Browsing by Author "Libra, Massimo (6603852432)"
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Publication Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021(2024) ;Vollset, Stein Emil (57196315778) ;Ababneh, Hazim S. (57371604000) ;Abate, Yohannes Habtegiorgis (58492166600) ;Abbafati, Cristiana (54917122400) ;Abbasgholizadeh, Rouzbeh (59152412000) ;Abbasian, Mohammadreza (9846109700) ;Abbastabar, Hedayat (57212441848) ;Abd Al Magied, Abdallah H.A. (59128864400) ;ElHafeez, Samar Abd (55551273300) ;Abdelkader, Atef (57203858681) ;Abdelmasseh, Michael (57356690000) ;Abd-Elsalam, Sherief (57189845325) ;Abdi, Parsa (58143779200) ;Abdollahi, Mohammad (57940559800) ;Abdoun, Meriem (20336514800) ;Abdullahi, Auwal (56102934500) ;Abebe, Mesfin (57223854886) ;Abiodun, Olumide (7003859089) ;Aboagye, Richard Gyan (57221438826) ;Abolhassani, Hassan (58597704600) ;Abouzid, Mohamed (57204445082) ;Aboye, Girma Beressa (58714462800) ;Abreu, Lucas Guimarães (55937631400) ;Absalan, Abdorrahim (55207184600) ;Abualruz, Hasan (57216547615) ;Abubakar, Bilyaminu (56389502700) ;Abukhadijah, Hana Jihad Jihad (57865346000) ;Addolorato, Giovanni (7006562766) ;Adekanmbi, Victor (53463192900) ;Adetunji, Charles Oluwaseun (57192176047) ;Adetunji, Juliana Bunmi (57192177427) ;Adeyeoluwa, Temitayo Esther (57218094241) ;Adha, Rishan (57216878096) ;Adhikary, Ripon Kumar (55847469100) ;Adnani, Qorinah Estiningtyas Sakilah (57211604149) ;Adzigbli, Leticia Akua (57899326600) ;Afrashteh, Fatemeh (57254714200) ;Afzal, Muhammad Sohail (56009310800) ;Afzal, Saira (7004381116) ;Agbozo, Faith (57190337078) ;Agodi, Antonella (36774232400) ;Agrawal, Anurag (59030333500) ;Agyemang-Duah, Williams (57190228903) ;Ahinkorah, Bright Opoku (57194684030) ;Ahlstrom, Austin J. (58960999900) ;Ahmad, Aqeel (57210400531) ;Ahmad, Firdos (55545862620) ;Ahmad, Muayyad M. (57208845008) ;Ahmad, Sajjad (57218961022) ;Ahmad, Shahzaib (57221790990) ;Ahmed, Anisuddin (25623145700) ;Ahmed, Ayman (57199492030) ;Ahmed, Haroon (57222316680) ;Ahmed, Safoora (59126707900) ;Ahmed, Syed Anees (56943018400) ;Akinosoglou, Karolina (16318655800) ;Akkaif, Mohammed Ahmed (57222709271) ;Akrami, Ashley E. (58558692000) ;Akter, Ema (57251034300) ;Awaidy, Salah Al (6508132710) ;Al Hasan, Syed Mahfuz (57201069050) ;Al Mosa, Amjad S. (59130177400) ;Al Ta'ani, Omar (58041829900) ;Al Zaabi, Omar Ali Mohammed (57211669993) ;Alahdab, Fares (55135922900) ;Alajlani, Muaaz M. (57191247693) ;Al-Ajlouni, Yazan (57192869693) ;Alalalmeh, Samer O. (57997924800) ;Al-Aly, Ziyad (9738161500) ;Alam, Khurshid (57203681299) ;Alam, Noore (57202437697) ;Alam, Tahiya (57205589820) ;Alam, Zufishan (57222957445) ;Al-Amer, Rasmieh Mustafa (24470785500) ;Alanezi, Fahad Mashhour (57213607595) ;Alanzi, Turki M. (55978240000) ;Albakri, Almaza (59276206200) ;Aldhaleei, Wafa A. (57201732596) ;Aldridge, Robert W. (57209842885) ;Alemohammad, Seyedeh Yasaman (58143670700) ;Alemu, Yihun Mulugeta (57188818777) ;Al-Gheethi, Adel Ali Saeed (57195533166) ;Al-Hanawi, Mohammed Khaled (57195715156) ;Ali, Abid (57822712300) ;Ali, Amjad (57694808600) ;Ali, Iman (57215117745) ;Ali, Mohammed Usman (57726370200) ;Ali, Rafat (57211501723) ;Ali, Syed Shujait Shujait (57188688612) ;Ali, Victor Ekoche (58914121000) ;Ali, Waad (57216492465) ;Al-Ibraheem, Akram (26428019900) ;Alicandro, Gianfranco (36766719200) ;Alif, Sheikh Mohammad (57190228064) ;Aljunid, Syed Mohamed (57215378130) ;Alla, François (6701580827) ;Almazan, Joseph Uy (57202002090) ;Al-Mekhlafi, Hesham M. (8625547100) ;Alqutaibi, Ahmed Yaseen (57144551500) ;Alrawashdeh, Ahmad (57209326108) ;Alrousan, Sahel Majed (57190412987) ;Al-Sabah, Salman Khalifah (23566537100) ;Alsabri, Mohammed A. (59458399400) ;Altaany, Zaid (35386241800) ;Al-Tammemi, Ala'a B. (57216892163) ;Al-Tawfiq, Jaffar A. (9436438200) ;Altirkawi, Khalid A. (57202762923) ;Aluh, Deborah Oyine (57194111987) ;Alvis-Guzman, Nelson (57210741239) ;Al-Wardat, Mohammad Sami (57221463260) ;Al-Worafi, Yaser Mohammed (58143034700) ;Aly, Hany (35571391500) ;Alyahya, Mohammad Sharif (54984844500) ;Alzoubi, Karem H. (8579544200) ;Al-Zyoud, Walid (57202970794) ;Amani, Reza (58822675000) ;Ameyaw, Edward Kwabena (57194076624) ;Amin, Tarek Tawfik (23007746000) ;Amindarolzarbi, Alireza (58489784300) ;Amiri, Sohrab (57195335343) ;Amirzade-Iranaq, Mohammad Hosein (57194381354) ;Amu, Hubert (57190183918) ;Amugsi, Dickson A. (24461463800) ;Ancuceanu, Robert (35728302200) ;Anderlini, Deanna (57202506549) ;Anderson, David B. (57206183701) ;Andrade, Pedro Prata (58155276500) ;Andrei, Catalina Liliana (36543507200) ;Andrei, Tudorel (24179349400) ;Andrews, Erick Adrian (59129813600) ;Anil, Abhishek (58164007300) ;Anil, Sneha (58960766900) ;Anoushiravani, Amir (16038674600) ;Antony, Catherine M. 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(58556411300) ;Choi, Dong-Woo (57201729586) ;Chong, Bryan (57395645100) ;Chong, Chean Lin (57202112816) ;Chopra, Hitesh (57217071283) ;Chu, Dinh-Toi (56239816300) ;Chung, Eric (22952996300) ;Chutiyami, Muhammad (57202967671) ;Clayton, Justin T. (59129430400) ;Cogen, Rebecca M. (57215876285) ;Cohen, Aaron J. (7404780942) ;Columbus, Alyssa (57222467769) ;Comfort, Haley (57218875721) ;Conde, Joao (56992468300) ;Connolly, Jon T. (59129051700) ;Cooper, Ezra E.K. (59130178600) ;Cortese, Samuele (8651678100) ;Cruz-Martins, Natália (57203415019) ;da Silva, Alanna Gomes (57201069954) ;Dadras, Omid (57205721978) ;Dai, Xiaochen (58530783700) ;Dai, Zhaoli (55515212800) ;Dalton, Bronte E. (58492890000) ;Damiani, Giovanni (57218701806) ;Dandona, Lalit (7007017243) ;Dandona, Rakhi (57203043697) ;Das, Jai K. (55644705500) ;Das, Saswati (57209810658) ;Das, Subasish (55531140000) ;Dash, Nihar Ranjan (57194876029) ;Davletov, Kairat (6602803024) ;De la Hoz, Fernando Pio (23134262800) ;De Leo, Diego (7006128644) ;Debopadhaya, Shayom (57221247845) ;Delgado-Enciso, Ivan (57193209409) ;Denova-Gutiérrez, Edgar (25228198700) ;Dervenis, Nikolaos (35368148900) ;Desai, Hardik Dineshbhai (57218293291) ;Devanbu, Vinoth Gnana Chellaiyan (55879226900) ;Dewan, Syed Masudur Rahman (7102176358) ;Dhama, Kuldeep (6507396956) ;Dhane, Amol S. (58542222900) ;Dhingra, Sameer (57363710300) ;da Silva, Diana Dias (58082632400) ;Diaz, Daniel (56644152500) ;Diaz, Luis Antonio (56888369100) ;Diaz, Michael J. (57993579500) ;Dima, Adriana (57424551400) ;Ding, Delaney D. (57395549300) ;Do, Thao Huynh Phuong (58955491100) ;do Prado, Camila Bruneli (57607953900) ;Dodangeh, Masoud (57212454106) ;Dodangeh, Milad (57212454107) ;Doegah, Phidelia Theresa (57191248790) ;Dohare, Sushil (55539568400) ;Dong, Wanyue (57202532927) ;D'Oria, Mario (57191958879) ;Doshi, Rajkumar (57193926619) ;Dowou, Robert Kokou (57220119787) ;Dsouza, Haneil Larson (55058745500) ;Dsouza, Viola (59137508900) ;Dube, John (57356760200) ;Dumith, Samuel C. (16834520200) ;Duncan, Bruce B. (35476478500) ;Duraes, Andre Rodrigues (30867558600) ;Duraisamy, Senbagam (58956978800) ;Durojaiye, Oyewole Christopher (55297361600) ;Dushpanova, Anar (55255161200) ;Dutta, Sulagna (56673475300) ;Dzianach, Paulina Agnieszka (57209452587) ;Dziedzic, Arkadiusz Marian (56155198800) ;Eboreime, Ejemai (57094151100) ;Ebrahimi, Alireza (59785086900) ;Kalan, Mohammad Ebrahimi (57201131024) ;Edinur, Hisham Atan (57287676500) ;Efendi, Ferry (55301269100) ;Eikemo, Terje Andreas (23110114800) ;Eini, Ebrahim (56031829700) ;Ekundayo, Temitope Cyrus (57204841448) ;El Arab, Rabie Adel (57204688079) ;Sayed, Iman El (57207466387) ;Elamin, Osman (58075503000) ;Elemam, Noha Mousaad (56442766900) ;ElGohary, Ghada Metwally Tawfik (56198204500) ;Elhadi, Muhammed (57212082248) ;Elmeligy, Omar Abdelsadek Abdou (57194788994) ;Elmoselhi, Adel B. (6602310901) ;Elshaer, Mohammed (57225739890) ;Elsohaby, Ibrahim (56401825200) ;Eltahir, Elmagzoub (57210316518) ;Emeto, Theophilus I. (36522397000) ;Eshrati, Babak (16030619200) ;Eslami, Majid (57201082050) ;Esmaeili, Zahra (58967346200) ;Fabin, Natalia (57218175196) ;Fagbamigbe, Adeniyi Francis (50861113000) ;Fagbule, Omotayo Francis (57205137316) ;Falzone, Luca (57057684700) ;Fareed, Mohammad (24491815600) ;e Sá Farinha, Carla Sofia (59217467700) ;Faris, MoezAlIslam Ezzat Mahmoud (57218603193) ;Faro, Andre (36770969600) ;Fasihi, Kiana (57218212686) ;Fatehizadeh, Ali (36782045000) ;Fauk, Nelsensius Klau (57070534400) ;Fazylov, Timur (58203307800) ;Feigin, Valery L. (57203677957) ;Fekadu, Ginenus (57207252461) ;Feng, Xiaoqi (57211144740) ;Fereshtehnejad, Seyed-Mohammad (57202557520) ;Ferrara, Pietro (58098198000) ;Ferreira, Nuno (36782210100) ;Firew, Belete Sewasew (59129432600) ;Fischer, Florian (55508208800) ;Fitriana, Ida (57156637800) ;Flavel, Joanne (57194398510) ;Flor, Luisa S. (54414102000) ;Folayan, Morenike Oluwatoyin (56725310700) ;Foley, Kristen Marie (57205879071) ;Fonzo, Marco (57190342880) ;Force, Lisa M. (57188548035) ;Foschi, Matteo (57192255295) ;Freitas, Alberto (57217280282) ;Fridayani, Ni Kadek Yuni (59129250600) ;Fukutaki, Kai Glenn (57204561888) ;Furtado, João M. (36801755000) ;Fux, Blima (23392713900) ;Gaal, Peter Andras (55966171600) ;Gadanya, Muktar A. (25957587400) ;Gallus, Silvano (7005387365) ;Ganesan, Balasankar (57191928063) ;Ganiyani, Mohammad Arfat (57226275639) ;Gautam, Rupesh K. (55216656700) ;Gebi, Tilaye Gebru (58660009700) ;Gebregergis, Miglas W. (58955738100) ;Gebrehiwot, Mesfin (57192100745) ;Getacher, Lemma (57219912857) ;Getahun, Genanew K.A. (57745321200) ;Gething, Peter W. (57193559189) ;Ghadimi, Delaram J. (58021951600) ;Ghadirian, Fataneh (56896149700) ;Ghafarian, Sadegh (57202875042) ;Ghailan, Khalid Yaser (57201443897) ;Ghasemi, MohammadReza (57222125520) ;Dabaghi, Ghazal Ghasempour (57421651400) ;Ghazy, Ramy Mohamed (57212085342) ;Ghoba, Sama (57372932700) ;Gholami, Ehsan (57219938628) ;Gholamrezanezhad, Ali (10044363200) ;Gholizadeh, Nasim (58674073100) ;Ghorbani, Mahsa (58166133000) ;Vajargah, Pooyan Ghorbani (59563493200) ;Ghotbi, Elena (58002582000) ;Gil, Artyom Urievich (58284852000) ;Gill, Tiffany K. (8545441900) ;Girmay, Alem (59792305600) ;Glasbey, James C. (57195948986) ;Glushkova, Ekaterina Vladimirovna (57208983629) ;Gnedovskaya, Elena V. (56806916500) ;Göbölös, Laszlo (18934536800) ;Goldust, Mohamad (38761345300) ;Goleij, Pouya (57217533849) ;Golinelli, Davide (57194230279) ;Gopalani, Sameer Vali (58332307200) ;Goulart, Alessandra C. (57201181348) ;Gouravani, Mahdi (57214230480) ;Goyal, Anmol (58956489900) ;Grivna, Michal (6602150133) ;Grosso, Giuseppe (57196998256) ;Guarducci, Giovanni (57259051500) ;Gubari, Mohammed Ibrahim Mohialdeen (57210795029) ;Guicciardi, Stefano (56571343600) ;Guimarães, Rafael Alves (56534712800) ;Gulati, Snigdha (58960555500) ;Gulisashvili, David (58960555600) ;Gunawardane, Damitha Asanga (57201316656) ;Guo, Cui (57196000764) ;Gupta, Anish Kumar (57225856558) ;Gupta, Rahul (57204120071) ;Gupta, Rajeev (55705295300) ;Gupta, Renu (57195246722) ;Gupta, Sapna (57217857409) ;Gupta, Vijai Kumar (36158104300) ;Haakenstad, Annie (56079498000) ;Hadi, Najah R. (40461430800) ;Haep, Nils (57200036971) ;Hafiz, Abdul (57202393213) ;Haghmorad, Dariush (36101153900) ;Haile, Demewoz (40861134200) ;Ali, Adel Hajj (57215589567) ;Ali, Ali Hajj (59228704800) ;Haj-Mirzaian, Arvin (57210768364) ;Halboub, Esam S. (36028027700) ;Haller, Sebastian (55806149600) ;Halwani, Rabih (15065354400) ;Abdullah, Kanaan Hamagharib (57201269359) ;Hamdy, Nadia M. (57190847144) ;Hamoudi, Rifat (7003699541) ;Hanifi, Nasrin (55010787800) ;Hankey, Graeme J. (7102816661) ;Haq, Zaim Anan (58758744200) ;Haque, Md Rabiul (57213945810) ;Harapan, Harapan (55844857500) ;Hargono, Arief (57208225627) ;Haro, Josep Maria (57215877903) ;Hasaballah, Ahmed I. (56002305300) ;Hasan, S.M. Mahmudul (59841679300) ;Hasanian, Mohammad (57218697987) ;Hasnain, Md Saquib (36809656200) ;Hassan, Amr (55618204400) ;Haubold, Johannes (57225257476) ;Hay, Simon I. (7101875313) ;Hebert, Jeffrey J. (35233589600) ;Hegazi, Omar E. (59333456400) ;Heidari, Mohammad (56494430400) ;Hemmati, Mehdi (56381650600) ;Henson, Claire A. (58852028800) ;Herrera-Serna, Brenda Yuliana (57204618451) ;Herteliu, Claudiu (26035943100) ;Heydari, Majid (57535658900) ;Hezam, Kamal (57199187791) ;Hidayana, Irma (57189852423) ;Hiraike, Yuta (55701690300) ;Hoan, Nguyen Quoc (58959927100) ;Holla, Ramesh (55270371800) ;Hoogar, Praveen (57204240256) ;Horita, Nobuyuki (57217110823) ;Hossain, Md Mahbub (57207311791) ;Hosseinzadeh, Hassan (55913030700) ;Hosseinzadeh, Mehdi (57201880569) ;Hostiuc, Mihaela (51763789200) ;Hostiuc, Sorin (24829099800) ;Hu, Chengxi (58956490200) ;Huang, Junjie (57199198962) ;Hultström, Michael (14070391700) ;Hundie, Tsegaye Gebreyes (57225953725) ;Hunt, Aliza J. (7201428246) ;Hushmandi, Kiavash (55151192300) ;Hussain, Javid (9535362000) ;Hussain, M. Azhar (55839488500) ;Hussein, Nawfal R. (24766000100) ;Huynh, Hong-Han (58260528100) ;Hwang, Bing-Fang (7201453928) ;Ibitoye, Segun Emmanuel (57212027408) ;Iftikhar, Pulwasha Maria (56131638800) ;Ikiroma, Adalia I. (57802826500) ;Ikwegbue, Paul Chukwudi (57200637986) ;Ilic, Irena M. (57210823522) ;Ilic, Milena D. (7102981394) ;Immurana, Mustapha (57215875071) ;Isa, Mustafa Alhaji (57202778508) ;Islam, Md. Rabiul (57215057958) ;Islam, Sheikh Mohammed Shariful (56400111100) ;Ismail, Faisal (57218801491) ;Ismail, Nahlah Elkudssiah (57885381900) ;Isola, Gaetano (25825125500) ;Iwagami, Masao (54381883100) ;Iyamu, Ihoghosa Osamuyi (57219860603) ;Jacob, Louis (56779678900) ;Jacobsen, Kathryn H. (26029163100) ;Jafarinia, Morteza (57194211648) ;Jahankhani, Kasra (58165039000) ;Jahanmehr, Nader (57203122718) ;Jain, Nityanand (57219123557) ;Jairoun, Ammar Abdulrahman (57208735762) ;Mani, Ruchi Jakhmola (56844825700) ;Jamil, Safayet (57779252400) ;Jamora, Roland Dominic G. (8896661800) ;Jatau, Abubakar Ibrahim (57193384550) ;Javadov, Sabzali (6602916796) ;Javaheri, Tahereh (36102883000) ;Jayaram, Shubha (57221589240) ;Jee, Sun Ha (16039275900) ;Jeganathan, Jayakumar (55312958400) ;Jiang, Heng (56149161900) ;Jokar, Mohammad (57221729841) ;Jonas, Jost B. (7202492953) ;Joseph, Nitin (35292547200) ;Joshua, Charity Ehimwenma (58491197900) ;Jürisson, Mikk (55547524800) ;Vaishali, K. (57222526820) ;Kabir, Ali (23050698400) ;Kabir, Zubair (57207901718) ;Kadashetti, Vidya (56724219200) ;Kalankesh, Laleh R. (57200529685) ;Kalra, Sanjay (13408725200) ;Kamath, Ashwin (35724313100) ;Kamath, Rajesh (35546251600) ;Kamireddy, Arun (57719836700) ;Kanaan, Mona (9636696900) ;Kanchan, Tanuj (35237157900) ;Kanmiki, Edmund Wedam (56823634100) ;Kanmodi, Kehinde Kazeem (57193860523) ;Kansal, Sushil Kumar (8636613600) ;Karim, Asima (57188657071) ;Karkhah, Samad (57219866571) ;Kashoo, Faizan Zaffar (57208602574) ;Kasraei, Hengameh (57194520224) ;Kassel, Molly B. (58955990600) ;Katikireddi, Srinivasa Vittal (59000218300) ;Kauppila, Joonas H. (37665210400) ;Kaur, Harkiran (57860762900) ;Kayode, Gbenga A. (53463867400) ;Kazemi, Foad (58881461600) ;Kazemian, Sina (57221397269) ;Kebede, Fassikaw (57218606802) ;Kendal, Evie Shoshannah (57140616700) ;Kesse-Guyot, Emmanuelle (35573782000) ;Khademvatan, Shahram (28567880500) ;Khajuria, Himanshu (56639982500) ;Khalaji, Amirmohammad (57801096100) ;Khalid, Asaad (7005705767) ;Khalid, Nauman (57204561542) ;Khalilian, Alireza (59357174700) ;Khamesipour, Faham (55236513800) ;Khan, Fayaz (57189525469) ;Khan, Mohammad Jobair (57298003900) ;Khan, Moien A.B. (57209800900) ;Khanmohammadi, Shaghayegh (57216530776) ;Khatab, Khaled (27267685100) ;Khatatbeh, Haitham (57218610483) ;Khatatbeh, Moawiah Mohammad (26421267800) ;Khatib, Mahalaqua Nazli (25825057100) ;Kashani, Hamid Reza Khayat (57132486000) ;Kheirallah, Khalid A. (47161432800) ;Khokhar, Manoj (56351826200) ;Khormali, Moein (57193114653) ;Khorrami, Zahra (57003491300) ;Khosla, Atulya Aman (57219789185) ;Khosravi, Majid (57749061200) ;Khosrowjerdi, Mahmood (35092543000) ;Khubchandani, Jagdish (57211720011) ;Kifle, Zemene Demelash (57216524881) ;Kim, Grace (57204812303) ;Kim, Julie Sojin (59868068800) ;Kim, Min Seo (57203591936) ;Kim, Yun Jin (57211086375) ;Kimokoti, Ruth W. (8647554600) ;Kisa, Adnan (6603346067) ;Kisa, Sezer (14030019900) ;Knibbs, Luke D. 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(57211558396) ;Listl, Stefan (35759488300) ;Liu, Gang (57189061134) ;Liu, Shiwei (57209574351) ;Liu, Shuke (59129816800) ;Liu, Xiaofeng (57193764777) ;Liu, Xuefeng (37050047900) ;Llanaj, Erand (57204154387) ;López-Bueno, Rubén (57204275020) ;López-Gil, José Francisco (57211391916) ;Loreche, Arianna Maever (58094114300) ;Lotufo, Paulo A. (7003331101) ;Lozano, Rafael (57570224000) ;Lubinda, Jailos (56700387300) ;Lucchetti, Giancarlo (35790096500) ;Luo, Lisha (57192420067) ;Lusk, Jay B. (57226167327) ;Lv, Lei (58238332100) ;Amin, Hawraz Ibrahim M. (57189760740) ;Ma, Zheng Feei (56248284800) ;Maass, Kelsey Lynn (57211536483) ;Machairas, Nikolaos (55761474700) ;Machoy, Monika (56123551300) ;Madureira-Carvalho, Áurea M. (57201779481) ;El Razek, Hassan Magdy Abd (57195948755) ;Maghazachi, Azzam A. (7004562043) ;Prasad, D.R. Mahadeshwara (57220181627) ;Mahalleh, Mehrdad (57212591499) ;Mahasha, Phetole Walter (28767805500) ;Mahmoud, Mansour Adam (55461775000) ;Mahmoudi, Elham (37034395100) ;Mahmoudvand, Golnaz (57349095500) ;Makama, Maureen (57221801687) ;Rad, Elaheh Malakan (55105272200) ;Malhotra, Kashish (57224508895) ;Malik, Ahmad Azam (57198682313) ;Malta, Deborah Carvalho (15835283500) ;Manla, Yosef (57218291420) ;Mansour, Ali (7202587376) ;Mansouri, Mohammad Hadi (57214679568) ;Mansouri, Pejman (57191708855) ;Mansouri, Vahid (59348187900) ;Mansourian, Marjan (26027945700) ;Mansournia, Mohammad Ali (34570618600) ;Marasini, Bishnu P. (51565657000) ;Marateb, Hamid Reza (35759194200) ;Maravilla, Joemer C. (57008289000) ;Mardi, Parham (57209858695) ;Marjani, Abdoljalal (16643027900) ;Moghadam, Hamed Markazi (57203818899) ;Arnedo, Carlos Alberto Marrugo (57216635948) ;Martinez, Gabriel (57208099155) ;Martinez-Piedra, Ramon (57226114681) ;Martins-Melo, Francisco Rogerlândio (57204796807) ;Martorell, Miquel (57211415589) ;Marx, Wolfgang (55920693000) ;Marzo, Roy Rillera (57163427600) ;Masoudi, Sahar (57188985486) ;Mathangasinghe, Yasith (57193006575) ;Mathioudakis, Alexander G. (55452222600) ;Mathur, Medha (57193831433) ;Mathur, Navgeet (57193832639) ;Mathur, Neeta (57211826204) ;Matozinhos, Fernanda Penido (36696568300) ;Mattumpuram, Jishanth (57218167884) ;Maude, Richard James (25625222500) ;Maugeri, Andrea (56740683100) ;Mayeli, Mahsa (57195405671) ;Mazidi, Mohsen (57200232563) ;Mazzotti, Antonio (53164388700) ;McGrath, John J. (57215198193) ;McKee, Martin (7202304775) ;McKowen, Anna Laura W. (57222260344) ;McPhail, Michael A. (58955742600) ;McPhail, Steven M. (35234404800) ;Mehmood, Asim (57219905276) ;Mehrabani-Zeinabad, Kamran (57202425863) ;Mehravar, Sepideh (57993808900) ;Meto, Tesfahun Mekene (59156731000) ;Melese, Endalkachew Belayneh (12773823200) ;Mendez-Lopez, Max Alberto Mendez (57207774180) ;Mendoza, Walter (57216905642) ;Menezes, Ritesh G. (55517099900) ;Mensah, George A. (57196028147) ;Mensah, Laverne G. (57914140100) ;Mentis, Alexios-Fotios A. (7003278838) ;Meo, Sultan Ayoub (7003732623) ;Meretoja, Atte (12775885500) ;Meretoja, Tuomo J. (57219008708) ;Mersha, Abera M. (57205064523) ;Mestrovic, Tomislav (6507240107) ;Mettananda, Kukulege Chamila Dinushi (56069894000) ;Mettananda, Sachith (58272092100) ;Mhlanga, Adquate (59591079100) ;Mhlanga, Laurette (57743632800) ;Miazgowski, Tomasz (6701404689) ;Michalek, Irmina Maria (56982945900) ;de Sá, Ana Carolina Micheletti Gomide Nogueira (57211324345) ;Miller, Ted R. (7403948600) ;Minh, Le Huu Nhat (57201722696) ;Mirahmadi, Alireza (57752668600) ;Mirijello, Antonio (22634678000) ;Mirrakhimov, Erkin M. (57508336100) ;Mirzaei, Roya (55745833800) ;Mitchell, Philip B. (35354747000) ;Mittal, Chaitanya (57200363487) ;Moberg, Madeline E. (57820324700) ;Fard, Atousa Moghadam (58528589100) ;Mohajelin, Seyedehfatemeh (59129056500) ;Mohamadkhani, Ashraf (9747546000) ;Mohamed, Ahmed Ismail (57340126500) ;Mohamed, Jama (57340126400) ;Mohamed, Mouhand F.H. (57209007025) ;Mohamed, Nouh Saad (57208820453) ;Mohammad, Ameen Mosa (56104792300) ;Mohammadi, Soheil (57193239265) ;Mohammed, Hussen (57208445079) ;Mohammed, Mustapha (58144884000) ;Mohammed, Shafiu (57838689000) ;Mokdad, Ali H. (7004813962) ;Molokhia, Mariam (7004121920) ;Momani, Shaher Mohammad (8842321100) ;Momtazmanesh, Sara (57212649454) ;Monasta, Lorenzo (7801520497) ;Mondello, Stefania (23094881100) ;Moni, Mohammad Ali (35119094400) ;Montazeri, Fateme (57924899400) ;Ghalibaf, AmirAli Moodi (57226579608) ;Moradi, Maryam (57736564200) ;Moradi, Yousef (55338348700) ;Moraga, Paula (46761426800) ;Morawska, Lidia (7004773965) ;Moreira, Rafael Silveira (57819635000) ;Morovatdar, Negar (55221857000) ;Morrison, Shane Douglas (45661573100) ;Mosapour, Abbas (16425956900) ;Mosser, Jonathan F. (56111776300) ;Mossialos, Elias (7004354602) ;Motappa, Rohith (57577479200) ;Mougin, Vincent (58857561500) ;Mousavi, Parsa (58627198400) ;Mrejen, Matías (57211239633) ;Mubarik, Sumaira (57202290474) ;Mueller, Ulrich Otto (8512347500) ;Mulita, Francesk (57200275021) ;Munjal, Kavita (57359972400) ;Murillo-Zamora, Efrén (55496438100) ;Musallam, Khaled M. (24335608600) ;Musina, Ana-Maria (57192831523) ;Mustafa, Ghulam (57190395960) ;Myung, Woojae (37099034100) ;Nafei, Ayoub (59126538800) ;Nagarajan, Ahamarshan Jayaraman (57204562074) ;Naghavi, Pirouz (58857110800) ;Naik, Ganesh R. (14825548600) ;Naik, Gurudatta (56020694000) ;Nainu, Firzan (57120069200) ;Najdaghi, Soroush (57218267592) ;Ansari, Noureddin Nakhostin (14015121200) ;Nangia, Vinay (57201490837) ;Swamy, Sreenivas Narasimha (57222706843) ;Nargus, Shumaila (58491929300) ;Davani, Delaram Narimani (57934653600) ;Nascimento, Bruno Ramos (14424406800) ;Nascimento, Gustavo G. (55849893800) ;Naser, Abdallah Y. (57200532990) ;Nashwan, Abdulqadir J. (22985634100) ;Natto, Zuhair S. (37000768500) ;Nauman, Javaid (35334911400) ;Navaratna, Samidi N.K. (56382542100) ;Naveed, Muhammad (58953995300) ;Nawsherwan (57190755436) ;Nayak, Biswa Prakash (56639942500) ;Nayak, Vinod C. (24385399000) ;Negash, Hadush (57209110507) ;Negoi, Ionut (57200640014) ;Negoi, Ruxandra Irina (55566106200) ;Nejadghaderi, Seyed Aria (57218948511) ;Nejjari, Chakib (6602168304) ;Nematollahi, Soroush (58947392700) ;Netsere, Henok Biresaw (57218199940) ;Ng, Marie (36155754200) ;Nguefack-Tsague, Georges (55198921200) ;Ngunjiri, Josephine W. (57195296110) ;Nguyen, Anh Hoang (59284955800) ;Nguyen, Dang H. (57220970272) ;Nguyen, Duc Hoang (58693553700) ;Nguyen, Hau Thi Hien (58492170200) ;Nguyen, Nhan (59129056600) ;Nguyen, Nhien Ngoc Y. (59126827800) ;Nguyen, Phat Tuan (58366936400) ;Nguyen, QuynhAnh P. (57211556351) ;Nguyen, Van Thanh (58491437100) ;Minh, Duc Nguyen Tran (57199622107) ;Niazi, Robina Khan (57204666021) ;Nigatu, Yeshambel T. (56491170000) ;Niknam, Mahdieh (55548656400) ;Nikoobar, Ali (57580752700) ;Nikpoor, Amin Reza (55544292000) ;Nikravangolsefid, Nasrin (57216919994) ;Noman, Efaq Ali (57191746290) ;Nomura, Shuhei (55632290700) ;Noor, Syed Toukir Ahmed (57999331500) ;Noroozi, Nafise (57219412726) ;Nouri, Mehran (57207824453) ;Nozari, Majid (57196151420) ;Nri-Ezedi, Chisom Adaobi (57218593582) ;Ntaios, George (16426036800) ;Nunemo, Mengistu H. (57208104658) ;Nurrika, Dieta (57204936262) ;Nutor, Jerry John (57200143951) ;Nzoputam, Chimezie Igwegbe (57217058740) ;Nzoputam, Ogochukwu Janet (57819279400) ;Oancea, Bogdan (26658614800) ;Obamiro, Kehinde O. (57190161875) ;Odetokun, Ismail A. (58518431400) ;Oduro, Michael Safo (57671872600) ;Ogundijo, Oluwaseun Adeolu (57253773900) ;Ogunfowokan, Adesola Adenike (15923805800) ;Ogunkoya, Abiola (57279728300) ;Oguntade, Ayodipupo Sikiru (57194328445) ;Oh, In-Hwan (57204090669) ;Ojo-Akosile, Tolulope R. (58566223700) ;Okati-Aliabad, Hassan (57211186862) ;Okekunle, Akinkunmi Paul (56668691000) ;Okonji, Osaretin Christabel (57222864302) ;Olagunju, Andrew T. (26029995700) ;Olatubi, Matthew Idowu (57200278115) ;Oliveira, Gláucia Maria Moraes (6505822894) ;Olusanya, Bolajoko Olubukunola (57218504682) ;Olusanya, Jacob Olusegun (57222488860) ;Oluwafemi, Yinka Doris (57215413986) ;Omar, Hany A. (35213612000) ;Omer, Goran Latif (57933555400) ;Ong, Sokking (36614524300) ;Onie, Sandersan (57193354692) ;Onwujekwe, Obinna E. (7003992855) ;Opejin, Abdulahi Opejin (59129819200) ;Ordak, Michal (55992015900) ;Orish, Verner N. (55253440500) ;Ortiz, Alberto (7201911399) ;Ortiz-Prado, Esteban (56037076100) ;Osman, Wael M.S. (57195344402) ;Ostojic, Sergej M. (8552029600) ;Ostroff, Samuel M. (57219860984) ;Osuagwu, Uchechukwu Levi (46062324800) ;Otoiu, Adrian (56375694100) ;Otstavnov, Stanislav S. (57204561394) ;Ouyahia, Amel (36499964800) ;Owolabi, Mayowa O. (57222581892) ;Oyeyemi, Oyetunde T. (56732871100) ;Ozair, Ahmad (57215601638) ;Mahesh Padukudru, P.A. (57195664371) ;Padron-Monedero, Alicia (56532107100) ;Padubidri, Jagadish Rao (58295062300) ;Pal, Pramod Kumar (35578625800) ;Palicz, Tamás (57218865382) ;Pan, Feng (57220873446) ;Pan, Hai-Feng (35234356200) ;Panda-Jonas, Songhomitra (6603112353) ;Pandey, Anamika (55633420800) ;Pando-Robles, Victoria (49964327500) ;Pangaribuan, Helena Ullyartha (57217140455) ;Panos, Georgios D. (55629406000) ;Panos, Leonidas D. (57204439372) ;Pantazopoulos, Ioannis (35574470700) ;Stoian, Anca Mihaela Pantea (57200568822)Parikh, Romil R. (57204150124)Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions. 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 license - Some of the metrics are blocked by yourconsent settings
Publication Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021(2024) ;Schumacher, Austin E. (57209276410) ;Kyu, Hmwe Hmwe (57217040073) ;Aali, Amirali (57819452000) ;Abbafati, Cristiana (54917122400) ;Abbas, Jaffar (57217776454) ;Abbasgholizadeh, Rouzbeh (59152412000) ;Abbasi, Madineh Akram (57193923353) ;Abbasian, Mohammadreza (9846109700) ;Abd ElHafeez, Samar (55551273300) ;Abdelmasseh, Michael (57356690000) ;Abd-Elsalam, Sherief (57189845325) ;Abdelwahab, Ahmed (57862779500) ;Abdollahi, Mohammad (57940559800) ;Abdoun, Meriem (20336514800) ;Abdullahi, Auwal (56102934500) ;Abdurehman, Ame Mehadi (58660534900) ;Abebe, Mesfin (57223854886) ;Abedi, Aidin (56673854800) ;Abedi, Armita (57204607249) ;Abegaz, Tadesse M. 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(58955740600) ;Kucuk Bicer, Burcu (57204528360) ;Kuddus, Md Abdul (59471271200) ;Kuddus, Mohammed (8596487800) ;Kuitunen, Ilari (57189581253) ;Kujan, Omar (8889097500) ;Kulimbet, Mukhtar (57288600700) ;Kulkarni, Vishnutheertha (58587146700) ;Kumar, Ashish (59311506700) ;Kumar, Harish (59089763100) ;Kumar, Nithin (36678889900) ;Kumar, Rahul (57750022900) ;Kumar, Shiv (57213856169) ;Kumari, Madhulata (56597592700) ;Kurmanova, Almagul (56896046600) ;Kurmi, Om P. (57219034567) ;Kusnali, Asep (57947961700) ;Kusuma, Dian (57190047530) ;Kutluk, Tezer (20934856000) ;Kuttikkattu, Ambily (57860475200) ;Kyei, Evans F. (57214818508) ;Kyriopoulos, Ilias (6504795889) ;La Vecchia, Carlo (36063266200) ;Ladan, Muhammad Awwal (57201721917) ;Laflamme, Lucie (7005939330) ;Lahariya, Chandrakant (13205447400) ;Lahmar, Abdelilah (57866356300) ;Lai, Daphne Teck Ching (59553448200) ;Laksono, Tri (58537561100) ;Lal, Dharmesh Kumar (57222488984) ;Lalloo, Ratilal (57189334553) ;Lallukka, Tea (6508300634) ;Lám, Judit (7201973410) ;Lamnisos, Demetris (54404766700) ;Lan, Tuo (57218329495) ;Lanfranchi, Francesco (57196456066) ;Langguth, Berthold (6602352583) ;Lansingh, Van Charles (57209471470) ;Laplante-Lévesque, Ariane (6506488140) ;Larijani, Bagher (57205307740) ;Larsson, Anders O. (56381985300) ;Lasrado, Savita (36632480900) ;Latief, Kamaluddin (26428870800) ;Latif, Mahrukh (58142528000) ;Latifinaibin, Kaveh (58957217400) ;Lauriola, Paolo (7004129174) ;Le, Long Khanh Dao (57873296500) ;Le, Nhi Huu Hanh (57225941904) ;Le, Thao Thi Thu (57736182100) ;Le, Trang Diep Thanh (58955740800) ;Lee, Munjae (58964400000) ;Lee, Paul H. (57200302692) ;Lee, Sang-Woong (57193130569) ;Lee, Seung Won (57223118056) ;Lee, Wei-Chen (57394248700) ;Lee, Yo Han (57193632340) ;Legesse, Samson Mideksa (57562395800) ;Leigh, James (22957414600) ;Lenzi, Jacopo (57200000691) ;Leong, Elvynna (56462346200) ;Lerango, Temesgen L. (58124758800) ;Li, Ming-Chieh (56144176300) ;Li, Wei (59638602600) ;Li, Xiaopan (54389570600) ;Li, Yichong (57218426673) ;Li, Zhihui (56346333300) ;Libra, Massimo (6603852432) ;Ligade, Virendra S. (15769728900) ;Likaka, Andrew Tiyamike Makhiringa (55151159300) ;Lim, Lee-Ling (56988527400) ;Lin, Ro-Ting (15123000400) ;Lin, Shuzhi (57397981100) ;Lioutas, Vasileios-Arsenios (36114439100) ;Listl, Stefan (35759488300) ;Liu, Jue (56797105100) ;Liu, Simin (58636394800) ;Liu, Xiaofeng (57193764777) ;Livingstone, Katherine M. (55466317400) ;Llanaj, Erand (57204154387) ;Lo, Chun-Han (57216207024) ;Loreche, Arianna Maever (58094114300) ;Lorenzovici, László (57200941835) ;Lotfi, Mojgan (37109768200) ;Lotfizadeh, Masoud (55853761600) ;Lozano, Rafael (57570224000) ;Lubinda, Jailos (56700387300) ;Lucchetti, Giancarlo (35790096500) ;Lugo, Alessandra (55227636600) ;Lunevicius, Raimundas (57216165063) ;Ma, Jianing (58040920000)Ma, Stefan (7403723389)Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic. 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 license - Some of the metrics are blocked by yourconsent settings
Publication The Global, Regional, and National Burden of Adult Lip, Oral, and Pharyngeal Cancer in 204 Countries and Territories: A Systematic Analysis for the Global Burden of Disease Study 2019(2023) ;Da Cunha, Amanda Ramos (57214078354) ;Compton, Kelly (57205330541) ;Xu, Rixing (57204186670) ;Mishra, Rashmi (59585097000) ;Drangsholt, Mark Thomas (6701699849) ;Antunes, Jose Leopoldo Ferreira (7005765907) ;Kerr, Alexander R. (24477055900) ;Acheson, Alistair R. (57912642400) ;Lu, Dan (59057346200) ;Wallace, Lindsey E. (57356541900) ;Kocarnik, Jonathan M. (56041211800) ;Fu, Weijia (57218882680) ;Dean, Frances E. 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(36028027700) ;Halwani, Rabih (15065354400) ;Hanif, Asif (55360052800) ;Hariyani, Ninuk (57190349243) ;Harorani, Mehdi (57195316126) ;Hasani, Hamidreza (55632123200) ;Hassan, Abbas M. (57659064800) ;Hassanipour, Soheil (57191513993) ;Hassen, Mohammed Bheser (58491683100) ;Hay, Simon I. (7101875313) ;Hayat, Khezar (57219918947) ;Herrera-Serna, Brenda Yuliana (57204618451) ;Holla, Ramesh (55270371800) ;Horita, Nobuyuki (57217110823) ;Hosseinzadeh, Mehdi (57201880569) ;Hussain, Salman (57193956545) ;Ilesanmi, Olayinka Stephen (54782692800) ;Ilic, Irena M. (57210823522) ;Ilic, Milena D. (7102981394) ;Isola, Gaetano (25825125500) ;Jaiswal, Abhishek (57196884767) ;Jani, Chinmay T. (57218651211) ;Javaheri, Tahereh (36102883000) ;Jayarajah, Umesh (57192238672) ;Jayaram, Shubha (57221589240) ;Joseph, Nitin (35292547200) ;Kadashetti, Vidya (56724219200) ;Kandaswamy, Eswar (57191343580) ;Karanth, Shama D. (57208742503) ;Karaye, Ibraheem M. (55598638900) ;Kauppila, Joonas H. (37665210400) ;Kaur, Harkiran (57860762900) ;Keykhaei, Mohammad (57208162861) ;Khader, Yousef Saleh (55654192600) ;Khajuria, Himanshu (56639982500) ;Khanali, Javad (57219388410) ;Khatib, Mahalaqua Nazli (25825057100) ;Khayat Kashani, Hamid Reza (57132486000) ;Khazeei Tabari, Mohammad Amin (57217587801) ;Kim, Min Seo (57203591936) ;Kompani, Farzad (56071483000) ;Koohestani, Hamid Reza (26423051700) ;Kumar, G. Anil (57139550500) ;Kurmi, Om P. (57219034567) ;La Vecchia, Carlo (36063266200) ;Lal, Dharmesh Kumar (57222488984) ;Landires, Iván (15063040000) ;Lasrado, Savita (36632480900) ;Ledda, Caterina (54885410300) ;Lee, Yo Han (57193632340) ;Libra, Massimo (6603852432) ;Lim, Stephen S. (57201800433) ;Listl, Stefan (35759488300) ;Lopukhov, Platon D. (57191340780) ;Mafi, Ahmad R. (23571119200) ;Mahumud, Rashidul Alam (57188551083) ;Malik, Ahmad Azam (57198682313) ;Mathur, Manu Raj (55270329300) ;Maulud, Sazan Qadir (57205675578) ;Meena, Jitendra Kumar (57217997226) ;Mehrabi Nasab, Entezar (56062744400) ;Mestrovic, Tomislav (6507240107) ;Mirfakhraie, Reza (57923553700) ;Misganaw, Awoke (57202808713) ;Misra, Sanjeev (35501005200) ;Mithra, Prasanna (36018632500) ;Mohammad, Yousef (6603403710) ;Mohammadi, Mokhtar (57188972365) ;Mohammadi, Esmaeil (57210443452) ;Mokdad, Ali H. (7004813962) ;Moni, Mohammad Ali (35119094400) ;Moraga, Paula (46761426800) ;Morrison, Shane Douglas (45661573100) ;Mozaffari, Hamid Reza (56789924600) ;Mubarik, Sumaira (57202290474) ;Murray, Christopher J. L. (57224556036) ;Nair, Tapas Sadasivan (59496484400) ;Narasimha Swamy, Sreenivas (57226829643) ;Narayana, Aparna Ichalangod (26530691100) ;Nassereldine, Hasan (57226192220) ;Natto, Zuhair S. 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(57211144346) ;Sathian, Brijesh (27467953500) ;Satpathy, Maheswar (57202563691) ;Šekerija, Mario (30268005400) ;Senthilkumaran, Subramanian (36191387000) ;Seylani, Allen (57222325334) ;Shafaat, Omid (55567483500) ;Shahsavari, Hamid R. (6505834447) ;Shamsoddin, Erfan (57208402503) ;Sharew, Mequannent Melaku (57224505062) ;Sharifi-Rad, Javad (56022647300) ;Shetty, Jeevan K. (15844347300) ;Shivakumar, K.M. (57221603938) ;Shobeiri, Parnian (57218601156) ;Shorofi, Seyed Afshin (35086976700) ;Shrestha, Sunil (56453947500) ;Siddappa Malleshappa, Sudeep K. (57208838253) ;Singh, Paramdeep (57202809996) ;Singh, Jasvinder A. (58179112300) ;Singh, Garima (57224794687) ;Sinha, Dhirendra Narain (7201637609) ;Solomon, Yonatan (57220875005) ;Suleman, Muhammad (57196800921) ;Suliankatchi Abdulkader, Rizwan (57226832737) ;Taheri Abkenar, Yasaman (57211386327) ;Talaat, Iman M. (7801465176) ;Tan, Ker-Kan (16745396700) ;Tbakhi, Abdelghani (6602349888) ;Thiyagarajan, Arulmani (57208205338) ;Tiyuri, Amir (57201850751) ;Tovani-Palone, Marcos Roberto (56644977900) ;Unnikrishnan, Bhaskaran (12790012100) ;Vo, Bay (35147075900) ;Volovat, Simona Ruxandra (44961657900) ;Wang, Cong (15924372200) ;Westerman, Ronny (57218361023) ;Wickramasinghe, Nuwan Darshana (55326938000) ;Xiao, Hong (57214631433) ;Yu, Chuanhua (57208140344) ;Yuce, Deniz (57514476300) ;Yunusa, Ismaeel (57202137670) ;Zadnik, Vesna (57202975428) ;Zare, Iman (57224488480) ;Zhang, Zhi-Jiang (56068578400) ;Zoladl, Mohammad (53980736300) ;Force, Lisa M. (57188548035)Hugo, Fernando N. (13403199800)Importance: Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning. Objective: To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates. Evidence Review: The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019. Findings: In 2019, 370000 (95% uncertainty interval [UI], 338000-401000) cases and 199000 (95% UI, 181000-217000) deaths for LOC and 167000 (95% UI, 153000-180000) cases and 114000 (95% UI, 103000-126000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia. Conclusions and Relevance: In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts. © 2023 American Medical Association. All rights reserved. - Some of the metrics are blocked by yourconsent settings
Publication The Global, Regional, and National Burden of Adult Lip, Oral, and Pharyngeal Cancer in 204 Countries and Territories: A Systematic Analysis for the Global Burden of Disease Study 2019(2023) ;Da Cunha, Amanda Ramos (57214078354) ;Compton, Kelly (57205330541) ;Xu, Rixing (57204186670) ;Mishra, Rashmi (59585097000) ;Drangsholt, Mark Thomas (6701699849) ;Antunes, Jose Leopoldo Ferreira (7005765907) ;Kerr, Alexander R. (24477055900) ;Acheson, Alistair R. (57912642400) ;Lu, Dan (59057346200) ;Wallace, Lindsey E. (57356541900) ;Kocarnik, Jonathan M. (56041211800) ;Fu, Weijia (57218882680) ;Dean, Frances E. (57211949247) ;Pennini, Alyssa (57210820174) ;Henrikson, Hannah Jacqueline (57219861283) ;Alam, Tahiya (57205589820) ;Ababneh, Emad (57210792873) ;Abd-Elsalam, Sherief (57189845325) ;Abdoun, Meriem (20336514800) ;Abidi, Hassan (36769387800) ;Abubaker Ali, Hiwa (57441328600) ;Abu-Gharbieh, Eman (24586714800) ;Adane, Tigist Demssew (57219700847) ;Addo, Isaac Yeboah (56305995900) ;Ahmad, Aqeel (57210400531) ;Ahmad, Sajjad (57218961022) ;Ahmed Rashid, Tarik (57023479100) ;Akonde, Maxwell (57221786267) ;Al Hamad, Hanadi (56955516200) ;Alahdab, Fares (55135922900) ;Alimohamadi, Yousef (56069375900) ;Alipour, Vahid (56436629300) ;Al-Maweri, Sadeq Ali (36023535700) ;Alsharif, Ubai (57211633255) ;Ansari-Moghaddam, Alireza (57192807651) ;Anwar, Sumadi Lukman (55251130100) ;Anyasodor, Anayochukwu Edward (57192947419) ;Arabloo, Jalal (57208760927) ;Aravkin, Aleksandr Y. 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(23571119200) ;Mahumud, Rashidul Alam (57188551083) ;Malik, Ahmad Azam (57198682313) ;Mathur, Manu Raj (55270329300) ;Maulud, Sazan Qadir (57205675578) ;Meena, Jitendra Kumar (57217997226) ;Mehrabi Nasab, Entezar (56062744400) ;Mestrovic, Tomislav (6507240107) ;Mirfakhraie, Reza (57923553700) ;Misganaw, Awoke (57202808713) ;Misra, Sanjeev (35501005200) ;Mithra, Prasanna (36018632500) ;Mohammad, Yousef (6603403710) ;Mohammadi, Mokhtar (57188972365) ;Mohammadi, Esmaeil (57210443452) ;Mokdad, Ali H. (7004813962) ;Moni, Mohammad Ali (35119094400) ;Moraga, Paula (46761426800) ;Morrison, Shane Douglas (45661573100) ;Mozaffari, Hamid Reza (56789924600) ;Mubarik, Sumaira (57202290474) ;Murray, Christopher J. L. (57224556036) ;Nair, Tapas Sadasivan (59496484400) ;Narasimha Swamy, Sreenivas (57226829643) ;Narayana, Aparna Ichalangod (26530691100) ;Nassereldine, Hasan (57226192220) ;Natto, Zuhair S. (37000768500) ;Nayak, Biswa Prakash (56639942500) ;Negru, Serban Mircea (6602216697) ;Nggada, Haruna Asura (8376121100) ;Nouraei, Hasti (55360408900) ;Nuñez-Samudio, Virginia (15063201000) ;Oancea, Bogdan (26658614800) ;Olagunju, Andrew T. (26029995700) ;Omar Bali, Ahmed (57201273344) ;Padron-Monedero, Alicia (56532107100) ;Padubidri, Jagadish Rao (58295062300) ;Pandey, Anamika (55633420800) ;Pardhan, Shahina (7003706887) ;Patel, Jay (59222700400) ;Pezzani, Raffaele (6602481624) ;Piracha, Zahra Zahid (57189084862) ;Rabiee, Navid (57201008317) ;Radhakrishnan, Venkatraman (34873452800) ;Radhakrishnan, Raghu Anekal (7103113006) ;Rahmani, Amir Masoud (57204588830) ;Rahmanian, Vahid (55367908800) ;Rao, Chythra R. (35771430100) ;Rao, Sowmya J. (57195423591) ;Rath, Goura Kishor (35444818200) ;Rawaf, David Laith (57209228052) ;Rawaf, Salman (6602475959) ;Rawassizadeh, Reza (36634807900) ;Razeghinia, Mohammad Sadegh (57203060460) ;Rezaei, Nazila (36700192900) ;Rezaei, Negar (57218820767) ;Rezaei, Nima (57216077273) ;Rezapour, Aziz (55548281300) ;Riad, Abanoub (57218221621) ;Roberts, Thomas J. (57190111163) ;Romero-Rodríguez, Esperanza (57189989890) ;Roshandel, Gholamreza (14034446800) ;Manjula, S. (57405727400) ;Chandan, S.N. (58523385100) ;Saddik, Basema (23020079300) ;Saeb, Mohammad Reza (24833454900) ;Saeed, Umar (36612315100) ;Safaei, Mohsen (36612136800) ;Sahebazzamani, Maryam (57350889700) ;Sahebkar, Amirhossein (26639699900) ;Salek Farrokhi, Amir (57191290025) ;Samy, Abdallah M. (36973661300) ;Santric-Milicevic, Milena M. (57211144346) ;Sathian, Brijesh (27467953500) ;Satpathy, Maheswar (57202563691) ;Šekerija, Mario (30268005400) ;Senthilkumaran, Subramanian (36191387000) ;Seylani, Allen (57222325334) ;Shafaat, Omid (55567483500) ;Shahsavari, Hamid R. (6505834447) ;Shamsoddin, Erfan (57208402503) ;Sharew, Mequannent Melaku (57224505062) ;Sharifi-Rad, Javad (56022647300) ;Shetty, Jeevan K. (15844347300) ;Shivakumar, K.M. (57221603938) ;Shobeiri, Parnian (57218601156) ;Shorofi, Seyed Afshin (35086976700) ;Shrestha, Sunil (56453947500) ;Siddappa Malleshappa, Sudeep K. (57208838253) ;Singh, Paramdeep (57202809996) ;Singh, Jasvinder A. (58179112300) ;Singh, Garima (57224794687) ;Sinha, Dhirendra Narain (7201637609) ;Solomon, Yonatan (57220875005) ;Suleman, Muhammad (57196800921) ;Suliankatchi Abdulkader, Rizwan (57226832737) ;Taheri Abkenar, Yasaman (57211386327) ;Talaat, Iman M. (7801465176) ;Tan, Ker-Kan (16745396700) ;Tbakhi, Abdelghani (6602349888) ;Thiyagarajan, Arulmani (57208205338) ;Tiyuri, Amir (57201850751) ;Tovani-Palone, Marcos Roberto (56644977900) ;Unnikrishnan, Bhaskaran (12790012100) ;Vo, Bay (35147075900) ;Volovat, Simona Ruxandra (44961657900) ;Wang, Cong (15924372200) ;Westerman, Ronny (57218361023) ;Wickramasinghe, Nuwan Darshana (55326938000) ;Xiao, Hong (57214631433) ;Yu, Chuanhua (57208140344) ;Yuce, Deniz (57514476300) ;Yunusa, Ismaeel (57202137670) ;Zadnik, Vesna (57202975428) ;Zare, Iman (57224488480) ;Zhang, Zhi-Jiang (56068578400) ;Zoladl, Mohammad (53980736300) ;Force, Lisa M. (57188548035)Hugo, Fernando N. (13403199800)Importance: Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning. Objective: To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates. Evidence Review: The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019. Findings: In 2019, 370000 (95% uncertainty interval [UI], 338000-401000) cases and 199000 (95% UI, 181000-217000) deaths for LOC and 167000 (95% UI, 153000-180000) cases and 114000 (95% UI, 103000-126000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia. Conclusions and Relevance: In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts. © 2023 American Medical Association. All rights reserved. - Some of the metrics are blocked by yourconsent settings
Publication The NO-modified HIV protease inhibitor as a valuable drug for hematological malignancies: Role of p70S6K(2015) ;Maksimovic-Ivanic, Danijela (6507584634) ;Mojic, Marija (24179387300) ;Bulatovic, Mirna (55008945300) ;Radojkovic, Milica (57197430605) ;Kuzmanovic, Milos (6602721300) ;Ristic, Slobodan (35300292100) ;Stosic-Grujicic, Stanislava (7004253020) ;Miljkovic, Djordje (7006524033) ;Cavalli, Eugenio (56545345800) ;Libra, Massimo (6603852432) ;Fagone, Paolo (8748540600) ;McCubrey, James (7004993472) ;Nicoletti, Ferdinando (55335677000)Mijatovic, Sanja (6508347659)Covalent attachment of NO to the first approved HIV protease inhibitor Saquinavir (Saq-NO) expands the therapeutic potential of the original drug. Apart from retained antiviral activity, the modified drug exerts strong antitumor effects and lower toxicity. In the present study, we have evaluated the sensitivity of different hematological malignancies to Saq-NO. Saq-NO efficiently diminished the viability of Jurkat, Raji, HL-60 and K562 cells. While Jurkat and Raji cells (established from pediatric patients) displayed abrogated proliferative potential, HL-60 and K652 cells (originated from adults) exposed to Saq-NO treatment underwent caspase dependent apoptosis. In addition, similar sensitivity to Saq-NO was observed in mononuclear blood cells obtained from pediatric patients with acute lymphoblastic leukemia (ALL) and adult patients with acute myeloid leukemia (AML). Western blot analysis indicated p70S6 kinase as a possible intracellular target of Saq-NO action. Moreover, the addition of a NO moiety to Lopinavir resulted in improved antitumor potential as compared to the parental compound, suggesting that NO-derived HIV protease inhibitors are a potential new source of anticancer drugs with unique mode of action. © 2015 Elsevier Ltd. - Some of the metrics are blocked by yourconsent settings
Publication The NO-modified HIV protease inhibitor as a valuable drug for hematological malignancies: Role of p70S6K(2015) ;Maksimovic-Ivanic, Danijela (6507584634) ;Mojic, Marija (24179387300) ;Bulatovic, Mirna (55008945300) ;Radojkovic, Milica (57197430605) ;Kuzmanovic, Milos (6602721300) ;Ristic, Slobodan (35300292100) ;Stosic-Grujicic, Stanislava (7004253020) ;Miljkovic, Djordje (7006524033) ;Cavalli, Eugenio (56545345800) ;Libra, Massimo (6603852432) ;Fagone, Paolo (8748540600) ;McCubrey, James (7004993472) ;Nicoletti, Ferdinando (55335677000)Mijatovic, Sanja (6508347659)Covalent attachment of NO to the first approved HIV protease inhibitor Saquinavir (Saq-NO) expands the therapeutic potential of the original drug. Apart from retained antiviral activity, the modified drug exerts strong antitumor effects and lower toxicity. In the present study, we have evaluated the sensitivity of different hematological malignancies to Saq-NO. Saq-NO efficiently diminished the viability of Jurkat, Raji, HL-60 and K562 cells. While Jurkat and Raji cells (established from pediatric patients) displayed abrogated proliferative potential, HL-60 and K652 cells (originated from adults) exposed to Saq-NO treatment underwent caspase dependent apoptosis. In addition, similar sensitivity to Saq-NO was observed in mononuclear blood cells obtained from pediatric patients with acute lymphoblastic leukemia (ALL) and adult patients with acute myeloid leukemia (AML). Western blot analysis indicated p70S6 kinase as a possible intracellular target of Saq-NO action. Moreover, the addition of a NO moiety to Lopinavir resulted in improved antitumor potential as compared to the parental compound, suggesting that NO-derived HIV protease inhibitors are a potential new source of anticancer drugs with unique mode of action. © 2015 Elsevier Ltd.
