fasanmi, Ali Fatehizadeh, Nelsensius Klau Fauk, Pooria Fazeli, Valery L Feigin, Seyed-Mohammad Fereshtehnejad, Abdullah Hamid Feroze, Pietro Ferrara, Nuno Ferreira, Getahun Fetensa, Irina Filip, Florian Fischer, Joanne Flavel, Nataliya A Foigt, Morenike Oluwatoyin Folayan, Artem Alekseevich Fomenkov, Behzad Foroutan, Matteo Foschi, Kayode Raphael Fowobaje, Kate Louise Francis, Alberto Freitas, Takeshi Fukumoto, John E Fuller, Blima Fux, Peter Andras Gaal, Muktar A Gadanya, Abhay Motiramji Gaidhane, Yaseen Galali, Silvano Gallus, Aravind P Gandhi, Balasankar Ganesan, Mohammad Arfat Ganiyani, M.A. Garcia-Gordillo, Naval Garg, Rupesh K Gautam, Federica Gazzelloni, Semiu Olatunde Gbadamosi, Miglas W Gebregergis, Mesfin Gebrehiwot, Tesfay Brhane Gebremariam, Tesfay B B Gebremariam, Teferi Gebru Gebremeskel, Yohannes Fikadu Geda, Simona Roxana Georgescu, Urge Gerema, Habtamu Geremew, Motuma Erena Getachew, Peter W Gething, MohammadReza Ghasemi, Ghazal Ghasempour Dabaghi, Afsaneh Ghasemzadeh, Fariba Ghassemi, Ramy Mohamed Ghazy, Sailaja Ghimire, Asadollah Gholamian, Ali Gholamrezanezhad, Mahsa Ghorbani, Aloke Gopal Ghoshal, Arun Digambarrao Ghuge, Artyom Urievich Gil, Tiffany K Gill, Matteo Giorgi, Alem Girmay, James C Glasbey, Laszlo Göbölös, Amit Goel, Ali Golchin, Mahaveer Golechha, Pouya Goleij, Sameer Vali Gopalani, Houman Goudarzi, Alessandra C Goulart, Anmol Goyal, Simon Matthew Graham, Michal Grivna, Shi-Yang Guan, Giovanni Guarducci, Mohammed Ibrahim Mohialdeen Gubari, Mesay Dechasa Gudeta, Stefano Guicciardi, Snigdha Gulati, David Gulisashvili, Damitha Asanga Gunawardane, Cui Guo, Anish Kumar Gupta, Bhawna Gupta, Manoj Kumar Gupta, Mohak Gupta, Sapna Gupta, Veer Bala Gupta, Vijai Kumar Gupta, Vivek Kumar Gupta, Annie Haakenstad, Farrokh Habibzadeh, Najah R Hadi, Nils Haep, Ramtin Hajibeygi, Sebastian Haller, Rabih Halwani, Randah R Hamadeh, Nadia M Hamdy, Sajid Hameed, Samer Hamidi, Qiuxia Han, Alexis J Handal, Graeme J Hankey, Md Nuruzzaman Haque, Josep Maria Haro, Ahmed I Hasaballah, Ikramul Hasan, Mohammad Jahid Hasan, S.M. Mahmudul Hasan, Hamidreza Hasani, Md Saquib Hasnain, Amr Hassan, Ikrama Hassan, Soheil Hassanipour, Hadi Hassankhani, Simon I Hay, Jeffrey J Hebert, Omar E Hegazi, Mohammad Heidari, Bartosz Helfer, Mehdi Hemmati, Brenda Yuliana Herrera-Serna, Claudiu Herteliu, Kamran Hessami, Kamal Hezam, Yuta Hiraike, Nguyen Quoc Hoan, Ramesh Holla, Nobuyuki Horita, Md Mahbub Hossain, Mohammad Bellal Hossain Hossain, Hassan Hosseinzadeh, Mehdi Hosseinzadeh, Mihaela Hostiuc, Sorin Hostiuc, Mohamed Hsairi, Vivian Chia-rong Hsieh, Chengxi Hu, Junjie Huang, M Mamun Huda, Ayesha Humayun, Javid Hussain, Nawfal R Hussein, Hong-Han Huynh, Bing-Fang Hwang, Segun Emmanuel Ibitoye, Pulwasha Maria Iftikhar, Olayinka Stephen Ilesanmi, Irena M Ilic, Milena D Ilic, Mustapha Immurana, Leeberk Raja Inbaraj, Afrin Iqbal, Md. Rabiul Islam, Nahlah Elkudssiah Ismail, Hiroyasu Iso, Gaetano Isola, Masao Iwagami, Mahalaxmi Iyer, Linda Merin J, Jalil Jaafari, Louis Jacob, Farhad Jadidi-Niaragh, Khushleen Jaggi, Kasra Jahankhani, Nader Jahanmehr, Haitham Jahrami, Akhil Jain, Nityanand Jain, Ammar Abdulrahman Jairoun, Mihajlo Jakovljevic, Elham Jamshidi, Sabzali Javadov, Tahereh Javaheri, Sathish Kumar Jayapal, Shubha Jayaram, Sun Ha Jee, Jayakumar Jeganathan, Anil K Jha, Ravi Prakash Jha, Heng Jiang, Mohammad Jokar, Jost B Jonas, Tamas Joo, Nitin Joseph, Charity Ehimwenma Joshua, Farahnaz Joukar, Jacek Jerzy Jozwiak, Mikk Jürisson, Vaishali K, Billingsley Kaambwa, Abdulkareem Kabir, Ali Kabir, Hannaneh Kabir, Zubair Kabir, Rizwan Kalani, Leila R Kalankesh, Feroze Kaliyadan, Sanjay Kalra, Rajesh Kamath, Sagarika Kamath, Tanuj Kanchan, Edmund Wedam Kanmiki, Kehinde Kazeem Kanmodi, Suthanthira Kannan S, Sushil Kumar Kansal, Rami S Kantar, Neeti Kapoor, Mehrdad Karajizadeh, Manoochehr Karami, Ibraheem M Karaye, Faizan Zaffar Kashoo, Hengameh Kasraei, Nicholas J Kassebaum, Molly B Kassel, Joonas H Kauppila, Foad Kazemi, sara Kazeminia, John H Kempen, Evie Shoshannah Kendal, Kamyab Keshtkar, Mohammad Keykhaei, Himanshu Khajuria, Amirmohammad Khalaji, Nauman Khalid, Anees Ahmed Khalil, Alireza Khalilian, Faham Khamesipour, Ajmal Khan, Asaduzzaman Khan, Ikramullah Khan, M Nuruzzaman Khan, Maseer Khan, Mohammad Jobair Khan, Moien AB Khan, Young-Ho Khang, Shaghayegh Khanmohammadi, Khaled Khatab, Armin Khavandegar, Hamid Reza Khayat Kashani, Feriha Fatima Khidri, Moein Khormali, Mohammad Ali Khosravi, Mahmood Khosrowjerdi, Wondwosen Teklesilasie Kidane, Zemene Demelash Kifle, Julie Sojin Kim, Min Seo Kim, Ruth W Kimokoti, Kasey E Kinzel, Girmay Tsegay Kiross, Adnan Kisa, Sezer Kisa, Ali-Asghar Kolahi, Farzad Kompani, Gerbrand Koren, Oleksii Korzh, Soewarta Kosen, Sindhura Lakshmi Koulmane Laxminarayana, Kewal Krishan, Varun Krishna, Vijay Krishnamoorthy, Barthelemy Kuate Defo, Connor M Kubeisy, Burcu Kucuk Bicer, Md Abdul Kuddus, Mohammed Kuddus, Ilari Kuitunen, Mukhtar Kulimbet, Harish Kumar, Satyajit Kundu, Kunle Rotimi Kunle, Om P Kurmi, Asep Kusnali, Dian Kusuma, Evans F Kyei, Ilias Kyriopoulos, Carlo La Vecchia, Ben Lacey, Muhammad Awwal Ladan, Lucie Laflamme, Chandrakant Lahariya, Daphne Teck Ching Lai, Dharmesh Kumar Lal, Ratilal Lalloo, Judit Lám, Demetris Lamnisos, Iván Landires, Francesco Lanfranchi, Berthold Langguth, Ariane Laplante-Lévesque, Heidi Jane Larson, Anders O Larsson, Savita Lasrado, Kamaluddin Latief, Kaveh Latifinaibin, Long Khanh Dao Le, Nhi Huu Hanh Le, Trang Diep Thanh Le, Caterina Ledda, Munjae Lee, Paul H Lee, Seung Won Lee, Yo Han Lee, Gebretsadik Kiros Lema, Elvynna Leong, Temesgen L Lerango, An Li, Ming-Chieh Li, Shanshan Li, Wei Li, Xiaopan Li, Virendra S Ligade, Stephen S Lim, Ro-Ting Lin, Paulina A Lindstedt, Stefan Listl, Gang Liu, Jue Liu, Xiaofeng Liu, Xuefeng Liu, Yuewei Liu, Erand Llanaj, Rubén López-Bueno, Platon D Lopukhov, László Lorenzovici, Paulo A Lotufo, Jailos Lubinda, Giancarlo Lucchetti, Alessandra Lugo, Raimundas Lunevicius, Hengliang Lv, Zheng Feei Ma, Kelsey Lynn Maass, Monika Machoy, Áurea M Madureira-Carvalho, Mohammed Magdy Abd El Razek, Azzam A Maghazachi, Soleiman Mahjoub, Mansour Adam Mahmoud, Azeem Majeed, Jeadran N Malagón-Rojas, Elaheh Malakan Rad, Kashish Malhotra, Ahmad Azam Malik, Iram Malik, Deborah Carvalho Malta, Abdullah A Mamun, Yosef Manla, Yasaman Mansoori, Ali Mansour, Borhan Mansouri, Zeinab Mansouri, Mohammad Ali Mansournia, Joemer C Maravilla, Mirko Marino, Abdoljalal Marjani, Gabriel Martinez, Ramon Martinez-Piedra, Francisco Rogerlândio Martins-Melo, Miquel Martorell, Sharmeen Maryam, Roy Rillera Marzo, Alireza Masoudi, Jishanth Mattumpuram, Richard James Maude, Andrea Maugeri, Erin A May, Mahsa Mayeli, Maryam Mazaheri, John J McGrath, Martin McKee, Anna Laura Wensel McKowen, Susan A McLaughlin, Steven M McPhail, Rahul Mehra, Kamran Mehrabani-Zeinabad, Entezar Mehrabi Nasab, Tesfahun Mekene Meto, Max Alberto Mendez Mendez-Lopez, Walter Mendoza, Ritesh G Menezes, George A Mensah, Alexios-Fotios A Mentis, Sultan Ayoub Meo, Mohsen Merati, Atte Meretoja, Tuomo J Meretoja, Abera M Mersha, Tomislav Mestrovic, Pouya Metanat, Kukulege Chamila Dinushi Mettananda, Sachith Mettananda, Adquate Mhlanga, Laurette Mhlanga, Tianyue Mi, Tomasz Miazgowski, Georgia Micha, Irmina Maria Michalek, Ted R Miller, Le Huu Nhat Minh, Mojgan Mirghafourvand, Erkin M Mirrakhimov, Mizan Kiros Mirutse, Moonis Mirza, Roya Mirzaei, Ashim Mishra, Sanjeev Misra, Philip B Mitchell, Chaitanya Mittal, Babak Moazen, Abdalla Z Mohamed, Ahmed Ismail Mohamed, Jama Mohamed, Mouhand F H Mohamed, Nouh Saad Mohamed, Sakineh Mohammad-Alizadeh-Charandabi, Soheil Mohammadi, Abdollah Mohammadian-Hafshejani, Mustapha Mohammed, Salahuddin Mohammed, Shafiu Mohammed, Ali H Mokdad, Peyman Mokhtarzadehazar, Hossein Molavi Vardanjani, Sabrina Molinaro, Lorenzo Monasta, Mohammad Ali Moni, Maryam Moradi, Yousef Moradi, Paula Moraga, Rafael Silveira Moreira, Negar Morovatdar, Shane Douglas Morrison, Jakub Morze, Abbas Mosapour, Elias Mossialos, Rohith Motappa, Parsa Mousavi, Amin Mousavi Khaneghah, Christine Mpundu-Kaambwa, Sumaira Mubarik, Lorenzo Muccioli, Francesk Mulita, Kavita Munjal, Efrén Murillo-Zamora, Jonah Musa, Fungai Musaigwa, Ana-Maria Musina, Sathish Muthu, Saravanan Muthupandian, Muhammad Muzaffar, Woojae Myung, Ahamarshan Jayaraman Nagarajan, Gabriele Nagel, Pirouz Naghavi, Ganesh R Naik, Gurudatta Naik, Mukhammad David Naimzada, Firzan Nainu, Vinay Nangia, Sreenivas Narasimha Swamy, Bruno Ramos Nascimento, Gustavo G Nascimento, Abdallah Y Naser, Mohammad Javad Nasiri, Zuhair S Natto, Javaid Nauman, Muhammad Naveed, Biswa Prakash Nayak, Vinod C Nayak, Rawlance Ndejjo, Sabina Onyinye Nduaguba, Hadush Negash, Chernet Tafere Negesse, Ionut Negoi, Ruxandra Irina Negoi, Seyed Aria Nejadghaderi, Chakib Nejjari, Samata Nepal, Henok Biresaw Netsere, Georges Nguefack-Tsague, Josephine W. Ngunjiri, Dang H Nguyen, Hau Thi Hien Nguyen, Phuong The Nguyen, QuynhAnh P Nguyen, Van Thanh Nguyen, Robina Khan Niazi, Yeshambel T Nigatu, Taxiarchis Konstantinos Nikolouzakis, Ali Nikoobar, Amin Reza Nikpoor, Chukwudi A Nnaji, Lawrence Achilles Nnyanzi, Efaq Ali Noman, Shuhei Nomura, Mamoona Noreen, Nafise Noroozi, Chisom Adaobi Nri-Ezedi, Mengistu H Nunemo, Virginia Nuñez-Samudio, Dieta Nurrika, Jerry John Nutor, Bogdan Oancea, Kehinde O Obamiro, Ismail A Odetokun, Nkechi Martina Odogwu, Martin James O'Donnell, Oluwakemi Ololade Odukoya, Ayodipupo Sikiru Oguntade, James Odhiambo Oguta, In-Hwan Oh, Sylvester Reuben Okeke, Akinkunmi Paul Okekunle, Osaretin Christabel Okonji, Patrick Godwin Okwute, Andrew T Olagunju, Omotola O Olasupo, Matthew Idowu Olatubi, Gláucia Maria Moraes Oliveira, Bolajoko Olubukunola Olusanya, Jacob Olusegun Olusanya, Gideon Olamilekan Oluwatunase, Hany A Omar, Goran Latif Omer, Obinna E Onwujekwe, Michal Ordak, Orish Ebere Orisakwe, Verner N Orish, Doris V Ortega-Altamirano, Alberto Ortiz, Esteban Ortiz-Prado, Wael M S Osman, Uchechukwu Levi Osuagwu, Olayinka Osuolale, Adrian Otoiu, Stanislav S Otstavnov, Amel Ouyahia, Guoqing Ouyang, Mayowa O Owolabi, Yaz Ozten, Mahesh Padukudru P A, Mohammad Taha Pahlevan Fallahy, Feng Pan, Hai-Feng Pan, Adrian Pana, Paramjot Panda, Songhomitra Panda-Jonas, Helena Ullyartha Pangaribuan, Georgios D Panos, Leonidas D Panos, Ioannis Pantazopoulos, Anca Mihaela Pantea Stoian, Romil R Parikh, Seoyeon Park, Ashwaghosha Parthasarathi, Ava Pashaei, Roberto Passera, Hemal M Patel, Jay Patel, Shankargouda Patil, Dimitrios Patoulias, Venkata Suresh Patthipati, Uttam Paudel, Mihaela Paun, Hamidreza Pazoki Toroudi, Spencer A Pease, Amy E Peden, Paolo Pedersini, Minjin Peng, Umberto Pensato, Veincent Christian Filipino Pepito, Prince Peprah, Gavin Pereira, Mario F P Peres, Arokiasamy Perianayagam, Norberto Perico, Simone Perna, Richard G Pestell, Fanny Emily Petermann-Rocha, Hoang Tran Pham, Anil K Philip, Daniela Pierannunzio, Manon Pigeolet, David M Pigott, Evgenii Plotnikov, Dimitri Poddighe, Peter Pollner, Ramesh Poluru, Maarten J Postma, Ghazaleh Pourali, Akram Pourshams, Naeimeh Pourtaheri, Disha Prabhu, Sergio I Prada, Pranil Man Singh Pradhan, Manya Prasad, Akila Prashant, Bharathi M Purohit, Jagadeesh Puvvula, Nameer Hashim Qasim, Ibrahim Qattea, Deepthi R, Mehrdad Rabiee Rad, Amir Radfar, Venkatraman Radhakrishnan, Pourya Raee, Hadi Raeisi Shahraki, Alireza Rafiei, Seyedeh Niloufar Rafiei Alavi, Cat Raggi, Pankaja Raghav Raghav, Fakher Rahim, Md Jillur Rahim, Md. Mosfequr Rahman, Mohammad Hifz Ur Rahman, Mosiur Rahman, Muhammad Aziz Rahman, Vahid Rahmanian, Masoud Rahmati, Niloufar Rahnavard, Pramila Rai, Diego Raimondo, Ali Rajabpour-Sanati, Prashant Rajput, Prasanna Ram, Shakthi Kumaran Ramasamy, Juwel Rana, Kritika Rana, Shailendra Singh Rana, Chhabi Lal Ranabhat, Nemanja Rancic, Amey Rane, Shubham Ranjan, Chythra R Rao, Indu Ramachandra Rao, Deepthi Rapaka, Davide Rasella, Sina Rashedi, Vahid Rashedi, Mohammad-Mahdi Rashidi, Azad Rasul, Zubair Ahmed Ratan, Giridhara Rathnaiah Babu, Santosh Kumar Rauniyar, Nakul Ravikumar, David Laith Rawaf, Salman Rawaf, Reza Rawassizadeh, Bharat Rawlley, Murali Mohan Rama Krishna Reddy, Elrashdy Moustafa Mohamed Redwan, Giuseppe Remuzzi, Bhageerathy Reshmi, Nazila Rezaei, Aida Rezaei Nejad, Mohsen Rezaeian, Abanoub Riad, Mavra A Riaz, Jennifer Rickard, Reza Rikhtegar, Hannah Elizabeth Robinson-Oden, Célia Fortuna Rodrigues, Jefferson Antonio Buendia Rodriguez, Ravi Rohilla, Debby Syahru Romadlon, Luca Ronfani, Himanshu Sekhar Rout, Bedanta Roy, Nitai Roy, Priyanka Roy, Enrico Rubagotti, Guilherme de Andrade Ruela, Susan Fred Rumisha, Tilleye Runghien, Manjula S, Chandan S N, Aly M A Saad, Zahra Saadatian, Maha Mohamed Saber-Ayad, Morteza SaberiKamarposhti, Siamak Sabour, Fatos Sada, Basema Saddik, Bashdar Abuzed Sadee, Ehsan Sadeghi, Erfan Sadeghi, Mohammad Reza Saeb, Umar Saeed, Sher Zaman Safi, Dominic Sagoe, Manika Saha, Amirhossein Sahebkar, Soumya Swaroop Sahoo, Monalisha Sahu, Zahra Saif, Joseph W Sakshaug, Payman Salamati, Afeez Abolarinwa Salami, Mohamed A Saleh, Marwa Rashad Salem, Mohammed Z Y Salem, Sohrab Salimi, Sara Samadzadeh, Yoseph Leonardo Samodra, Vijaya Paul Samuel, Abdallah M Samy, Juan Sanabria, Nima Sanadgol, Francesca Sanna, Milena M Santric-Milicevic, Haaris Saqib, Sivan Yegnanarayana Iyer Saraswathy, Aswini Saravanan, Babak Saravi, Yaser Sarikhani, Tanmay Sarkar, Rodrigo Sarmiento-Suárez, Gargi Sachin Sarode, Sachin C Sarode, Arash Sarveazad, Brijesh Sathian, Thirunavukkarasu Sathish, Anudeep Sathyanarayan, Abu Sayeed, Md Abu Sayeed, Nikolaos Scarmeas, Winfried Schlee, Art Schuermans, David C Schwebel, Falk Schwendicke, Siddharthan Selvaraj, Pallav Sengupta, Subramanian Senthilkumaran, Sadaf G Sepanlou, Dragos Serban, Edson Serván-Mori, Yashendra Sethi, SeyedAhmad SeyedAlinaghi, Seyed Arsalan Seyedi, Allen Seylani, Mahan Shafie, Jaffer Shah, Pritik A Shah, Ataollah Shahbandi, Samiah Shahid, Moyad Jamal Shahwan, Ahme

    Spoligotype analysis of Mycobacterium bovis isolates from cattle and assessment of zoonotic TB transmission among individuals working in bovine TB-infected dairy farms in Ethiopia.

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    Bovine tuberculosis (bTB) is a disease with impact on dairy productivity, as well as having the potential for zoonotic transmission. Understanding the genetic diversity of the disease agent Mycobacterium bovis is important for identifying its routes of transmission. Here we investigated the level of genetic diversity of M. bovis isolates and assessed the zoonotic potential in risk groups of people working in bTB-infected dairy farms in central Ethiopia. M. bovis was isolated and spoligotyped from tissue lesions collected from slaughtered cattle as well as from raw milk collected from bTB positive cows in dairy farms from six urban areas of central Ethiopia. From consented dairy farm workers, knowledge and practices related to zoonotic TB transmission, together with demographic and clinical information, was collected through interviews. Sputum or Fine Needle Aspirate (FNA) samples were collected from suspected TB cases. Spoligotyping of 55 M. bovis isolates that originated either from cattle tissues with tuberculous lesion or from raw milk revealed seven spoligotype patterns where SB1176 was the most prevalent type (47.3%). Most isolates (89.1%) were of the M. bovis African 2 clonal complex. All sputum and FNA samples from 41 dairy farm workers with symptoms of TB were culture negative for any mycobacteria. Among the 41 TB suspected farm workers, 61% did not know about bTB in cattle and its zoonotic potential, and over two-third of these workers practiced raw milk consumption. Our spoligotype analysis suggests a wider transmission of a single spoligotype in the study area. The results reported here may be useful in guiding future work to identify the source and direction of bTB transmission and hence design of a control strategy. Isolation of M. bovis from milk, knowledge gap on zoonotic TB and practice of consumption of raw milk in the study population showed potential risk for zoonotic transmission

    Global fertility in 204 countries and territories, 1950–2021, with forecasts to 2100: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

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    Background: Accurate assessments of current and future fertility—including overall trends and changing population age structures across countries and regions—are essential to help plan for the profound social, economic, environmental, and geopolitical challenges that these changes will bring. Estimates and projections of fertility are necessary to inform policies involving resource and health-care needs, labour supply, education, gender equality, and family planning and support. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 produced up-to-date and comprehensive demographic assessments of key fertility indicators at global, regional, and national levels from 1950 to 2021 and forecast fertility metrics to 2100 based on a reference scenario and key policy-dependent alternative scenarios. Methods: To estimate fertility indicators from 1950 to 2021, mixed-effects regression models and spatiotemporal Gaussian process regression were used to synthesise data from 8709 country-years of vital and sample registrations, 1455 surveys and censuses, and 150 other sources, and to generate age-specific fertility rates (ASFRs) for 5-year age groups from age 10 years to 54 years. ASFRs were summed across age groups to produce estimates of total fertility rate (TFR). Livebirths were calculated by multiplying ASFR and age-specific female population, then summing across ages 10–54 years. To forecast future fertility up to 2100, our Institute for Health Metrics and Evaluation (IHME) forecasting model was based on projections of completed cohort fertility at age 50 years (CCF50; the average number of children born over time to females from a specified birth cohort), which yields more stable and accurate measures of fertility than directly modelling TFR. CCF50 was modelled using an ensemble approach in which three sub-models (with two, three, and four covariates variously consisting of female educational attainment, contraceptive met need, population density in habitable areas, and under-5 mortality) were given equal weights, and analyses were conducted utilising the MR-BRT (meta-regression—Bayesian, regularised, trimmed) tool. To capture time-series trends in CCF50 not explained by these covariates, we used a first-order autoregressive model on the residual term. CCF50 as a proportion of each 5-year ASFR was predicted using a linear mixed-effects model with fixed-effects covariates (female educational attainment and contraceptive met need) and random intercepts for geographical regions. Projected TFRs were then computed for each calendar year as the sum of single-year ASFRs across age groups. The reference forecast is our estimate of the most likely fertility future given the model, past fertility, forecasts of covariates, and historical relationships between covariates and fertility. We additionally produced forecasts for multiple alternative scenarios in each location: the UN Sustainable Development Goal (SDG) for education is achieved by 2030; the contraceptive met need SDG is achieved by 2030; pro-natal policies are enacted to create supportive environments for those who give birth; and the previous three scenarios combined. Uncertainty from past data inputs and model estimation was propagated throughout analyses by taking 1000 draws for past and present fertility estimates and 500 draws for future forecasts from the estimated distribution for each metric, with 95% uncertainty intervals (UIs) given as the 2·5 and 97·5 percentiles of the draws. To evaluate the forecasting performance of our model and others, we computed skill values—a metric assessing gain in forecasting accuracy—by comparing predicted versus observed ASFRs from the past 15 years (2007–21). A positive skill metric indicates that the model being evaluated performs better than the baseline model (here, a simplified model holding 2007 values constant in the future), and a negative metric indicates that the evaluated model performs worse than baseline. Findings: During the period from 1950 to 2021, global TFR more than halved, from 4·84 (95% UI 4·63–5·06) to 2·23 (2·09–2·38). Global annual livebirths peaked in 2016 at 142 million (95% UI 137–147), declining to 129 million (121–138) in 2021. Fertility rates declined in all countries and territories since 1950, with TFR remaining above 2·1—canonically considered replacement-level fertility—in 94 (46·1%) countries and territories in 2021. This included 44 of 46 countries in sub-Saharan Africa, which was the super-region with the largest share of livebirths in 2021 (29·2% [28·7–29·6]). 47 countries and territories in which lowest estimated fertility between 1950 and 2021 was below replacement experienced one or more subsequent years with higher fertility; only three of these locations rebounded above replacement levels. Future fertility rates were projected to continue to decline worldwide, reaching a global TFR of 1·83 (1·59–2·08) in 2050 and 1·59 (1·25–1·96) in 2100 under the reference scenario. The number of countries and territories with fertility rates remaining above replacement was forecast to be 49 (24·0%) in 2050 and only six (2·9%) in 2100, with three of these six countries included in the 2021 World Bank-defined low-income group, all located in the GBD super-region of sub-Saharan Africa. The proportion of livebirths occurring in sub-Saharan Africa was forecast to increase to more than half of the world's livebirths in 2100, to 41·3% (39·6–43·1) in 2050 and 54·3% (47·1–59·5) in 2100. The share of livebirths was projected to decline between 2021 and 2100 in most of the six other super-regions—decreasing, for example, in south Asia from 24·8% (23·7–25·8) in 2021 to 16·7% (14·3–19·1) in 2050 and 7·1% (4·4–10·1) in 2100—but was forecast to increase modestly in the north Africa and Middle East and high-income super-regions. Forecast estimates for the alternative combined scenario suggest that meeting SDG targets for education and contraceptive met need, as well as implementing pro-natal policies, would result in global TFRs of 1·65 (1·40–1·92) in 2050 and 1·62 (1·35–1·95) in 2100. The forecasting skill metric values for the IHME model were positive across all age groups, indicating that the model is better than the constant prediction. Interpretation: Fertility is declining globally, with rates in more than half of all countries and territories in 2021 below replacement level. Trends since 2000 show considerable heterogeneity in the steepness of declines, and only a small number of countries experienced even a slight fertility rebound after their lowest observed rate, with none reaching replacement level. Additionally, the distribution of livebirths across the globe is shifting, with a greater proportion occurring in the lowest-income countries. Future fertility rates will continue to decline worldwide and will remain low even under successful implementation of pro-natal policies. These changes will have far-reaching economic and societal consequences due to ageing populations and declining workforces in higher-income countries, combined with an increasing share of livebirths among the already poorest regions of the world. Funding: Bill & Melinda Gates Foundation. © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

    Adolescent transport and unintentional injuries: a systematic analysis using the Global Burden of Disease Study 2019

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    Globally, transport and unintentional injuries persist as leading preventable causes of mortality and morbidity for adolescents. We sought to report comprehensive trends in injury-related mortality and morbidity for adolescents aged 10-24 years during the past three decades

    Global burden of 292 causes of death in 204 countries and territories and 660 subnational locations, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023

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    Background: Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of dying before age 70 years (70q0) and the mean age at death by cause and sex. This study enables comparisons of the impact of causes of death over time, offering a deeper understanding of how these causes affect global populations. Methods: GBD 2023 produced estimates for 292 causes of death disaggregated by age-sex-location-year in 204 countries and territories and 660 subnational locations for each year from 1990 until 2023. We used a modelling tool developed for GBD, the Cause of Death Ensemble model (CODEm), to estimate cause-specific death rates for most causes. We computed YLLs as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. Probability of death was calculated as the chance of dying from a given cause in a specific age period, for a specific population. Mean age at death was calculated by first assigning the midpoint age of each age group for every death, followed by computing the mean of all midpoint ages across all deaths attributed to a given cause. We used GBD death estimates to calculate the observed mean age at death and to model the expected mean age across causes, sexes, years, and locations. The expected mean age reflects the expected mean age at death for individuals within a population, based on global mortality rates and the population's age structure. Comparatively, the observed mean age represents the actual mean age at death, influenced by all factors unique to a location-specific population, including its age structure. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 250-draw distribution for each metric. Findings are reported as counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2023 include a correction for the misclassification of deaths due to COVID-19, updates to the method used to estimate COVID-19, and updates to the CODEm modelling framework. This analysis used 55 761 data sources, including vital registration and verbal autopsy data as well as data from surveys, censuses, surveillance systems, and cancer registries, among others. For GBD 2023, there were 312 new country-years of vital registration cause-of-death data, 3 country-years of surveillance data, 51 country-years of verbal autopsy data, and 144 country-years of other data types that were added to those used in previous GBD rounds. Findings: The initial years of the COVID-19 pandemic caused shifts in long-standing rankings of the leading causes of global deaths: it ranked as the number one age-standardised cause of death at Level 3 of the GBD cause classification hierarchy in 2021. By 2023, COVID-19 dropped to the 20th place among the leading global causes, returning the rankings of the leading two causes to those typical across the time series (ie, ischaemic heart disease and stroke). While ischaemic heart disease and stroke persist as leading causes of death, there has been progress in reducing their age-standardised mortality rates globally. Four other leading causes have also shown large declines in global age-standardised mortality rates across the study period: diarrhoeal diseases, tuberculosis, stomach cancer, and measles. Other causes of death showed disparate patterns between sexes, notably for deaths from conflict and terrorism in some locations. A large reduction in age-standardised rates of YLLs occurred for neonatal disorders. Despite this, neonatal disorders remained the leading cause of global YLLs over the period studied, except in 2021, when COVID-19 was temporarily the leading cause. Compared to 1990, there has been a considerable reduction in total YLLs in many vaccine-preventable diseases, most notably diphtheria, pertussis, tetanus, and measles. In addition, this study quantified the mean age at death for all-cause mortality and cause-specific mortality and found noticeable variation by sex and location. The global all-cause mean age at death increased from 46·8 years (95% UI 46·6-47·0) in 1990 to 63·4 years (63·1-63·7) in 2023. For males, mean age increased from 45·4 years (45·1-45·7) to 61·2 years (60·7-61·6), and for females it increased from 48·5 years (48·1-48·8) to 65·9 years (65·5-66·3), from 1990 to 2023. The highest all-cause mean age at death in 2023 was found in the high-income super-region, where the mean age for females reached 80·9 years (80·9-81·0) and for males 74·8 years (74·8-74·9). By comparison, the lowest all-cause mean age at death occurred in sub-Saharan Africa, where it was 38·0 years (37·5-38·4) for females and 35·6 years (35·2-35·9) for males in 2023. Lastly, our study found that all-cause 70q0 decreased across each GBD super-region and region from 2000 to 2023, although with large variability between them. For females, we found that 70q0 notably increased from drug use disorders and conflict and terrorism. Leading causes that increased 70q0 for males also included drug use disorders, as well as diabetes. In sub-Saharan Africa, there was an increase in 70q0 for many non-communicable diseases (NCDs). Additionally, the mean age at death from NCDs was lower than the expected mean age at death for this super-region. By comparison, there was an increase in 70q0 for drug use disorders in the high-income super-region, which also had an observed mean age at death lower than the expected value. Interpretation: We examined global mortality patterns over the past three decades, highlighting-with enhanced estimation methods-the impacts of major events such as the COVID-19 pandemic, in addition to broader trends such as increasing NCDs in low-income regions that reflect ongoing shifts in the global epidemiological transition. This study also delves into premature mortality patterns, exploring the interplay between age and causes of death and deepening our understanding of where targeted resources could be applied to further reduce preventable sources of mortality. We provide essential insights into global and regional health disparities, identifying locations in need of targeted interventions to address both communicable and non-communicable diseases. There is an ever-present need for strengthened health-care systems that are resilient to future pandemics and the shifting burden of disease, particularly among ageing populations in regions with high mortality rates. Robust estimates of causes of death are increasingly essential to inform health priorities and guide efforts toward achieving global health equity. The need for global collaboration to reduce preventable mortality is more important than ever, as shifting burdens of disease are affecting all nations, albeit at different paces and scales. Funding: Gates Foundation

    Global fertility in 204 countries and territories, 1950–2021, with forecasts to 2100: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

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    Background Accurate assessments of current and future fertility—including overall trends and changing population age structures across countries and regions—are essential to help plan for the profound social, economic, environmental, and geopolitical challenges that these changes will bring. Estimates and projections of fertility are necessary to inform policies involving resource and health-care needs, labour supply, education, gender equality, and family planning and support. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 produced up-to-date and comprehensive demographic assessments of key fertility indicators at global, regional, and national levels from 1950 to 2021 and forecast fertility metrics to 2100 based on a reference scenario and key policy-dependent alternative scenarios
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