Author: "Vera Marisa Costa" / Topic: general medicine - Searchworks@Jio Institute Digital Library Search Results

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80 results on '"Vera Marisa Costa"'

1. Chemobrain: mitoxantrone-induced oxidative stress, apoptotic and autophagic neuronal death in adult CD-1 mice

Author: Ana Dias-Carvalho, Mariana Ferreira, Ana Reis-Mendes, Rita Ferreira, Maria Lourdes Bastos, Eduarda Fernandes, Susana Isabel Sá, João Paulo Capela, Félix Carvalho, and Vera Marisa Costa
Subjects: Male, Neurons, Mice, Oxidative Stress, Chemotherapy-Related Cognitive Impairment, Health, Toxicology and Mutagenesis, Autophagy, Animals, General Medicine, Mitoxantrone, Toxicology
Abstract: Mitoxantrone (MTX) is a topoisomerase II inhibitor used to treat a wide range of tumors and multiple sclerosis but associated with potential neurotoxic effects mediated by hitherto poorly understood mechanisms. In adult male CD-1 mice, the underlying neurotoxic pathways of a clinically relevant cumulative dose of 6 mg/kg MTX was evaluated after biweekly administration for 3 weeks and sacrifice 1 week after the last administration was undertaken. Oxidative stress, neuronal damage, apoptosis, and autophagy were analyzed in whole brain, while coronal brain sections were used for a closer look in the hippocampal formation (HF) and the prefrontal cortex (PFC), as these areas have been signaled out as the most affected in 'chemobrain'. In the whole brain, MTX-induced redox imbalance shown as increased endothelial nitric oxide synthase and reduced manganese superoxide dismutase expression, as well as a tendency to a decrease in glutathione levels. MTX also caused diminished ATP synthase β expression, increased autophagic protein LC3 II and tended to decrease p62 expression. Postsynaptic density protein 95 expression decreased in the whole brain, while hyperphosphorylation of Tau was seen in PFC. A reduction in volume was observed in the dentate gyrus (DG) and CA1 region of the HF, while GFAP-ir astrocytes increased in all regions of the HF except in the DG. Apoptotic marker Bax increased in the PFC and in the CA3 region, whereas p53 decreased in all brain areas evaluated. MTX causes damage in the brain of adult CD-1 mice in a clinically relevant cumulative dose in areas involved in memory and cognition.
Published: 2022

2. An updated review on synthetic cathinones

Author: Vera Marisa Costa, Jorge Soares, Félix Carvalho, Maria de Lourdes Bastos, and João Paulo Capela
Subjects: 0301 basic medicine, Drugs of abuse, biology, Recreational Drug, Cathinone, business.industry, Health, Toxicology and Mutagenesis, medicine.medical_treatment, Pharmacology toxicology, Internet privacy, General Medicine, 010501 environmental sciences, Toxicology, biology.organism_classification, 01 natural sciences, Stimulant, 03 medical and health sciences, 030104 developmental biology, Khat, medicine, business, 0105 earth and related environmental sciences, medicine.drug
Abstract: Cathinone, the main psychoactive compound found in the plant Catha edulis Forsk. (khat), is a β-keto analogue of amphetamine, sharing not only the phenethylamine structure, but also the amphetamine-like stimulant effects. Synthetic cathinones are derivatives of the naturally occurring cathinone that largely entered the recreational drug market at the end of 2000s. The former “legal status”, impressive marketing strategies and their commercial availability, either in the so-called “smartshops” or via the Internet, prompted their large spread, contributing to their increasing popularity in the following years. As their popularity increased, the risks posed for public health became clear, with several reports of intoxications and deaths involving these substances appearing both in the social media and scientific literature. The regulatory measures introduced thereafter to halt these trending drugs of abuse have proved to be of low impact, as a continuous emergence of new non-controlled derivatives keep appearing to replace those prohibited. Users resort to synthetic cathinones due to their psychostimulant properties but are often unaware of the dangers they may incur when using these substances. Therefore, studies aimed at unveiling the pharmacological and toxicological properties of these substances are imperative, as they will provide increased expertise to the clinicians that face this problem on a daily basis. The present work provides a comprehensive review on history and legal status, chemistry, pharmacokinetics, pharmacodynamics, adverse effects and lethality in humans, as well as on the current knowledge of the neurotoxic mechanisms of synthetic cathinones.
Published: 2021

3. Autophagy (but not metabolism) is a key event in mitoxantrone-induced cytotoxicity in differentiated AC16 cardiac cells

Author: Ana Reis-Mendes, Félix Carvalho, Fernando Remião, Emília Sousa, Maria de Lourdes Bastos, and Vera Marisa Costa
Subjects: Health, Toxicology and Mutagenesis, General Medicine, Toxicology
Abstract: Mitoxantrone (MTX) is an antineoplastic agent used to treat advanced breast cancer, prostate cancer, acute leukemia, lymphoma and multiple sclerosis. Although it is known to cause cumulative dose-related cardiotoxicity, the underlying mechanisms are still poorly understood. This study aims to compare the cardiotoxicity of MTX and its' pharmacologically active metabolite naphthoquinoxaline (NAPHT) in an in vitro cardiac model, human-differentiated AC16 cells, and determine the role of metabolism in the cardiotoxic effects. Concentration-dependent cytotoxicity was observed after MTX exposure, affecting mitochondrial function and lysosome uptake. On the other hand, the metabolite NAPHT only caused concentration-dependent cytotoxicity in the MTT reduction assay. When assessing the effect of different inhibitors/inducers of metabolism, it was observed that metyrapone (a cytochrome P450 inhibitor) and phenobarbital (a cytochrome P450 inducer) slightly increased MTX cytotoxicity, while 1-aminobenzotriazole (a suicide cytochrome P450 inhibitor) decreased fairly the MTX-triggered cytotoxicity in differentiated AC16 cells. When focusing in autophagy, the mTOR inhibitor rapamycin and the autophagy inhibitor 3-methyladenine exacerbated the cytotoxicity caused by MTX and NAPHT, while the autophagy blocker, chloroquine, partially reduced the cytotoxicity of MTX. In addition, we observed a decrease in p62, beclin-1, and ATG5 levels and an increase in LC3-II levels in MTX-incubated cells. In conclusion, in our in vitro model, neither metabolism nor exogenously given NAPHT are major contributors to MTX toxicity as seen by the residual influence of metabolism modulators used on the observed cytotoxicity and by NAPHT's low cytotoxicity profile. Conversely, autophagy is involved in MTX-induced cytotoxicity and MTX seems to act as an autophagy inducer, possibly through p62/LC3-II involvement.
Published: 2022

4. Molecular alterations underlying Doxorubicin’s Chronic Cardiotoxicity in a mouse model

Author: Sofia Reis Brandão, Ana Reis-Mendes, Margarida Duarte-Araújo, Maria João Neuparth, Félix Carvalho, Rita Ferreira, and Vera Marisa Costa
Subjects: General Medicine
Published: 2022

5. Mitoxantrone-induced neurotoxicity in CD-1 mice

Author: Ana Dias-Carvalho, Mariana Ferreira, Ana Reis Mendes, Rita Ferreira, Eduarda Fernandes, Susana Isabel Sá, João Paulo Capela, Félix Carvalho, and Vera Marisa Costa
Subjects: General Medicine
Published: 2022

6. In vivo toxicometabolomics reveals multi-organ and urine metabolic changes in mice upon acute exposure to human-relevant doses of 3,4-methylenedioxypyrovalerone (MDPV)

Author: Félix Carvalho, Maria de Lourdes Bastos, Ricardo Jorge Dinis-Oliveira, Ana Margarida Araújo, Vera Marisa Costa, Paula Guedes de Pinho, Márcia Carvalho, and José Alberto Duarte
Subjects: Male, 0301 basic medicine, Pyrrolidines, Health, Toxicology and Mutagenesis, Toxicometabolomics, Urine, 010501 environmental sciences, Pharmacology, Kidney, Toxicology, medicine.disease_cause, 01 natural sciences, Energy homeostasis, Mice, Homeostasis, Medicine, GC–MS, 3-Hydroxybutyric Acid, Fatty Acids, Brain, Multi-organ toxicity, General Medicine, Liver, Toxicity, Metabolome, medicine.drug, Methylenedioxypyrovalerone, Neuroprotection, Gas Chromatography-Mass Spectrometry, MDPV, Biological pathway, 03 medical and health sciences, In vivo, Animals, Humans, Benzodioxoles, 0105 earth and related environmental sciences, Dose-Response Relationship, Drug, business.industry, Myocardium, Metabolic acidosis, Synthetic Cathinone, medicine.disease, 030104 developmental biology, business, Biomarkers, Blood Chemical Analysis, Oxidative stress
Abstract: 3,4-Methylenedioxypyrovalerone (MDPV) is consumed worldwide, despite its potential to cause toxicity in several organs and even death. There is a recognized need to clarify the biological pathways through which MDPV elicits general and target-organ toxicity. In this work, a comprehensive untargeted GC-MS-based metabolomics analysis was performed, aiming to detect metabolic changes in putative target organs (brain, heart, kidneys and liver) but also in urine of mice after acute exposure to human-relevant doses of MDPV. Male CD-1 mice received binge intraperitoneal administrations of saline or MDPV (2.5 mg/kg or 5 mg/kg) every 2 h, for a total of three injections. Twenty-four hours after the first administration, target organs, urine and blood samples were collected for metabolomics, biochemical and histological analysis. Hepatic and renal tissues of MDPV-treated mice showed moderate histopathological changes but no significant differences were found in plasma and tissue biochemical markers of organ injury. In contrast, the multivariate analysis significantly discriminated the organs and urine of MDPV-treated mice from the control (except for the lowest dose in the brain), allowing the identification of a panoply of metabolites. Those levels were significantly deviated in relation to physiological conditions and showed an organ specific response towards the drug. Kidneys and liver showed the greatest metabolic changes. Metabolites related with energetic metabolism, antioxidant defenses and inflammatory response were significantly changed in the liver of MDPV-dosed animals, while the kidneys seem to have developed an adaptive response against oxidative stress caused by MDPV. On the other hand, the dysregulation of metabolites that contribute to metabolic acidosis was also observed in this organ. The heart showed an increase of fatty acid biosynthesis, possibly as an adaptation to maintain the cardiac energy homeostasis. In the brain, changes in 3-hydroxybutyric acid levels may reflect the activation of a neurotoxic pathway. However, the increase in metabolites with neuroprotective properties seems to counteract this change. Metabolic profiling of urine from MDPV-treated mice suggested that glutathione-dependent antioxidant pathways may be particularly involved in the compensatory mechanism to counteract oxidative stress induced by MDPV. Overall, this study reports, for the first time, the metabolic profile of liver, kidneys, heart, brain, and urine of MDPV-dosed mice, providing unique insights into the biological pathways of toxicity. Our findings also underline the value of toxicometabolomics as a robust and sensitive tool for detecting adaptive/toxic cellular responses upon exposure to a physiologically relevant dose of a toxic agent, earlier than conventional toxicity tests.
Published: 2020

7. Mitoxantrone impairs proteasome activity and prompts early energetic and proteomic changes in HL-1 cardiomyocytes at clinically relevant concentrations

Author: Félix Carvalho, Fernando Remião, José Luís Dores-Sousa, M. Gabriela Almeida, Rui A. Carvalho, Rute P. Eleutério, Patricia Rodrigues, Vera Marisa Costa, João Paulo Capela, Maria de Lourdes Bastos, José Alberto Duarte, Joana R. Sousa, and Kurt J. Varner
Subjects: musculoskeletal diseases, 0301 basic medicine, Health, Toxicology and Mutagenesis, 010501 environmental sciences, Pharmacology, Toxicology, medicine.disease_cause, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, Lactate dehydrogenase, medicine, Cytotoxicity, Caspase, 0105 earth and related environmental sciences, Mitoxantrone, Cardiotoxicity, biology, Chemistry, General Medicine, Glutathione, 030104 developmental biology, biology.protein, Oxidative stress, Homeostasis, medicine.drug
Abstract: Mitoxantrone (MTX) is used to treat several types of cancers and to improve neurological disability in multiple sclerosis. Unfortunately, cardiotoxicity is a severe and common adverse effect in MTX-treated patients. Herein, we aimed to study early and late mechanisms of MTX-induced cardiotoxicity using murine HL-1 cardiomyocytes. Cells were exposed to MTX (0.1, 1 or 10 µM) during short (2, 4, 6, or 12 h) or longer incubation periods (24 or 48 h). At earlier time points, (6 and 12 h) cytotoxicity was already observed for 1 and 10 µM MTX. Proteomic analysis of total protein extracts found 14 proteins with higher expression and 26 with lower expression in the cells exposed for 12 h to MTX (pH gradients 4–7 and 6–11). Of note, the expression of the regulatory protein 14-3-3 protein epsilon was increased by a factor of two and three, after exposure to 1 and 10 µM MTX, respectively. At earlier time-points, 10 µM MTX increased intracellular ATP levels, while decreasing media lactate levels. At later stages (24 and 48 h), MTX-induced cytotoxicity was concentration and time-dependent, according to the MTT reduction and lactate dehydrogenase leakage assays, while caspase-9, -8 and -3 activities increased at 24 h. Regarding cellular redox status, total glutathione increased in 1 µM MTX (24 h), and that increase was dependent on gamma-glutamylcysteine synthetase activity. Meanwhile, for both 1 and 10 µM MTX, oxidized glutathione was significantly higher than control at 48 h. Moreover, MTX was able to significantly decrease proteasomal chymotrypsin-like activity in a concentration and time-independent manner. In summary, MTX significantly altered proteomic, energetic and oxidative stress homeostasis in cardiomyocytes at clinically relevant concentrations and our data clearly demonstrate that MTX causes early cardiotoxicity that needs further study.
Published: 2020

8. Adverse outcome pathways induced by 3,4-dimethylmethcathinone and 4-methylmethcathinone in differentiated human SH-SY5Y neuronal cells

Author: Susana Santos, Félix Carvalho, Maria de Lourdes Bastos, Jorge Soares, Vera Marisa Costa, Helena Gaspar, and João Paulo Capela
Subjects: 0301 basic medicine, Time Factors, SH-SY5Y, Neurogenesis, Health, Toxicology and Mutagenesis, Toxicological pathways, Apoptosis, 010501 environmental sciences, Pharmacology, Cathinones, Toxicology, medicine.disease_cause, 01 natural sciences, SH-SY5Y cells, Methamphetamine, 03 medical and health sciences, chemistry.chemical_compound, Adenosine Triphosphate, Cell Line, Tumor, medicine, Humans, Cytotoxicity, 0105 earth and related environmental sciences, Membrane Potential, Mitochondrial, Propiophenones, Dose-Response Relationship, Drug, METH, Chemistry, Dopaminergic Neurons, Neurotoxicity, General Medicine, Meth, Glutathione, medicine.disease, Mitochondria, Oxidative Stress, 030104 developmental biology, Mitochondrial impairment, Oxidative stress, Trolox, Reactive Oxygen Species, medicine.drug
Abstract: Jorge Soares acknowledges University of Porto/Faculty of Medicine University of Porto through FSE—Fundo Social Europeu, NORTE2020—Programa Operacional Regional do Norte for his grant (NORTE-08-5369-FSE-000011). This work was supported by the Applied Molecular Biosciences Unit—UCIBIO through UID/MULTI/04378/2019 support with funding from FCT/MCTES through national funds. Centro de Química Estrutural, BioISI—Biosystems and Integrative Sciences Institute, and MARE—Marine and Environmental Sciences Centre, acknowledges the fnancial support of Fundação para a Ciência e Tecnologia—FCT (UIDB/00100/2020, UID/MULTI/04046/2019 and UIDB/04292/2020, respectively). Vera Marisa Costa acknowledges Fundação da Ciência e Tecnologia (FCT) for her grant (SFRH/BPD/110001/2015) that was funded by national funds through FCT—Fundação para a Ciência e a Tecnologia, I.P., under the Norma Transitória—DL57/2016/CP1334/CT0006. The authors wish to thank the Laboratório de Polícia Científca da Polícia Judiciária (LPC-PJ) for providing the smartshop product within the scope of the protocol established between LPC-PJ, FCUL, and FFUP. Cathinones (β-keto amphetamines), widely abused in recreational settings, have been shown similar or even worse toxicological profile than classical amphetamines. In the present study, the cytotoxicity of two β-keto amphetamines [3,4-dimethylmethcathinone (3,4-DMMC) and 4-methylmethcathinone (4-MMC)], was evaluated in differentiated dopaminergic SH-SY5Y cells in comparison to methamphetamine (METH). MTT reduction and NR uptake assays revealed that both cathinones and METH induced cytotoxicity in a concentration- and time-dependent manner. Pre-treatment with trolox (antioxidant) partially prevented the cytotoxicity induced by all tested drugs, while N-acetyl-l-cysteine (NAC; antioxidant and glutathione precursor) and GBR 12909 dopamine transporter inhibitor) partially prevented the cytotoxicity induced by cathinones, as evaluated by the MTT reduction assay. Unlike METH, cathinones induced oxidative stress evidenced by the increase on intracellular levels of reactive oxygen species (ROS), and also by the decrease of intracellular glutathione levels. Trolox prevented, partially but significantly, the ROS generation elicited by cathinones, while NAC inhibited it completely. All tested drugs induced mitochondrial dysfunction, since they led to mitochondrial membrane depolarization and to intracellular ATP depletion. Activation of caspase-3, indicative of apoptosis, was seen both for cathinones and METH, and confirmed by annexin V and propidium iodide positive staining. Autophagy was also activated by all drugs tested. Pre-incubation with bafilomycin A1, an inhibitor of the vacuolar H+- ATPase, only protected against the cytotoxicity induced by METH, which indicates dissimilar toxicological pathways for the tested drugs. In conclusion, the mitochondrial impairment and oxidative stress observed for the tested cathinones may be key factors for their neurotoxicity, but different outcome pathways seem to be involved in the adverse effects, when compared to METH. info:eu-repo/semantics/publishedVersion
Published: 2020

9. In vitro mechanistic studies on α-amanitin and its putative antidotes

Author: Félix Carvalho, Daniela Ferreira Rodrigues, Maria de Lourdes Bastos, Ricardo Pires das Neves, Vera Marisa Costa, and Alexandra T. P. Carvalho
Subjects: 0301 basic medicine, endocrine system, Time Factors, animal structures, Oligomycin, Cell Survival, Health, Toxicology and Mutagenesis, Antidotes, Cell, Mitochondria, Liver, RNA polymerase II, Mushroom Poisoning, 010501 environmental sciences, Pharmacology, Toxicology, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, Adenosine Triphosphate, Transcription (biology), polycyclic compounds, medicine, Humans, Buthionine sulfoximine, Cytotoxicity, Alpha-Amanitin, 0105 earth and related environmental sciences, Dose-Response Relationship, Drug, biology, RNA, Hep G2 Cells, General Medicine, Glutathione, 030104 developmental biology, medicine.anatomical_structure, chemistry, Hepatocytes, biology.protein, RNA Polymerase II, Lysosomes, HeLa Cells
Abstract: α-Amanitin plays a key role in Amanita phalloides intoxications. The liver is a major target of α-amanitin toxicity, and while RNA polymerase II (RNA Pol II) transcription inhibition is a well-acknowledged mechanism of α-amanitin toxicity, other possible toxicological pathways remain to be elucidated. This study aimed to assess the mechanisms of α-amanitin hepatotoxicity in HepG2 cells. The putative protective effects of postulated antidotes were also tested in this cell model and in permeabilized HeLa cells. α-Amanitin (0.1-20 µM) displayed time- and concentration-dependent cytotoxicity, when evaluated through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction and neutral red uptake assays. Additionally, α-amanitin decreased nascent RNA synthesis in a concentration- and time-dependent manner. While α-amanitin did not induce changes in mitochondrial membrane potential, it caused a significant increase in intracellular ATP levels, which was not prevented by incubation with oligomycin, an ATP synthetase inhibitor. Concerning the cell redox status, α-amanitin did not increase reactive species production, but caused a significant increase in total and reduced glutathione, which was abolished by pre-incubation with the inhibitor of gamma-glutamylcysteine synthase, buthionine sulfoximine. None of the tested antidotes [N-acetyl cysteine, silibinin, benzylpenicillin, and polymyxin B (PolB)] conferred any protection against α-amanitin-induced cytotoxicity in HepG2 cells or reversed the inhibition of nascent RNA caused by the toxin in permeabilized HeLa cells. Still, PolB interfered with RNA Pol II activity at high concentrations, though not impacting on α-amanitin observed cytotoxicity. New hepatotoxic mechanisms of α-amanitin were described herein, but the lack of protection observed in clinically used antidotes may reflect the lack of knowledge on their true protection mechanisms and may explain their relatively low clinical efficacy.
Published: 2020

10. The global burden of cancer attributable to risk factors, 2010–19 : A systematic analysis for the Global Burden of Disease Study 2019

Author: Khanh Bao Tran, Justin J Lang, Kelly Compton, Rixing Xu, Alistair R Acheson, Hannah Jacqueline Henrikson, Jonathan M Kocarnik, Louise Penberthy, Amirali Aali, Qamar Abbas, Behzad Abbasi, Mohsen Abbasi-Kangevari, Zeinab Abbasi-Kangevari, Hedayat Abbastabar, Michael Abdelmasseh, Sherief Abd-Elsalam, Ahmed Abdelwahab Abdelwahab, Gholamreza Abdoli, Hanan Abdulkadir Abdulkadir, Aidin Abedi, Kedir Hussein Abegaz, Hassan Abidi, Richard Gyan Aboagye, Hassan Abolhassani, Abdorrahim Absalan, Yonas Derso Abtew, Hiwa Abubaker Ali, Eman Abu-Gharbieh, Basavaprabhu Achappa, Juan Manuel Acuna, Daniel Addison, Isaac Yeboah Addo, Oyelola A Adegboye, Miracle Ayomikun Adesina, Mohammad Adnan, Qorinah Estiningtyas Sakilah Adnani, Shailesh M Advani, Sumia Afrin, Muhammad Sohail Afzal, Manik Aggarwal, Bright Opoku Ahinkorah, Araz Ramazan Ahmad, Rizwan Ahmad, Sajjad Ahmad, Sohail Ahmad, Sepideh Ahmadi, Haroon Ahmed, Luai A Ahmed, Muktar Beshir Ahmed, Tarik Ahmed Rashid, Wajeeha Aiman, Marjan Ajami, Gizachew Taddesse Akalu, Mostafa Akbarzadeh-Khiavi, Addis Aklilu, Maxwell Akonde, Chisom Joyqueenet Akunna, Hanadi Al Hamad, Fares Alahdab, Fahad Mashhour Alanezi, Turki M Alanzi, Saleh Ali Alessy, Abdelazeem M Algammal, Mohammed Khaled Al-Hanawi, Robert Kaba Alhassan, Beriwan Abdulqadir Ali, Liaqat Ali, Syed Shujait Ali, Yousef Alimohamadi, Vahid Alipour, Syed Mohamed Aljunid, Motasem Alkhayyat, Sadeq Ali Ali Al-Maweri, Sami Almustanyir, Nivaldo Alonso, Shehabaldin Alqalyoobi, Rajaa M Al-Raddadi, Rami H Hani Al-Rifai, Salman Khalifah Al-Sabah, Ala'a B Al-Tammemi, Haya Altawalah, Nelson Alvis-Guzman, Firehiwot Amare, Edward Kwabena Ameyaw, Javad Javad Aminian Dehkordi, Mohammad Hosein Amirzade-Iranaq, Hubert Amu, Ganiyu Adeniyi Amusa, Robert Ancuceanu, Jason A Anderson, Yaregal Animut Animut, Amir Anoushiravani, Ali Arash Anoushirvani, Alireza Ansari-Moghaddam, Mustafa Geleto Ansha, Benny Antony, Maxwell Hubert Antwi, Sumadi Lukman Anwar, Razique Anwer, Anayochukwu Edward Anyasodor, Jalal Arabloo, Morteza Arab-Zozani, Olatunde Aremu, Ayele Mamo Argaw, Hany Ariffin, Timur Aripov, Muhammad Arshad, Al Artaman, Judie Arulappan, Raphael Taiwo Aruleba, Armin Aryannejad, Malke Asaad, Mulusew A Asemahagn, Zatollah Asemi, Mohammad Asghari-Jafarabadi, Tahira Ashraf, Reza Assadi, Mohammad Athar, Seyyed Shamsadin Athari, Maha Moh'd Wahbi Atout, Sameh Attia, Avinash Aujayeb, Marcel Ausloos, Leticia Avila-Burgos, Atalel Fentahun Awedew, Mamaru Ayenew Awoke, Tewachew Awoke, Beatriz Paulina Ayala Quintanilla, Tegegn Mulatu Ayana, Solomon Shitu Ayen, Davood Azadi, Sina Azadnajafabad, Saber Azami-Aghdash, Melkalem Mamuye Azanaw, Mohammadreza Azangou-Khyavy, Amirhossein Azari Jafari, Hosein Azizi, Ahmed Y Y Azzam, Amirhesam Babajani, Muhammad Badar, Ashish D Badiye, Nayereh Baghcheghi, Nader Bagheri, Sara Bagherieh, Saeed Bahadory, Atif Amin Baig, Jennifer L Baker, Ahad Bakhtiari, Ravleen Kaur Bakshi, Maciej Banach, Indrajit Banerjee, Mainak Bardhan, Francesco Barone-Adesi, Fabio Barra, Amadou Barrow, Nasir Z Bashir, Azadeh Bashiri, Saurav Basu, Abdul-Monim Mohammad Batiha, Aeysha Begum, Alehegn Bekele Bekele, Alemayehu Sayih Belay, Melaku Ashagrie Belete, Uzma Iqbal Belgaumi, Arielle Wilder Bell, Luis Belo, Habib Benzian, Alemshet Yirga Berhie, Amiel Nazer C Bermudez, Eduardo Bernabe, Akshaya Srikanth Bhagavathula, Neeraj Bhala, Bharti Bhandari Bhandari, Nikha Bhardwaj, Pankaj Bhardwaj, Krittika Bhattacharyya, Vijayalakshmi S Bhojaraja, Soumitra S Bhuyan, Sadia Bibi, Awraris Hailu Bilchut, Bagas Suryo Bintoro, Antonio Biondi, Mesfin Geremaw Birega Birega, Habitu Eshetu Birhan, Tone Bjørge, Oleg Blyuss, Belay Boda Abule Bodicha, Srinivasa Rao Bolla, Archith Boloor, Cristina Bosetti, Dejana Braithwaite, Michael Brauer, Hermann Brenner, Andrey Nikolaevich Briko, Nikolay Ivanovich Briko, Christina Maree Buchanan, Norma B Bulamu, Maria Teresa Bustamante-Teixeira, Muhammad Hammad Butt, Nadeem Shafique Butt, Zahid A Butt, Florentino Luciano Caetano dos Santos, Luis Alberto Cámera, Chao Cao, Yin Cao, Giulia Carreras, Márcia Carvalho, Francieli Cembranel, Ester Cerin, Promit Ananyo Chakraborty, Periklis Charalampous, Vijay Kumar Chattu, Odgerel Chimed-Ochir, Jesus Lorenzo Chirinos-Caceres, Daniel Youngwhan Cho, William C S Cho, Devasahayam J Christopher, Dinh-Toi Chu, Isaac Sunday Chukwu, Aaron J Cohen, Joao Conde, Sandra Cortés, Vera Marisa Costa, Natália Cruz-Martins, Garland T Culbreth, Omid Dadras, Fentaw Teshome Dagnaw, Saad M A Dahlawi, Xiaochen Dai, Lalit Dandona, Rakhi Dandona, Parnaz Daneshpajouhnejad, Anna Danielewicz, An Thi Minh Dao, Reza Darvishi Cheshmeh Soltani, Aso Mohammad Darwesh, Saswati Das, Dragos Virgil Davitoiu, Elham Davtalab Esmaeili, Fernando Pio De la Hoz, Sisay Abebe Debela, Azizallah Dehghan, Biniyam Demisse, Fitsum Wolde Demisse, Edgar Denova-Gutiérrez, Afshin Derakhshani, Meseret Derbew Molla, Diriba Dereje, Kalkidan Solomon Deribe, Rupak Desai, Markos Desalegn Desalegn, Fikadu Nugusu Dessalegn, Samuel Abebe A Dessalegni, Gashaw Dessie, Abebaw Alemayehu Desta, Syed Masudur Rahman Dewan, Samath Dhamminda Dharmaratne, Meghnath Dhimal, Mostafa Dianatinasab, Nancy Diao, Daniel Diaz, Lankamo Ena Digesa, Shilpi Gupta Dixit, Saeid Doaei, Linh Phuong Doan, Paul Narh Doku, Deepa Dongarwar, Wendel Mombaque dos Santos, Tim Robert Driscoll, Haneil Larson Dsouza, Oyewole Christopher Durojaiye, Sareh Edalati, Fatemeh Eghbalian, Elham Ehsani-Chimeh, Ebrahim Eini, Michael Ekholuenetale, Temitope Cyrus Ekundayo, Donatus U Ekwueme, Maha El Tantawi, Mostafa Ahmed Elbahnasawy, Iffat Elbarazi, Hesham Elghazaly, Muhammed Elhadi, Waseem El-Huneidi, Mohammad Hassan Emamian, Luchuo Engelbert Bain, Daniel Berhanie Enyew, Ryenchindorj Erkhembayar, Tegegne Eshetu, Babak Eshrati, Sharareh Eskandarieh, Juan Espinosa-Montero, Farshid Etaee, Azin Etemadimanesh, Tahir Eyayu, Ifeanyi Jude Ezeonwumelu, Sayeh Ezzikouri, Adeniyi Francis Fagbamigbe, Saman Fahimi, Ildar Ravisovich Fakhradiyev, Emerito Jose A Faraon, Jawad Fares, Abbas Farmany, Umar Farooque, Hossein Farrokhpour, Abidemi Omolara Fasanmi, Ali Fatehizadeh, Wafa Fatima, Hamed Fattahi, Ginenus Fekadu, Berhanu Elfu Feleke, Allegra Allegra Ferrari, Simone Ferrero, Lorenzo Ferro Desideri, Irina Filip, Florian Fischer, Roham Foroumadi, Masoud Foroutan, Takeshi Fukumoto, Peter Andras Gaal, Mohamed M Gad, Muktar A Gadanya, Abduzhappar Gaipov, Nasrin Galehdar, Silvano Gallus, Tushar Garg, Mariana Gaspar Fonseca, Yosef Haile Gebremariam, Teferi Gebru Gebremeskel, Mathewos Alemu Gebremichael, Yohannes Fikadu Geda, Yibeltal Yismaw Gela, Belete Negese Belete Gemeda, Melaku Getachew, Motuma Erena Getachew, Kazem Ghaffari, Mansour Ghafourifard, Seyyed-Hadi Ghamari, Mohammad Ghasemi Nour, Fariba Ghassemi, Ajnish Ghimire, Nermin Ghith, Maryam Gholamalizadeh, Jamshid Gholizadeh Navashenaq, Sherief Ghozy, Syed Amir Gilani, Paramjit Singh Gill, Themba G Ginindza, Abraham Tamirat T Gizaw, James C Glasbey, Justyna Godos, Amit Goel, Mahaveer Golechha, Pouya Goleij, Davide Golinelli, Mohamad Golitaleb, Giuseppe Gorini, Bárbara Niegia Garcia Goulart, Giuseppe Grosso, Habtamu Alganeh Guadie, Mohammed Ibrahim Mohialdeen Gubari, Temesgen Worku Gudayu, Maximiliano Ribeiro Guerra, Damitha Asanga Gunawardane, Bhawna Gupta, Sapna Gupta, Veer Bala Gupta, Vivek Kumar Gupta, Mekdes Kondale Gurara, Alemu Guta, Parham Habibzadeh, Atlas Haddadi Avval, Nima Hafezi-Nejad, Adel Hajj Ali, Arvin Haj-Mirzaian, Esam S Halboub, Aram Halimi, Rabih Halwani, Randah R Hamadeh, Sajid Hameed, Samer Hamidi, Asif Hanif, Sanam Hariri, Netanja I Harlianto, Josep Maria Haro, Risky Kusuma Hartono, Ahmed I Hasaballah, S M Mahmudul Hasan, Hamidreza Hasani, Seyedeh Melika Hashemi, Abbas M Hassan, Soheil Hassanipour, Khezar Hayat, Golnaz Heidari, Mohammad Heidari, Zahra Heidarymeybodi, Brenda Yuliana Herrera-Serna, Claudiu Herteliu, Kamal Hezam, Yuta Hiraike, Mbuzeleni Mbuzeleni Hlongwa, Ramesh Holla, Marianne Holm, Nobuyuki Horita, Mohammad Hoseini, Md Mahbub Hossain, Mohammad Bellal 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Jayaram, S, Jazayeri, S, Jebai, R, Jemal, B, Jeong, W, Jha, R, Jindal, H, John-Akinola, Y, Jonas, J, Joo, T, Joseph, N, Joukar, F, Jozwiak, J, Jurisson, M, Kabir, A, Kacimi, S, Kadashetti, V, Kahe, F, Kakodkar, P, Kalankesh, L, Kalhor, R, Kamal, V, Kamangar, F, Kamath, A, Kanchan, T, Kandaswamy, E, Kandel, H, Kang, H, Kanno, G, Kapoor, N, Kar, S, Karanth, S, Karaye, I, Karch, A, Karimi, A, Kassa, B, Katoto, P, Kauppila, J, Kaur, H, Kebede, A, Keikavoosi-Arani, L, Kejela, G, Kemp Bohan, P, Keramati, M, Keykhaei, M, Khajuria, H, Khan, A, Khan, E, Khan, G, Khan, M, Khanali, J, Khatab, K, Khatatbeh, M, Khatib, M, Khayamzadeh, M, Khayat Kashani, H, Khazeei Tabari, M, Khezeli, M, Khodadost, M, Kim, M, Kim, Y, Kisa, A, Kisa, S, Klugar, M, Klugarova, J, Kolahi, A, Kolkhir, P, Kompani, F, Koul, P, Koulmane Laxminarayana, S, Koyanagi, A, Krishan, K, Krishnamoorthy, Y, Kucuk Bicer, B, Kugbey, N, Kulimbet, M, Kumar, A, Kumar, G, Kumar, N, Kurmi, O, Kuttikkattu, A, La Vecchia, C, Lahiri, A, Lal, D, Lam, J, Lan, Q, Landires, I, Larijani, B, Lasrado, S, Lau, J, Lauriola, P, Ledda, C, Lee, S, Lee, W, Lee, Y, Legesse, S, Leigh, J, Leong, E, Li, M, Lim, S, Liu, G, Liu, J, Lo, C, Lohiya, A, Lopukhov, P, Lorenzovici, L, Lotfi, M, Loureiro, J, Lunevicius, R, Madadizadeh, F, Mafi, A, Magdeldin, S, Mahjoub, S, Mahmoodpoor, A, Mahmoudi, M, Mahmoudimanesh, M, Mahumud, R, Majeed, A, Majidpoor, J, Makki, A, Makris, K, Malakan Rad, E, Malekpour, M, Malekzadeh, R, Malik, A, Mallhi, T, Mallya, S, Mamun, M, Manda, A, Mansour-Ghanaei, F, Mansouri, B, Mansournia, M, Mantovani, L, Martini, S, Martorell, M, Masoudi, S, Masoumi, S, Matei, C, Mathews, E, Mathur, M, Mathur, V, Mckee, M, Meena, J, Mehmood, K, Mehrabi Nasab, E, Mehrotra, R, Melese, A, Mendoza, W, Menezes, R, Mengesha, S, Mensah, L, Mentis, A, Mera-Mamian, A, Meretoja, T, Merid, M, Mersha, A, Meselu, B, Meshkat, M, Mestrovic, T, Miao Jonasson, J, Miazgowski, T, Michalek, I, Mijena, G, Miller, T, Mir, S, Mirinezhad, S, Mirmoeeni, S, Mirza-Aghazadeh-Attari, M, Mirzaei, H, Misganaw, A, Misra, S, Mohammad, K, Mohammadi, E, Mohammadi, M, Mohammadian-Hafshejani, A, Mohammadpourhodki, R, Mohammed, A, Mohammed, S, Mohan, S, Mohseni, M, Moka, N, Mokdad, A, Molassiotis, A, Molokhia, M, Momenzadeh, K, Momtazmanesh, S, Monasta, L, Mons, U, Montasir, A, Montazeri, F, Montero, A, Moosavi, M, Moradi, A, Moradi, Y, Moradi Sarabi, M, Moraga, P, Morawska, L, Morrison, S, Morze, J, Mosapour, A, Mostafavi, E, Mousavi, S, Mousavi Isfahani, H, Mousavi Khaneghah, A, Mpundu-Kaambwa, C, Mubarik, S, Mulita, F, Munblit, D, Munro, S, Murillo-Zamora, E, Musa, J, Nabhan, A, Nagarajan, A, Nagaraju, S, Nagel, G, Naghipour, M, Naimzada, M, Nair, T, Naqvi, A, Narasimha Swamy, S, Narayana, A, Nassereldine, H, Natto, Z, Nayak, B, Ndejjo, R, Nduaguba, S, Negash, W, Nejadghaderi, S, Nejati, K, Neupane Kandel, S, Nguyen, H, Niazi, R, Noor, N, Noori, M, Noroozi, N, Nouraei, H, Nowroozi, A, Nunez-Samudio, V, Nzoputam, C, Nzoputam, O, Oancea, B, Odukoya, O, Oghenetega, O, Ogunsakin, R, Oguntade, A, Oh, I, Okati-Aliabad, H, Okekunle, A, Olagunju, A, Olagunju, T, Olakunde, B, Olufadewa, I, Omer, E, Omonisi, A, Ong, S, Onwujekwe, O, Orru, H, Otstavnov, S, Oulhaj, A, Oumer, B, Owopetu, O, Oyinloye, B, P A, M, Padron-Monedero, A, Padubidri, J, Pakbin, B, Pakshir, K, Pakzad, R, Palicz, T, Pana, A, Pandey, A, Pant, S, Pardhan, S, Park, E, Park, S, Patel, J, Pati, S, Paudel, R, Paudel, U, Paun, M, Pazoki Toroudi, H, Peng, M, Pereira, J, Pereira, R, Perna, S, Perumalsamy, N, Pestell, R, Pezzani, R, Piccinelli, C, Pillay, J, Piracha, Z, Pischon, T, Postma, M, Pourabhari Langroudi, A, Pourshams, A, Pourtaheri, N, Prashant, A, Qadir, M, Quazi Syed, Z, Rabiee, M, Rabiee, N, Radfar, A, Radhakrishnan, R, Radhakrishnan, V, Raeisi, M, Rafiee, A, Rafiei, A, Raheem, N, Rahim, F, Rahman, M, Rahmani, A, Rahmani, S, Rahmanian, V, Rajai, N, Rajesh, A, Ram, P, Ramezanzadeh, K, Rana, J, Ranabhat, K, Ranasinghe, P, Rao, C, Rao, S, Rashedi, S, Rashidi, A, Rashidi, M, Ratan, Z, Rawaf, D, Rawaf, S, Rawal, L, Rawassizadeh, R, Razeghinia, M, Rehman, A, Rehman, I, Reitsma, M, Renzaho, A, Rezaei, M, Rezaei, N, Rezaei, S, Rezaeian, M, Rezapour, A, Riad, A, Rikhtegar, R, Rios-Blancas, M, Roberts, T, Rohloff, P, Romero-Rodriguez, E, Roshandel, G, Rwegerera, G, S, M, Saber-Ayad, M, Saberzadeh-Ardestani, B, Sabour, S, Saddik, B, Sadeghi, E, Saeb, M, Saeed, U, Safaei, M, Safary, A, Sahebazzamani, M, Sahebkar, A, Sahoo, H, Sajid, M, Salari, H, Salehi, S, Salem, M, Salimzadeh, H, Samodra, Y, Samy, A, Sanabria, J, Sankararaman, S, Sanmarchi, F, Santric-Milicevic, M, Saqib, M, Sarveazad, A, Sarvi, F, Sathian, B, Satpathy, M, Sayegh, N, Schneider, I, Schwarzinger, M, Sekerija, M, Senthilkumaran, S, Sepanlou, S, Seylani, A, Seyoum, K, Sha, F, Shafaat, O, Shah, P, Shahabi, S, Shahid, I, Shahrbaf, M, Shahsavari, H, Shaikh, M, Shaka, M, Shaker, E, Shannawaz, M, Sharew, M, Sharifi, A, Sharifi-Rad, J, Sharma, P, Shashamo, B, Sheikh, A, Sheikh, M, Sheikhbahaei, S, Sheikhi, R, Sheikhy, A, Shepherd, P, Shetty, A, Shetty, J, Shetty, R, Shibuya, K, Shirkoohi, R, Shirzad-Aski, H, Shivakumar, K, Shivalli, S, Shivarov, V, Shobeiri, P, Shokri Varniab, Z, Shorofi, S, Shrestha, S, Sibhat, M, Siddappa Malleshappa, S, Sidemo, N, Silva, D, Silva, L, Silva Julian, G, Silvestris, N, Simegn, W, Singh, A, Singh, G, Singh, H, Singh, J, Singh, P, Singh, S, Sinha, D, Sinke, A, Siraj, M, Sitas, F, Siwal, S, Skryabin, V, Skryabina, A, Socea, B, Soeberg, M, Sofi-Mahmudi, A, Solomon, Y, Soltani-Zangbar, M, Song, S, Song, Y, Sorensen, R, Soshnikov, S, Sotoudeh, H, Sowe, A, Sufiyan, M, Suk, R, Suleman, M, Suliankatchi Abdulkader, R, Sultana, S, Sur, D, Szocska, M, Tabaeian, S, Tabares-Seisdedos, R, Tabatabaei, S, Tabuchi, T, Tadbiri, H, Taheri, E, Taheri, M, Taheri Soodejani, M, Takahashi, K, Talaat, I, Tampa, M, Tan, K, Tat, N, Tat, V, Tavakoli, A, Tehrani-Banihashemi, A, Tekalegn, Y, Tesfay, F, Thapar, R, Thavamani, A, Thoguluva Chandrasekar, V, Thomas, N, Ticoalu, J, Tiyuri, A, Tollosa, D, Topor-Madry, R, Touvier, M, Tovani-Palone, M, Traini, E, Tran, M, Tripathy, J, Ukke, G, Ullah, I, Ullah, S, Unnikrishnan, B, Vacante, M, Vaezi, M, Valadan Tahbaz, S, Valdez, P, Vardavas, C, Varthya, S, Vaziri, S, Velazquez, D, Veroux, M, Villeneuve, P, Violante, F, Vladimirov, S, Vlassov, V, Vo, B, Vu, L, Wadood, A, Waheed, Y, Walde, M, Wamai, R, Wang, C, Wang, F, Wang, N, Wang, Y, Ward, P, Waris, A, Westerman, R, Wickramasinghe, N, Woldemariam, M, Woldu, B, Xiao, H, Xu, S, Xu, X, Yadav, L, Yahyazadeh Jabbari, S, Yang, L, Yazdanpanah, F, Yeshaw, Y, Yismaw, Y, Yonemoto, N, Younis, M, Yousefi, Z, Yousefian, F, Yu, C, Yu, Y, Yunusa, I, Zahir, M, Zaki, N, Zaman, B, Zangiabadian, M, Zare, F, Zare, I, Zareshahrabadi, Z, Zarrintan, A, Zastrozhin, M, Zeineddine, M, Zhang, D, Zhang, J, Zhang, Y, Zhang, Z, Zhou, L, Zodpey, S, Zoladl, M, Vos, T, Hay, S, Force, L, Murray, C, Epidemiologie, RS: NUTRIM - R3 - Respiratory & Age-related Health, Bill & Melinda Gates Foundation, Kuwait University (Kuwait), Ministry of Higher Education (Malasia), Lega Italiana per la Lotta ai Tumori, Health Effects Institute (Estados Unidos), Unión Europea. Comisión Europea. European Research Council (ERC), Unión Europea. Comisión Europea. H2020, Fundação para a Ciência e Tecnologia (Portugal), African-German Network of Excellence in Science (AGNES), Federal Ministry of Education & Research (Alemania), Alexander von Humboldt Foundation, Novo Nordisk Foundation, National Institute for Health Research (Reino Unido), National Health and Medical Research Council (Australia), Romanian National Authority for Scientific Research and Innovation, Romanian Ministry of Research Innovation and Digitalization, Ministry of Education, Science and Technological Development (Serbia), Sigrid Jusélius Foundation, Finnish Cancer Foundation, Datta Meghe Institute of Medical Sciences (India), Xiamen University (Malasia), Manipal Academy of Higher Education (India), Panjab University (India), Sistema Nacional de Investigación (Panamá), Secretaría Nacional de Ciencia, Tecnología e Innovación (Panamá), Ministry of Science and Technology (Taiwan), Lung Foundation Australia, National Natural Science Foundation of China, Wellcome Trust, UNSW Sydney (Australia), ICMR - National Institute of Epidemiology (India), University of Tasmania (Australia), National Council for Scientific and Technological Development (Brasil), Coordenação de Aperfeicoamento de Pessoal de Nível Superior (Brasil), Institute for Advanced Studies in Basic Sciences (Irán), Ain Shams University (Egipto), International Center of Medical Sciences Research (Islamabad), National Institutes of Health (Estados Unidos), University of Oxford (Reino Unido), National Institute of Genetic Engineering and Biotechnology (Irán), Marga und Walter Boll - Stiftung, Ministero della Salute (Italia), IRCCS Materno Infantile Burlo Garofolo (Italia), King College London, Wellcome Trust/DBT India Alliance (India), Public Health, University of St Andrews. School of Medicine, and University of St Andrews. Population and Behavioural Science Division
Subjects: Male, DEATHS, DALY, cancer, risk factors, Medizin, systematic analysis, Global Health, Risk Assessment, Cancer prevention, Global Burden of Disease, RC0254, Risk-attributable cancer deaths, SDG 3 - Good Health and Well-being, RA0421, Risk Factors, RA0421 Public health. Hygiene. Preventive Medicine, Quality-Adjusted Life Year, Neoplasms, cancer, Humans, Global Burden of Disease Study, UK, Medicine(all), MCC, RC0254 Neoplasms. Tumors. Oncology (including Cancer), Risk Factor, Smoking, COVID-19, 3rd-DAS, General Medicine, Disability-adjusted life-years, SOCIAL DETERMINANTS, Risk assessments, risk factor, Cardiovascular and Metabolic Diseases, 3121 General medicine, internal medicine and other clinical medicine, OBESITY, Cancer burden, Neoplasm, Female, LIFE-STYLE, Quality-Adjusted Life Years, HEALTH, RA, Human, RC
Abstract: Background: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01-4·94) deaths and 105 million (95·0-116) DALYs for both sexes combined, representing 44·4% (41·3-48·4) of all cancer deaths and 42·0% (39·1-45·6) of all DALYs. There were 2·88 million (2·60-3·18) risk-attributable cancer deaths in males (50·6% [47·8-54·1] of all male cancer deaths) and 1·58 million (1·36-1·84) risk-attributable cancer deaths in females (36·3% [32·5-41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6-28·4) and DALYs by 16·8% (8·8-25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9-42·8] and 33·3% [25·8-42·0]). Interpretation: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. We are grateful to the surveillance systems, including cancer registries, that generated and shared observed cancer burden data. S M Aljunid acknowledges the Department of Health Policy and Management, College of Public Health, Kuwait University for the approval and support to participate in this research project. H Ariffin acknowledges support from the Ministry of Higher Education, Malaysia (grant FRGS/1/2021/SKK0/UM/01/1). F Barra acknowledges support from Lega Italiana per la Lotta contro i Tumori - LILT - Bando 5 x 1000 anno 2019. L Belo and M Carvalho acknowledge the support from FCT in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of UCIBIO and the project LA/P/0140/2020 of i4HB. A J Cohen was supported by the Health Effects Institute, Boston, MA, USA. J Conde acknowledges financial support from the European Research Council - ERC Starting Grant 848325. V M Costa acknowledges her grant (SFRH/BHD/110001/2015), received by Portuguese national funds through Fundação para a Ciência e Tecnologia (FCT), IP, under the Norma Transitória DL57/2016/CP1334/CT0006. T C Ekundayo was supported by the African-German Network of Excellence in Science (AGNES), the Federal Ministry of Education and Research (BMBF) and the Alexander von Humboldt Foundation (AvH). N Ghith acknowledges support from a grant from Novo Nordisk Foundation (NNF16OC0021856). J C Glasbey is support by a Doctoral Research Fellowship from the National Institute of Health Research (NIHR300175). V K Gupta and V B Gupta acknowledge funding support from National Health and Medical Research Council (NHMRC), Australia. C Herteliu, A Pana, and M Ausloos acknowledge partial support by a grant of the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. C Herteliu is also partially supported by a grant of the Romanian Ministry of Research Innovation and Digitalization, MCID, project number ID-585-CTR-42-PFE-2021. S Hussain was supported from Operational Programme Research, Development and Education–Project, Postdoc2MUNI (number CZ.02.2. 69/0.0/0.0/18_053/0016952). M Jakovljevic acknowledges partial support through the grant OI 175 014 of the Ministry of Education Science and Technological Development of the Republic of Serbia. J H Kauppila acknowledges research grants from Sigrid Jusélius Foundation and the Finnish Cancer Foundation. M N Khatib acknowledges support from Datta Meghe Institute of Medical Sciences (deemed-to-be-university). Y J Kim was supported by the Research Management Centre, Xiamen University Malaysia [XMUMRF/2020-C6/ITCM/0004]. S L Koulmane Laxminarayana acknowledges institutional assistance by Manipal Academy of Higher Education, Manipal. K Krishan is supported by the UGC Centre of Advanced Study (Phase II), awarded to the Department of Anthropology, Panjab University, Chandigarh, India. I Landires is a member of the Sistema Nacional de Investigación (SNI), which is supported by Panama’s Secretaría Nacional de Ciencia, Tecnología e Innovación (SENACYT). M-C Li was supported by the Ministry of Science and Technology, Taiwan (MOST 110-2314-B-003-001). G Liu acknowledges support from the CREATE Hope scientific fellowship from Lung Foundation Australia. J Liu acknowledges support from the National Natural Science Foundation (72122001). J A Loureiro was supported by Scientific Employment Stimulus (FCT; CEECINST/00049/2018). E Mathews is supported by a Clinical and Public Health Early Career Fellowship (grant number IA/CPHE/17/1/503345) from the DBT India Alliance/Wellcome Trust Department of Biotechnology, India Alliance (2018–2023). T J Meretoja was supported by an unrestricted grant from Cancer Foundation Finland sr. S Mohammed acknowledges a fellowship grant from Alexander von Humboldt Foundation, outside the submitted work. M Molokhia is supported by the National Institute for Health Research Biomedical Research Center at Guy’s and St Thomas’ National Health Service Foundation Trust and King’s College London. L Monasta received support from the Italian Ministry of Health at the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste - Italy (RC 34/2017). U Mons is supported by the Marga and Walter Boll Foundation, Kerpen, Germany. M A Moosavi acknowledges the financial support of National Institute of Genetics Engineering and Biotechnology (NIGEB). J Musa acknowledges support from the NIH/FICK43TW011416 for research-protected time for cervical cancer research and career development at University of Jos. V Nuñez-Samudio is a member of the Sistema Nacional de Investigación (SNI), which is supported by Panama’s Secretaría Nacional de Ciencia, Tecnología e Innovación (SENACYT). O O Odukoya acknowledges support by the Fogarty International Center of the National Institutes of Health under the award number K43TW010704 for research-protected time. The content is solely the responsibility of all the authors and does not necessarily represent the official views of the National Institutes of Health. A S Oguntade acknowledges funding by a doctoral scholarship from the Nuffield Department of Population Health, University of Oxford (Oxford Population Health). J R Padubidri acknowledges Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal for their constant support in research collaborations. R G Pestell acknowledges support from NIH grant W81XWH1810605 Breast Cancer Research, Breakthrough Grant R21 CA235139-01. Z Z Piracha acknowledges the International Center of Medical Sciences Research (ICMSR), Islamabad (44000), Pakistan. R A Radhakrishnan acknowledges support from Wellcome Trust/DBT India Alliance - IA/CPHI/18/1/503927. U Saeed acknowledges the International Center of Medical Sciences Research (ICMSR), Islamabad, Pakistan. A M Samy acknowledges the support from Ain Shams University and the Egyptian Fulbright Mission Program. F Sha was supported by the Shenzhen Science and Technology Program (grant number KQTD20190929172835662). H R Shahsavari acknowledges the Institute for Advanced Studies in Basic Sciences (IASBS) Research Council. A Shetty acknowledges Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal for all the academic support. D A S Silva acknowledges financing in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brazil (CAPES)—Finance Code 001 and D A S Silva is supported in part by CNPq-Brazil (309589/2021-5). L M L R Silva was supported by project CENTRO-04-3559-FSE-000162, Fundo Social Europeu (FSE). Am Singh is supported by the International Graduate Research Scholarship, University of Tasmania. R Suliankatchi Abdulkader acknowledges support from ICMR—National Institute of Epidemiology. B Unnikrishnan acknowledges Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal. H Xiao acknowledges support from the Public Health Sciences Division of the Fred Hutchinson Cancer Research Center. X Xu is supported by the University of New South Wales (Australia) Scientia Program. C Yu was supported by the National Natural Science Foundation of China (grant number 82173626) and Wuhan Medical Research Program of Joint Fund of Hubei Health Committee (grant number WJ2019H304). Sí
Published: 2022

11. The Secretome of Human Neonatal Mesenchymal Stem Cells Modulates Doxorubicin-Induced Cytotoxicity: Impact in Non-Tumor Cells

Author: Vera Marisa Costa, Nuno G. Oliveira, Matilde Castro, Bernardo Antunes, Volkan Yazar, Ana S. Serras, Joana P. Miranda, Fernando Remião, S.P. Camões, Flávio Dionísio, and Rui Vitorino
Subjects: QH301-705.5, cardiotoxicity, Inflammation, Breast Neoplasms, medicine.disease_cause, doxorubicin, Catalysis, Article, Cell Line, Inorganic Chemistry, Immunomodulation, breast cancer, Cell Line, Tumor, medicine, Humans, Doxorubicin, Myocytes, Cardiac, Physical and Theoretical Chemistry, Biology (General), Cytotoxicity, Molecular Biology, QD1-999, Spectroscopy, TIMP1, mesenchymal stem cells, secretome, 3D cultures, Cardiotoxicity, Cell growth, Chemistry, Organic Chemistry, Mesenchymal stem cell, General Medicine, Combined Modality Therapy, Computer Science Applications, Oxidative Stress, Cancer research, Female, medicine.symptom, Oxidative stress, medicine.drug
Abstract: Doxorubicin (Dox) is one of the most widely used treatments for breast cancer, although limited by the well-documented cardiotoxicity and other off-target effects. Mesenchymal stem cell (MSC) secretome has shown immunomodulatory and regenerative properties, further potentiated under 3D conditions. This work aimed to uncover the effect of the MSC-derived secretome from 3D (CM3D) or 2D (CM2D) cultures, in human malignant breast cells (MDA-MB-231), non-tumor breast epithelial cells (MCF10A) and differentiated AC16 cardiomyocytes, co-treated with Dox. A comprehensive proteomic analysis of CM3D/CM2D was also performed to unravel the underlying mechanism. CM3D/CM2D co-incubation with Dox revealed no significant differences in MDA-MB-231 viability when compared to Dox alone, whereas MCF10A and AC16 viability was consistently improved in Dox+CM3D-treated cells. Moreover, neither CM2D nor CM3D affected Dox anti-migratory and anti-invasive effects in MDA-MB-231. Notably, Ge-LC-MS/MS proteomic analysis revealed that CM3D displayed protective features that might be linked to the regulation of cell proliferation (CAPN1, CST1, LAMC2, RANBP3), migration (CCN3, MMP8, PDCD5), invasion (TIMP1/2), oxidative stress (COX6B1, AIFM1, CD9, GSR) and inflammation (CCN3, ANXA5, CDH13, GDF15). Overall, CM3D decreased Dox-induced cytotoxicity in non-tumor cells, without compromising Dox chemotherapeutic profile in malignant cells, suggesting its potential use as a chemotherapy adjuvant to reduce off-target side effects.
Published: 2021

12. Cardiotoxicity of cyclophosphamide's metabolites: an in vitro metabolomics approach in AC16 human cardiomyocytes

Author: Flávio Dionísio, Ana Margarida Araújo, Margarida Duarte-Araújo, Maria de Lourdes Bastos, Paula Guedes de Pinho, Félix Carvalho, and Vera Marisa Costa
Subjects: Dose-Response Relationship, Drug, Health, Toxicology and Mutagenesis, Humans, Metabolomics, Antineoplastic Agents, Myocytes, Cardiac, General Medicine, Acrolein, Toxicology, Cyclophosphamide, Cardiotoxicity, Immunosuppressive Agents, Cell Line
Abstract: Cyclophosphamide is a widely used anticancer and immunosuppressive prodrug that unfortunately causes severe adverse effects, including cardiotoxicity. Although the exact cardiotoxic mechanisms are not completely understood, a link between cyclophosphamide's pharmacologically active metabolites, namely 4-hydroxycyclophosphamide and acrolein, and the toxicity observed after the administration of high doses of the prodrug is likely. Therefore, the objective of this study is to shed light on the cardiotoxic mechanisms of cyclophosphamide and its main biotransformation products, through classic and metabolomics studies. Human cardiac proliferative and differentiated AC16 cells were exposed to several concentrations of the three compounds, determining their basic cytotoxic profile and preparing the next study, using subtoxic and toxic concentrations for morphological and biochemical studies. Finally, metabolomics studies were applied to cardiac cells exposed to subtoxic concentrations of the aforementioned compounds to determine early markers of damage. The cytotoxicity, morphological and biochemical assays showed that 4-hydroxycyclophosphamide and acrolein induced marked cardiotoxicity at µM concentrations (lower than 5 µM), being significantly lower than the ones observed for cyclophosphamide (higher than 2500 μM). Acrolein led to increased levels of ATP and total glutathione on proliferative cells at 25 µM, while no meaningful changes were observed in differentiated cells. Higher levels of carbohydrates and decreased levels of fatty acids and monoacylglycerols indicated a metabolic cardiac shift after exposure to cyclophosphamide's metabolites, as well as a compromise of precursor amino acids used in the synthesis of glutathione, seen in proliferative cells' metabolome. Overall, differences in cytotoxic mechanisms were observed for the two different cellular states used and for the three molecules, which should be taken into consideration in the study of cyclophosphamide cardiotoxic mechanisms.
Published: 2021

13. Antidotal effect of cyclosporine A against α-amanitin toxicity in CD-1 mice, at clinical relevant doses

Author: Juliana Garcia, Alexandra Carvalho, Ricardo Pires das Neves, Rui Malheiro, Daniela F. Rodrigues, Pedro R. Figueiredo, Antonio Bovolini, José Alberto Duarte, Vera Marisa Costa, and Félix Carvalho
Subjects: Mice, Liver, Amanita, Antidotes, Cyclosporine, Animals, Humans, Mushroom Poisoning, General Medicine, Toxicology, Alpha-Amanitin, Food Science
Abstract: Amanita phalloides is one of the most toxic mushrooms worldwide, being responsible for the majority of human fatal cases of mushroom intoxications. α-Amanitin, the most deleterious toxin of A. phalloides, inhibits RNA polymerase II (RNAP II), causing hepatic and renal failure. Herein, we used cyclosporine A after it showed potential to displace RNAP II α-amanitin in silico. That potential was not confirmed either by the incorporation of ethynyl-UTP or by the monitoring of fluorescent RNAP II levels. Nevertheless, concomitant incubation of cyclosporine A with α-amanitin, for a short period, provided significant protection against its toxicity in differentiated HepaRG cells. In mice, the concomitant administration of α-amanitin [0.45 mg/kg intraperitoneal (i.p.)] with cyclosporine A (10 mg/kg i.p. plus 2 × 10 mg/kg cyclosporine A i.p. at 8 and 12 h post α-amanitin) resulted in the full survival of α-amanitin-intoxicated mice, up to 30 days after the toxin's administration. Since α-amanitin is a substrate of the organic-anion-transporting polypeptide 1B3 and cyclosporine A inhibits this transporter and is a potent anti-inflammatory agent, we hypothesize that these mechanisms are responsible for the protection observed. These results indicate a potential antidotal effect of cyclosporine A, and its safety profile advocates for its use at an early stage of α-amanitin intoxications.
Published: 2022

14. An update of the molecular mechanisms underlying doxorubicin plus trastuzumab induced cardiotoxicity

Author: Vera Marisa Costa, Miguel Anjos, Mário Santos, Marta Fontes-Oliveira, and Rita Ferreira
Subjects: 0301 basic medicine, MAPK/ERK pathway, Receptor, ErbB-2, Neuregulin-1, Antineoplastic Agents, 030226 pharmacology & pharmacy, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Trastuzumab, Neoplasms, Antineoplastic Combined Chemotherapy Protocols, medicine, Animals, Humans, Doxorubicin, Myocytes, Cardiac, General Pharmacology, Toxicology and Pharmaceutics, Protein kinase A, Protein kinase B, PI3K/AKT/mTOR pathway, Cardiotoxicity, business.industry, General Medicine, Oxidative Stress, 030104 developmental biology, Cancer research, Signal transduction, business, medicine.drug, Signal Transduction
Abstract: Cardiotoxicity is a major side effect of the chemotherapeutic drug doxorubicin (Dox), which is further exacerbated when it is combined with trastuzumab, a standard care approach for Human Epidermal growth factor Receptor-type 2 (HER2) positive cancer patients. However, the molecular mechanisms of the underlying cardiotoxicity of this combination are still mostly elusive. Increased oxidative stress, impaired energetic substrate uses and topoisomerase IIB inhibition are among the biological processes proposed to explain Dox-induced cardiomyocyte dysfunction. Since cardiomyocytes express HER2, trastuzumab can also damage these cells by interfering with neuroregulin-1 signaling and mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/Akt and focal adhesion kinase (FAK)-dependent pathways. Nevertheless, Dox and trastuzumab target other cardiac cell types, such as endothelial cells, fibroblasts, cardiac progenitor cells and leukocytes, which can contribute to the clinical cardiotoxicity observed. This review aims to summarize the current knowledge on the cardiac signaling pathways modulated by these two antineoplastic drugs highly used in the management of breast cancer, not only focusing on cardiomyocytes but also to broaden the knowledge of the potential impact on other cells found in the heart.
Published: 2021

15. The secretome of mesenchymal stem cells ameliorates the cytotoxic effects of doxorubicin in non-tumoral cells

Author: Nuno G. Oliveira, S.P. Camões, A.S. Serras, Fernando Remião, Joana P. Miranda, Matilde Castro, Vera Marisa Costa, F. Dionísio, Bernardo Antunes, V. Yazar, and Rui Vitorino
Subjects: Chemistry, Mesenchymal stem cell, medicine, Cancer research, Cytotoxic T cell, Doxorubicin, General Medicine, Toxicology, medicine.drug
Published: 2021

16. Involvement of inflammation in DOX-induced cardiotoxicity: an in vivo study

Author: José Alberto Duarte, M.D.L. Bastos, E. Sousa, Ana Reis-Mendes, F. Carvalho, Vera Marisa Costa, Ana Isabel Padrão, Fernando Remião, Margarida Duarte-Araújo, and S. Gonçalves-Monteiro
Subjects: Cardiotoxicity, In vivo, business.industry, medicine, Inflammation, General Medicine, medicine.symptom, Pharmacology, Toxicology, business
Published: 2021

17. The influence of the anticancer drugs doxorubicin and mitoxantrone on cardiac metabolism and autophagy

Author: Ana Reis-Mendes, M.J. Neuparth, Ricardo B. Ferreira, F. Carvalho, M.D. Araújo, Vera Marisa Costa, M.D.L. Bastos, and S.R. Brandão
Subjects: Mitoxantrone, business.industry, Autophagy, Cancer research, Medicine, Cardiac metabolism, Doxorubicin, General Medicine, Toxicology, business, medicine.drug
Published: 2021

18. Early pathways of toxicity triggered by 3,4-methylene-dioxypyrovalerone unveiled by in vivo toxicometabolomics

Author: Vera Marisa Costa, Ricardo Jorge Dinis-Oliveira, Márcia Carvalho, M.D.L. Bastos, José Alberto Duarte, F. Carvalho, Ana Margarida Araújo, and P. Guedes de Pinho
Subjects: chemistry.chemical_compound, chemistry, In vivo, Toxicity, General Medicine, Methylene, Pharmacology, Toxicology
Published: 2021

19. Global burden of 87 risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Author: Soufiane Boufous, Yousef Veisani, Mehran Asadi-Aliabadi, Sharath Burugina Nagaraja, Maziar Moradi-Lakeh, Getachew Mullu Kassa, Edward J Mills, Dimas Ria Angga Pribadi, William James Dangel, Mohamad-Hani Temsah, Catherine O. Johnson, Gregory A. Roth, Giuseppe Gorini, Fariborz Mansour-Ghanaei, Alberto Ortiz, Samad Azari, Assefa Ayalew Ayalew Ayalew Gebreslassie, Salime Goharinezhad, Stephanie R. M. Zimsen, Peng Zheng, Michael Assmus, Elisabetta Pupillo, Bach Xuan Tran, Lal B. Rawal, Narayanaswamy Venketasubramanian, Noushin Mohammadifard, Stephen S Lim, Ata Rafiee, Maria Inês Schmidt, Vincent C. Iannucci, Suzanne Lyn Barker-Collo, Leah E. Cahill, Tauseef Ahmad, Platon D. Lopukhov, Kazumasa Yamagishi, Abdullah Al Mamun, Iqbal R. F. Elyazar, Giovanni Damiani, Mohammad Hossein Bakhshaei, Mehdi Fazlzadeh, Virginia Núñez-Samudio, Alyssa Pennini, Dietrich Plass, Atkilt Esaiyas Etisso, Gebre Teklemariam Demoz, Alexandrea Watson, Arvin Haj-Mirzaian, Paul S Briant, Frank B. Osei, Blair R. Bumgarner, Maciej Banach, Ravensara S. Travillian, Kai-Lan Chang, Shirin Djalalinia, Hasan Yusefzadeh, Silvano Gallus, Seyyed Meysam Mousavi, Bernhard T. Baune, Aaron van Donkelaar, Azeem Majeed, Hans Kromhout, Robert Ancuceanu, Blessing J. Akombi, Pushpendra Singh, Nayu Ikeda, William M. Gardner, Zahid A Butt, Mohammad Abdollahi, Temesgen Yihunie Akalu, Rahman Shiri, Benn Sartorius, Ai-Min Wu, Bing Fang Hwang, Flavia M. Cicuttini, Hiroyasu Iso, Luis Camera, Amin Soheili, Félix Carvalho, Yun Jin Kim, Caleb Mackay Salpeter Irvine, Mehdi Mirzaei-Alavijeh, Iman Halvaei, Saqib Ali, Giulio Castelpietra, Catalina Liliana Andrei, Ali Kazemi Karyani, Parkes J Kendrick, Hamidreza Haririan, Lucas Guimarães Abreu, Mukhammad David Naimzada, Jeff T. Zhao, Samiah Alam, Sorin Hostiuc, Shaun Wen Huey Lee, João Mauricio Castaldelli-Maia, Behzad Karami Matin, Cyrus Alinia, Takahiro Tabuchi, Manu Raj Mathur, Søren Thorgaard Skou, Thomas Khaled Dwayne Classen, Reza Heidari-Soureshjani, Massimo Cirillo, Nikita Otstavnov, Mehdi Bohluli, Ruth W. Kimokoti, Animut Tagele Tamiru, Masoumeh Sadeghi, Mohammad Ali Jahani, Itamar S. Santos, Mekdes Tigistu Yilma, Lars Johansson, Arielle Wilder Eagan, Nevine El Nahas, Silvia Schiavolin, Kevin D. Shield, Dinh-Toi Chu, Shiva Borzouei, Paul S. F. Yip, Beatrix Haddock, Gianfranco Alicandro, Vasily Vlassov, Deanna Anderlini, Giuseppe Remuzzi, Khalid A Altirkawi, Farahnaz Joukar, Aso Mohammad Darwesh, Ratilal Lalloo, Panniyammakal Jeemon, Rohollah Kalhor, Daniel Youngwhan Cho, Weijia Fu, João Pedro Silva, Rodrigo Sarmiento-Suarez, Seth Christopher Yaw Appiah, Mehdi Ahmadi, Jacob Olusegun Olusanya, José Neves, Gaorui Guo, Tomas Y. Yeheyis, John S. Ji, Charles D. H. Parry, Maryam Ghadimi, Seyed-Mohammad Fereshtehnejad, Serge Resnikoff, Anna E. Torre, Vinod C Nayak, Jamileh Shadid, Susanne Breitner, Mohammad Khammarnia, Mathilde Touvier, Ensiyeh Jenabi, Hosna Janjani, Floriane Ausloos, Irmina Maria Michalek, Alexandra S. Boon-Dooley, Jessica A. Cruz, Syed Mohamed Aljunid, Abiodun M. Adeoye, André Faro, Bartosz Miazgowski, Jobert Richie Nansseu, Erin C Mullany, Giannina Ferrara, Martin McKee, Emmanuel Peprah, Oommen John, Reza Saeedi, Yasser Vasseghian, Dragos Virgil Davitoiu, Sarah Wulf Hanson, Yingxi Zhao, Omid Shafaat, Ali Rajabpour-Sanati, Farid Najafi, Ana Maria Mantilla Herrera, Fatemeh Rajati, Tarun Gupta, Łukasz Szumowski, Mohammed Ibrahim Mohialdeen Gubari, Peter Njenga Keiyoro, Dharmesh Kumar Lal, Zhi Jiang Zhang, Osayomwanbo Osarenotor, Tanvir M. Huda, Perminder S. Sachdev, Farhad Ghamari, Era Upadhyay, Vivek Kumar, Guoqing Hu, Vinay Nangia, Vladimir Andreevich Korshunov, Saeed Shahabi, Golnaz Heidari, Ashraf Nabhan, Robert C. Reiner, Aziz Rezapour, Justin J. Lang, Rakhi Dandona, Josephine W. Ngunjiri, Anna-Karin Danielsson, André Karch, Filippo Ariani, Ahmed Abdelalim, Masih Tajdini, Stefanos Tyrovolas, Mohamed Hsairi, Jae Il Shin, Jasvinder A. Singh, Meghan D. Mooney, Fiona B. Bennitt, Hesam Alizade, Segun Emmanuel Ibitoye, Pradhum Ram, Soraya Siabani, Evanson Z. Sambala, Reza Malekzadeh, Falk Schwendicke, Lalit Dandona, Masoud Moradi, Molly R Nixon, Roya Mirzaei, Rachel Feldman, Hosni Salem, Alberto L. García-Basteiro, Lorainne Tudor Car, Sharareh Eskandarieh, Ramesh Holla, Ritesh G. Menezes, Taraneh Yousefinezhadi, Hai Quang Pham, Hamideh Salimzadeh, Luisa Sorio Flor, Priya Rathi, Ali Bijani, Harvey Whiteford, Shanshan Li, Aleksandr Y. Aravkin, Joshua A. Salomon, Franz Castro, Lisa M. Force, Abdilahi Yousuf Yousuf, Mina Anjomshoa, Ken Takahashi, Maigeng Zhou, Telma Zahirian Moghadam, Maseer Khan, Irina Filip, Santi Martini, Randah R. Hamadeh, Somayeh Bohlouli, Joana Morgado-da-Costa, Tim Driscoll, Jingkai Wei, Hermann Brenner, Reza Rawassizadeh, Radoslaw Sierpinski, Saman Esmaeilnejad, Emmanuel Wandera Okunga, Marisa Freitas, Srikanta Banerjee, Feleke Mekonnen Demeke, Shahin Soltani, Naser Mohammad Gholi Mezerji, Reed J D Sorensen, Elena V. Gnedovskaya, Johan Ärnlöv, Ivo Rakovac, Reza Mohammadpourhodki, Hussain Jafari, Atte Meretoja, Yasir Waheed, Fahad Alanezi, Arya Haj-Mirzaian, Sezer Kisa, Jaifred Christian F. Lopez, Khalid F. Alhabib, Basema Saddik, Michael R. Phillips, Vishnu Renjith, Yafeng Wang, Kevan R. Polkinghorne, Liliana G Ciobanu, Jacek Jerzy Jozwiak, Gelin Xu, Richard C. Franklin, Junjie Wu, Thomas R. Hird, Mohammad Zamani, Diana Silva, Fotis Topouzis, Irena Ilic, Jeffrey D. Stanaway, Hadi Pourjafar, Huong Lan Thi Nguyen, Khaled Khatab, Ammas Siraj Mohammed, Ziyad Al-Aly, A. A. Fomenkov, Charlie Ashbaugh, Mowafa Househ, Paul I. Dargan, Endalkachew Worku Mengesha, Shaimaa I. El-Jaafary, Ernoiz Antriyandarti, Iffat Elbarazi, Dara K. Mohammad, Naznin Hossain, Reza Shirkoohi, João M. Furtado, Arash Ziapour, Morteza Jafarinia, M. Mofizul Islam, Anamika Pandey, Ahmed I. Hasaballah, Tanuj Kanchan, Lee Ling Lim, Muktar Omer Omer, Charles D.A. Wolfe, Ulrich O Mueller, Helen Bitew, V. Prakash, Fereshteh Mehri, Randall V. Martin, Claudiu Herteliu, Constance D. Pond, Min Jeong Shin, Morteza Oladnabi, Antonio Maria Borzì, Yousef Mohammad, Yuichiro Yano, Luke D. Knibbs, Kevin S Ikuta, Maryam Mirzaei, Andreea Mirica, Sofia Boston Redford, Siamak Sabour, Mariya Vladimirovna Titova, Davood Anvari, Ghobad Moradi, Jordi Alonso, Shiwei Liu, Theo Vos, Tuomo J. Meretoja, Ireneous N. Soyiri, Owen R. Cooper, Seyed Sina Naghibi Irvani, Kejia Hu, Hannah J. Henrikson, Sanni Yaya, Robert P. Dellavalle, Chidozie Declan Iwu, Sergey Soshnikov, Jee-Young Jasmine Choi, Satinath Mukhopadhyay, Zabihollah Yousefi, Iman El Sayed, Biresaw Wassihun Alemu, Neeti Kapoor, Ahmad Daryani, Cathleen Keller, Ibrahim Abdollahpour, Nuno Taveira, Masoud Foroutan, Fatemeh Amiri, Mariam Molokhia, Songhomitra Panda-Jonas, Amy E. Peden, Rufus Akinyemi, Ejaz Ahmad Khan, Mostafa Amini-Rarani, J. Becker, Hamidreza Pazoki Toroudi, Ben Lacey, Kidanemaryam Berhe, Simon Yadgir, Spencer L. James, Cory N. Spencer, Aletta E. Schutte, Mu'awiyyah Babale Sufiyan, Arash Tehrani-Banihashemi, Govinda Prasad Dhungana, Fereshteh Ansari, Rixing Xu, Jonathan F. Mosser, Josep Maria Haro, Enrico Rubagotti, Anurag Agrawal, Zahiruddin Quazi Syed, Hoa Thi Do, Ettore Beghi, Seyed Mohammad Kazem Aghamir, Abraham Geremew, Alireza Esteghamati, Paramjit Gill, Farzad Jalilian, J. Jason West, Mikhail Sergeevich Zastrozhin, Albertino Damasceno, Bruce Bartholow Duncan, Nazir Fattahi, Daniel Cury Ribeiro, Michael Brauer, Mark A. Stokes, Veincent Christian Filipino Pepito, Lidia Morawska, Fiona J Charlson, Babak Moazen, Dejana Braithwaite, Jonathan M. Kocarnik, Sergio I. Prada, Andrea Farioli, Zahra Atafar, Heather Orpana, Daniela Balzi, Marco Vacante, Rahmatollah Moradzadeh, Jacek A. Kopec, Iván Landires, Robert G. Weintraub, Leonardo Roever, Yannick Béjot, Markus P. Schlaich, Hamed Zandian, Subramanian Senthilkumaran, Klara Dokova, Vahid Alipour, Sowmya J. Rao, Rakesh Ghosh, Omar Mukhtar Salman, Faris Lami, Marcos Roberto Tovani-Palone, Hamid Reza Tohidinik, Seyed Mohammad Riahi, Adnan Kisa, Ghasem Azarian, Caroline Stein, Zulfiqar A. Bhutta, Sinead Langan, Kunihiro Matsushita, Lauren E. Schaeffer, Kathryn H. Jacobsen, Mehdi Naderi, Mehdi Hosseinzadeh, Nizal Sarrafzadegan, Bahram Armoon, Dan J. Stein, Jessica Fanzo, Morenike Oluwatoyin Folayan, Luca Ronfani, Phetole Walter Mahasha, Nicholas J K Breitborde, Adrian Oţoiu, Arash Sarveazad, Marc L. Serre, Mostafa Hosseini, Nicolas Cherbuin, George D. Thurston, Jalal Arabloo, Mokhtar Mahdavi, Andre Rodrigues Duraes, Ana Laura Manda, Ahmed Abualhasan, Nima Rezaei, Yuan-Pang Wang, Theodore Patrick Younker, Alireza Ansari-Moghaddam, Borhan Mansouri, Adam E. Berman, Khezar Hayat, Rosario Cárdenas, Bolajoko O. Olusanya, Tommi Vasankari, Simon I. Hay, Fatemeh Ghaffarifar, Leo Stockfelt, Ai Koyanagi, Giorgia Giussani, Yuming Guo, Sonia Saxena, Deborah Carvalho Malta, Mehedi Hasan, Negar Rezaei, Maja Pasovic, Jukka Takala, Bogdan Oancea, Sare Safi, A. Werdecker, Florian Fischer, Beatriz Paulina Ayala Quintanilla, Muhammad Shahdaat Bin Sayeed, Takeshi Fukumoto, Maha Atout, Brijesh Sathian, Cristina Bosetti, Mitchell T. Wallin, Agegnehu Bante, Helen Ippolito, Anthony Masaka, Chantal Huynh, Justin Lo, Jordan Weiss, Joemer C. Maravilla, Alberto Raggi, Peter W. Gething, Cristiana Abbafati, Daniela Ribeiro, Mohammad Farahmand, Yetunde O. John-Akinola, Isabela M. Benseñor, Emilie R Maddison, John J. McGrath, Salman Khazaei, Scott B. Patten, Jean Jacques Noubiap, Emmanuela Gakidou, Celine M. Barthelemy, Ashish Badiye, George C. Patton, Obinna Onwujekwe, Peter Allebeck, Victor Aboyans, Olayinka Stephen Ilesanmi, Mousa Yaminfirooz, Neeraj Bedi, Nicholas L S Roberts, Joht Singh Chandan, Hans W. Hoek, Usman Iqbal, Nima Hafezi-Nejad, Haley Lescinsky, Naohiro Yonemoto, Ahmad Ghashghaee, Anders Larsson, David C. Schwebel, Milena Ilic, Richard T. Burnett, Yang Liu, Carlo La Vecchia, Felix Akpojene Ogbo, Morteza Naserbakht, Sangram Kishor Patel, Melanie S. Hammer, Prasanna Mithra, Mohammad Amin Bahrami, Kanyin L. Ong, Mona Pathak, Afshin Maleki, Saeid Safiri, Masood Ali Shaikh, Kate Causey, Michael R.M. Abrigo, Jost B. Jonas, Dian Kusuma, Jagadish Rao Padubidri, Mihajlo Jakovljevic, Ali S. Shalash, Abdiwahab Hashi, Ionut Negoi, Nataliya A. Foigt, Andrey Nikolaevich Briko, François Alla, Giuseppe Grosso, Houman Goudarzi, Di H. 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Mohammad Sajadi, Francisco Rogerlândio Martins-Melo, Shankar M Bakkannavar, Themba G.G. Ginindza, Sadaf G. Sepanlou, Sheikh Mohammed Shariful Islam, Sanjay Basu, Getinet Ayano, Paula Moraga, Soheil Hassanipour, Jason A. Anderson, Catherine Bisignano, Iyad Sultan, Deepak Kumar Pasupula, Keivan Ahmadi, Fariba Dorostkar, Rajeev Gupta, David M. Pereira, Mustafa Z. Younis, Adel Spotin, Rasmus Havmoeller, Yeshambel T. Nigatu, Barthelemy Kuate Defo, Mithila Faruque, Alan D. Lopez, Shailesh Advani, Behshad Naghshtabrizi, Shane D. Morrison, Inga Dora Sigfusdottir, Konrad Pesudovs, Anna Gershberg Hayoon, Raaj Kishore Biswas, Reshmi Bhageerathy, H. Dean Hosgood, Giulia Carreras, Sarika Chaturvedi, James L. Fisher, In-Hwan Oh, G Anil Kumar, Christoph Nowak, Vijay Kumar Chattu, Puja C Rao, Marcel Ausloos, Ali Kabir, Rannveig Sigurvinsdottir, Leeberk Raja Inbaraj, Edgar Denova-Gutiérrez, Rafael Tabarés-Seisdedos, Minh Nguyen, Ashkan Afshin, Payman Salamati, Colin Angus, Mona M. Khater, Ehsan Sadeghi, Mahalaqua Nazli Khatib, Antonio Biondi, Valentin Yurievich Skryabin, Mohsen Abbasi-Kangevari, Andrew T Olagunju, Amir Radfar, Laith J. Abu-Raddad, Marcello Tonelli, Hesam Ghiasvand, Hanne Christensen, Juan Jesus Carrero, Maryam Adabi, Saravanan Muthupandian, Kurt Straif, Hossein Samadi Kafil, Lope H Barrero, Harish Chander Gugnani, Mohammad Fareed, Morteza Shamsizadeh, Jemal Abdu Mohammed, Juan A Rivera, Shai Linn, Saad M.A. Dahlawi, Janni Leung, Shokofeh Maleki, Mohd Anisul Karim, Kamarul Imran Musa, Farshad Pourmalek, Dietrich Rothenbacher, Kiomars Sharafi, Alessandra C. Goulart, Leila Doshmangir, Gabriele Nagel, Helena Manguerra, Olatunji O. Adetokunboh, Srinivasa Vittal Katikireddi, Nermin Ghith, Maha El Tantawi, Awoke Misganaw, Yunquan Zhang, Carl Abelardo T. Antonio, Vahid Rashedi, Mehran Shams-Beyranvand, Bhaskaran Unnikrishnan, Holly E. Erskine, Ann Kristin Knudsen, Marissa B Reitsma, Getayeneh Antehunegn Tesema, Javad Javidnia, Ismael R. Campos-Nonato, Biniyam Sahiledengle Geberemariyam, Godfrey Mutashambara Rwegerera, Alaa Badawi, James Leigh, Morteza Arab-Zozani, Kyle E. Simpson, Muluken Bekele Sorrie, Roghiyeh Faridnia, Vivekanand Jha, Tomasz Miazgowski, Aaron J Cohen, Chukwuma David Umeokonkwo, Alessandra Lugo, Adhanom Gebreegziabher Baraki, Akshaya Srikanth Bhagavathula, Caitlyn Steiner, Gholamreza Roshandel, Cuong Tat Nguyen, Tania G Sánchez-Pimienta, Ahamarshan Jayaraman Nagarajan, Laura Kemmer, Ihoghosa Osamuyi Iyamu, Seyedeh Zahra Masoumi, Vivian Chia-Rong Hsieh, Kris J. Krohn, Phoebe Anne Rhinehart, Sarah Wozniak, Sahar Saeedi Moghaddam, Kate E. LeGrand, Christian Kieling, Vahid Yazdi-Feyzabadi, Robin Room, Zelalem Nigussie Azene, Kelly Cercy, Paul H. Lee, Stanislav S. Otstavnov, Dinesh Bhandari, Rafael Alves Guimarães, Zemenu Tadesse Tessema, Aziz Sheikh, Michellr L. Bell, Marwa Rashad Salem, Kirsten E. Wiens, Emma U.R. Smith, Hassan Abolhassani, Cristiano Piccinelli, Kedir Hussein Abegaz, G.K. Mini, Christian Razo, Manuela L. Ferreira, Diego De Leo, Francesco Saverio Violante, Aristidis Tsatsakis, Zahra Sadat Dibaji Forooshani, Tea Lallukka, Dickson A. Amugsi, Anna Poznańska, Graeme J. Hankey, Kewal Krishan, Maryam Zamanian, Eirini Skiadaresi, Jai K Das, Felix Greaves, Tessa M. Pilz, Sameer Vali Gopalani, Mansour Ghafourifard, M. DeLang, Morteza Mahmoudi, Alton Lu, Brian J. Hall, Ravi Prakash Jha, David Edvardsson, Xiu Ju George Zhao, Farshad Farzadfar, Hadi Hassankhani, Samuel M. Ostroff, Gerhard Sulo, Keyghobad Ghadiri, Neeraj Bhala, Stefan Lorkowski, Mohammad Rabiee, Sivan Yegnanarayana Iyer Saraswathy, Amirhossein Sahebkar, Rashid Abdi Guled, Abdallah M. Samy, Roman Topor-Madry, Michal Grivna, Afsaneh Arzani, Ayesha Humayun, Simin Liu, Maryam Khayamzadeh, Davoud Adham, Ahad Bakhtiari, Shafiu Mohammed, Paolo Lauriola, Abbas Mosapour, Sophia Emmons-Bell, Khurshid Alam, Rajat Das Gupta, Matilde Leonardi, Muktar Beshir Ahmed, Jeffrey V. Lazarus, Mohamed M. Gad, Kelly Compton, Leila R Kalankesh, Abdelrahman Ibrahim Abushouk, Mikk Jürisson, Catherine M. Antony, Ali A. Asadi-Pooya, Daniel Diaz, Salman Rawaf, Gina Agarwal, Ted R. Miller, Rebecca Ivers, João Vasco Santos, Savita Lasrado, Abdul Moiz Hafiz, Amir Almasi-Hashiani, Praveen Hoogar, Fares Alahdab, Om P Kurmi, Anbissa Muleta Senbeta, Tomi Akinyemiju, Boris Bikbov, Muhammad Aziz Rahman, Amin Mousavi Khaneghah, Yahya Safari, Guilherme Borges, Carlos A Castañeda-Orjuela, Kenji Shibuya, Bahman Yousefi, Berrin Serdar, Karen M. Tabb, Sonali Kochhar, Till Bärnighausen, Kala M. Mehta, Mostafa Dianatinasab, Arash Etemadi, Melissa Y. Wei, Kiana Ramezanzadeh, Lingkan Barua, Zubair Kabir, Rade Vukovic, Hesham M. Al-Mekhlafi, Shoshana H. Ballew, Miriam Levi, Zainab Samad, Florentino Luciano Caetano dos Santos, Juan Sanabria, Ramu Rawat, Chinwe Juliana Iwu, Gabrielle B. Britton, Colm McAlinden, Mohsen Naghavi, Maarten J. Postma, Chhabi Lal Ranabhat, Jalil Jaafari, Walter Mendoza, Mahesh P A, Pallab K. Maulik, Ali H. Mokdad, Andre M. N. Renzaho, Milena Santric-Milicevic, Parvaiz A Koul, Foad Abd-Allah, Mihaela Hostiuc, Richard G. Cowden, Ronny Westerman, Meghdad Pirsaheb, Department of Earth Observation Science, UT-I-ITC-ACQUAL, Faculty of Geo-Information Science and Earth Observation, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Value, Affordability and Sustainability (VALUE), Microbes in Health and Disease (MHD), Tampere University, Tays Research Services, Health Sciences, Murray, C. J. L., Aravkin, A. Y., Zheng, P., Abbafati, C., Abbas, K. M., Abbasi-Kangevari, M., Abd-Allah, F., Abdelalim, A., Abdollahi, M., Abdollahpour, I., Abegaz, K. H., Abolhassani, H., Aboyans, V., Abreu, L. G., Abrigo, M. R. M., Abualhasan, A., Abu-Raddad, L. J., Abushouk, A. I., Adabi, M., Adekanmbi, V., Adeoye, A. M., Adetokunboh, O. O., Adham, D., Advani, S. M., Agarwal, G., Aghamir, S. M. K., Agrawal, A., Ahmad, T., Ahmadi, K., Ahmadi, M., Ahmadieh, H., Ahmed, M. B., Akalu, T. Y., Akinyemi, R. O., Akinyemiju, T., Akombi, B., Akunna, C. J., Alahdab, F., Al-Aly, Z., Alam, K., Alam, S., Alam, T., Alanezi, F. M., Alanzi, T. M., Alemu, B. W., Alhabib, K. F., Ali, M., Ali, S., Alicandro, G., Alinia, C., Alipour, V., Alizade, H., Aljunid, S. M., Alla, F., Allebeck, P., Almasi-Hashiani, A., Al-Mekhlafi, H. M., Alonso, J., Altirkawi, K. A., Amini-Rarani, M., Amiri, F., Amugsi, D. A., Ancuceanu, R., Anderlini, D., Anderson, J. A., Andrei, C. L., Andrei, T., Angus, C., Anjomshoa, M., Ansari, F., Ansari-Moghaddam, A., Antonazzo, I. C., Antonio, C. A. T., Antony, C. M., Antriyandarti, E., Anvari, D., Anwer, R., Appiah, S. C. Y., Arabloo, J., Arab-Zozani, M., Ariani, F., Armoon, B., Arnlov, J., Arzani, A., Asadi-Aliabadi, M., Asadi-Pooya, A. A., Ashbaugh, C., Assmus, M., Atafar, Z., Atnafu, D. D., Atout, M. M. W., Ausloos, F., Ausloos, M., Ayala Quintanilla, B. P., Ayano, G., Ayanore, M. A., Azari, S., Azarian, G., Azene, Z. N., Badawi, A., Badiye, A. D., Bahrami, M. A., Bakhshaei, M. H., Bakhtiari, A., Bakkannavar, S. M., Baldasseroni, A., Ball, K., Ballew, S. H., Balzi, D., Banach, M., Banerjee, S. K., Bante, A. B., Baraki, A. G., Barker-Collo, S. L., Barnighausen, T. W., Barrero, L. H., Barthelemy, C. M., Barua, L., Basu, S., Baune, B. T., Bayati, M., Becker, J. S., Bedi, N., Beghi, E., Bejot, Y., Bell, M. L., Bennitt, F. B., Bensenor, I. M., Berhe, K., Berman, A. E., Bhagavathula, A. S., Bhageerathy, R., Bhala, N., Bhandari, D., Bhattacharyya, K., Bhutta, Z. A., Bijani, A., Bikbov, B., Bin Sayeed, M. S., Biondi, A., Birihane, B. M., Bisignano, C., Biswas, R. K., Bitew, H., Bohlouli, S., Bohluli, M., Boon-Dooley, A. S., Borges, G., Borzi, A. M., Borzouei, S., Bosetti, C., Boufous, S., Braithwaite, D., Breitborde, N. J. K., Breitner, S., Brenner, H., Briant, P. S., Briko, A. N., Briko, N. I., Britton, G. B., Bryazka, D., Bumgarner, B. R., Burkart, K., Burnett, R. T., Burugina Nagaraja, S., Butt, Z. A., Caetano dos Santos, F. L., Cahill, L. E., Camera, L. L. A., Campos-Nonato, I. R., Cardenas, R., Carreras, G., Carrero, J. J., Carvalho, F., Castaldelli-Maia, J. M., Castaneda-Orjuela, C. A., Castelpietra, G., Castro, F., Causey, K., Cederroth, C. R., Cercy, K. M., Cerin, E., Chandan, J. S., Chang, K. -L., Charlson, F. J., Chattu, V. K., Chaturvedi, S., Cherbuin, N., Chimed-Ochir, O., Cho, D. Y., Choi, J. -Y. J., Christensen, H., Chu, D. -T., Chung, M. T., Chung, S. -C., Cicuttini, F. M., Ciobanu, L. G., Cirillo, M., Classen, T. K. D., Cohen, A. J., Compton, K., Cooper, O. R., Costa, V. M., Cousin, E., Cowden, R. G., Cross, D. H., Cruz, J. A., Dahlawi, S. M. A., Damasceno, A. A. M., Damiani, G., Dandona, L., Dandona, R., Dangel, W. J., Danielsson, A. -K., Dargan, P. I., Darwesh, A. M., Daryani, A., Das, J. K., Das Gupta, R., das Neves, J., Davila-Cervantes, C. A., Davitoiu, D. V., De Leo, D., Degenhardt, L., Delang, M., Dellavalle, R. P., Demeke, F. M., Demoz, G. T., Demsie, D. G., Denova-Gutierrez, E., Dervenis, N., Dhungana, G. P., Dianatinasab, M., Dias da Silva, D., Diaz, D., Dibaji Forooshani, Z. S., Djalalinia, S., Do, H. T., Dokova, K., Dorostkar, F., Doshmangir, L., Driscoll, T. R., Duncan, B. B., Duraes, A. R., Eagan, A. W., Edvardsson, D., El Nahas, N., El Sayed, I., El Tantawi, M., Elbarazi, I., Elgendy, I. Y., El-Jaafary, S. I., Elyazar, I. R., Emmons-Bell, S., Erskine, H. E., Eskandarieh, S., Esmaeilnejad, S., Esteghamati, A., Estep, K., Etemadi, A., Etisso, A. E., Fanzo, J., Farahmand, M., Fareed, M., Faridnia, R., Farioli, A., Faro, A., Faruque, M., Farzadfar, F., Fattahi, N., Fazlzadeh, M., Feigin, V. L., Feldman, R., Fereshtehnejad, S. -M., Fernandes, E., Ferrara, G., Ferrari, A. J., Ferreira, M. L., Filip, I., Fischer, F., Fisher, J. L., Flor, L. S., Foigt, N. A., Folayan, M. O., Fomenkov, A. A., Force, L. M., Foroutan, M., Franklin, R. C., Freitas, M., Fu, W., Fukumoto, T., Furtado, J. M., Gad, M. M., Gakidou, E., Gallus, S., Garcia-Basteiro, A. L., Gardner, W. M., Geberemariyam, B. S., Gebreslassie, A. A. A. A., Geremew, A., Gershberg Hayoon, A., Gething, P. W., Ghadimi, M., Ghadiri, K., Ghaffarifar, F., Ghafourifard, M., Ghamari, F., Ghashghaee, A., Ghiasvand, H., Ghith, N., Gholamian, A., Ghosh, R., Gill, P. S., Ginindza, T. G. G., Giussani, G., Gnedovskaya, E. V., Goharinezhad, S., Gopalani, S. V., Gorini, G., Goudarzi, H., Goulart, A. C., Greaves, F., Grivna, M., Grosso, G., Gubari, M. I. M., Gugnani, H. C., Guimaraes, R. A., Guled, R. A., Guo, G., Guo, Y., Gupta, R., Gupta, T., Haddock, B., Hafezi-Nejad, N., Hafiz, A., Haj-Mirzaian, A., Hall, B. J., Halvaei, I., Hamadeh, R. R., Hamidi, S., Hammer, M. S., Hankey, G. J., Haririan, H., Haro, J. M., Hasaballah, A. I., Hasan, M. M., Hasanpoor, E., Hashi, A., Hassanipour, S., Hassankhani, H., Havmoeller, R. J., Hay, S. I., Hayat, K., Heidari, G., Heidari-Soureshjani, R., Henrikson, H. J., Herbert, M. E., Herteliu, C., Heydarpour, F., Hird, T. R., Hoek, H. W., Holla, R., Hoogar, P., Hosgood, H. D., Hossain, N., Hosseini, M., Hosseinzadeh, M., Hostiuc, M., Hostiuc, S., Househ, M., Hsairi, M., Hsieh, V. C. -R., Hu, G., Hu, K., Huda, T. M., Humayun, A., Huynh, C. K., Hwang, B. -F., Iannucci, V. C., Ibitoye, S. E., Ikeda, N., Ikuta, K. S., Ilesanmi, O. S., Ilic, I. M., Ilic, M. D., Inbaraj, L. R., Ippolito, H., Iqbal, U., Irvani, S. S. N., Irvine, C. M. S., Islam, M. M., Islam, S. M. S., Iso, H., Ivers, R. Q., Iwu, C. C. D., Iwu, C. J., Iyamu, I. O., Jaafari, J., Jacobsen, K. H., Jafari, H., Jafarinia, M., Jahani, M. A., Jakovljevic, M., Jalilian, F., James, S. L., Janjani, H., Javaheri, T., Javidnia, J., Jeemon, P., Jenabi, E., Jha, R. P., Jha, V., Ji, J. S., Johansson, L., John, O., John-Akinola, Y. O., Johnson, C. O., Jonas, J. B., Joukar, F., Jozwiak, J. J., Jurisson, M., Kabir, A., Kabir, Z., Kalani, H., Kalani, R., Kalankesh, L. R., Kalhor, R., Kanchan, T., Kapoor, N., Karami Matin, B., Karch, A., Karim, M. A., Kassa, G. M., Katikireddi, S. V., Kayode, G. A., Kazemi Karyani, A., Keiyoro, P. N., Keller, C., Kemmer, L., Kendrick, P. J., Khalid, N., Khammarnia, M., Khan, E. A., Khan, M., Khatab, K., Khater, M. M., Khatib, M. N., Khayamzadeh, M., Khazaei, S., Kieling, C., Kim, Y. J., Kimokoti, R. W., Kisa, A., Kisa, S., Kivimaki, M., Knibbs, L. D., Knudsen, A. K. S., Kocarnik, J. M., Kochhar, S., Kopec, J. A., Korshunov, V. A., Koul, P. A., Koyanagi, A., Kraemer, M. U. G., Krishan, K., Krohn, K. J., Kromhout, H., Kuate Defo, B., Kumar, G. A., Kumar, V., Kurmi, O. P., Kusuma, D., La Vecchia, C., Lacey, B., Lal, D. K., Lalloo, R., Lallukka, T., Lami, F. H., Landires, I., Lang, J. J., Langan, S. M., Larsson, A. O., Lasrado, S., Lauriola, P., Lazarus, J. V., Lee, P. H., Lee, S. W. H., Legrand, K. E., Leigh, J., Leonardi, M., Lescinsky, H., Leung, J., Levi, M., Li, S., Lim, L. -L., Linn, S., Liu, S., Liu, Y., Lo, J., Lopez, A. D., Lopez, J. C. F., Lopukhov, P. D., Lorkowski, S., Lotufo, P. A., Lu, A., Lugo, A., Maddison, E. R., Mahasha, P. W., Mahdavi, M. M., Mahmoudi, M., Majeed, A., Maleki, A., Maleki, S., Malekzadeh, R., Malta, D. C., Mamun, A. A., Manda, A. L., Manguerra, H., Mansour-Ghanaei, F., Mansouri, B., Mansournia, M. A., Mantilla Herrera, A. M., Maravilla, J. C., Marks, A., Martin, R. V., Martini, S., Martins-Melo, F. R., Masaka, A., Masoumi, S. Z., Mathur, M. R., Matsushita, K., Maulik, P. K., Mcalinden, C., Mcgrath, J. J., Mckee, M., Mehndiratta, M. M., Mehri, F., Mehta, K. M., Memish, Z. A., Mendoza, W., Menezes, R. G., Mengesha, E. W., Mereke, A., Mereta, S. T., Meretoja, A., Meretoja, T. J., Mestrovic, T., Miazgowski, B., Miazgowski, T., Michalek, I. M., Miller, T. R., Mills, E. J., Mini, G. K., Miri, M., Mirica, A., Mirrakhimov, E. 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S. B., Caetano Dos Santos, F. L., Camera, L. A., Elyazar, I. R. F., Ayalew Gebreslassie, A. A. A., Ginindza, T. G., Matin, B. K., Morgado-Da-Costa, J., Khaneghah, A. M., Mahesh, P. A., Toroudi, H. P., Syed, Z. Q., Salem, M. R., Skou, S. T., Tovani-Palone, M. R., Tudor Car, L. T., and Moghadam, T. Z.
Subjects: Male, Nutritional Sciences, Specific risk, Contaminación del Aire Interior, 030204 cardiovascular system & hematology, Socioeconomic Factor, systematic analysis, Global Health, Body Mass Index, Global Burden of Disease, Health Risk Behavior, Health Risk Behaviors, Disease studies, 0302 clinical medicine, Risk Factors, METABOLIC RISKS, 030212 general & internal medicine, 11 Medical and Health Sciences, Factores de Riesgo, 2. Zero hunger, education.field_of_study, Public health, Injuries, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, GBD, risck factors, attributable burden of disease, 3142 Public health care science, environmental and occupational health, 3. Good health, Relative risk, Environmental health, Health, Hypertension, Global Burden of Diseases, Injuries, Risk Factors, A990 Medicine and Dentistry not elsewhere classified, Female, Leading risk factors, Global Health Metrics, Cohort study, Human, medicine.medical_specialty, Substance-Related Disorders, Population, UNITED-STATES, Risk Assessment, DIET, ITC-HYBRID, 03 medical and health sciences, Life Expectancy, MORTALITY, DISABILITY, POLLUTION, CLUSTERS, SDG 3 - Good Health and Well-being, General & Internal Medicine, medicine, Humans, Global Burden of Disease Study, Risk factor, education, Global burden, business.industry, Risk Factor, Malnutrition, Klinisk medicin, Global Burden of Diseases, Environmental Exposure, medicine.disease, Enfermedades, purl.org/pe-repo/ocde/ford#3.02.00 [https], Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Years of potential life lost, Socioeconomic Factors, Risk factors, Disease study, Hyperglycemia, ITC-ISI-JOURNAL-ARTICLE, NA, Clinical Medicine, business, RA
Abstract: Background Rigorous analysis of levels and trends in exposure to leading risk factors and quantification of their effect on human health are important to identify where public health is making progress and in which cases current efforts are inadequate. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a standardised and comprehensive assessment of the magnitude of risk factor exposure, relative risk, and attributable burden of disease. Methods GBD 2019 estimated attributable mortality, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 87 risk factors and combinations of risk factors, at the global level, regionally, and for 204 countries and territories. GBD uses a hierarchical list of risk factors so that specific risk factors (eg, sodium intake), and related aggregates (eg, diet quality), are both evaluated. This method has six analytical steps. (1) We included 560 risk-outcome pairs that met criteria for convincing or probable evidence on the basis of research studies. 12 risk-outcome pairs included in GBD 2017 no longer met inclusion criteria and 47 risk-outcome pairs for risks already included in GBD 2017 were added based on new evidence. (2) Relative risks were estimated as a function of exposure based on published systematic reviews, 81 systematic reviews done for GBD 2019, and meta-regression. (3) Levels of exposure in each age-sex-location-year included in the study were estimated based on all available data sources using spatiotemporal Gaussian process regression, DisMod-MR 2.1, a Bayesian meta-regression method, or alternative methods. (4) We determined, from published trials or cohort studies, the level of exposure associated with minimum risk, called the theoretical minimum risk exposure level. (5) Attributable deaths, YLLs, YLDs, and DALYs were computed by multiplying population attributable fractions (PAFs) by the relevant outcome quantity for each age-sex-location-year. (6) PAFs and attributable burden for combinations of risk factors were estimated taking into account mediation of different risk factors through other risk factors. Across all six analytical steps, 30 652 distinct data sources were used in the analysis. Uncertainty in each step of the analysis was propagated into the final estimates of attributable burden. Exposure levels for dichotomous, polytomous, and continuous risk factors were summarised with use of the summary exposure value to facilitate comparisons over time, across location, and across risks. Because the entire time series from 1990 to 2019 has been re-estimated with use of consistent data and methods, these results supersede previously published GBD estimates of attributable burden. Findings The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure. Global declines also occurred for tobacco smoking and lead exposure. The largest increases in risk exposure were for ambient particulate matter pollution, drug use, high fasting plasma glucose, and high body-mass index. In 2019, the leading Level 2 risk factor globally for attributable deaths was high systolic blood pressure, which accounted for 10.8 million (95% uncertainty interval [UI] 9.51-12.1) deaths (19.2% [16.9-21.3] of all deaths in 2019), followed by tobacco (smoked, second-hand, and chewing), which accounted for 8.71 million (8.12-9.31) deaths (15.4% [14.6-16.2] of all deaths in 2019). The leading Level 2 risk factor for attributable DALYs globally in 2019 was child and maternal malnutrition, which largely affects health in the youngest age groups and accounted for 295 million (253-350) DALYs (11.6% [10.3-13.1] of all global DALYs that year). The risk factor burden varied considerably in 2019 between age groups and locations. Among children aged 0-9 years, the three leading detailed risk factors for attributable DALYs were all related to malnutrition. Iron deficiency was the leading risk factor for those aged 10-24 years, alcohol use for those aged 25-49 years, and high systolic blood pressure for those aged 50-74 years and 75 years and older. Interpretation Overall, the record for reducing exposure to harmful risks over the past three decades is poor. Success with reducing smoking and lead exposure through regulatory policy might point the way for a stronger role for public policy on other risks in addition to continued efforts to provide information on risk factor harm to the general public. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.
Published: 2020

20. The global distribution of lymphatic filariasis, 2000–18:a geospatial analysis

Author: Nataliya Foigt, Dina Nur Anggraini Ningrum, Ayenew Negesse Abejie, Samath Dhamminda Dharmaratne, Paramjit Gill, Marcela Agudelo-Botero, Alyssa N. Sbarra, Mario Poljak, Siavash Rahimi, Olalekan A. Uthman, Animut Alebel, Mohsen Naghavi, Olatunji O. Adetokunboh, Maarten J. Postma, Zemichael Gizaw, Chhabi Lal Ranabhat, Leonardo Roever, Mojtaba Bagherzadeh, Smita Pakhale, Seyyed Meysam Mousavi, Morenike Oluwatoyin Folayan, Robert C. Reiner, Phetole Walter Mahasha, Walter Mendoza, Azeem Majeed, Agus Sudaryanto, Dessalegn Ajema Berbada, Kate E. LeGrand, Takeshi Fukumoto, Mehdi Sayyah, Konrad Pesudovs, Mahesh P A, Nihal Thomas, Man Mohan Mehndiratta, Malede Mequanent Sisay, Azadeh Shafieesabet, Muhammad Usman, Balbir Singh, Ahsan Saleem, Ahmed Abualhasan, Maheswar Satpathy, Vijay Kumar Chattu, Mehdi Fazlzadeh, Ali H. Mokdad, Irfan Ullah, Sahar Saeedi Moghaddam, Luca Ronfani, James Albright, Si Si, Bartosz Miazgowski, Moses K. Muriithi, Catalina Liliana Andrei, Isaac Oluwafemi Dipeolu, Brijesh Sathian, Shishay Wahdey Tekelemedhin, Tufa Kolola, Mona M. Khater, Reta Tsegaye Gayesa, Andrew T Olagunju, Achala Upendra Jayatilleke, David L. Smith, Raaj Kishore Biswas, Rosario Cardenas, Andre M. N. Renzaho, Benjamin K. Mayala, Soraya Siabani, Ebrahim Babaee, Tsegaye Lolaso Lenjebo, Miliva Mozaffor, Bolajoko O. Olusanya, Joseph Frostad, Emma Elizabeth Spurlock, Hesham M. Al-Mekhlafi, Aso Mohammad Darwesh, Quynh Anh P. Nguyen, Kebede Embaye Gezae, Junaid Khan, Dessalegn Haile, Marcel Ausloos, David C. Schwebel, Bruno Piassi Sao Jose, Milena Ilic, Ionut Negoi, Ninuk Hariyani, Jost B. Jonas, Dian Kusuma, Sachin R Atre, Goura Kishor Rath, Muhammad Aziz Rahman, Dereje Bayissa Demissie, Eirini Skiadaresi, Simon I. Hay, Preeti Dhillon, Ejaz Ahmad Khan, Mohammad Hasan Imani-Nasab, Gebrehiwot G. Kassa, Nicole Davis Weaver, Mowafa Househ, Soumyadeep Bhaumik, Bahram Armoon, Martin Amogre Ayanore, Shaimaa I. El-Jaafary, Deborah Carvalho Malta, Rufus Adesoji Adedoyin, Alexandria Brown, Zewdie Aderaw Alemu, Mihiretu Kebede, Charles Shey Wiysonge, Bach Xuan Tran, Lal B. Rawal, Kala M. Mehta, Guoqing Hu, Yousef Khader, Heather J. Zar, Shiwei Liu, Norberto Perico, I A Adedeji, Sergio I. Prada, Shai Linn, Saad M.A. Dahlawi, Brigette F. Blacker, Anusha Ganapati Bhat, Desta Haftu Hayelom, Amit Arora, Mohammad Hossein Khosravi, Sanjay Zodpey, Farshad Farzadfar, Mehran Asadi-Aliabadi, Bárbara Niegia Garcia de Goulart, D. R. Mahadeshwara Prasad, Ajay Patle, Daniel Adane Endalew, Jagdish Khubchandani, Sharareh Eskandarieh, Mohammed Ibrahim Mohialdeen Gubari, Derrick A Bennett, Ziad A. Memish, Eduarda Fernandes, Chandrashekhar T Sreeramareddy, Seyed Mohammad Riahi, Hisham Atan Edinur, Taddese Alemu Zerfu, Robert S. Bernstein, Nader Jahanmehr, Yuming Guo, Tomohide Yamada, Manfred Mario Kokou Accrombessi, Mohamed I Hegazy, Liliana Preotescu, Sanjay Basu, Mohammad Reza Sobhiyeh, Frank B. Osei, Adhena Ayaliew Werkneh, Hamideh Salimzadeh, Ali Bijani, Shanshan Li, Alem Girmay, Sonali Kochhar, Meghnath Dhimal, Yonatal Mesfin Tefera, Saravanan Muthupandian, Francesco Saverio Violante, Monika Sawhney, Shally Awasthi, Samer Hamidi, Davide Guido, Van C. Lansingh, Engida Yisma, Muhammad Redzwan S Rashid Ali, Nima Hafezi-Nejad, Sadaf G. Sepanlou, Ali Kiadaliri, Hamed Zandian, Aparna Lal, Diana Fernanda Bejarano Ramirez, Dhirendra N Sinha, Florian Fischer, Hebat Allah Salah A. Yousof, Khanh Bao Tran, Kimberly B. Johnson, Senthilkumar Balakrishnan, Vo Dinh Bay, Arianna Maever L. Amit, Gbenga A. Kayode, John S. Ji, Akhil Soman ThekkePurakkal, Santi Martini, Behzad Heibati, Kebreab Paulos, Tefera Chane Mekonnen, Hagazi Gebre Meles, Vishnu Renjith, Paulina A. Lindstedt, Dinh Toi Chu, Gregory M. Garcia, Ahamarshan Jayaraman Nagarajan, Krishna K. Aryal, Irina Filip, Michelle L. Bell, Manfred S. Green, Alaa Badawi, Daniel Bekele Ketema, Claudio Alberto Dávila-Cervantes, Mohamad-Hani Temsah, Anton Sokhan, Julio Cesar Campuzano Rincon, Navid Manafi, Siddhesh Zadey, Davide Rasella, Hedayat Abbastabar, Manu Raj Mathur, Till Bärnighausen, Paula Moraga, Joan B. Soriano, Victor Adekanmbi, Seid Tiku Mereta, Mehran Shams-Beyranvand, Osayomwanbo Osarenotor, Mahya Beheshti, Farnam Mohebi, Genet Melak Alamene, Andem Effiong, Thomas R. Hird, Colm McAlinden, In-Hwan Oh, Arash Etemadi, Thirunavukkarasu Sathish, Rajesh Sharma, Puja C Rao, Masoud Foroutan, Sangram Kishor Patel, Sheikh Mohammed Shariful Islam, Aniruddha Deshpande, Paul H. Lee, Tukur Dahiru, Chinwe Juliana Iwu, Alireza Rafiei, Somayeh Bohlouli, Juan Sanabria, Javad Nazari, Siamak Sabour, Izza Shahid, Tuomo J. Meretoja, Ireneous N. Soyiri, André Karch, Mehdi Yaseri, Huong Lan Thi Nguyen, Khaled Khatab, Pushpendra Kumar, Ziyad Al-Aly, Khalid A. Altirkawi, Emerito Jose A. Faraon, Hagos Tasew Atalay, Sojib Bin Zaman, Gillian I. Hollerich, Hajer Elkout, Jonathan F. Mosser, Fakher Rahim, Kavumpurathu Raman Thankappan, Benny Antony, Nelson Alvis-Guzman, Ismael R. Campos-Nonato, Mohammad Moradi-Joo, Bineyam Taye, Ghulam Mustafa, Cheru Tesema Leshargie, Jacek Jerzy Jozwiak, Krittika Bhattacharyya, Tariq Jamal Siddiqi, Rafael Alves Guimarães, Vahid Alipour, Themba G. Ginindza, Wubalem Fekadu, Rafael Tabarés-Seisdedos, Mika Shigematsu, Bryan L. Sykes, Gebrekiros Gebremichael Meles, Delia Hendrie, Santosh Varughese, Manasi Kumar, Govinda Prasad Dhungana, Aziz Sheikh, Oladimeji M. Adebayo, Mohsen Bayati, B. Suresh Kumar Shetty, Kinley Wangdi, Hiroshi Yatsuya, Marzieh Nojomi, Carlo La Vecchia, Nuworza Kugbey, Zubair Kabir, Aslam Pervaiz, Muhammed Magdy Abd El Razek, Farzaneh Ghazi Sherbaf, Narinder Pal Singh, Jan Walter De Neve, Mohammad Khazaei, G. K. Mini, Eun-Kee Park, Haileab Fekadu Wolde, Zemenu Tadesse Tessema, Amir Radfar, Syed Ather Hussain, Gebre Teklemariam Demoz, Nasir Salam, Mohammad Ali Mansournia, Babak Moazen, Adnan Kisa, Milena Santric-Milicevic, Mitchell T. Wallin, Doris D. V. Ortega-Altamirano, Anwar Ahmed, Yousef Mohammad, Tanuj Kanchan, Feleke Gebremeskel W, Rajesh Sagar, Marwa Rashad Salem, Michael R.M. Abrigo, Fatemeh Heydarpour, Ammar Albujeer, Yasir Waheed, Noore Alam, Vera Marisa Costa, Rajat Das Gupta, Ritesh G. Menezes, Molly K. Miller-Petrie, Amira Shaheen, Seyyede Masoume Athari, Marcos Roberto Tovani-Palone, Ken Lee Chin, Ghobad Moradi, Ruth W Kimokoti, Peter Njenga Keiyoro, Kirsten E. Wiens, Nikolay Ivanovich Briko, K M Shivakumar, Ziad El-Khatib, Narayan Bahadur Mahotra, Ronny Westerman, Kamarul Imran Musa, Farshad Pourmalek, Kiomars Sharafi, Yared Asmare Aynalem, Entezar Mehrabi Nasab, Mu'awiyyah Babale Sufiyan, D J Christopher, Valery L. Feigin, Harish Chander Gugnani, Mathew M. Baumann, Platon D. Lopukhov, Tewodros Eshete Wonde, Hai Quang Pham, Luis Alberto Cámera, Meghdad Pirsaheb, Nelson J. Alvis-Zakzuk, Ahmad Daryani, Teferi Mekonnen, Yousef Veisani, Sharath Burugina Nagaraja, Parvaiz A Koul, Daniel Diaz, Ali S. Akanda, Mohammad Hifz Ur Rahman, Getachew Mullu Kassa, Daniel J. Weiss, Nauman Khalid, Hassen Mohammed, Edson Serván-Mori, Foad Abd-Allah, Fisaha Haile Tesfay, Abdullah Al Mamun, Yoshan Moodley, Adrian Pana, Salman Rawaf, Amir Almasi-Hashiani, Abdu A. Adamu, Fatemeh Rajati, German Martinez, Habib Benzian, Georgy Lebedev, Ben Lacey, Amir Hasanzadeh, Amir Khater, Merhawi Gebremedhin Tekle, Juanita A. Haagsma, Segun Emmanuel Ibitoye, Ahmed I. Hasaballah, Telma Zahirian Moghadam, Mehdi Hosseinzadeh, Virendra Singh, Demelash Woldeyohannes Handiso, Gabrielle Britton, Tiffany K. Gill, Sezer Kisa, Zahid A. Butt, Bruno Ramos Nascimento, Ian Pollock, Ted R. Miller, Rebecca Ivers, Savita Lasrado, Rovshan Khalilov, Ai Koyanagi, Benn Sartorius, Maciej Banach, Berhe Etsay Tesfay, Hedley Quintana, Joseph Adel Mattar Banoub, Praveen Hoogar, Ehsan Sadeghi, Kedir Hussein Abegaz, Hasan Yusefzadeh, Bogdan Oancea, Vafa Rahimi-Movaghar, Anbissa Muleta Senbeta, Subramanian Senthilkumaran, Ole Frithjof Norheim, Ester Cerin, Zulfiqar A Bhutta, Jennifer Rickard, M Alijanzadeh, Ali Almasi, Erkin M. Mirrakhimov, Seyed Hossein Yahyazadeh Jabbari, Sandra B. Munro, Ambrish Singh, Naohiro Yonemoto, Rahman Shiri, Girmay Teklay Weldesamuel, Jacqueline Elizabeth Alcalde-Rabanal, Daniel Asmelash, Mekdes Tigistu Yilma, Ahmad Ghashghaee, Natalie Maria Cormier, Samiah Alam, Yahya Salimi, Henok Biresaw Netsere, Anh Kim Dang, Jae Il Shin, S. Mohammad Sajadi, Francisco Rogerlândio Martins-Melo, Taweewat Wiangkham, Shankar M Bakkannavar, Eleonora Dubljanin, Itamar S. Santos, Temesgen Yihunie Akalu, Amir Kasaeian, Yahya Safari, Abel Fekadu Fekadu Dadi, Mohammad Fareed, Peter Memiah, Ali Kabir, Ensiyeh Jenabi, Ali Yadollahpour, Josephine W. Ngunjiri, Barthelemy Kuate Defo, Carlos A Castañeda-Orjuela, Reza Malekzadeh, Shymaa Enany, Hamidreza Haririan, Ayman Grada, Amador Goodridge, Salvatore Rubino, Jacob Olusegun Olusanya, Jalal Arabloo, Mohammad Reza Salahshoor, Masoud Behzadifar, Fernando de la Hoz, Mohammed Shannawaz, Hosni Salem, Syed Mohamed Aljunid, G Anil Kumar, Veincent Christian Filipino Pepito, Andre Rodrigues Duraes, Duduzile Ndwandwe, Jasvinder A. Singh, Yuan-Pang Wang, Tissa Wijeratne, Ingan Ukur Tarigan, Giuseppe Remuzzi, Sebastian Vollmer, Rakhi Dandona, Ahmed Abdelalim, Akram Pourshams, Felix Akpojene Ogbo, Alan J Thomson, Yves Miel H Zuniga, Alex Yeshaneh, Birhanu Geta Meharie, Mihajlo Jakovljevic, Obinna Onwujekwe, Ali S. Shalash, Bahram Mohajer, Nefsu Awoke, Hoa Thi Do, Jaifred Christian F. Lopez, Ernoiz Antriyandarti, Yilma Chisha Dea Geramo, Lucas Guimarães Abreu, Mohammad Ali Sahraian, Giang Hai Ha, Nizal Sarrafzadegan, Vinay Nangia, David M. Pigott, Arash Ziapour, Seyed Sina Naghibi Irvani, Andrew S. Azman, Amira Hamed Darwish, MohammadBagher Shamsi, Soewarta Kosen, Degena Bahrey Tadesse, Soufiane Boufous, Mehedi Hasan, Franz Castro, Adauto Martins Soares Filho, Oliver J. Brady, Elizabeth A. Cromwell, Olatunde Aremu, Samad Azari, Hala Rashad Elhabashy, Hamid Yimam Hassen, Julia Moreira Pescarini, Saeed Amini, Mehdi Ahmadi, Andualem Henok, Yafeng Wang, Nevine El Nahas, Paul S. F. Yip, Miguel A Barboza, Ibrahim Abdollahpour, Augustine Mwangi Gatotoh, Gurudatta Naik, Carl Abelardo T. Antonio, Morteza Abdullatif Khafaie, Meysam Behzadifar, hawariat, Enrico Rubagotti, Andre Faro, Kebede Deribe, Bhaskaran Unnikrishnan, Robert L. Thompson, Muhammad Shahdaat Bin Sayeed, Lalit Dandona, Seyyed Shamsadin Athari, Ashish Pathak, Masoud Moradi, Muluken Bekele Sorrie, Vivekanand Jha, Cuong Tat Nguyen, Naser Mohammad Gholi Mezerji, Chabila C Mapoma, Aubrey J. Levine, Solomon Gedlu Nigatu, Keivan Ahmadi, Hailay Abrha Gesesew, Getasew Taddesse Worku, Kewal Krishan, Hany Aref, Alebachew Fasil Fasil, Aziz Eftekhari, Claudiu Herteliu, Wasiq Faraz Rawasia, Zoubida Zaidi, Simin Mouodi, Dawit Zewdu Wondafrash, Hafiz Ansar Rasul Suleria, Oluchi Ezekannagha, Getinet Ayano, Gebremicheal Gebreslassie Kasahun, Usman Iqbal, Andrey Nikolaevich Briko, Workua Mekonnen Metekiya, Chuanhua Yu, Pascual R. Valdez, Mohsen Mazidi, Hamidreza Komaki, Turki Alanzi, Amir Jalali, Mina Anjomshoa, Chukwudi A Nnaji, Mostafa Leili, Hagos Degefa Hidru, Morteza Shamsizadeh, Tomislav Mestrovic, Beatriz Paulina Ayala Quintanilla, Chi Linh Hoang, Jemal Abdu Mohammed, Christopher J L Murray, Reza Shirkoohi, Aditya Prasad Dash, Thomas Pilgrim, Alessandra C. Goulart, Rajeev Gupta, Mustafa Z. Younis, Maha El Tantawi, Maysaa El Sayed Zaki, Aleksandra Barac, Christiane Dolecek, Mohammad Mahdi Zamani, Jean Jacques Noubiap, Faris Lami, Mehdi Naderi, Yunquan Zhang, Babak Eshrati, Jagadish Rao Padubidri, Navid Rabiee, Mayowa O. Owolabi, Netsanet Fentahun, Nuruzzaman Khan, Roghayeh Mohammadibakhsh, Seyed-Mohammad Fereshtehnejad, Serge Resnikoff, Dharmesh Kumar Lal, Habtamu Kebebe Kasaye, Ketema Bizuwork Gebremedhin, Surendra Karki, Edgar Denova-Gutiérrez, Félix Carvalho, Yun Jin Kim, Sonia Lewycka, Rashmi Gupta, Olayinka Stephen Ilesanmi, Neeraj Bedi, Binaya Chalise, Masood Ali Shaikh, Lauren E. Schaeffer, Kerrie E. Doyle, Gianna Gayle Herrera Amul, Richard C. Franklin, Dara K. Mohammad, Naznin Hossain, Jorge Cano, Jai K Das, Ana Isabel Ribeiro, Boris Bikbov, Sameer Vali Gopalani, Mohsen Afarideh, Behnam Heidari, Fares Alahdab, Takahiro Tabuchi, J. Car, Hilton Y. Lam, Diego Augusto Santos Silva, Linda Morales, Brian J. Hall, Mamusha Aman Hussen, Carsten Flohr, Ravi Prakash Jha, Shafiu Mohammed, Tara Ballav Adhikari, Abbas Mosapour, Muktar Beshir Ahmed, Wondimeneh Shibabaw Shiferaw, Mohamed M. Gad, Assefa Desalew, Eugenio Traini, Aisha Elsharkawy, Benjamin Uzochukwu, Anas M. Saad, Mohammad Rabiee, Sivan Yegnanarayana Iyer Saraswathy, Ansariadi Ansariadi, Abdallah M. Samy, Roman Topor-Madry, Afsaneh Arzani, Ayesha Humayun, Michael Tamene Haile, Maryam Khayamzadeh, Farah Daoud, Arash Tehrani-Banihashemi, Public Health, Johnson, KB, Local Burden of Disease 2019 Neglected Tropical Diseases Collaborator, Violante FS, Department of Earth Observation Science, UT-I-ITC-ACQUAL, Faculty of Geo-Information Science and Earth Observation, GeoHealth, and Instituto de Saúde Pública da Universidade do Porto
Subjects: medicine.medical_specialty, Geospatial analysis, 030231 tropical medicine, Elephantiasis, ELIMINATION, computer.software_genre, Article, Local Burden of Disease 2019 Neglected Tropical Diseases Collaborators, 1117 Public Health and Health Services, 03 medical and health sciences, 0302 clinical medicine, RA0421, Environmental health, Global health, medicine, 030212 general & internal medicine, Mass drug administration, Lymphatic filariasis, Public health, lcsh:Public aspects of medicine, Tropical disease, lcsh:RA1-1270, General Medicine, medicine.disease, 3. Good health, QR, Geography, Lymphatic system, ITC-ISI-JOURNAL-ARTICLE, A990 Medicine and Dentistry not elsewhere classified, ITC-GOLD, computer, 0605 Microbiology
Abstract: Background Lymphatic filariasis is a neglected tropical disease that can cause permanent disability through disruption of the lymphatic system. This disease is caused by parasitic filarial worms that are transmitted by mosquitos. Mass drug administration (MDA) of antihelmintics is recommended by WHO to eliminate lymphatic filariasis as a public health problem. This study aims to produce the first geospatial estimates of the global prevalence of lymphatic filariasis infection over time, to quantify progress towards elimination, and to identify geographical variation in distribution of infection. Methods A global dataset of georeferenced surveyed locations was used to model annual 2000–18 lymphatic filariasis prevalence for 73 current or previously endemic countries. We applied Bayesian model-based geostatistics and time series methods to generate spatially continuous estimates of global all-age 2000–18 prevalence of lymphatic filariasis infection mapped at a resolution of 5 km2 and aggregated to estimate total number of individuals infected. Findings We used 14 927 datapoints to fit the geospatial models. An estimated 199 million total individuals (95% uncertainty interval 174–234 million) worldwide were infected with lymphatic filariasis in 2000, with totals for WHO regions ranging from 3·1 million (1·6–5·7 million) in the region of the Americas to 107 million (91–134 million) in the South-East Asia region. By 2018, an estimated 51 million individuals (43–63 million) were infected. Broad declines in prevalence are observed globally, but focal areas in Africa and southeast Asia remain less likely to have attained infection prevalence thresholds proposed to achieve local elimination. Interpretation Although the prevalence of lymphatic filariasis infection has declined since 2000, MDA is still necessary across large populations in Africa and Asia. Our mapped estimates can be used to identify areas where the probability of meeting infection thresholds is low, and when coupled with large uncertainty in the predictions, indicate additional data collection or intervention might be warranted before MDA programmes cease. Funding Bill & Melinda Gates Foundation.
Published: 2020

21. Mapping geographical inequalities in access to drinking water and sanitation facilities in low-income and middle-income countries, 2000-17

Author: Joseph Frostad, Eirini Skiadaresi, Mehran Asadi-Aliabadi, Aleksandra Barac, Simon I. Hay, Deborah Carvalho Malta, Achala Upendra Jayatilleke, David L. Smith, Mohamad-Hani Temsah, Brigette F. Blacker, Nuworza Kugbey, Bineyam Taye, Carlo La Vecchia, Kavumpurathu Raman Thankappan, Benny Antony, Cheru Tesema Leshargie, Eduarda Fernandes, Chandrashekhar T Sreeramareddy, Turki Alanzi, Amir Jalali, Chukwudi A Nnaji, Daniel Asmelash, Manu Raj Mathur, Jai K Das, Ana Isabel Ribeiro, Sachin R Atre, Tomislav Mestrovic, Rajeev Gupta, Smita Pakhale, Félix Carvalho, Yun Jin Kim, Quynh Anh P. Nguyen, Sameer Vali Gopalani, Chi Linh Hoang, Jean Jacques Noubiap, Manfred Accrombessi, Christopher J L Murray, Ninuk Hariyani, Ken Lee Chin, Jagadish Rao Padubidri, Mehdi Fazlzadeh, Mohammad Fareed, Mustafa Z. Younis, Navid Rabiee, Osayomwanbo Osarenotor, Brian J. Hall, Ejaz Ahmad Khan, Daniel Diaz, Salman Rawaf, Tara Ballav Adhikari, Mayowa O. Owolabi, Sonia Lewycka, Catalina Liliana Andrei, Henok Biresaw Netsere, Hagos Degefa Hidru, Morteza Shamsizadeh, Shai Linn, Saad M.A. Dahlawi, Demelash Woldeyohannes Handiso, Jemal Abdu Mohammed, Thomas Pilgrim, Alessandra C. Goulart, Ravi Prakash Jha, Norberto Perico, Sergio I. Prada, Ted R. Miller, Rebecca Ivers, Habib Benzian, David C. Schwebel, Milena Ilic, Siddhesh Zadey, Davide Rasella, Hedayat Abbastabar, Aso Mohammad Darwesh, Kinley Wangdi, Ritesh G. Menezes, Jost B. Jonas, Dian Kusuma, Molly K. Miller-Petrie, Savita Lasrado, Goura Kishor Rath, Lalit Dandona, Farshad Farzadfar, Georgy Lebedev, Ahmed I. Hasaballah, Shaimaa I. El-Jaafary, Aniruddha Deshpande, Jacek Jerzy Jozwiak, Joseph Adel Mattar Banoub, Amir Almasi-Hashiani, Praveen Hoogar, Fares Alahdab, Vafa Rahimi-Movaghar, Anbissa Muleta Senbeta, Subramanian Senthilkumaran, Ambrish Singh, Fatemeh Rajati, Sonali Kochhar, Amir Khater, Ali Almasi, Juanita A. Haagsma, Segun Emmanuel Ibitoye, Telma Zahirian Moghadam, Rajesh Sharma, Abel Fekadu Dadi, Sezer Kisa, Arash Etemadi, Zubair Kabir, Aslam Pervaiz, Muhammed Magdy Abd El Razek, Syed Ather Hussain, Mohsen Mazidi, Hamidreza Komaki, Reza Shirkoohi, Alex Yeshaneh, Faris Lami, Maha El Tantawi, Yunquan Zhang, Hamidreza Haririan, Lucas Guimarães Abreu, Tissa Wijeratne, Giuseppe Remuzzi, Bahram Mohajer, Christiane Dolecek, Vinay Nangia, Gebremicheal Gebreslassie Kasahun, Usman Iqbal, Nataliya A. Foigt, Andrey Nikolaevich Briko, Workua Mekonnen Metekiya, Chuanhua Yu, Elizabeth A. Cromwell, Pascual R. Valdez, Jennifer Rickard, Masoud Moradi, Hailay Abrha Gesesew, Naser Mohammad Gholi Mezerji, Getasew Taddesse Worku, Dinh-Toi Chu, Claudiu Herteliu, Dawit Zewdu Wondafrash, Gianna Gayle Herrera Amul, Mostafa Leili, Gebrehiwot G. Kassa, Soumyadeep Bhaumik, Ester Cerin, Bahram Armoon, Martin Amogre Ayanore, Shafiu Mohammed, Alexandria Brown, Charles Shey Wiysonge, Abbas Mosapour, Bach Xuan Tran, Lal B. Rawal, Muktar Beshir Ahmed, Wondimeneh Shibabaw Shiferaw, Mohamed M. Gad, Eugenio Traini, Aisha Elsharkawy, David M. Pigott, Temesgen Yihunie Akalu, Syed Mohamed Aljunid, Reza Malekzadeh, Ahmad Daryani, Olatunde Aremu, Mohammad Reza Salahshoor, Merhawi Gebremedhin Tekle, Derrick A Bennett, Oladimeji M. Adebayo, Bogdan Oancea, Jagdish Khubchandani, Sandra B. Munro, Naohiro Yonemoto, Ahmad Ghashghaee, Mohammed Ibrahim Mohialdeen Gubari, Marcela Agudelo-Botero, Bárbara Niegia Garcia de Goulart, Daniel Adane Endalew, Davide Guido, Alyssa N. Sbarra, Kerrie E. Doyle, Olalekan A. Uthman, Olatunji O. Adetokunboh, Zemichael Gizaw, Muhammad Usman, Farzaneh Ghazi Sherbaf, MohammadBagher Shamsi, Degena Bahrey Tadesse, Aziz Eftekhari, André Karch, Narinder Pal Singh, Carl Abelardo T. Antonio, Morteza Abdullatif Khafaie, Meysam Behzadifar, Amira Hamed Darwish, Soufiane Boufous, Mohammad Reza Sobhiyeh, Frank B. Osei, Adhena Ayaliew Werkneh, Zahid A Butt, Paulina A. Lindstedt, Gregory M. Garcia, Balbir Bagicha Singh, Daniel Bekele Ketema, Genet Melak Alamene, Andem Effiong, André Faro, Amit Arora, Mohammad Hossein Khosravi, Dhirendra N Sinha, Amir Kasaeian, Ali Kabir, Josephine W. Ngunjiri, Hosni Salem, Sharareh Eskandarieh, Akhil Soman ThekkePurakkal, Anwar Ahmed, Tanuj Kanchan, Mu'awiyyah Babale Sufiyan, Bhaskaran Unnikrishnan, Daniel J. Weiss, Ziad El-Khatib, Jorge Cano, Javad Nazari, Ashish Pathak, Krishna Kumar Aryal, Nuruzzaman Khan, Roghayeh Mohammadibakhsh, Seyed-Mohammad Fereshtehnejad, Serge Resnikoff, Dharmesh Kumar Lal, Habtamu Kebebe Kasaye, Harish Chander Gugnani, Ali S. Akanda, Mohammad Hifz Ur Rahman, Muluken Bekele Sorrie, Vivekanand Jha, Abdu A. Adamu, Zulfiqar A. Bhutta, Mohsen Afarideh, Tiffany K. Gill, Nelson Alvis-Guzman, Oliver J. Brady, Ebrahim Babaee, Takahiro Tabuchi, Alebachew Fasil, Anusha Ganapati Bhat, Marwa Rashad Salem, Till Winfried Bärnighausen, Sadaf G. Sepanlou, Paula Moraga, J. Car, Hoa Thi Do, Samad Azari, hawariat, Cuong Tat Nguyen, Michelle L. Bell, Mohamed I Hegazy, Mehedi Hasan, Mamusha Aman Hussen, Erkin M. Mirrakhimov, Seyed Hossein Yahyazadeh Jabbari, Santi Martini, Vishnu Renjith, Haileab Fekadu Wolde, Chabila C Mapoma, Aubrey J. Levine, Solomon Gedlu Nigatu, Hamid Yimam Hassen, Anh Kim Dang, S. Mohammad Sajadi, Francisco Rogerlândio Martins-Melo, Shankar M Bakkannavar, Doris D. V. Ortega-Altamirano, Kala M. Mehta, Boris Bikbov, Assefa Desalew, Carsten Flohr, Yahya Safari, Michael R.M. Abrigo, Mohammad Moradi-Joo, Jan-Walter De Neve, Carlos A Castañeda-Orjuela, Julia Moreira Pescarini, Saeed Amini, Mehdi Ahmadi, Benjamin Uzochukwu, Anas M. Saad, Robert C. Reiner, Ammar Albujeer, Narayan Bahadur Mahotra, Nelson J. Alvis-Zakzuk, Teferi Mekonnen, Lauren E. Schaeffer, Irina Filip, Ali Yadollahpour, Ali Kiadaliri, Hamed Zandian, Fisaha Haile Tesfay, Seyed Mohammad Riahi, Nader Jahanmehr, Yuming Guo, Rafael Tabarés-Seisdedos, Paramjit Gill, Ketema Bizuwork Gebremedhin, Nicole Davis Weaver, Surendra Karki, Masoud Behzadifar, Vo Dinh Bay, Giang Hai Ha, Nizal Sarrafzadegan, In-Hwan Oh, Puja C Rao, Van Charles Lansingh, Kewal Krishan, Hany Aref, Man Mohan Mehndiratta, Shymaa Enany, Ayman Grada, Amador Goodridge, Salvatore Rubino, Zemenu Tadesse Tessema, Maheswar Satpathy, Amir Radfar, Aparna Lal, Isaac Akinkunmi Adedeji, Mehdi Naderi, Siavash Rahimi, Animut Alebel, Mohammad Rabiee, Diana Fernanda Bejarano Ramirez, Sivan Yegnanarayana Iyer Saraswathy, Sojib Bin Zaman, Alem Girmay, Ansariadi Ansariadi, Abdallah M. Samy, Mario Poljak, G Anil Kumar, Beatriz Paulina Ayala Quintanilla, Andrew S. Azman, Ronny Westerman, Thomas R. Hird, Themba G. Ginindza, Babak Moazen, Feleke Gebremeskel W, Meghdad Pirsaheb, Shally Awasthi, Morenike Oluwatoyin Folayan, Roman Topor-Madry, Phetole Walter Mahasha, Kamarul Imran Musa, Hebat Allah Salah A. Yousof, Afsaneh Arzani, Yousef Veisani, Farshad Pourmalek, Sharath Burugina Nagaraja, Ayesha Humayun, Michael Tamene Haile, Kiomars Sharafi, Wasiq Faraz Rawasia, Zoubida Zaidi, Getachew Mullu Kassa, Tsegaye Lolaso Lenjebo, Maryam Khayamzadeh, Nima Hafezi-Nejad, Mohammad Zamani, Takeshi Fukumoto, Masoud Foroutan, Noore Alam, Simin Mouodi, Miliva Mozaffor, Khanh Bao Tran, Farnam Mohebi, Sanjay Basu, Robert L. Thompson, Behzad Heibati, Santosh Varughese, Olayinka Stephen Ilesanmi, Neeraj Bedi, Hafiz Ansar Rasul Suleria, Oluchi Ezekannagha, Gabriel Martinez, Getinet Ayano, Farah Daoud, Konrad Pesudovs, Julio Cesar Campuzano Rincon, Tukur Dahiru, Mehdi Hosseinzadeh, Andualem Henok, Mina Anjomshoa, Rovshan Khalilov, Ai Koyanagi, Raaj Kishore Biswas, Navid Manafi, Yousef Mohammad, Keivan Ahmadi, Seyyed Shamsadin Athari, Binaya Chalise, Masood Ali Shaikh, Joan B. Soriano, Victor Adekanmbi, Seid Tiku Mereta, Delia Hendrie, Vijay Kumar Chattu, Gebrekiros Gebremichael Meles, Si Si, Manasi Kumar, Netsanet Fentahun, Amira Shaheen, Seyyede Masoume Athari, Marcos Roberto Tovani-Palone, Ben Lacey, Peter Njenga Keiyoro, Yared Asmare Aynalem, Entezar Mehrabi Nasab, K M Shivakumar, Tewodros Eshete Wonde, Dessalegn Ajema Berbada, Yahya Salimi, Adnan Kisa, Hisham Atan Edinur, Benn Sartorius, Kate E. LeGrand, Azadeh Shafieesabet, Richard C. Franklin, Dara K. Mohammad, Naznin Hossain, Mona M. Khater, Reta Tsegaye Gayesa, Natalie Maria Cormier, Ghulam Mustafa, Ehsan Sadeghi, Nikolay Ivanovich Briko, Robert S. Bernstein, Samiah Alam, Duduzile Ndwandwe, Andrew T Olagunju, Obinna Onwujekwe, B. Suresh Kumar Shetty, Behnam Heidari, Arianna Maever L. Amit, John S. Ji, Pushpendra Kumar, Sangram Kishor Patel, Vera Marisa Costa, Yafeng Wang, Irfan Ullah, Sahar Saeedi Moghaddam, Virendra Singh, Tufa Kolola, Mehdi Yaseri, Abdullah Al Mamun, Hilton Y. Lam, Diego Augusto Santos Silva, Samath D Dharmaratne, Hajer Elkout, Yoshan Moodley, Linda Morales, Adrian Pana, Nauman Khalid, Hassen Mohammed, Fakher Rahim, Emma Elizabeth Spurlock, Mika Shigematsu, Bryan L. Sykes, Isaac Oluwafemi Dipeolu, Platon D. Lopukhov, Marzieh Nojomi, Khalid A Altirkawi, Dessalegn Haile, Mohsen Bayati, Senthilkumar Balakrishnan, Mohammad Ali Sahraian, Yasir Waheed, Ernoiz Antriyandarti, Tomohide Yamada, Alireza Rafiei, Bruno Ramos Nascimento, Ian Pollock, Ahamarshan Jayaraman Nagarajan, Kebede Embaye Gezae, Anton Sokhan, Mehran Shams-Beyranvand, Junaid Khan, Jacqueline Elizabeth Alcalde-Rabanal, Enrico Rubagotti, Mehran Alijanzadeh, Gillian I. Hollerich, Ismael R. Campos-Nonato, Eleonora Dubljanin, Itamar S. Santos, Wubalem Fekadu, Ole Frithjof Norheim, Florian Fischer, Kedir Hussein Abegaz, Nihal Thomas, Alaa Badawi, Amir Hasanzadeh, Nasir Salam, Muhammad Ali, Mohammad Ali Mansournia, Marcel Ausloos, Ensiyeh Jenabi, Bruno Piassi Sao Jose, Edgar Denova-Gutiérrez, Jae Il Shin, Jacob Olusegun Olusanya, Mohammad Hasan Imani-Nasab, Rajesh Sagar, Ahmed Abdelalim, Benjamin K. Mayala, Fatemeh Heydarpour, Maysaa El Sayed Zaki, Shiwei Liu, Soraya Siabani, Jonathan F. Mosser, Veincent Christian Filipino Pepito, Andre Rodrigues Duraes, Valery L. Feigin, Yuan-Pang Wang, Mathew M. Baumann, Saravanan Muthupandian, Ingan Ukur Tarigan, Jasvinder A. Singh, Sebastian Vollmer, Felix Akpojene Ogbo, Alan J Thomson, Agus Sudaryanto, Birhanu Geta Meharie, Mihajlo Jakovljevic, Ahsan Saleem, Ali S. Shalash, Rakhi Dandona, Mojtaba Bagherzadeh, Ahmed Abualhasan, Muhammad Shahdaat Bin Sayeed, Meghnath Dhimal, Yves Miel H Zuniga, Akram Pourshams, Ionut Negoi, Yilma Chisha Dea Geramo, Franz Castro, Nefsu Awoke, Vahid Alipour, Rosario Cárdenas, Mohammad Khazaei, Mitchell T. Wallin, Yonatal Mesfin Tefera, Sanjay Zodpey, Bolajoko O. Olusanya, Ziad A. Memish, Taddese Alemu Zerfu, Claudio Alberto Dávila-Cervantes, Samer Hamidi, Gbenga A. Kayode, Peter Memiah, Sheikh Mohammed Shariful Islam, Francesco Saverio Violante, Bartosz Miazgowski, Babak Eshrati, Moses K. Muriithi, Mihiretu Kebede, Mowafa Househ, Monika Sawhney, Preeti Dhillon, Desta Haftu Hayelom, Ajay Patle, Thirunavukkarasu Sathish, Krittika Bhattacharyya, Hiroshi Yatsuya, Jaifred Christian F. Lopez, Barthelemy Kuate Defo, Arash Ziapour, Paul H. Lee, Emerito Jose A. Faraon, Seyed Sina Naghibi Irvani, Hagos Tasew Atalay, Tariq Jamal Siddiqi, Rafael Alves Guimarães, Aziz Sheikh, Adauto Martins Soares Filho, Eun-Kee Park, Kirsten E. Wiens, Hai Quang Pham, Berhe Etsay Tesfay, G. K. Mini, Zewdie Aderaw Alemu, Hedley Quintana, Milena Santric-Milicevic, Rajat Das Gupta, Parvaiz A Koul, Edson Serván-Mori, Foad Abd-Allah, Rahul Gupta, Dereje Bayissa Demissie, Chinwe Juliana Iwu, Gabrielle B. Britton, Colm McAlinden, Ayenew Negesse Abejie, Mohsen Naghavi, Maarten J. Postma, Chhabi Lal Ranabhat, Liliana Preotescu, Walter Mendoza, Manfred S. Green, Mahesh P A, Somayeh Bohlouli, Huong Lan Thi Nguyen, Khaled Khatab, Ziyad Al-Aly, Ali H. Mokdad, Aditya P Dash, Andre M. N. Renzaho, Muhammad Aziz Rahman, Ghobad Moradi, Ruth W Kimokoti, Jalal Arabloo, Kimberly B. Johnson, Seyyed Meysam Mousavi, Hesham M. Al-Mekhlafi, D. R. Mahadeshwara Prasad, Rufus A. Adedoyin, Arash Tehrani-Banihashemi, Govinda Prasad Dhungana, Engida Yisma, Azeem Majeed, Dina Nur Anggraini Ningrum, Hagazi Gebre Meles, Hala Elhabashy, Devasahayam J. Christopher, Malede Mequanent Sisay, Juan Sanabria, Gebre Teklemariam Demoz, Leonardo Roever, Shishay Wahdey Tekelemedhin, Guoqing Hu, Yousef Khader, Heather J. Zar, Hamideh Salimzadeh, Ali Bijani, Mehdi Sayyah, Shanshan Li, Kebreab Paulos, Tefera Chane Mekonnen, Mahya Beheshti, Siamak Sabour, Izza Shahid, Tuomo J. Meretoja, Ireneous N. Soyiri, Luca Ronfani, James Albright, Brijesh Sathian, Maciej Banach, Hasan Yusefzadeh, Rahman Shiri, Girmay Teklay Weldesamuel, Mekdes Tigistu Yilma, Taweewat Wiangkham, Soewarta Kosen, Fernando de la Hoz, Mohammed Shannawaz, Luis Camera, Nevine El Nahas, Paul S. F. Yip, Miguel A Barboza, Ibrahim Abdollahpour, Augustine Mwangi Gatotoh, Gurudatta Naik, Kebede Deribe, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Value, Affordability and Sustainability (VALUE), Microbes in Health and Disease (MHD), Instituto de Saúde Pública da Universidade do Porto, IRAS OH Epidemiology Chemical Agents, Local Burden of Disease WaSH Collaborator, Violante FS, Public Health, Department of Earth Observation Science, UT-I-ITC-ACQUAL, Faculty of Geo-Information Science and Earth Observation, GeoHealth, HUS Comprehensive Cancer Center, Clinicum, University of Helsinki, Department of Oncology, Yisma, Engida, and Local Burden of Disease WaSH Collaborators
Subjects: Drinking water access, Sanitation, Universal design, Geographic Mapping, Socioeconomic Factor, DISEASE, 0302 clinical medicine, RA0421, Hygiene, 11. Sustainability, Global health, 030212 general & internal medicine, media_common, 2. Zero hunger, Public health, lcsh:Public aspects of medicine, 1. No poverty, General Medicine, 3142 Public health care science, environmental and occupational health, 6. Clean water, Low-income countries, 3. Good health, A990 Medicine and Dentistry not elsewhere classified, CHILD GROWTH, TERRITORIES, HYGIENE, Human, 0605 Microbiology, Diarrhea, AFRICA, medicine.medical_specialty, media_common.quotation_subject, 030231 tropical medicine, Local Burden of Disease WaSH Collaborators, Developing country, Article, Geographical inequalities, 1117 Public Health and Health Services, 12. Responsible consumption, Developing Countrie, 03 medical and health sciences, NUTRITIONAL INTERVENTIONS, Environmental health, medicine, SYSTEMATIC ANALYSIS, Humans, QUALITY, Sanitation/statistics & numerical data, Open defecation, Improved sanitation, hand washing, Developing Countries, Models, Statistical, Middle-income countries, Drinking Water, lcsh:RA1-1270, Bayes Theorem, GLOBAL BURDEN, diarrheal disease, DIARRHEA, Diarrhea/epidemiology, Local Burden of Disease WaSH Collaborator, Socioeconomic Factors, 0605 Microbiology, 1117 Public Health and Health Services, ITC-ISI-JOURNAL-ARTICLE, Business, Human medicine, Sanitation facilities, ITC-GOLD
Abstract: Background: Universal access to safe drinking water and sanitation facilities is an essential human right, recognised in the Sustainable Development Goals as crucial for preventing disease and improving human wellbeing. Comprehensive, high-resolution estimates are important to inform progress towards achieving this goal. We aimed to produce highresolution geospatial estimates of access to drinking water and sanitation facilities. Methods: We used a Bayesian geostatistical model and data from 600 sources across more than 88 low-income and middle-income countries (LMICs) to estimate access to drinking water and sanitation facilities on continuous continent-wide surfaces from 2000 to 2017, and aggregated results to policy-relevant administrative units. We estimated mutually exclusive and collectively exhaustive subcategories of facilities for drinking water (piped water on or off premises, other improved facilities, unimproved, and surface water) and sanitation facilities (septic or sewer sanitation, other improved, unimproved, and open defecation) with use of ordinal regression. We also estimated the number of diarrhoeal deaths in children younger than 5 years attributed to unsafe facilities and estimated deaths that were averted by increased access to safe facilities in 2017, and analysed geographical inequality in access within LMICs. Findings: Across LMICs, access to both piped water and improved water overall increased between 2000 and 2017, with progress varying spatially. For piped water, the safest water facility type, access increased from 40·0% (95% uncertainty interval [UI] 39·4–40·7) to 50·3% (50·0–50·5), but was lowest in sub-Saharan Africa, where access to piped water was mostly concentrated in urban centres. Access to both sewer or septic sanitation and improved sanitation overall also increased across all LMICs during the study period. For sewer or septic sanitation, access was 46·3% (95% UI 46·1–46·5) in 2017, compared with 28·7% (28·5–29·0) in 2000. Although some units improved access to the safest drinking water or sanitation facilities since 2000, a large absolute number of people continued to not have access in several units with high access to such facilities (>80%) in 2017. More than 253 000 people did not have access to sewer or septic sanitation facilities in the city of Harare, Zimbabwe, despite 88·6% (95% UI 87·2–89·7) access overall. Many units were able to transition from the least safe facilities in 2000 to safe facilities by 2017; for units in which populations primarily practised open defecation in 2000, 686 (95% UI 664–711) of the 1830 (1797–1863) units transitioned to the use of improved sanitation. Geographical disparities in access to improved water across units decreased in 76·1% (95% UI 71·6–80·7) of countries from 2000 to 2017, and in 53·9% (50·6–59·6) of countries for access to improved sanitation, but remained evident subnationally in most countries in 2017. Interpretation: Our estimates, combined with geospatial trends in diarrhoeal burden, identify where efforts to increase access to safe drinking water and sanitation facilities are most needed. By highlighting areas with successful approaches or in need of targeted interventions, our estimates can enable precision public health to effectively progress towards universal access to safe water and sanitation. This work was primarily supported by a grant from the Gates Foundation (OPP1132415). LGA has received support from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Finance Code 001), Conselho Nacional de Desenvolvimento Científico e Tecnológico and Fundação de Amparo à Pesquisa do Estado de Minas Gerais. OOA acknowledges the Department of Science and Innovation, National Research Foundation, and DSI/NRF Centre of Excellence for Epidemiological Modelling and Analysis, Stellenbosch, South Africa. SMAl acknowledges the Department of Health Policy and Management, Faculty of Public Health, Kuwait University and International Centre for Casemix and Clinical Coding, Faculty of Medicine, National University of Malaysia for the approval and support to participate in this research project. HTA acknowledges Aksum University. MAu and CH are partly supported by a grant from the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. AAz acknowledges funding from the Gates Foundation (OPP1171700). ABad is supported by the Public Health Agency of Canada. TWB was supported by the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research; the EU; the Wellcome Trust; and from National Institute of Child Health and Human Development of National Institutes of Health (NIH; R01-HD084233), National Institute on Aging of NIH (P01AG041710), National Institute of Allergy and Infectious Diseases of NIH (R01-AI124389 and R01-AI112339), as well as Fogarty International Center of NIH (D43-TW009775). DABen was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, or the UK Department of Health and Social Care. GBB is supported by Sistema Nacional de Investigación (SNI) de la Secretaría Nacional de Ciencia, Tecnología e Innovación (SENACYT) of Panamá. FCar acknowledges UID/ MULTI/04378/2019 and UID/QUI/50006/2019 support with funding from FCT/Ministério da Ciência, Tecnologia e Ensino Superior through national funds. VMC acknowledges her grant (SFRH/BHD/110001/2015), received by Portuguese national funds through Fundação para a Ciência e Tecnologia (FCT), IP, under the Norma Transitória DL57/2016/CP1334/CT0006. JDN acknowledges support from the Alexander von Humboldt Foundation. DBD acknowledges support from the Gates Foundation. KD is supported by a Wellcome Trust grant (number 201900/Z/16/Z) as part of his International Intermediate Fellowship. AGo acknowledges Sistema Nacional de Investigadores de Panamá (SNI), Secretaría Nacional de Ciencia, Tecnología e Innovación (SENACYT). CH is partly supported by a grant co-funded by European Fund for Regional Development through the Operational Program for Competitiveness (project ID P_40_382). SMSI is funded by a Fellowship from National Heart Foundation of Australia and Deakin University. MJ and the Serbian part of this GBD contribution was co-funded through grant OI175014 of the Ministry of Education Science and Technological Development of the Republic of Serbia. JK is a recipient of the 2020 Benjamin V Cohen Peace Fellowship from Ball State University Center for Peace and Conflict Studies. YJK’s work was supported by the Research Management Centre, Xiamen University Malaysia, grants number XMUMRF/2018-C2/ ITCM/0001. KKr is supported by a DST PURSE grant and UGC Center of Advanced Study awarded to the Department of Anthropology, Panjab University, Chandigarh, India. BL acknowledges support from the NIHR Oxford Biomedical Research Centre and the British Heart Foundation Centre of Research Excellence, Oxford. PTNM acknowledges the Council for the Development of Social Science Research in Africa. ANA acknowledges Debre Markos University for its support in-terms of office and internet access while reviewing this paper. AMSam received a fellowship from the Egyptian Fulbright Mission programme. MMS-M acknowledges the support of the Ministry of Education, Science and Technological Development of the Republic of Serbia (contract number 175087). AShi acknowledges the support of Health Data Research UK. MRS acknowledges the Clinical Research Development Center of Imam Reza Hospital, Kermanshah university of Medical sciences for their wise advice. JBS is part of Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. RT-S was supported in part by grant PI17/00719 from Instituto de Salud Carlos III–FEDER. BU acknowledges Manipal Academy of Higher Education, Manipal. TWij acknowledges the Migraine Foundation Australia and the Department of Medicine, Faculty of Medicine, University of Rajarata, Saliyapura, Anuradhapuraya, Sri Lanka. CSW was supported by the South African Medical Research Council. SBZ received a scholarship from the Australian Government research training program in support of his academic career.
Published: 2020

22. Author correction: Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

Author: SAVITA LASRADO, Fakher Rahim, Saeid Safari, Hassan Magdy Abd El Razek, Baye Dagnew, Farshad Pourmalek, Ali Rostami, Daniel Ketema, Aletta Schutte, Nasir Salam, Nicole Davis Weaver, Agus Sudaryanto, Martin Ayanore, Nataliya Foigt, Masoud Moradi, Susanna Dunachie, Ziad El-Khatib, Zahra Kamiab, Ashish Badiye, Vijay Kumar Chattu, Maryam Khazaee-Pool, Dabere Nigatu, Jalal Arabloo, Garumma Feyissa, Khalil Eskandari, Kewal Krishan, Bolajoko Olusanya, Gebremicheal Gebreslassie Kasahun, Takahiro Tabuchi, Gebrekiros Meles, Babak Moazen, Jaifred Christian Lopez, Ivy Shiue, Keyvan Pakshir, Tomasz Miazgowski, Surendra Karki, Shivakumar KM, Yasir Waheed, Hamideh Salimzadeh, Ali Akbar Fazaeli, Akram Pourshams, Manoochehr Karami, Yasser El-Sherbiny, Tinuke Olagunju, Vafa Rahimi-Movaghar, Ali Yadollahpour, Assefa Desalew, Ali Shalash, Preeti Dhillon, Ali Asadi-Pooya, Venkatesh Maled, Mihajlo Jakovljevic, John Ji, RAJESH SAGAR, GK Mini, Sebastian Vollmer, Ayman Grada, Boris Bikbov, Neda Izadi, Muhammad Aziz Rahman, Victor Adekanmbi, Reza Mohammadpourhodki, Rahman Shiri, Turki Alanzi, Afsaneh Arzani, Om Prakash Kurmi, Rajat Das Gupta, Masoumeh Sadeghi, Irfan Ullah, Phetole Mahasha, Neeti Kapoor, Hamed Zandian, Bruno Sunguya, Khalid Altirkawi, João Fernandes, Simon Hay, Ana Isabel Ribeiro, Krittika Bhattacharyya, Parastoo Ansari, Gebre Teklemariam Demoz, Hossein Samadi Kafil, Sojib Bin Zaman, Joan B Soriano, Sandra B Munro, Josip Car, Collins Chansa, Navid Rabiee, Sharath Burugina Nagaraja, Palash Banik, Maha El Tantawi, Muawiyyah Babale Sufiyan, Rupak Desai, Davide Rasella, Nicola Bragazzi, Borhan Mansouri, Keivan Ahmadi, Yogesh Sabde, Sergio Ivan Prada Rios, Amir Hasanzadeh, Chinwe Juliana Iwu-Jaja, Syed Amir Gilani, Seyed Sina Naghibi Irvani, Lucero Cahuana-Hurtado, Arya Haj-mirzaian, Reza Heidari-Soureshjani, Rajaa Al-Raddadi, Hagazi Gebre Meles, Muhammad Shahdaat Bin Sayeed, Peng Jia, Mostafa Dianatinasab, Ireneous Soyiri, Jennifer Ross, Erkin Mirrakhimov, Ali Koolivand, Diego Augusto Santos Silva, Olufemi Ajumobi, Muhammad Usman, Hesham Al-Mekhlafi, Enayatollah Homaie Rad, Farhad Moradpour, Fatemeh Rajati, Norberto Perico, Francis Zotor, Omid Shafaat, Joel Francis, Muktar Omer, Hedayat Abbastabar, Mohammad Aghaali, Mulat Tirfie Bayih, Sorin Hostiuc, Era Upadhyay, Daniel Diaz, Mustafa Younis, Ambrish Singh, Mohammad Zamani, Mehran Asadi-Aliabadi, Andre Pascal Kengne, Mohammad Sadegh Rezai, Bruce Duncan, Javad Nazari, Vahid Yazdi-Feyzabadi, Anemaw Asrat, Biagio Simonetti, Neda Milevska Kostova, Mariya Titova, Mohammad Rabiee, Hassan Abolhassani, Morteza Shamsizadeh, Shyam Sundar Budhathoki, Zelalem Nigussie Azene, Pallab Kumar Maulik, Rafael Tabares-Seisdedos, Maha Atout, ANDRE RENZAHO, Fatemeh Amiri, Nelsensius Klau Fauk, Yousef Khader, Mohammad Saud Khan, Davood Anvari, Shymaa Enany, Ahad Bakhtiari, Farnam Mohebi, Yuan-Pang Wang, Naser Kamyari, Tewodros Wonde, Dadi Marami, Arash Ziapour, Azmeraw T. Amare, Nima Rezaei, S.mohammad Sajadi, Vahid Rashedi, Ayesha Humayun, Jacob Olusanya, Yousef Moradi, Reta Tsegaye, Dr. Dereje Bayissa Demissie, Vivekanand Jha, Behnam Nabavizadeh, Vivek Kumar, Andrew Olagunju, Mehran Shams-beyranvand, Farshad Farzadfar, Hagos Tasew, Ninuk Hariyani, Nelson Alvis-Guzmán, Girmay Teklay, Jan-Walter De Neve, Bereket Duko Adema, Jagadish Rao Padubidri, Md Nuruzzaman Khan, Abbas Yadegar, Anurag Agrawal, Vera Marisa Costa, Francisco Rogerlândio Martins-Melo, ORISH EBERE ORISAKWE, Khem Pokhrel, Amir Kasaeian, Artem Fomenkov, Birkneh Tilahun Tadesse, Georgy Lebedev, Razique Anwer, Dimas Ria Angga Pribadi, Alex Yeshaneh, Nuno Taveira, Deepesh Lad, Claudiu Herteliu, Ali Bijani, Zahiruddin Quazi Syed, Elena Varavikova, Antonio Maria Borzì, Phuc Huyen Do, Demelash Elemineh, Abel Fekadu Dadi, Taweewat Wiangkham, Ted Miller, Zubair Kabir, Duduzile Ndwandwe, Habtamu Kasaye, Mario Herrero, Nauman Khalid, Adnan Kisa, Sergey Soshnikov, Alberto Ortiz Arduan, Paul Doku, Saravanan Muthupandian, Bing-Fang Hwang, Meghnath Dhimal, Hamidreza Komaki, Ritesh Menezes, Kedir Abegaz, Claudio Davila, Dinesh Bhandari, Mohamad-Hani Temsah, André Faro, Navid Manafi, Hamidreza Haririan, Nazli Khatib, Wahengbam Bigyananda Meitei, RAVI PRAKASH JHA, Mahdi Mirzaei, Abdallah Samy, Priya Rathi, Alireza Esteghamati, Hailay Gesesew, Eduarda Fernandes, Ghasem Azarian, Shafiu Mohammed, Tauseef Ahmad, Derrick Bennett, Stefan Lorkowski, Yunquan Zhang, Karzan Mohammad, Carlos Castañeda-Orjuela, Mohd Anisul Karim, Tissa Wijeratne, Ahmed I. Hasaballah, Somayeh Bohlouli, Mohammed Madadin, and Mohd Shannawaz
Subjects: Immunology, General Medicine, Medical and Health Sciences, General Biochemistry, Genetics and Molecular Biology, Geography, Childhood Overweight, Low and middle income countries, Environmental health, medicine, medicine.symptom, Wasting, LBD Double Burden of Malnutrition Collaborators, 11 Medical and Health Sciences
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Published: 2020

23. Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000-17: analysis for the Global Burden of Disease Study 2017

Author: Manisha Dubey, Fatemeh Rajati, Mehran Shams-Beyranvand, Amir Khater, Reza Shirkoohi, Segun Emmanuel Ibitoye, David C. Schwebel, Milena Ilic, Kebede Embaye Gezae, Ali Akbar Fazaeli, Ronny Westerman, Taye Abuhay Zewale, Ravi Mehrotra, Sezer Kisa, Junaid Khan, Jost B. Jonas, Dian Kusuma, Marcel Ausloos, Getnet Gedefaw, Hamed Zandian, Edward J Mills, Aparna Lal, Atalay Goshu Muluneh, Leeberk Raja Inbaraj, Edgar Denova-Gutiérrez, Jacqueline Elizabeth Alcalde Rabanal, Yousef Veisani, Sharath Burugina Nagaraja, Christopher Troeger, Ismael R. Campos-Nonato, Kidane Tadesse Gebremariam, Maysaa El Sayed Zaki, Oliver J. Brady, David Laith Rawaf, Tamer H. Farag, Simin Mouodi, Hafiz Ansar Rasul Suleria, Saleh Salehi Zahabi, Soumyadeep Bhaumik, Samad Azari, Getinet Ayano, Faris Lami, Raaj Kishore Biswas, Maryam Adabi, Alaa Badawi, Saravanan Muthupandian, Amir Hasanzadeh, Martin Amogre Ayanore, Maziar Moradi-Lakeh, Mohamad-Hani Temsah, Kavumpurathu Raman Thankappan, Bineyam Taye, Nader Jafari Balalami, Hamid Yimam Hassen, Karzan Abdulmuhsin Mohammad, Paul H. Lee, Emerito Jose A. Faraon, Kewal Krishan, Muhammad Ali, Ehsan Sadeghi, Richard C. Franklin, Dara K. Mohammad, Naznin Hossain, Lal B. Rawal, Alyssa N. Sbarra, Behnam Heidari, Dietrich Rothenbacher, Hagos Tasew Atalay, Eric L. Ding, Noushin Mohammadifard, Nihal Thomas, Man Mohan Mehndiratta, Sanghamitra Pati, Addisu Melese, Niranjan Kissoon, Farzad Manafi, Carl Abelardo T. Antonio, Morteza Abdullatif Khafaie, Meysam Behzadifar, Mohammad Reza Sobhiyeh, Frank B. Osei, Koku Sisay Tamirat, Yahya Salimi, Pranab Chatterjee, Gebreamlak Gebremedhn Gebremeskel, Olatunji O. Adetokunboh, Benjamin K. Mayala, Bhaskaran Unnikrishnan, Zahid A Butt, Olufemi Ajumobi, Fiseha Wadilo Wada, Shafiu Mohammed, Charles Shey Shey Wiysonge, Félix Carvalho, Masresha Tessema Anegago, Yun Jin Kim, Ai-Min Wu, Ketema Bizuwork Gebremedhin, Paulina A. Lindstedt, Ana-Laura Manda, Aziz Eftekhari, Rakhi Dandona, Mehdi Fazlzadeh, Nicole Davis Weaver, Muluken Bekele Sorrie, Marwa Rashad Salem, Kassawmar Angaw Bogale, Dongyu Zhang, Saeed Safari, Vivekanand Jha, Keivan Ahmadi, Turki Alanzi, Amir Jalali, Hamidreza Haririan, Chukwudi A Nnaji, Kebadnew Mulatu Mihretie, Lucas Guimarães Abreu, Gessessew Bugssa Hailu, Surendra Karki, Kirsten E. Wiens, Boikhutso Tlou, Soraya Siabani, Muluken Azage Yenesew, Asnakew Achaw Ayele, Ayalew Jejaw Zeleke, Osayomwanbo Osarenotor, Susanna Dunachie, Marcos Roberto Tovani-Palone, Daniel Bekele Ketema, Tissa Wijeratne, Dessalegn Ajema Berbada, André Karch, Ebrahim Babaee, Akram Pourshams, Seyyed Meysam Mousavi, Bal Govind Chauhan, Giuseppe Remuzzi, Vera Marisa Costa, Mehdi Yaseri, Tahereh Pashaei, Benn Sartorius, Helen Derara Diro, Anelisa Jaca, Mostafa Hosseini, Nikolay Ivanovich Briko, Franz Castro, Cuong Tat Nguyen, Chalachew Genet Akal, Natalie Maria Cormier, Ghulam Mustafa, Sonia Lewycka, Achala Upendra Jayatilleke, David L. Smith, Ibrahim A Khalil, Genet Melak Alamene, George C Patton, Andem Effiong, Gebrekiros Gebremichael Meles, Collins Chansa, Tsegaye Lolaso Lenjebo, Van C. Lansingh, Chabila C Mapoma, Olayinka Stephen Ilesanmi, Aso Mohammad Darwesh, Aubrey J. Levine, Miliva Mozaffor, Till Bärnighausen, Ali Rostami, André Faro, Rushdia Ahmed, Colm McAlinden, Duduzile Ndwandwe, Neeraj Bedi, Irfan Ullah, Winfried März, Rajeev Gupta, Masood Ali Shaikh, Catalina Liliana Andrei, Ali Kazemi Karyani, Shaimaa I. El-Jaafary, Abbas Mosapour, Javad Nazari, Obinna Onwujekwe, Narinder Pal Singh, Dabere Nigatu, Tanuj Kanchan, Jagdish Khubchandani, Aklilu Endalamfaw, Hajer Elkout, Michelle L. Bell, Beyene Meressa Adhena, Evanson Z. Sambala, Nelson Alvis-Guzman, Nefsu Awoke, Mohammad Ali Sahraian, Muki Shey, Christiane Dolecek, Kedir Hussein Abegaz, Syed Ather Hussain, Birhan Tamene Alemnew, Arash Etemadi, Anwar E. Ahmed, Vinay Nangia, Sachin R Atre, Roghiyeh Faridnia, Robert C. Reiner, Rajat Das Gupta, Aniruddha Deshpande, Sanjay Zodpey, Birhanu Geta, Amaha Kahsay, Muktar Beshir Ahmed, Kiana Ramezanzadeh, Jacek Jerzy Jozwiak, Chi Linh Hoang, Bahram Armoon, Manfred Accrombessi, Christopher J L Murray, Ebrahim M Yimer, Rashmi Gupta, Ahmed Omar Bali, Dadi Marami, Arash Tehrani-Banihashemi, Getnet Mengistu, Govinda Prasad Dhungana, Fereshteh Ansari, Dina Nur Anggraini Ningrum, Mu'awiyyah Babale Sufiyan, Harish Chander Gugnani, Ali S. Akanda, Satar Rezaei, Wondimeneh Shibabaw Shiferaw, Irina Filip, Mohammad Fareed, Hagos Degefa Hidru, Morteza Shamsizadeh, Mojtaba Hoseini-Ghahfarokhi, Yared A Asmare Aynalem, Gelin Xu, Zubair Kabir, Khalid A Altirkawi, Beatriz Paulina Ayala Quintanilla, Kenean Getaneh Tlaye, Devasahayam J. Christopher, Malede Mequanent Sisay, Yibeltal Alemu Bekele, Mika Shigematsu, Bryan L. Sykes, Quique Bassat, Jemal Abdu Mohammed, Seyed Mostafa Mir, Moslem Soofi, Nuruzzaman Khan, Ensiyeh Jenabi, Seyed-Mohammad Fereshtehnejad, Alireza Esteghamati, Paramjit Gill, Nathaniel J Henry, Meghnath Dhimal, Hosein Shabaninejad, Trang Huyen Nguyen, Amjad Mohamadi-Bolbanabad, Eugenio Traini, Mohammad Zamani, Arianna Maever L. Amit, Mehran Alijanzadeh, Florian Fischer, Rafael Moreira Claro, Pushpendra Kumar, Shai Linn, Lucas Earl, Haileab Fekadu Wolde, Getenet Dessie, Doris D. V. Ortega-Altamirano, John S. Ji, Moritz U. G. Kraemer, Saeed Amini, Ziad A. Memish, Aisha Elsharkawy, Ken Lee Chin, Mustafa Z. Younis, Daniel Diaz, Hebat Allah Salah A. Yousof, Seifadin Ahmed Shallo, Tomohide Yamada, Adrian Pana, Salman Rawaf, Amir Almasi-Hashiani, Platon D. Lopukhov, Alireza Rafiei, Dragos Virgil Davitoiu, Hossein Poustchi, Ayele Geleto Bali, Francesco Saverio Violante, Leonardo Roever, Giovanni Damiani, Maha El Tantawi, Nuworza Kugbey, Hadi Pourjafar, Michael R.M. Abrigo, Dinh-Toi Chu, Farkhonde Salehi, Phetole Walter Mahasha, Farnam Mohebi, Sathish Thirunavukkarasu, Dharmesh Kumar Lal, Senbagam Duraisamy, Demelash Woldeyohannes Handiso, Eleonora Dubljanin, Takeshi Fukumoto, Biruck Desalegn Yirsaw, Fakher Rahim, Jasvinder A. Singh, Jai K Das, Savita Lasrado, Ana Isabel Ribeiro, Santosh Varughese, Adnan Kisa, Laurie B. Marczak, Amira Shaheen, Peter Njenga Keiyoro, Nader Jahanmehr, Yuming Guo, Arash Ziapour, Alex Yeshaneh, Ninuk Hariyani, Seyed Sina Naghibi Irvani, Sameer Vali Gopalani, Joel M. Francis, Asmamaw Demis, Ahamarshan Jayaraman Nagarajan, Praveen Hoogar, Nicola Luigi Bragazzi, Yunquan Zhang, Yousef Mohammad, Iman El Sayed, Vafa Rahimi-Movaghar, Anbissa Muleta Senbeta, Subramanian Senthilkumaran, Marzieh Nojomi, Tewodros Eshete Wonde, Sameh Magdeldin, Anton Sokhan, Nauman Khalid, Nima Hafezi-Nejad, Ben Lacey, Luca Ronfani, James Albright, Senthilkumar Balakrishnan, Ejaz Ahmad Khan, Khanh Bao Tran, Guoqing Hu, Yousef Khader, Parvaneh Mirabi, Boris Bikbov, Feleke Mekonnen Demeke, Assefa Desalew, Yasir Waheed, Berhe Etsay Tesfay, Julio Cesar Campuzano Rincon, Ernoiz Antriyandarti, Brian J. Hall, James A Platts-Mills, Gbenga A. Kayode, Jan-Walter De Neve, Maria Jesus Rios-Blancas, Navid Manafi, Ravi Prakash Jha, Yilma Chisha Dea Geramo, Hamideh Salimzadeh, Fisaha Haile Tesfay, Abdullah Al Mamun, Ali Bijani, Hedley Quintana, Shanshan Li, Kebreab Paulos, Joan B. Soriano, Victor Adekanmbi, Oladimeji Adebayo, David Teye Doku, Brijesh Sathian, Bakhtiar Piroozi, MohammadBagher Shamsi, Netsanet Fentahun, Shymaa Enany, Ayman Grada, Salvatore Rubino, Kenji Shibuya, Norberto Perico, Sergio I. Prada, Andrea Farioli, Gebremicheal Gebreslassie Kasahun, Mohsen Afarideh, Maciej Banach, Andrey Nikolaevich Briko, Mohsen Asadi-Lari, Rakesh Lodha, David M. Pigott, Bárbara Niegia Garcia de Goulart, Hadi Hassankhani, Daniel Adane Endalew, Siamak Sabour, Yoshan Moodley, Preeti Dhillon, Dilaram Acharya, Anas M. Saad, Ibrahim Abdelmageed Ginawi, Theo Vos, Tuomo J. Meretoja, Ireneous N. Soyiri, Hasan Yusefzadeh, Mohammad Rabiee, Ajay Patle, Rahman Shiri, Girmay Teklay Weldesamuel, Sivan Yegnanarayana Iyer Saraswathy, Mekdes Tigistu Yilma, Davide Guido, Chuanhua Yu, Abdallah M. Samy, Ali Talha Khalil, Ashish Awasthi, Pascual R. Valdez, Nelson G.M. Gomes, Nejimu Biza Zepro, Taweewat Wiangkham, Anthony Masaka, Afsaneh Arzani, Ayesha Humayun, Michael Tamene Haile, Huyen Phuc Do, Krittika Bhattacharyya, Maryam Khayamzadeh, Seth Christopher Yaw Appiah, Mehdi Ahmadi, Farah Daoud, QuynhAnh P Nguyen, Suleman Atique, Sheikh Mohammed Shariful Islam, Indang Trihandini, Mario Poljak, Bartosz Miazgowski, Huda Basaleem, Rafael Alves Guimares, Mina Anjomshoa, Peng Jia, Yafeng Wang, Erkin M. Mirrakhimov, Seyed Hossein Yahyazadeh Jabbari, Itamar S. Santos, Alireza Khatony, Desalegn Tadese Mengistu, Samath D Dharmaratne, S. Mohammad Sajadi, Francisco Rogerlândio Martins-Melo, Shankar M Bakkannavar, Konrad Pesudovs, Tina Beyranvand, Liliana Preotescu, Leticia Avila-Burgos, Enrico Rubagotti, Amira Hamed Darwish, Mahdi Safdarian, Ali Yadollahpour, Vijay Kumar Chattu, Moses K. Muriithi, Azmeraw T. Amare, Si Si, Joshua Longbottom, Somayeh Bohlouli, Khaled Khatab, Masoud Behzadifar, Anusha Ganapati Bhat, G Anil Kumar, Margaret Kosek, Mona M. Khater, Reta Tsegaye Gayesa, Ghobad Moradi, Srinivas Goli, Ruth W Kimokoti, Jalal Arabloo, Kimberly B. Johnson, Andrew T Olagunju, Mowafa Househ, In-Hwan Oh, Arya Haj-Mirzaian, Desta Haftu Hayelom, Jae Il Shin, Ahmed Abdelalim, Catherine A. Welgan, Veincent Christian Filipino Pepito, Andre Rodrigues Duraes, Yuan-Pang Wang, Rosario Cárdenas, Mohammad Khazaei, Sebastian Vollmer, Xiu-Ju Zhao, Mihajlo Jakovljevic, Degu Abate, Ali S. Shalash, Davide Rasella, Melese Abate Reta, Hedayat Abbastabar, Manu Raj Mathur, Aliasghar Ahmad Kiadaliri, Ritesh G. Menezes, Molly K. Miller-Petrie, Beriwan Abdulqadir Ali, Ahmed I. Hasaballah, Joseph Frostad, Eirini Skiadaresi, Aleksandra Barac, Simon I. Hay, Deborah Carvalho Malta, Brigette F. Blacker, Carlo La Vecchia, Eduarda Fernandes, Chandrashekhar T Sreeramareddy, Zewdie Aderaw Alemu, Foad Abd-Allah, Elias Merdassa Roro, Agus Sudaryanto, Fariba Ghassemi, Behzad Karami Matin, Mohsen Naghavi, Maarten J. Postma, Chhabi Lal Ranabhat, Maheswar Satpathy, Mahesh P A, Carlos Miguel Rios González, Pallab K. Maulik, Amir Kasaeian, Ali H. Mokdad, Alemayehu Toma Mena, Tamirat Tesfaye Dasa, Abdur Razzaque Sarker, Andre M. N. Renzaho, Muhammad Aziz Rahman, Ali Kabir, Josephine W. Ngunjiri, Aberash Abay Tassew, Kala M. Mehta, Ionut Negoi, Hosni Salem, Hesham M. Al-Mekhlafi, Sharareh Eskandarieh, Rufus A. Adedoyin, Saleem M Rana, Engida Yisma, Sahel Valadan Tahbaz, Hossein Farzam, Krishna K. Aryal, Lalit Dandona, Masoud Moradi, Juan Sanabria, Gebre Teklemariam Demoz, Naser Mohammad Gholi Mezerji, Shirin Djalalinia, Suraj Bhattarai, Ammas Siraj Mohammed, Claudiu Herteliu, Dawit Zewdu Wondafrash, Mohsen Bayati, Arvin Haj-Mirzaian, Gulfaraz Khan, Mostafa Leili, Nasir Salam, Ehsan Khodamoradi, Jean Jacques Noubiap, Vahid Alipour, Mohammad Ali Mansournia, Rajesh Sagar, Jagadish Rao Padubidri, Manasi Kumar, Mehdi Sharif, Fatemeh Heydarpour, Navid Rabiee, Gvs Murthy, Hamed Kalani, Mayowa O. Owolabi, Claudio Alberto Davila, Oluchi Okpala, Shivakumar K.M. Kondlahalli, Mathew M. Baumann, Bereket Duko Adema, Lorenzo Monasta, Paul S. F. Yip, Mohammad Hossein Khosravi, Rizwan Suliankatchi Abdulkader, Ibrahim Abdollahpour, Dhirendra N Sinha, Farid Najafi, Kebede Deribe, Paula Moraga, Mehedi Hasan, Mohammad Moradi-Joo, Melkamu Merid Mengesha, Temesgen Yihunie Akalu, Vishnu Renjith, Syed Mohamed Aljunid, Zemenu Tadesse Tessema, Amir Radfar, Nuno Taveira, Masoud Foroutan, Demelash Abewa Elemineh, Chinwe Juliana Iwu, Kamarul Imran Musa, Getaneh Alemu Abebe, Farshad Pourmalek, Olatunde Aremu, Mohammad Reza Salahshoor, Derrick A Bennett, Ahmad Daryani, Alebachew Fasil Ashagre, Apurba Shil, Narayan Bahadur Mahotra, Nelson J. Alvis-Zakzuk, Lauren E. Schaeffer, Alexandre C. Pereira, Mehdi Naderi, Mehdi Hosseinzadeh, Rovshan Khalilov, Ai Koyanagi, Salman Khazaei, Jennifer Rickard, Ali Almasi, Sandra B. Munro, Carlos Zambrana-Torrelio, Naohiro Yonemoto, Ahmad Ghashghaee, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Value, Affordability and Sustainability (VALUE), Microbes in Health and Disease (MHD), Instituto de Saúde Pública da Universidade do Porto, Local Burden Dis Diarrhoea, Department of Earth Observation Science, UT-I-ITC-ACQUAL, Faculty of Geo-Information Science and Earth Observation, GeoHealth, Reiner, Robert C, Wiens, Kirsten E, Deshpande, Aniruddha, Baumann, Mathew M, Adema, Bereket Duko, Yirsaw, Biruck Desalegn, Yisma, Engida, Hay, Simon I, Local Burden of Disease Diarrhoea Collaborators, Tampere University, Health Sciences, University of Helsinki, Institute for Molecular Medicine Finland, Clinicum, HUS Comprehensive Cancer Center, Local Burden of Disease Diarrhoea Collaborator, and Violante FS
Subjects: Low income countries, medicine.medical_treatment, 030204 cardiovascular system & hematology, Global Health, THERAPY, Global Burden of Disease, 0302 clinical medicine, Prevalence, Global health, Medicine, WATER, 030212 general & internal medicine, Children, 11 Medical and Health Sciences, Incidence, Mortality rate, Incidence (epidemiology), 1. No poverty, General Medicine, 3142 Public health care science, environmental and occupational health, Diarrhoea, 3. Good health, Child, Preschool, Middle income countries, A990 Medicine and Dentistry not elsewhere classified, TERRITORIES, Life Sciences & Biomedicine, Infants, Diarrhea, AFRICA, medicine.medical_specialty, Childhood deaths, RJ, sanitation, Developing country, Childhood diarrhoeal morbidity, ITC-HYBRID, 03 medical and health sciences, Medicine, General & Internal, General & Internal Medicine, Environmental health, SYSTEMATIC ANALYSIS, Life Science, Humans, Healthcare Disparities, Oral rehydration therapy, Risk factor, hand washing, Developing Countries, Disease burden, Global Nutrition, Wereldvoeding, Science & Technology, SEX-SPECIFIC MORTALITY, business.industry, CHOLERA, Public health, Bayes Theorem, diarrheal disease, Local Burden of Disease Diarrhoea Collaborators, ITC-ISI-JOURNAL-ARTICLE, NA, Human medicine, Diarrea, business
Abstract: Background: Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea. Methods: We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor estimates. Findings: The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1-65·8), 17·4% (7·7-28·4), and 59·5% (34·2-86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy coverage. Interpretation: By co-analysing geospatial trends in diarrhoeal burden and its key risk factors, we could assess candidate drivers of subnational death reduction. Further, by doing a counterfactual analysis of the remaining disease burden using key risk factors, we identified potential intervention strategies for vulnerable populations. In view of the demands for limited resources in LMICs, accurately quantifying the burden of diarrhoea and its drivers is important for precision public health. This work was primarily supported by a grant from the Bill & Melinda Gates Foundation (OPP1132415). S Aljunid reports additional funding from the International Centre for Casemix and Clinical Coding, Faculty of Medicine, National University of Malaysia and Department of Health Policy and Management, Faculty of Public Health, Kuwait University for the approval and support to participate in this research project outside of the study. A Awasthi is supported by the Department of Science and Technology, Government of India, New Delhi, through the INSPIRE Faculty Program outside of the study. A Badawi reports additional funding from the Public Health Agency of Canada outside of the study. A Barac reports additional funding from the Project of Ministry of Education, Science and Technology of the Republic of Serbia (no III45005) outside of the study. T Bärnighausen reports additional funding by the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research outside of the study. F Carvalho and E Fernandez report additional funding from the Portuguese national funds (UID/MULTI/04378/2019 and UID/QUI/50006/2019) outside of the study. V M Costa reports additional funding from Fundação da Ciência e Tecnologia (FCT) for her grant (SFRH/BPD/110001/2015), which was funded by national funds through FCT – Fundação para a Ciência e a Tecnologia, IP, under the Norma Transitória – DL57/2016/CP1334/CT0006 outside of the study. J De Neve reports additional funding from the Alexander von Humboldt Foundation outside of the study. K Deribe reports additional funding from the Wellcome Trust (grant number 201900) as part of his International Intermediate Fellowship outside of the study. D Endalew and M Moradi report additional funding from Wolkite University. M Ausloos, C Herteliu, and A Pana report additional funding from the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI (project number PN-III-P4-ID-PCCF-2016-0084) outside of the study. C Herteliu reports additional funding from the European Fund for Regional Development through Operational Program for Competitiveness (Project ID P_40_382) and the European Fund for Regional Development, through InterReg Romania-Hungary (project code EMS ROHU 217) outside of the study. P Hoogar reports additional funding from the Centre for Holistic Development and Research (CHDR), Kalaghatagi and The Department of Studies in Anthropology, Karnatak University, D S Islam reports additional funding from the National Heart Foundation of Australia and the Institute for Physical Activity and Nutrition, Deakin University outside of the study. A Khatony reports additional funding from the Clinical Research Development Center of Imam Reza Hospital in Kermanshah outside of the study. J Khubchandani reports additional funding from Merck Research Laboratories outside of the study. K Krishan reports additional funding from the UGC Center of Advanced Study (CAS II) awarded to the Department of Anthropology, Panjab University, Chandigarh, India outside of the study. M Kumar reports additional funding from the Fogarty Foundation/NIH through a K43 award (TW010716-01A1) outside of the study. B Lacey reports additional funding from the National Institute for Health Research Oxford Biomedical Research Centre and the British Heart Foundation Centre of Research Excellence (Oxford, UK) outside of the study. A M Samy reports additional funding from the Egyptian Fulbright Mission Program (EFMP) outside of the study. S Seyedmousavi reports additional funding from the Intramural Program of National Institute of Health Clinical Center, Bethesda, MD, USA outside of the study. M Shey reports additional funding from the Wellcome Trust Kenji Shibuya reports additional funding from Japan's Ministry of Health, Labour and Welfare and Japan's Ministry of Education, Culture, Sport, Science and Technology outside of the study. M Sobhiyeh reports additional funding from the Clinical Research Development Center of Imam Reza Hospital, Kermanshah University of Medical Sciences outside of the study. J Soriano reports additional funding from Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain outside of the study. N Taveira reports additional funding from the LIFE study (RIA2016MC-1615) of the European and Developing Countries Clinical Trials Partnership (EDCTP) program supported by the European Union outside of the study. B Unnikrishnan reports additional funding from the Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, India outside of the study. T Wijeratne reports additional funding from the Department of Medicine, Faculty of Medicine, University of Rajarata, Saliyapura, Sri Lanka outside of the study. C S Wiysonge reports additional funding from the South African Medical Research Council and the National Research Foundation of South Africa outside of the study.
Published: 2020

24. Mapping geographical inequalities in oral rehydration therapy coverage in low-income and middle-income countries, 2000-17

Author: Ninuk Hariyani, Benjamin Uzochukwu, Anas M. Saad, Sivan Yegnanarayana Iyer Saraswathy, Amirhossein Sahebkar, Behzad Karami Matin, Abdallah M. Samy, Roman Topor-Madry, Nelson G.M. Gomes, Afsaneh Arzani, Simin Liu, Maryam Khayamzadeh, Ejaz Ahmad Khan, Asmamaw Bizuneh Demis, Anelisa Jaca, Amir Kasaeian, Fereshteh Ansari, Abdur Razzaque Sarker, Ali Kabir, Jorge Cano, Marcos Roberto Tovani-Palone, Tufa Kolola, Josephine W. Ngunjiri, Roghiyeh Faridnia, Kedir Hussein Abegaz, Hosni Salem, Sharareh Eskandarieh, Norberto Perico, Sergio I. Prada, Fisaha Haile Tesfay, Jai K Das, Ana Isabel Ribeiro, Sameer Vali Gopalani, Dessalegn Haile, Shivakumar Km Marulasiddaiah M. KMShivakumar, Narayan Prasad, Pranab Chatterjee, Shafiu Mohammed, Ravi Prakash Jha, Xiu Ju George Zhao, Farshad Farzadfar, Ahmad Daryani, Pramesh Raj Ghimire, Abbas Mosapour, Ebrahim Babaee, Rajat Das Gupta, Jean Jacques Noubiap, Daniel Bekele Ketema, Teshome Bekele Elema I, Erkin M. Mirrakhimov, Seyed Hossein Yahyazadeh Jabbari, Muktar Beshir Ahmed, Wondimeneh Shibabaw Shiferaw, Mehran Asadi-Aliabadi, Mohamed M. Gad, Eugenio Traini, Milena Santric-Milicevic, Bakhtiar Piroozi, Mohsen Afarideh, Duduzile Ndwandwe, Ibrahim Abdollahpour, Aisha Elsharkawy, Bárbara Niegia Garcia de Goulart, Soufiane Boufous, Obinna Onwujekwe, Seyyed Meysam Mousavi, Azeem Majeed, Meghnath Dhimal, Bruno F. Sunguya, Daniel Adane Endalew, Hosein Shabaninejad, Siddhesh Zadey, Takahiro Tabuchi, Gebrekiros Gebremichael Meles, Davide Guido, Trang Huyen Nguyen, Yonatal Mesfin Tefera, Hala Elhabashy, Devasahayam J. Christopher, Malede Mequanent Sisay, Davide Rasella, Hedayat Abbastabar, Maziar Moradi-Lakeh, Anthony Masaka, Wagaye Fentahun Chanie, B. Suresh Kumar Shetty, Matiwos Soboka Daba, Tesfaye Yitna Yitna Chichiabellu, Arianna Maever L. Amit, Tomohide Yamada, Alireza Rafiei, Reinhard Busse, Abdullah Al Mamun, Genet Melak Alamene, George C Patton, Andem Effiong, Rushdia Ahmed, Jagadish Rao Padubidri, Mohamad-Hani Temsah, Nizal Sarrafzadegan I, Francesco Saverio Violante, Monika Sawhney, Eyal Oren, Kimberly B. Johnson, Benn Sartorius, Shirin Djalalinia, Mohsen Bayati, Merhawi Gebremedhin Tekle, Navid Rabiee, Javad Nazari, Krishna K. Aryal, Kavumpurathu Raman Thankappan, Yoshan Moodley, Anh Kim Dang, Mohammad Khazaei, Parvaiz A Koul, Edson Serván-Mori, Foad Abd-Allah, Seyed Mohammad Riahi, Nader Jahanmehr, Yuming Guo, Sonia Saxena, Bayu Begashaw Bekele, Hagos Degefa de Hidru I, Enayatollah Homaie Rad, Richard C. Franklin, Dara K. Mohammad, Naznin Hossain, Oliver J. Brady, Natalie Maria Cormier, Ghulam Mustafa, Samiah Alam, Guoqing Hu, Yousef Khader, Mohsen Mazidi, Hamed Kalani, Hamideh Salimzadeh, Mayowa O. 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Hasaballah, Virendra Singh, Arash Ziapour, Zahid A Butt, Hebat Allah Salah A. Yousof, Tewodros Eshete Wonde, Sanjay Zodpey, Amaha Kahsay, Achala Upendra Jayatilleke, Segun Emmanuel Ibitoye, Beriwan Abdulqadir Ali, Simin Mouodi, Salman Rawaf, Iqbal R. F. Elyazar, Ai-Min Wu, Seyed Sina Naghibi Irvani, Yasir Waheed, Delia Hendrie, Hadi Pourjafar, Farnam Mohebi, Naohiro Yonemoto, Ahmad Ghashghaee, Veincent Christian Filipino Pepito, Paulina A. Lindstedt, Nauman Khalid, Sezer Kisa, Chi Linh Hoang, Niranjan Kissoon, Kindie Fentahun Muchie, Valery L. Feigin, Mathew M. Baumann, Alemayehu Toma, Andre Rodrigues Duraes, Benjamin B. Massenburg, Santosh Varughese, Yuan-Pang Wang, Ingan Ukur Tarigan, Ali Kiadaliri, Hamed Zandian, Demelash Woldeyohannes Handiso, Hassan Magdy Abd El Razek, Ketema Bizuwork Gebremedhin, Hafiz Ansar Rasul Suleria, Oluchi Ezekannagha, Getinet Ayano, Bolajoko O. Olusanya, Manu Raj Mathur, Manfred Accrombessi, Christopher J L Murray, Moritz U. G. Kraemer, Saeed Amini, Ziad A. Memish, Yousef Mohammad, Luis Camera, Ernoiz Antriyandarti, Ronny Westerman, Meghdad Pirsaheb, Negar Rezaei, Ted R. Miller, Aziz Eftekhari, Nevine El Nahas, Sebastian Vollmer, Sanjay Basu, Hesham M. Al-Mekhlafi, D. R. Mahadeshwara Prasad, Rufus A. Adedoyin, Miliva Mozaffor I, Mihiretu Kebede, Preeti Dhillon, Dilaram Acharya, Iman El Sayed, Narendar Manohar, Paul S. F. Yip, Ben Lacey, Felix Akpojene Ogbo, Adrian Davis, Dinh-Toi Chu, Ranjani Somayaji, Raaj Kishore Biswas, Taddese Alemu Zerfu, Claudio Alberto Dávila-Cervantes, Sharath Burugina Nagaraja, Getachew Mullu Kassa, Mohan Bairwa, Gurudatta Naik, André Karch, Gudlavalleti V S Murthy, Avula Laxmaiah, Farid Najafi, Birhanu Geta Meharie, Lorenzo Monasta, Amit Arora, Christopher S Yilgwan, Samer Hamidi, Keivan Ahmadi, Kebede Deribe, Ehimario U. Igumbor, Engida Yisma, Henok Biresaw Netsere, Mihajlo Jakovljevic, Ali S. Shalash, Thirunavukkarasu Sathish, Sachin R Atre, Mohamed I Hegazy, Mehedi Hasan, Hamidreza Haririan, Lucas Guimarães Abreu, Nejimu Biza Zepro, Surendra Karki, Krittika Bhattacharyya, Hiroshi Yatsuya, Gbenga A. Kayode, Osayomwanbo Osarenotor, Paul H. Lee, Deepak Paudel, Hagos Tasew Atalay, Hatem S Shehata, Mohammad Fareed, Adnan Kisa, Hisham Atan Edinur, Mehran Alijanzadeh, Shafiur Rahman, Mohammad Hossein Khosravi, Anusha Ganapati Bhat, Bahram Mohajer, Narinder Pal Singh, Shai Linn, Savita Lasrado, Joseph Adel Mattar Banoub, Amir Almasi-Hashiani, Mohd Anisul Karim, Praveen Hoogar, Kerrie E. Doyle, Bedilu Girma Weji, Juan Sanabria, Olatunji O. Adetokunboh, Mohamed Hsairi, Alireza Esteghamati, Seok Jun Yoon, Paramjit Gill, Dabere Nigatu, Tariq Jamal Siddiqi, Muhammad Usman, Rafael Alves Guimarães, Zemenu Tadesse Tessema, Aziz Sheikh, Florian Fischer, Peter Memiah, Rakesh Lodha, Nihal Thomas, Karzan Abdulmuhsin Mohammad, Mohammad Sadegh Rezai, Tanuj Kanchan, Vinay Nangia, Ashraf Nabhan, Gebre Teklemariam Demoz, Eirini Skiadaresi, Aleksandra Barac, Simon I. Hay, Sadaf G. Sepanlou, Michellr L. Bell, Nicola Luigi Bragazzi, Aklilu Endalamaw, Vishnu Renjith, Chinwe Juliana Iwu, Gabrielle B. Britton, Colm McAlinden, Ayenew Negesse Abejie, Smita Pakhale, Doris V.V. Ortega-Altamirano, Noushin Mohammadifard, Deborah Carvalho Malta, Vo Dinh Bay, Kirsten E. Wiens, Hamidreza Karimi-Sari, Mustafa Z. Younis, Shaimaa I. El-Jaafary, Morenike Oluwatoyin Folayan, Phetole Walter Mahasha, Mu'awiyyah Babale Sufiyan, Harish Chander Gugnani, Mohammad Hifz Ur Rahman, Sheikh Mohammed Shariful Islam, Maarten J. Postma, Usman Iqbal, Abdu A. Adamu, Marwa R.Rashad Salem I, Fares Alahdab, Vafa Rahimi-Movaghar, Zulfiqar A. Bhutta, Masoud Foroutan, Muhammad Shahzeb Khan, In-Hwan Oh, Yahya Salimi, Takeshi Fukumoto, Chhabi Lal Ranabhat, Tiffany K. Gill, Angel Paternina-Caicedo, Walter Mendoza, Sojib Bin Zaman, Olayinka Stephen Ilesanmi, Brigette F. Blacker, Anbissa Muleta Senbeta, Subramanian Senthilkumaran, Ambrish Singh, Mehdi Fazlzadeh, Mahesh P A, Carlo La Vecchia, Alex Yeshaneh, Benjamin K. Mayala, Aniruddha Deshpande, Agus Sudaryanto, Neeraj Bedi, Morteza Shamsizadeh, Jemal Abdu Mohammed, Vahid Alipour, Haileab Fekadu Wolde, Boris Bikbov, Ahmed Abualhasan, Ali H. Mokdad, Eduarda Fernandes, Chandrashekhar T Sreeramareddy, Jacek Jerzy Jozwiak, Alessandra C. Goulart, Mahmoud Yousefifard, Masood Ali Shaikh, Roya Safari-Faramani, MohammadBagher Shamsi, Aso Mohammad Darwesh, Amir Anoushiravani, Kebede Embaye Gezae, Degena Bahrey Tadesse, Paula Moraga, Maha El Tantawi, Rosario Cárdenas, Assefa Desalew, Vivek Kumar, Mina Anjomshoa, Junaid Khan, Jagdish Khubchandani, Marcel Ausloos, Soraya Siabani, Anwar E. Ahmed, Mohammed Ibrahim Mohialdeen Gubari, Andre M. N. Renzaho, Vuong Minh Nong, Kaushik Sarkar, Bruno Piassi Sao Jose, Yafeng Wang, Mitchell T. Wallin, Edgar Denova-Gutiérrez, Mohammad Hasan Imani-Nasab, Melese Abate Reta, Kala M. Mehta, Yahya Safari, Marufa Sultana, David C. Schwebel, Roghayeh Mohammadibakhsh, Samath D Dharmaratne, Maysaa El Sayed Zaki, Shiwei Liu, Gail Davey, Milena Ilic, Yunquan Zhang, Bahram Armoon, Seyed-Mohammad Fereshtehnejad, Jost B. Jonas, Dian Kusuma, Yawukal chane Kasahun, Beatriz Paulina Ayala Quintanilla, Mohammad Moradi-Joo, Gebrehiwot G. Kassa, Maria Jesus Rios-Blancas, Serge Resnikoff, Seifadin Ahmed Shallo, Bartosz Miazgowski, Huda Basaleem, Jobert Richie Nansseu, Enrico Rubagotti, Carl Abelardo T. Antonio, Morteza Abdullatif Khafaie, Meysam Behzadifar, Maryam Adabi, Saravanan Muthupandian, Soumyadeep Bhaumik, hawariat, Carlos A Castañeda-Orjuela, Bhaskaran Unnikrishnan, Martin Amogre Ayanore, Dragos Virgil Davitoiu, Hossein Poustchi, Moses K. Muriithi, Dharmesh Kumar Lal, Ayman Grada, Rafael Tabarés-Seisdedos, Seyyed Shamsadin Athari, Ashish Pathak, Salvatore Rubino, Kenji Shibuya, Ana Laura Manda, Muluken Bekele Sorrie, Vivekanand Jha, Habtamu Kebebe Kasaye, Mohammad Hoseini, Sonali Kochhar, Van C. Lansingh, Ali Almasi, Amir Radfar, Till Bärnighausen, Marcia R. Weaver, Mowafa Househ, Arya Haj-Mirzaian, Gebremicheal Gebreslassie Kasahun, Arash Etemadi, Getahun Fentaw Mulaw, Zubair Kabir, Cuong Tat Nguyen, Chabila C Mapoma, Aubrey J. Levine, Solomon Gedlu Nigatu, Aslam Pervaiz, Muhammed Magdy Abd El Razek, Nataliya A. Foigt, Andrey Nikolaevich Briko, Sadaf Esteghamati, Chuanhua Yu, Pascual R. Valdez, Jennifer Rickard, Jennifer M. Ross, Ionut Negoi, Hailay Abrha Gesesew, Kamarul Imran Musa, Farshad Pourmalek, Kiomars Sharafi, Sangram Kishor Patel, Vera Marisa Costa, Mostafa Hosseini, Hajer Elkout, Mika Shigematsu, Bryan L. Sykes, Afarin Rahimi-Movaghar, Nuworza Kugbey, Vijay Kumar Chattu, Payman Salamati, Mona M. Khater, Reta Tsegaye Gayesa, Ehsan Sadeghi, Andrew T Olagunju, Govinda Prasad Dhungana, Dina Nur Anggraini Ningrum, Yaschilal Muche Belayneh, Leonardo Roever, Luca Ronfani, Nathaniel J. Henry, Brijesh Sathian, Hamid Sharifi, Liliana Preotescu, Joshua Longbottom, Somayeh Bohlouli, Huong Lan Thi Nguyen, Khaled Khatab, Ziyad Al-Aly, Ghobad Moradi, Ruth W Kimokoti, Jalal Arabloo, Mariam Molokhia, Maciej Banach, Hasan Yusefzadeh, Rahman Shiri, Girmay Teklay Weldesamuel, Mekdes Tigistu Yilma, Taweewat Wiangkham, Soewarta Kosen, Kovin Naidoo, Fernando de la Hoz, Mohammed Shannawaz, Berhe Etsay Tesfay I, Yogesh Sabde, Syed Mohamed Aljunid, Belay Tessema, Reza Malekzadeh, Tinuke O Olagunju, Olatunde Aremu, Mohammad Reza Salahshoor, Derrick A Bennett, Oladimeji M. Adebayo, Teshome Gebre, Narayan Bahadur Mahotra, Nelson J. Alvis-Zakzuk, Lauren E. Schaeffer, Alexandre C. Pereira, Mehdi Naderi, Mehdi Hosseinzadeh, Mehran Shams-Beyranvand, Ilais Moreno Velásquez, Rovshan Khalilov, Ai Koyanagi, Salman Khazaei, Ismael R. Campos-Nonato, Alaa Badawi, Amir Hasanzadeh, Gebreamlak Gebremedhn Gebremeskel, Gessessew Bugssa Hailu, Dessalegn Ajema Berbada, Kate E. LeGrand, Azadeh Shafieesabet, Nikolay Ivanovich Briko, Robert S. Bernstein, Irfan Ullah, Isaac Oluwafemi Dipeolu, Hadi Hassankhani, Keyghobad Ghadiri, Local Burden of Disease Diarrhoea Collaborator, Violante FS, Wiens, KE, Lindstedt, PA, Blacker, BF, Johnson, KB, Yisma, E, Ahmed, Muktar Beshir, Reiner, Robert C, Duko, Bereket, Local Burden of Disease Diarrhoea Collaborators, Microbes in Health and Disease (MHD), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Value, Affordability and Sustainability (VALUE), Local Burden Dis Diarrhoea, Department of Earth Observation Science, UT-I-ITC-ACQUAL, Faculty of Geo-Information Science and Earth Observation, GeoHealth, HUS Comprehensive Cancer Center, Clinicum, Institute for Molecular Medicine Finland, Department of Oncology, University of Helsinki, and Instituto de Saúde Pública da Universidade do Porto
Subjects: RJ101, medicine.medical_treatment, CHILDREN, ZINC, 0302 clinical medicine, 030212 general & internal medicine, media_common, Geography, lcsh:Public aspects of medicine, 1. No poverty, Low income and middle income countries, General Medicine, 3142 Public health care science, environmental and occupational health, 3. Good health, Child, Preschool, A990 Medicine and Dentistry not elsewhere classified, Geographical inequalities, 0605 Microbiology, Diarrhea, AFRICA, Inequality, DEATHS, media_common.quotation_subject, 030231 tropical medicine, Developing country, Article, RS, 1117 Public Health and Health Services, 03 medical and health sciences, MORBIDITY, Environmental health, DIARRHEAL DISEASE, medicine, Humans, Oral rehydration therapy, Healthcare Disparities, Developing Countries, Models, Statistical, CHOLERA, MORTALITY, Infant, Newborn, Infant, lcsh:RA1-1270, Bayes Theorem, Middle income, GLOBAL BURDEN, Child mortality, 0605 Microbiology, 1117 Public Health and Health Services, Health Care Surveys, ITC-ISI-JOURNAL-ARTICLE, Fluid Therapy, NA, Human medicine, ITC-GOLD
Abstract: Background: Oral rehydration solution (ORS) is a form of oral rehydration therapy (ORT) for diarrhoea that has the potential to drastically reduce child mortality; yet, according to UNICEF estimates, less than half of children younger than 5 years with diarrhoea in low-income and middle-income countries (LMICs) received ORS in 2016. A variety of recommended home fluids (RHF) exist as alternative forms of ORT; however, it is unclear whether RHF prevent child mortality. Previous studies have shown considerable variation between countries in ORS and RHF use, but subnational variation is unknown. This study aims to produce high-resolution geospatial estimates of relative and absolute coverage of ORS, RHF, and ORT (use of either ORS or RHF) in LMICs. Methods: We used a Bayesian geostatistical model including 15 spatial covariates and data from 385 household surveys across 94 LMICs to estimate annual proportions of children younger than 5 years of age with diarrhoea who received ORS or RHF (or both) on continuous continent-wide surfaces in 2000-17, and aggregated results to policy-relevant administrative units. Additionally, we analysed geographical inequality in coverage across administrative units and estimated the number of diarrhoeal deaths averted by increased coverage over the study period. Uncertainty in the mean coverage estimates was calculated by taking 250 draws from the posterior joint distribution of the model and creating uncertainty intervals (UIs) with the 2·5th and 97·5th percentiles of those 250 draws. Findings: While ORS use among children with diarrhoea increased in some countries from 2000 to 2017, coverage remained below 50% in the majority (62·6%; 12 417 of 19 823) of second administrative-level units and an estimated 6 519 000 children (95% UI 5 254 000-7 733 000) with diarrhoea were not treated with any form of ORT in 2017. Increases in ORS use corresponded with declines in RHF in many locations, resulting in relatively constant overall ORT coverage from 2000 to 2017. Although ORS was uniformly distributed subnationally in some countries, within-country geographical inequalities persisted in others; 11 countries had at least a 50% difference in one of their units compared with the country mean. Increases in ORS use over time were correlated with declines in RHF use and in diarrhoeal mortality in many locations, and an estimated 52 230 diarrhoeal deaths (36 910-68 860) were averted by scaling up of ORS coverage between 2000 and 2017. Finally, we identified key subnational areas in Colombia, Nigeria, and Sudan as examples of where diarrhoeal mortality remains higher than average, while ORS coverage remains lower than average. Interpretation: To our knowledge, this study is the first to produce and map subnational estimates of ORS, RHF, and ORT coverage and attributable child diarrhoeal deaths across LMICs from 2000 to 2017, allowing for tracking progress over time. Our novel results, combined with detailed subnational estimates of diarrhoeal morbidity and mortality, can support subnational needs assessments aimed at furthering policy makers' understanding of within-country disparities. Over 50 years after the discovery that led to this simple, cheap, and life-saving therapy, large gains in reducing mortality could still be made by reducing geographical inequalities in ORS coverage. This work was primarily supported by a grant from the Bill & Melinda Gates Foundation (OPP1132415). L G Abreu has received support from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Finance Code 001), Conselho Nacional de Desenvolvimento Científico e Tecnológico and Fundação de Amparo à Pesquisa do Estado de Minas Gerais. O O Adetokunboh acknowledges the South African Department of Science and Innovation and the National Research Foundation. S M Aljunid acknowledges the Department of Health Policy and Management, Faculty of Public Health, Kuwait University and International Centre for Casemix and Clinical Coding, Faculty of Medicine, National University of Malaysia for the approval and support to participate in this research project. H T Atalay acknowledges Aksum University. M Ausloos and C Herteliu are partially supported by a grant of the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. P S Azzopardi was supported by an Australian National Health and Medical Research Council (NHMRC) early career fellowship. A Badawi is supported by the Public Health Agency of Canada. T W Bärnighausen was supported by the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research; the EU; the Wellcome Trust; and from National Institute of Child Health and Human Development of National Institutes of Health (NIH; R01-HD084233), National Institute on Aging of NIH (P01-AG041710), National Institute of Allergy and Infectious Diseases of NIH (R01-AI124389 and R01-AI112339), as well as Fogarty International Center of NIH (D43-TW009775). G B Britton is supported by Sistema Nacional de Investigación (SNI) de la Secretaría Nacional de Ciencia, Tecnología e Innovación (SENACYT) of Panamá. A Barac is funded by the Project of Ministry of Education, Science and Technology of the Republic of Serbia (number III45005). D A Bennett was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, or the UK Department of Health and Social Care. V M Costa acknowledges her grant (SFRH/BHD/110001/2015), received by Portuguese national funds through Fundação para a Ciência e Tecnologia (FCT), IP, under the Norma Transitória DL57/2016/CP1334/CT0006. F Carvalho acknowledges UID/MULTI/04378/2019 and UID/QUI/50006/2019 support with funding from FCT/Ministério da Ciência, Tecnologia e Ensino Superior through national funds. K Deribe is supported by a Wellcome Trust grant (number 201900/Z/16/Z) as part of his International Intermediate Fellowship. C Herteliu is partially supported by a grant co-funded by European Fund for Regional Development through the Operational Program for Competitiveness (project ID P_40_382). P Hoogar thanks Centre for Bio Cultural Studies, Directorate of Research, Manipal Academy of Higher Education, Manipal and Centre for Holistic Development and Research, Kalaghatgi-Karnataka. S M S Islam is funded by a Fellowship from National Heart Foundation of Australia and Deakin University. M Jakovljevic and the Serbian part of this GBD contribution was co-funded through grant OI175014 of the Ministry of Education Science and Technological Development of the Republic of Serbia. A P Kengne is supported by the South African Medical Research Council. Y J Kim's work was supported by the Research Management Centre, Xiamen University Malaysia, grants number XMUMRF/2018-C2/ITCM/0001. K Krishan is supported by a DST PURSE grant and UGC Center of Advanced Study awarded to the Department of Anthropology, Panjab University, Chandigarh, India. M Kumar acknowledges K43 TW010716-03. B Lacey acknowledges support from the NIHR Oxford Biomedical Research Centre and the British Heart Foundation Centre of Research Excellence, Oxford. P T N Memiah acknowledges the Council for the Development of Social Science Research in Africa. M Molokhia is supported by the NIHR Biomedical Research Center at Guy's and St Thomas' National Health Service Foundation Trust and King's College London. I Moreno Velásquez is supported by the Sistema Nacional de Investigación (SENACYT, Panamá). G C Patton is funded by an NHMRC Fellowship. A M Samy received a fellowship from the Egyptian Fulbright Mission programme. M M Santric-Milicevic acknowledges the support of the Ministry of Education, Science and Technological Development of the Republic of Serbia (contract number 175087). A Sheikh acknowledges the support of Health Data Research UK. M R Sobhiyeh acknowledges the Clinical Research Development Center of Imam Reza Hospital, Kermanshah University of Medical Sciences for their wise advice. R Tabarés-Seisdedos was supported in part by grant PI17/00719 from Instituto de Salud Carlos III–FEDER. B Unnikrishnan acknowledges Manipal Academy of Higher Education, Manipal. M R Weaver was supported by the Bill & Melinda Gates Foundation grant OPP1127433. C S Wiysonge was supported by the South African Medical Research Council.
Published: 2020

25. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Author: Sorin Hostiuc, Shaun Wen Huey Lee, Jorge R. Ledesma, Carsten Flohr, Masoumeh Sadeghi, João Mauricio Castaldelli-Maia, Behzad Karami Matin, Cyrus Alinia, Mehdi Bohluli, Félix Carvalho, Yun Jin Kim, Catalina Liliana Andrei, Seyyed Meysam Mousavi, Bernhard T. Baune, Ehsan Ahmadpour, Dinh-Toi Chu, Beatrix Haddock, Gianfranco Alicandro, Vasily Vlassov, Mohammad Taghi Khodayari, Gianna Gayle Herrera Amul, Arash Tehrani-Banihashemi, Govinda Prasad Dhungana, Fereshteh Ansari, Michael K. Hole, Azeem Majeed, Iman Halvaei, Saqib Ali, Arianna Maever L. Amit, Tomas Y. Yeheyis, John S. Ji, Martin McKee, Jamileh Shadid, Leonardo Roever, Peng Jia, Ettore Beghi, Pablo M. Lavados, Young Eun Kim, Vahid Alipour, Sowmya J. Rao, Ahmad Daryani, Cathleen Keller, Ibrahim Abdollahpour, Nicole K. DeCleene, Ebrahim Babaee, Saman Esmaeilnejad, Boris Bikbov, William M. Gardner, Lydia M. Haile, Luca Ronfani, Azalea M. Thomson, Irena Ilic, Ruth W. Kimokoti, Yingxi Zhao, Guoqing Hu, Mehran Shams-Beyranvand, Ilais Moreno Velásquez, Nathaniel J. Henry, Brijesh Sathian, Daniel Kim, Peter Memiah, Mohammad Hadi Abbasi, Andrea Farioli, Zahra Kamiab, Bolajoko O. Olusanya, Matthew C. Doxey, Tommi Vasankari, Hamideh Salimzadeh, Luisa Sorio Flor, Priya Rathi, Shanshan Li, Tanvir M. Huda, Dillon O Sylte, Rosario Cárdenas, Agegnehu Bante, Helen Ippolito, Alyssa Acebedo, Jeffrey D. Stanaway, Anwar Faraj, João Pedro Silva, Amin Mousavi Khaneghah, Pushpendra Kumar, Sangram Kishor Patel, Josephine W. Ngunjiri, Holly E. Erskine, Eugene Sobngwi, Filippo Ariani, Shane D. Morrison, Mohammad Aghaali, Meghan D. Mooney, Vera Marisa Costa, Palash Chandra Banik, Rupak Desai, Ken Takahashi, Maigeng Zhou, Morteza Oladnabi, Bogdan Oancea, Daniela Ribeiro, Mohammad Farahmand, Irmina Maria Michalek, Yetunde O. John-Akinola, Khem Narayan Pokhrel, Emilie R Maddison, Syed Mohamed Aljunid, Damian G. Hoy, Hosni Salem, V. Prakash, Shuhei Nomura, Inga Dora Sigfusdottir, Anders Larsson, Sharareh Eskandarieh, Abdollah Mohammadian-Hafshejani, Somayeh Bohlouli, Joana Morgado-da-Costa, Siamak Sabour, Theo Vos, Han Yong Wunrow, Khaled Khatab, Alireza Zangeneh, Ann Kristin Knudsen, Marissa B Reitsma, Hannah J. Henrikson, Randah R. Hamadeh, Tuomo J. Meretoja, Ireneous N. Soyiri, Giuseppe Grosso, Ziyad Al-Aly, Taraneh Yousefinezhadi, Joseph L Ward, Roba Khundkar, Ricardo Santiago Gomez, Reza Malekzadeh, John J. McGrath, Sandra B. Munro, Shahin Soltani, Amy E. Peden, Rufus Akinyemi, Marcel Ausloos, Naohiro Yonemoto, Bogdan Wojtyniak, Ahmad Ghashghaee, Guilherme Borges, Sadia Bibi, Farhad Islami, Hamed Mirzaei, Mohammad Ali Sahraian, M. Ashworth Dirac, Hosna Janjani, Kairat Davletov, Hermann Brenner, Yuichiro Yano, Elissa M. Abrams, Ana Vukovic, Bartosz Miazgowski, Jobert Richie Nansseu, Jennifer O Lam, Mona Pathak, Leeberk Raja Inbaraj, Thirunavukkarasu Sathish, Asadollah Gholamian, Carlos A Castañeda-Orjuela, Babak Eshrati, Edgar Denova-Gutiérrez, Atte Meretoja, Lorenzo Monasta, Ronan A. Lyons, Neda Kianipour, Desalegn Getnet Demsie, Yasir Waheed, Desta Debalkie Atnafu, Davide Sattin, Kevin S Ikuta, Ghobad Moradi, Srinivas Goli, Krittika Bhattacharyya, Mika Kivimäki, Christopher Troeger, Jordi Alonso, Alireza Ahmadi, Navid Manafi, Caroline Stein, Songhomitra Panda-Jonas, Jason Nguyen, Moses K. Muriithi, Aziz Rezapour, Ismael R. Campos-Nonato, Adrian Pana, H. Dean Hosgood, Noore Alam, James L. Fisher, Mariam Molokhia, Susan F. Rumisha, Ernoiz Antriyandarti, Ayman Grada, Emma Nichols, Babak Asghari, André Luiz Sena Guimarães, Ferrán Catalá-López, Aletta E. Schutte, Fiona B. Bennitt, Maciej Banach, Antonio Biondi, Donal Bisanzio, Josip Car, Ronny Westerman, Shafiu Mohammed, Biniyam Sahiledengle Geberemariyam, Kenji Shibuya, Meghdad Pirsaheb, Milena Santric-Milicevic, Karen M. Tabb, Paula Moraga, Soheil Hassanipour, Hasan Yusefzadeh, Avina Vongpradith, Dara K. Mohammad, Ralph Maddison, Babak Moazen, Getachew Mullu Kassa, Rahman Shiri, Fernando Neves Hugo, Hmwe H Kyu, Zachary V Dingels, Florian Fischer, Valentin Yurievich Skryabin, Rafael Tabarés-Seisdedos, Massimo Cirillo, Nikita Otstavnov, Robert C. Reiner, Van C. Lansingh, Rodrigo Sarmiento-Suarez, Ashkan Afshin, Benjamin A Stark, Mohsen Abbasi-Kangevari, Natalie C. Galles, Behnam Heidari, Eun-Kee Park, Mohammad Ali Jahani, Suzanne Polinder, Mahalaqua Nazli Khatib, Farhad Jadidi-Niaragh, Amir Radfar, Mowafa Househ, Derrick A Bennett, Gaorui Guo, Hesam Ghiasvand, Taweewat Wiangkham, Tamás Joó, Cristiana Abbafati, Kathryn Mei Ming Lau, Anita K. Nandi, Miklós Szócska, Manasi Kumar, Eduardo A. Undurraga, Oladimeji M. Adebayo, Simon Yadgir, Victor Aboyans, Justin J. Lang, Catherine O. Johnson, Soewarta Kosen, Carla Sofia e.Sá Farinha, Marcos Roberto Tovani-Palone, Kamarul Imran Musa, Farshad Pourmalek, Kiomars Sharafi, Heather Orpana, Samuel B. Albertson, Mahdi Afshari, Nicholas J K Breitborde, Nelson J. Alvis-Zakzuk, Adrian Oţoiu, Iván Landires, Robert G. Weintraub, Kidanemaryam Berhe, André Faro, Sophia Emmons-Bell, Lauren E. Schaeffer, Alexandre C. Pereira, Mehdi Naderi, Yordanos Gizachew Yeshitila, Mehdi Hosseinzadeh, Arash Etemadi, Oleguer Plana-Ripoll, Theodore Patrick Younker, Joemer C. Maravilla, Alireza Ansari-Moghaddam, Borhan Mansouri, Narayanaswamy Venketasubramanian, Seyed Mohammad Kazem Aghamir, Linda Morales, Amanda Deen, Noushin Mohammadifard, Obinna Onwujekwe, Ai Koyanagi, Michele Nguyen, Chieh Han, Kiana Ramezanzadeh, Mika Shigematsu, Mohammed Shannawaz, Khurshid Alam, Javad Nazari, Bryan L. 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Jonas, Dian Kusuma, Benjamin B. Massenburg, Santosh Varughese, Yousef Mohammad, Beatriz Paulina Ayala Quintanilla, Mihaela Hostiuc, Richard G. Cowden, Morteza Shamsizadeh, Thomas Pilgrim, Alessandra C. Goulart, Leila Doshmangir, Gabriele Nagel, Saravanan Muthupandian, Zahra Sadat Dibaji Forooshani, Maryam Mirzaei, Zabihollah Yousefi, Shadrach Wilson, Iman El Sayed, Juanita A. Haagsma, Segun Emmanuel Ibitoye, Eirini Skiadaresi, Reza Shirkoohi, Tim Driscoll, Morteza Jafarinia, Maha El Tantawi, Telma Zahirian Moghadam, Katarzyna Kissimova-Skarbek, Abdilahi Yousuf Yousuf, Dickson A. Amugsi, Awoke Misganaw, Maseer Khan, Norito Kawakami, Jingkai Wei, Jai K Das, Vishnu Renjith, Tessa M. Pilz, Sameer Vali Gopalani, Roghiyeh Faridnia, Islam Y. Elgendy, Prateek Rastogi, Lauren B. Wilner, Josep Maria Haro, Zahiruddin Quazi Syed, Ben Lacey, Ketema Bizuwork Gebremedhin, Sam Rolfe, Iffat Elbarazi, Yannick Béjot, Raimundas Lunevicius, Sezer Kisa, Harish Chander Gugnani, Basema Saddik, Manu Raj Mathur, Mansour Ghafourifard, Riaz Uddin, Anna Poznańska, Faris Lami, Niguse Meles Alema, Michael T. Chung, Arya Aminorroaya, Arash Sarveazad, Erkin M. Mirrakhimov, Seyed Hossein Yahyazadeh Jabbari, João M. Furtado, Hamid Ahmadieh, Sara Conti, Yunquan Zhang, Manthan D Janodia, Aislyn U. Orji, S. Mohammad Sajadi, Jalal Arabloo, Gabrielle B. Britton, Colm McAlinden, Francisco Rogerlândio Martins-Melo, Simona Cătălina Ştefan, Ester Cerin, Nuno Taveira, Lars Jacob Stovner, Amir Taherkhani, Masoud Foroutan, Tomasz Miazgowski, Amir Manafi, Yeshambel T. Nigatu, Barthelemy Kuate Defo, Mithila Faruque, Alan D. Lopez, Man Mohan Mehndiratta, Graeme J. 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L., Department of Public Health, Clinicum, Department of Neurosciences, HUS Comprehensive Cancer Center, Environmental Sciences, Public Health, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Value, Affordability and Sustainability (VALUE), Microbes in Health and Disease (MHD), Sálfræðideild (HR), Department of Psychology (RU), Samfélagssvið (HR), School of Social Sciences (RU), Háskólinn í Reykjavík, Reykjavik University, GBD 2019 Diseases and Injuries Collaborator, Violante FS, Department of Earth Observation Science, Faculty of Geo-Information Science and Earth Observation, and UT-I-ITC-ACQUAL
Subjects: Male, Life expectancy, Disability-Adjusted Life Year, Diseases, Disease, communicable disease, systematic analysis, Global Burden of Disease, 0302 clinical medicine, 80 and over, Medicine, 10. No inequality, Child, 11 Medical and Health Sciences, injuries, Aged, 80 and over, education.field_of_study, Sjúkdómar, DEMENTIA, FALLS, General Medicine, Forvarnir, 3. Good health, Child, Preschool, Human, GBD, Population health, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Humans, Global Burden of Disease Study, education, Aged, Spatial Analysis, Global burden, Disability, Prevention, DISABILITY, Infant, Spatial Analysi, Mortality rate, Global Burden of Disease, Diseases, Injuries, Systematic analysis, PREVENTION, Years of potential life lost, Risk factors, Disease study, ITC-ISI-JOURNAL-ARTICLE, RISK-FACTORS, Clinical Medicine, RA, Demography, Fötlun, Dánartíðni, Áhættuþættir, 030204 cardiovascular system & hematology, Risk Factors, Cause of Death, Global health, 030212 general & internal medicine, 1. No poverty, Disability-Adjusted Life Years, Public Health, Global Health, Social Medicine and Epidemiology, Middle Aged, 3142 Public health care science, environmental and occupational health, Adolescent, Adult, Age Distribution, Female, Infant, Newborn, Young Adult, Lýðheilsa, CLINICAL-TRIALS, Population, Settore MED/01 - Statistica Medica, diseases, ITC-HYBRID, Heilbrigðisvísindi, General & Internal Medicine, Mortality, Preschool, Disease burden, business.industry, Risk Factor, Klinisk medicin, Newborn, purl.org/pe-repo/ocde/ford#3.02.00 [https], Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Áverkar, Systematic analysis, NA, business
Abstract: Publisher's version (útgefin grein), Background In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990-2010 time period, with the greatest annualised rate of decline occurring in the 0-9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10-24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10-24 years were also in the top ten in the 25-49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50-74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and development investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd., Research reported in this publication was supported by the Bill & Melinda Gates Foundation; the University of Melbourne; Queensland Department of Health, Australia; the National Health and Medical Research Council, Australia; Public Health England; the Norwegian Institute of Public Health; St Jude Children's Research Hospital; the Cardiovascular Medical Research and Education Fund; the National Institute on Ageing of the National Institutes of Health (award P30AG047845); and the National Institute of Mental Health of the National Institutes of Health (award R01MH110163). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders. The authors alone are responsible for the views expressed in this Article and they do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated, the National Health Service (NHS), the National Institute for Health Research (NIHR), the UK Department of Health and Social Care, or Public Health England; the United States Agency for International Development (USAID), the US Government, or MEASURE Evaluation; or the European Centre for Disease Prevention and Control (ECDC). This research used data from the Chile National Health Survey 2003, 2009-10, and 2016-17. The authors are grateful to the Ministry of Health, the survey copyright owner, for allowing them to have the database. All results of the study are those of the authors and in no way committed to the Ministry. The Costa Rican Longevity and Healthy Aging Study project is a longitudinal study by the University of Costa Rica's Centro Centroamericano de Poblacion and Instituto de Investigaciones en Salud, in collaboration with the University of California at Berkeley. The original pre-1945 cohort was funded by the Wellcome Trust (grant 072406), and the 1945-55 Retirement Cohort was funded by the US National Institute on Aging (grant R01AG031716). The principal investigators are Luis Rosero-Bixby and William H Dow and co-principal investigators are Xinia Fernandez and Gilbert Brenes. The accuracy of the authors' statistical analysis and the findings they report are not the responsibility of ECDC. ECDC is not responsible for conclusions or opinions drawn from the data provided. ECDC is not responsible for the correctness of the data and for data management, data merging and data collation after provision of the data. ECDC shall not be held liable for improper or incorrect use of the data. The Health Behaviour in School-Aged Children (HBSC) study is an international study carried out in collaboration with WHO/EURO. The international coordinator of the 1997-98, 2001-02, 2005-06, and 2009-10 surveys was Candace Currie and the databank manager for the 1997-98 survey was Bente Wold, whereas for the following surveys Oddrun Samdal was the databank manager. A list of principal investigators in each country can be found on the HBSC website. Data used in this paper come from the 2009-10 Ghana Socioeconomic Panel Study Survey, which is a nationally representative survey of more than 5000 households in Ghana. The survey is a joint effort undertaken by the Institute of Statistical, Social and Economic Research (ISSER) at the University of Ghana and the Economic Growth Centre (EGC) at Yale University. It was funded by EGC. ISSER and the EGC are not responsible for the estimations reported by the analysts. The Palestinian Central Bureau of Statistics granted the researchers access to relevant data in accordance with license number SLN2014-3-170, after subjecting data to processing aiming to preserve the confidentiality of individual data in accordance with the General Statistics Law, 2000. The researchers are solely responsible for the conclusions and inferences drawn upon available data. Data for this research was provided by MEASURE Evaluation, funded by USAID. The authors thank the Russia Longitudinal Monitoring Survey, conducted by the National Research University Higher School of Economics and ZAO Demoscope together with Carolina Population Center, University of North Carolina at Chapel Hill and the Institute of Sociology, Russia Academy of Sciences for making data available. This paper uses data from the Bhutan 2014 STEPS survey, implemented by the Ministry of Health with the support of WHO; the Kuwait 2006 and 2014 STEPS surveys, implemented by the Ministry of Health with the support of WHO; the Libya 2009 STEPS survey, implemented by the Secretariat of Health and Environment with the support of WHO; the Malawi 2009 STEPS survey, implemented by Ministry of Health with the support of WHO; and the Moldova 2013 STEPS survey, implemented by the Ministry of Health, the National Bureau of Statistics, and the National Center of Public Health with the support of WHO. This paper uses data from Survey of Health, Ageing and Retirement in Europe (SHARE) Waves 1 (DOI:10.6103/SHARE. w1.700), 2 (10.6103/SHARE.w2.700), 3 (10.6103/SHARE.w3.700), 4 (10.6103/SHARE.w4.700), 5 (10.6103/SHARE.w5.700), 6 (10.6103/SHARE.w6.700), and 7 (10.6103/SHARE.w7.700); see Borsch-Supan and colleagues (2013) for methodological details. The SHARE data collection has been funded by the European Commission through FP5 (QLK6-CT-2001-00360), FP6 (SHARE-I3: RII-CT-2006-062193, COMPARE: CIT5-CT-2005-028857, SHARELIFE: CIT4-CT-2006-028812), FP7 (SHARE-PREP: GA N degrees 211909, SHARE-LEAP: GA N degrees 227822, SHARE M4: GA N degrees 261982) and Horizon 2020 (SHARE-DEV3: GA N degrees 676536, SERISS: GA N degrees 654221) and by DG Employment, Social Affairs & Inclusion. Additional funding from the German Ministry of Education and Research, the Max Planck Society for the Advancement of Science, the US National Institute on Aging (U01_AG09740-13S2, P01_AG005842, P01_AG08291, P30_AG12815, R21_AG025169, Y1-AG-4553-01, IAG_BSR06-11, OGHA_04-064, HHSN271201300071C), and from various national funding sources is gratefully acknowledged. This study has been realised using the data collected by the Swiss Household Panel, which is based at the Swiss Centre of Expertise in the Social Sciences. The project is financed by the Swiss National Science Foundation. The United States Aging, Demographics, and Memory Study is a supplement to the Health and Retirement Study (HRS), which is sponsored by the National Institute of Aging (grant number NIA U01AG009740). It was conducted jointly by Duke University and the University of Michigan. The HRS is sponsored by the National Institute on Aging (grant number NIA U01AG009740) and is conducted by the University of Michigan. This paper uses data from Add Health, a program project designed by J Richard Udry, Peter S Bearman, and Kathleen Mullan Harris, and funded by a grant P01-HD31921 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, with cooperative funding from 17 other agencies. Special acknowledgment is due to Ronald R Rindfuss and Barbara Entwisle for assistance in the original design. Information on how to obtain the Add Health data files is available on the Add Health website. No direct support was received from grant P01-HD31921 for this analysis. The data reported here have been supplied by the United States Renal Data System. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US Government. Collection of data for the Mozambique National Survey on the Causes of Death 2007-08 was made possible by USAID under the terms of cooperative agreement GPO-A-00-08-000_D3-00. This manuscript is based on data collected and shared by the International Vaccine Institute (IVI) from an original study IVI conducted. L G Abreu acknowledges support from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (Brazil; finance code 001) and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, a Brazilian funding agency). I N Ackerman was supported by a Victorian Health and Medical Research Fellowship awarded by the Victorian Government. O O Adetokunboh acknowledges the South African Department of Science and Innovation and the National Research Foundation. A Agrawal acknowledges the Wellcome Trust DBT India Alliance Senior Fellowship. S M Aljunid acknowledges the Department of Health Policy and Management, Faculty of Public Health, Kuwait University and International Centre for Casemix and Clinical Coding, Faculty of Medicine, National University of Malaysia for the approval and support to participate in this research project. M Ausloos, C Herteliu, and A Pana acknowledge partial support by a grant of the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. A Badawi is supported by the Public Health Agency of Canada. D A Bennett was supported by the NIHR Oxford Biomedical Research Centre. R Bourne acknowledges the Brien Holden Vision Institute, University of Heidelberg, Sightsavers, Fred Hollows Foundation, and Thea Foundation. G B Britton and I Moreno Velasquez were supported by the Sistema Nacional de Investigacion, SNI-SENACYT, Panama. R Buchbinder was supported by an Australian National Health and Medical Research Council (NHMRC) Senior Principal Research Fellowship. J J Carrero was supported by the Swedish Research Council (2019-01059). F Carvalho acknowledges UID/MULTI/04378/2019 and UID/QUI/50006/2019 support with funding from FCT/MCTES through national funds. A R Chang was supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases grant K23 DK106515. V M Costa acknowledges the grant SFRH/BHD/110001/2015, received by Portuguese national funds through Fundacao para a Ciencia e Tecnologia, IP, under the Norma Transitaria DL57/2016/CP1334/CT0006. A Douiri acknowledges support and funding from the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care South London at King's College Hospital NHS Foundation Trust and the Royal College of Physicians, and support from the NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. B B Duncan acknowledges grants from the Foundation for the Support of Research of the State of Rio Grande do Sul (IATS and PrInt) and the Brazilian Ministry of Health. H E Erskine is the recipient of an Australian NHMRC Early Career Fellowship grant (APP1137969). A J Ferrari was supported by a NHMRC Early Career Fellowship grant (APP1121516). H E Erskine and A J Ferrari are employed by and A M Mantilla-Herrera and D F Santomauro affiliated with the Queensland Centre for Mental Health Research, which receives core funding from the Queensland Department of Health. M L Ferreira holds an NHMRC Research Fellowship. C Flohr was supported by the NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust. M Freitas acknowledges financial support from the EU (European Regional Development Fund [FEDER] funds through COMPETE POCI-01-0145-FEDER-029248) and National Funds (Fundacao para a Ciencia e Tecnologia) through project PTDC/NAN-MAT/29248/2017. A L S Guimaraes acknowledges support from CNPq. C Herteliu was partially supported by a grant co-funded by FEDER through Operational Competitiveness Program (project ID P_40_382). P Hoogar acknowledges Centre for Bio Cultural Studies, Directorate of Research, Manipal Academy of Higher Education and Centre for Holistic Development and Research, Kalaghatagi. F N Hugo acknowledges the Visiting Professorship, PRINT Program, CAPES Foundation, Brazil. B-F Hwang was supported by China Medical University (CMU107-Z-04), Taichung, Taiwan. S M S Islam was funded by a National Heart Foundation Senior Research Fellowship and supported by Deakin University. R Q Ivers was supported by a research fellowship from the National Health and Medical Research Council of Australia. M Jakovljevic acknowledges the Serbian part of this GBD-related contribution was co-funded through Grant OI175014 of the Ministry of Education Science and Technological Development of the Republic of Serbia. P Jeemon was supported by a Clinical and Public Health intermediate fellowship (grant number IA/CPHI/14/1/501497) from the Wellcome Trust-Department of Biotechnology, India Alliance (2015-20). O John is a recipient of UIPA scholarship from University of New South Wales, Sydney. S V Katikireddi acknowledges funding from a NRS Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_12017/13, MC_UU_12017/15), and the Scottish Government Chief Scientist Office (SPHSU13, SPHSU15). C Kieling is a CNPq researcher and a UK Academy of Medical Sciences Newton Advanced Fellow. Y J Kim was supported by Research Management Office, Xiamen University Malaysia (XMUMRF/2018-C2/ITCM/00010). K Krishan is supported by UGC Centre of Advanced Study awarded to the Department of Anthropology, Panjab University, Chandigarh, India. M Kumar was supported by K43 TW 010716 FIC/NIMH. B Lacey acknowledges support from the NIHR Oxford Biomedical Research Centre and the BHF Centre of Research Excellence, Oxford. J V Lazarus was supported by a Spanish Ministry of Science, Innovation and Universities Miguel Servet grant (Instituto de Salud Carlos III [ISCIII]/ESF, the EU [CP18/00074]). K J Looker thanks the NIHR Health Protection Research Unit in Evaluation of Interventions at the University of Bristol, in partnership with Public Health England, for research support. S Lorkowski was funded by the German Federal Ministry of Education and Research (nutriCARD, grant agreement number 01EA1808A). R A Lyons is supported by Health Data Research UK (HDR-9006), which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, NIHR (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation, and Wellcome Trust. J J McGrath is supported by the Danish National Research Foundation (Niels Bohr Professorship), and the Queensland Health Department (via West Moreton HHS). P T N Memiah acknowledges support from CODESRIA. U O Mueller gratefully acknowledges funding by the German National Cohort Study BMBF grant number 01ER1801D. S Nomura acknowledges the Ministry of Education, Culture, Sports, Science, and Technology of Japan (18K10082). A Ortiz was supported by ISCIII PI19/00815, DTS18/00032, ISCIII-RETIC REDinREN RD016/0009 Fondos FEDER, FRIAT, Comunidad de Madrid B2017/BMD-3686 CIFRA2-CM. These funding sources had no role in the writing of the manuscript or the decision to submit it for publication. S B Patten was supported by the Cuthbertson & Fischer Chair in Pediatric Mental Health at the University of Calgary. G C Patton was supported by an aNHMRC Senior Principal Research Fellowship. M R Phillips was supported in part by the National Natural Science Foundation of China (NSFC, number 81371502 and 81761128031). A Raggi, D Sattin, and S Schiavolin were supported by grants from the Italian Ministry of Health (Ricerca Corrente, Fondazione Istituto Neurologico C Besta, Linea 4-Outcome Research: dagli Indicatori alle Raccomandazioni Cliniche). P Rathi and B Unnikrishnan acknowledge Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal. A L P Ribeiro was supported by Brazilian National Research Council, CNPq, and the Minas Gerais State Research Agency, FAPEMIG. D C Ribeiro was supported by The Sir Charles Hercus Health Research Fellowship (#18/111) Health Research Council of New Zealand. D Ribeiro acknowledges financial support from the EU (FEDER funds through the Operational Competitiveness Program; POCI-01-0145-FEDER-029253). P S Sachdev acknowledges funding from the NHMRC of Australia Program Grant. A M Samy was supported by a fellowship from the Egyptian Fulbright Mission Program. M M Santric-Milicevic acknowledges the Ministry of Education, Science and Technological Development of the Republic of Serbia (contract number 175087). R Sarmiento-Suarez received institutional support from Applied and Environmental Sciences University (Bogota, Colombia) and ISCIII (Madrid, Spain). A E Schutte received support from the South African National Research Foundation SARChI Initiative (GUN 86895) and Medical Research Council. S T S Skou is currently funded by a grant from Region Zealand (Exercise First) and a grant from the European Research Council under the EU's Horizon 2020 research and innovation program (grant agreement number 801790). J B Soriano is funded by Centro de Investigacion en Red de Enfermedades Respiratorias, ISCIII. R Tabares-Seisdedos was supported in part by the national grant PI17/00719 from ISCIII-FEDER. N Taveira was partially supported by the European & Developing Countries Clinical Trials Partnership, the EU (LIFE project, reference RIA2016MC-1615). S Tyrovolas was supported by the Foundation for Education and European Culture, the Sara Borrell postdoctoral programme (reference number CD15/00019 from ISCIII-FEDER). S B Zaman received a scholarship from the Australian Government research training programme in support of his academic career., "Peer Reviewed"
Published: 2020

26. Measuring universal health coverage based on an index of effective coverage of health services in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019

Author: William M. Gardner, Rawlance Ndejjo, Govinda Prasad Dhungana, Fereshteh Ansari, Kathleen Pillsbury Hopf, João Pedro Silva, M. Mofizul Islam, Cong Zhu, Abdul Hafiz, Irmina Maria Michalek, Syed Mohamed Aljunid, Leonardo Roever, Mustefa Glagn, Davood Anvari, Tessa M. Pilz, Sameer Vali Gopalani, Joel M. Francis, Man Mohan Mehndiratta, Rakhi Dandona, Abbas Sheikhtaheri, Mansour Ghafourifard, Simon Øverland, David Laith Rawaf, Jaykaran Charan, Akram Pourshams, Mostafa Dianatinasab, Morteza Mahmoudi, Alton Lu, Alyssa N. Sbarra, Lorainne Tudor Car, Franz Castro, Hafiz Ansar Rasul Suleria, Luca Ronfani, Marina Pinheiro, Mehran Asadi-Aliabadi, Maziar Moradi-Lakeh, Hoa Thi Do, Whitney L. Teagle, Sofia Androudi, Carl Abelardo T. Antonio, Myron Anthony Godinho, Bhaskaran Unnikrishnan, Oluchi Ezekannagha, Getinet Ayano, Seyyed Shamsadin Athari, Dimas Ria Angga Pribadi, Kyle E. Simpson, Muluken Bekele Sorrie, Vivekanand Jha, Chukwuma David Umeokonkwo, Akshaya Srikanth Bhagavathula, Cuong Tat Nguyen, Amr Hassan, Akine Eshete Abosetugn, Hailay Abrha Gesesew, Anna V. Korotkova, Brijesh Sathian, Marcello Tonelli, Olatunde Aremu, Mohammad Reza Salahshoor, Juan Jesus Carrero, Cameron J. Kneib, Ravi Prakash Jha, David H. Shaw, Hossein Samadi Kafil, Tanuj Kanchan, Khezar Hayat, Hamid Sharifi, Morteza Shamsizadeh, Muktar Omer Omer, Fatemeh Amiri, Hamidreza Pazoki Toroudi, David Edvardsson, Xiu Ju George Zhao, Hannah Han, Leticia Avila-Burgos, Adam E. Berman, Jemal Abdu Mohammed, Thomas Pilgrim, Leila Doshmangir, Mu'awiyyah Babale Sufiyan, David M. Pigott, Hadi Hassankhani, Beatriz Paulina Ayala Quintanilla, Teklemariam Gultie, Arash Ziapour, Seyed Sina Naghibi Irvani, Ilse N. Dippenaar, Jean Jacques Noubiap, Emmanuela Gakidou, Abiyu Mekonnen Gebrehiwot, Maha El Tantawi, Xuefeng Liu, Zulfiqar A. Bhutta, Keyghobad Ghadiri, João Mauricio Castaldelli-Maia, Behzad Karami Matin, Yunquan Zhang, Vera Marisa Costa, Iyad Sultan, Mostafa Hosseini, Abdulaziz Khalid Abu Haimed, Haidong Wang, Kaleab Alemayehu Zewdie, Celine M. Barthelemy, Hosna Janjani, Bartosz Miazgowski, Jobert Richie Nansseu, Arianna Maever L. Amit, John S. Ji, Ata Rafiee, Maria Inês Schmidt, Alireza Rafiei, Somayeh Bohlouli, Joana Morgado-da-Costa, Huong Lan Thi Nguyen, Pradyumna Agasthi, Tiffany K. Gill, Martin McKee, Khaled Khatab, Jae Il Shin, Animut Tagele Tamiru, Giancarlo Logroscino, Hassan Abolhassani, Syed Saoud Zaidi, Sivan Yegnanarayana Iyer Saraswathy, Garumma Tolu Feyissa, Ahmad Daryani, Ziyad Al-Aly, Gebreamlak Gebremedhn Gebremeskel, Michael T. Chung, Amirhossein Sahebkar, Mehedi Hasan, Saeed Shahabi, Diep Ngoc Nguyen, Yohannes Kinfu, Nicholas L S Roberts, Jagadish Rao Padubidri, Mika Shigematsu, Lucero Cahuana-Hurtado, Deepa Jahagirdar, Islam Y. Elgendy, Erkin M. Mirrakhimov, Tanvir M. Huda, Fakher Rahim, Dara K. Mohammad, Yingxi Zhao, Ruxandra Irina Negoi, Vinod C. Nayak, Reinhard Busse, Andrew T. Leever, Muhammad Aziz Rahman, Kathryn Mei Ming Lau, Stefania Mondello, Vivian Chia-Rong Hsieh, Kris J. Krohn, Reza Rawassizadeh, Vishnu Renjith, Jianing Ma, Moses K. Muriithi, Mark G. Shrime, Mayowa O. Owolabi, Nobuyuki Horita, Seyed Hossein Yahyazadeh Jabbari, Daniel Y. Cho, Miloje Savic, Moslem Soofi, Iqbal R. F. Elyazar, Freweini Gebrearegay G. Tela, Jonathan F. Mosser, Palash Chandra Banik, Andre Rodrigues Duraes, Yuan-Pang Wang, Natalie C. Galles, Rashid Abdi Guled, Abdallah M. Samy, Hadi Pourjafar, Roman Topor-Madry, Ayesha Humayun, Leila Zaki, Nuworza Kugbey, Maryam Khayamzadeh, Naznin Hossain, Jiregna Darega Gela, Jordi Alonso, Ruth W Kimokoti, A. A. Fomenkov, Jalal Arabloo, Aletta E. Schutte, Biruk Wogayehu Taddele, Teklehaimanot Gereziher Haile, Diego Augusto Santos Silva, Seyed Mohammad Kazem Aghamir, Maciej Banach, Deanna Anderlini, Moses J. Bockarie, Saleem Muhammad Rana, Randah R. Hamadeh, Farhad Islami, Olalekan A. Uthman, S. Mohammad Sajadi, Francisco Rogerlândio Martins-Melo, Shankar M Bakkannavar, Kairat Davletov, Soraya Seedat, Alan D. Lopez, Masoud Behzadifar, Benjamin B. Massenburg, Santosh Varughese, Ingan Ukur Tarigan, Amin Soheili, Félix Carvalho, Yun Jin Kim, Catalina Liliana Andrei, Caleb Mackay Salpeter Irvine, Mojgan Gitimoghaddam, G Anil Kumar, Rasmus J. Havmoeller, Hiroyasu Iso, Atte Meretoja, Yasir Waheed, João M. Furtado, Christian Razo, Neeti Kapoor, Mowafa Househ, Rajaa Al-Raddadi, Mohammad Khammarnia, Santi Martini, Feng Sha, Marco Vacante, Jacek A. Kopec, Hunduma Amensisa Bojia, Jacob Olusegun Olusanya, Kate E. LeGrand, Nikolay Ivanovich Briko, Robert S. Bernstein, Arun Balachandran, Davoud Adham, Ahad Bakhtiari, Shafiu Mohammed, Leake G. Gebremeskel, Smita Pakhale, Ejaz Ahmad Khan, Daniel Cury Ribeiro, Yousef Mohammad, Bernhard T. Baune, Azeem Majeed, Luis Camera, Mohammad Ali Jahani, Hasan Yusefzadeh, Rahman Shiri, Massimo Cirillo, Nikita Otstavnov, Vahid Yazdi-Feyzabadi, Paolo Lauriola, Irfan Ullah, Aruna M Kamath, Maryam Mirzaei, Zabihollah Yousefi, Iman El Sayed, Mohammad Farahmand, Yetunde O. John-Akinola, Khem Narayan Pokhrel, Felix Akpojene Ogbo, Megan Knight, Nelson J. Alvis-Zakzuk, Teferi Mekonnen, Iván Landires, Robert G. Weintraub, Chukwudi A Nnaji, Lauren E. Schaeffer, Paulo A. Lotufo, Mehdi Naderi, Tomislav Mestrovic, André Faro, Mohsen Bayati, Raffaele Palladino, Shahin Soltani, Vladimir Andreevich Korshunov, Birhanu Geta Meharie, Mihajlo Jakovljevic, Abdiwahab Hashi, Olatunji O. Adetokunboh, Dejana Braithwaite, Sergio I. Prada, Bárbara Niegia Garcia de Goulart, Reza Pourmirza Kalhori, Jee-Young Jasmine Choi, Ernoiz Antriyandarti, Ronny Westerman, Meghdad Pirsaheb, Paul S. F. Yip, Mehdi Mirzaei-Alavijeh, Gebremariam Woldu, Rashmi Gupta, Onome Bright Oghenetega, Shane D. Morrison, Inga Dora Sigfusdottir, Marcel Ausloos, Mehdi Hosseinzadeh, Marcos Roberto Tovani-Palone, K M Shivakumar, Alireza Ansari-Moghaddam, Archith Boloor, Aidin Abedi, Binyam Minuye Birihane, Mohammad Ali Mansournia, Nihad A. Almasri, Simachew Animen Bante, Carlo Eduardo Medina-Solís, Leeberk Raja Inbaraj, Edgar Denova-Gutiérrez, Antonio Biondi, Valentin Yurievich Skryabin, Srinivasa Vittal Katikireddi, Sarika Chaturvedi, Francesco Saverio Violante, Abhay Gaidhane, George A. Mensah, Naohiro Yonemoto, Ahmad Ghashghaee, Ebrahim Babaee, Saman Esmaeilnejad, Sharath Burugina Nagaraja, Avina Vongpradith, Javad Nazari, Amir Khater, Michael K. Hole, Ben Lacey, Razique Anwer, Łukasz Szumowski, Ai Koyanagi, Rajesh Sagar, Ali Rajabpour-Sanati, Seyed M Karimi, Yordanos Gizachew Yeshitila, Mona Pathak, Nithin Kumar, Masoud Foroutan, Mehdi Fazlzadeh, Anusha Ganapati Bhat, Abbas Mosapour, Kebede Deribe, Nermin Ghith, Vaman Kulkarni, Sanjay Zodpey, Asadollah Gholamian, Mohammed Shannawaz, Nancy Fullman, Benn Sartorius, Giulio Castelpietra, Ghulam Mustafa, Silvia Schiavolin, Nelson Alvis-Guzman, Jeffrey D. Stanaway, Rafael Lozano, Christopher J L Murray, Guoqing Hu, Andrew M. Briggs, Ashish Badiye, Yousef Khader, Masoud Moghadaszadeh, Rahmatollah Moradzadeh, Valery L. Feigin, Claudia I. Mastrogiacomo, Emma Smith, Yasser Vasseghian, Saeed Amini, Asif Hanif, Achala Upendra Jayatilleke, Maryam Adabi, Sarah Wulf Hanson, Bhaskar Thakur, Ravi Mehrotra, Virginia Núñez-Samudio, Lalit Dandona, Segun Emmanuel Ibitoye, Simon I. Hay, Kiirithio N. Ngari, Obinna Onwujekwe, Deborah Carvalho Malta, Lorenzo Monasta, Neda Kianipour, Khurshid Alam, Luisa Sorio Flor, Priya Rathi, Ali Bijani, Khalid A Altirkawi, Jaimie Adelson, Hamed Zandian, Frank Tanser, Dharmesh Kumar Lal, John Everett Mumford, Morteza Oladnabi, Telma Zahirian Moghadam, Rodrigo Sarmiento-Suárez, Masoud Moradi, Maseer Khan, Mohammad Ali Sahraian, Amy E. Peden, Dhirendra N Sinha, Shanshan Li, Shailesh Advani, Behshad Naghshtabrizi, Matilde Leonardi, Lope H Barrero, Nicholas Steel, Dinh-Toi Chu, Claudio Alberto Dávila-Cervantes, Pushpendra Singh, Adrian Otoiu, Fabrizio Tediosi, Yonas Getaye Tefera, Pawan Faris, George C. Patton, Christopher Troeger, Mohammed Madadin, Jeffrey V. Lazarus, Paul H. Lee, Mohammad Amin Bahrami, Wondimeneh Shibabaw Shiferaw, Emmanuel Wandera Okunga, Biniyam Sahiledengle Geberemariyam, Samer Hamidi, Young-Ho Khang, Rufus Akinyemi, Farhad Jadidi-Niaragh, Godfrey Mutashambara Rwegerera, Naser Mohammad Gholi Mezerji, Rupak Desai, Eduardo Bernabé, Jamal A. Yearwood, Nima Rezaei, Emerito Jose A. Faraon, Vasily Vlassov, Stanislav S. Otstavnov, Reed J D Sorensen, Elena V. Gnedovskaya, Johan Ärnlöv, Mukhammad David Naimzada, Tahereh Javaheri, Tamer H. Farag, Paolo Cortesi, Gbenga A. Kayode, Lucas Guimarães Abreu, Manu Raj Mathur, Getie Lake Aynalem, Narayanaswamy Venketasubramanian, Doris V.V. Ortega-Altamirano, Giorgia Giussani, Liliana G Ciobanu, Suraj Bhattarai, Basema Saddik, Mustafa Z. Younis, Ensiyeh Jenabi, Ira Martopullo, Mohamed M. Gad, Kanyin L. Ong, Addisu Melese, Fotis Topouzis, Hanne Christensen, In-Hwan Oh, Arash Sarveazad, Shuhei Nomura, Peter Memiah, Sergej M. 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Subjects: Index (economics), Servicios de Salud, SUSTAINABLE DEVELOPMENT GOALS, 030204 cardiovascular system & hematology, universal health coverage, sustaibale develpment goal, global burden of disease, performance, systematic analysis, Global Burden of Disease, 0302 clinical medicine, Universal Health Insurance, RA0421, 11. Sustainability, Per capita, Medical economics, Disease, 030212 general & internal medicine, 10. No inequality, 11 Medical and Health Sciences, effective coverage of health services, GBD 2019 Universal Health Coverage Collaborators, education.field_of_study, Public health, Medical care, Sjúkdómar, 4. Education, 1. No poverty, Health coverage, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, Hälsovetenskaper, 3142 Public health care science, environmental and occupational health, Health services, 3. Good health, Global burden of disease, Health Expenditures, Humans, World Health Organization, Purchasing power parity, Scale (social sciences), Lýðheilsa, universal health coverag, CANCER SURVIVAL, ACCESS, Human, Heilsuhagfræði, medicine.medical_specialty, Health coverage, GBD, GBD, Universal health, GBD 2019, Population, Health expenditures, 3122 Cancers, Population health, 03 medical and health sciences, Health systems, Heilbrigðisvísindi, SDG 3 - Good Health and Well-being, General & Internal Medicine, Development economics, Health Sciences, medicine, Heilbrigðisstefna, Alþjóðaheilbrigðisstofnunin, QUALITY, Global Burden of Disease Study, education, PROGRESS, Disease burden, Health services accessibility, CARE, Heilbrigðisþjónusta, purl.org/pe-repo/ocde/ford#3.02.00 [https], Health Expenditure, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, 3121 General medicine, internal medicine and other clinical medicine, Morbility, Administración de los Servicios de Salud, Medical policy, Business, Heilbrigðiskerfi
Abstract: Publisher's version (útgefin grein), Background Achieving universal health coverage (UHC) involves all people receiving the health services they need, of high quality, without experiencing financial hardship. Making progress towards UHC is a policy priority for both countries and global institutions, as highlighted by the agenda of the UN Sustainable Development Goals (SDGs) and WHO's Thirteenth General Programme of Work (GPW13). Measuring effective coverage at the health-system level is important for understanding whether health services are aligned with countries' health profiles and are of sufficient quality to produce health gains for populations of all ages. Methods Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we assessed UHC effective coverage for 204 countries and territories from 1990 to 2019. Drawing from a measurement framework developed through WHO's GPW13 consultation, we mapped 23 effective coverage indicators to a matrix representing health service types (eg, promotion, prevention, and treatment) and five population-age groups spanning from reproductive and newborn to older adults (>= 65 years). Effective coverage indicators were based on intervention coverage or outcome-based measures such as mortality-to-incidence ratios to approximate access to quality care; outcome-based measures were transformed to values on a scale of 0-100 based on the 2.5th and 97.5th percentile of location-year values. We constructed the UHC effective coverage index by weighting each effective coverage indicator relative to its associated potential health gains, as measured by disability-adjusted life-years for each location-year and population-age group. For three tests of validity (content, known-groups, and convergent), UHC effective coverage index performance was generally better than that of other UHC service coverage indices from WHO (ie, the current metric for SDG indicator 3.8.1 on UHC service coverage), the World Bank, and GBD 2017. We quantified frontiers of UHC effective coverage performance on the basis of pooled health spending per capita, representing UHC effective coverage index levels achieved in 2019 relative to country-level government health spending, prepaid private expenditures, and development assistance for health. To assess current trajectories towards the GPW13 UHC billion target-1 billion more people benefiting from UHC by 2023-we estimated additional population equivalents with UHC effective coverage from 2018 to 2023. Findings Globally, performance on the UHC effective coverage index improved from 45.8 (95% uncertainty interval 44.2-47.5) in 1990 to 60.3 (58.7-61.9) in 2019, yet country-level UHC effective coverage in 2019 still spanned from 95 or higher in Japan and Iceland to lower than 25 in Somalia and the Central African Republic. Since 2010, sub-Saharan Africa showed accelerated gains on the UHC effective coverage index (at an average increase of 2.6% [1.9-3.3] per year up to 2019); by contrast, most other GBD super-regions had slowed rates of progress in 2010-2019 relative to 1990-2010. Many countries showed lagging performance on effective coverage indicators for non-communicable diseases relative to those for communicable diseases and maternal and child health, despite non-communicable diseases accounting for a greater proportion of potential health gains in 2019, suggesting that many health systems are not keeping pace with the rising non-communicable disease burden and associated population health needs. In 2019, the UHC effective coverage index was associated with pooled health spending per capita (r=0.79), although countries across the development spectrum had much lower UHC effective coverage than is potentially achievable relative to their health spending. Under maximum efficiency of translating health spending into UHC effective coverage performance, countries would need to reach $1398 pooled health spending per capita (US$ adjusted for purchasing power parity) in order to achieve 80 on the UHC effective coverage index. From 2018 to 2023, an estimated 388.9 million (358.6-421.3) more population equivalents would have UHC effective coverage, falling well short of the GPW13 target of 1 billion more people benefiting from UHC during this time. Current projections point to an estimated 3.1 billion (3.0-3.2) population equivalents still lacking UHC effective coverage in 2023, with nearly a third (968.1 million [903.5-1040.3]) residing in south Asia. Interpretation The present study demonstrates the utility of measuring effective coverage and its role in supporting improved health outcomes for all people-the ultimate goal of UHC and its achievement. Global ambitions to accelerate progress on UHC service coverage are increasingly unlikely unless concerted action on non-communicable diseases occurs and countries can better translate health spending into improved performance. Focusing on effective coverage and accounting for the world's evolving health needs lays the groundwork for better understanding how close-or how far-all populations are in benefiting from UHC., Lucas Guimaraes Abreu acknowledges support from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior -Brasil (Capes) -Finance Code 001, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) and Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG). Olatunji O Adetokunboh acknowledges South African Department of Science & Innovation, and National Research Foundation. Anurag Agrawal acknowledges support from the Wellcome Trust DBT India Alliance Senior Fellowship IA/CPHS/14/1/501489. Rufus Olusola Akinyemi acknowledges Grant U01HG010273 from the National Institutes of Health (NIH) as part of the H3Africa Consortium. Rufus Olusola Akinyemi is further supported by the FLAIR fellowship funded by the UK Royal Society and the African Academy of Sciences. Syed Mohamed Aljunid acknowledges the Department of Health Policy and Management, Faculty of Public Health, Kuwait University and International Centre for Casemix and Clinical Coding, Faculty of Medicine, National University of Malaysia for the approval and support to participate in this research project. Marcel Ausloos, Claudiu Herteliu, and Adrian Pana acknowledge partial support by a grant of the Romanian National Authority for Scientific Research and Innovation, CNDSUEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. Till Winfried Barnighausen acknowledges support from the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research. Juan J Carrero was supported by the Swedish Research Council (2019-01059). Felix Carvalho acknowledges UID/MULTI/04378/2019 and UID/QUI/50006/2019 support with funding from FCT/MCTES through national funds. Vera Marisa Costa acknowledges support from grant (SFRH/BHD/110001/2015), received by Portuguese national funds through Fundacao para a Ciencia e a Tecnologia (FCT), IP, under the Norma TransitA3ria DL57/2016/CP1334/CT0006. Jan-Walter De Neve acknowledges support from the Alexander von Humboldt Foundation. Kebede Deribe acknowledges support by Wellcome Trust grant number 201900/Z/16/Z as part of his International Intermediate Fellowship. Claudiu Herteliu acknowledges partial support by a grant co-funded by European Fund for Regional Development through Operational Program for Competitiveness, Project ID P_40_382. Praveen Hoogar acknowledges the Centre for Bio Cultural Studies (CBiCS), Manipal Academy of Higher Education(MAHE), Manipal and Centre for Holistic Development and Research (CHDR), Kalghatgi. Bing-Fang Hwang acknowledges support from China Medical University (CMU108-MF-95), Taichung, Taiwan. Mihajlo Jakovljevic acknowledges the Serbian part of this GBD contribution was co-funded through the Grant OI175014 of the Ministry of Education Science and Technological Development of the Republic of Serbia. Aruna M Kamath acknowledges funding from the National Institutes of Health T32 grant (T32GM086270). Srinivasa Vittal Katikireddi acknowledges funding from the Medical Research Council (MC_UU_12017/13 & MC_UU_12017/15), Scottish Government Chief Scientist Office (SPHSU13 & SPHSU15) and an NRS Senior Clinical Fellowship (SCAF/15/02). Yun Jin Kim acknowledges support from the Research Management Centre, Xiamen University Malaysia (XMUMRF/2018-C2/ITCM/0001). Kewal Krishan acknowledges support from the DST PURSE grant and UGC Center of Advanced Study (CAS II) awarded to the Department of Anthropology, Panjab University, Chandigarh, India. Manasi Kumar acknowledges support from K43 TW010716 Fogarty International Center/NIMH. Ben Lacey acknowledges support from the NIHR Oxford Biomedical Research Centre and the BHF Centre of Research Excellence, Oxford. Ivan Landires is a member of the Sistema Nacional de InvestigaciA3n (SNI), which is supported by the Secretaria Nacional de Ciencia Tecnologia e Innovacion (SENACYT), Panama. Jeffrey V Lazarus acknowledges support by a Spanish Ministry of Science, Innovation and Universities Miguel Servet grant (Instituto de Salud Carlos III/ESF, European Union [CP18/00074]). Peter T N Memiah acknowledges CODESRIA; HISTP. Subas Neupane acknowledges partial support from the Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital. Shuhei Nomura acknowledges support from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (18K10082). Alberto Ortiz acknowledges support by ISCIII PI19/00815, DTS18/00032, ISCIII-RETIC REDinREN RD016/0009 Fondos FEDER, FRIAT, Comunidad de Madrid B2017/BMD-3686 CIFRA2-CM. These funding sources had no role in the writing of the manuscript or the decision to submit it for publication. George C Patton acknowledges support from a National Health & Medical Research Council Fellowship. Marina Pinheiro acknowledges support from FCT for funding through program DL 57/2016 -Norma transitA3ria. Alberto Raggi, David Sattin, and Silvia Schiavolin acknowledge support by a grant from the Italian Ministry of Health (Ricerca Corrente, Fondazione Istituto Neurologico C Besta, Linea 4 -Outcome Research: dagli Indicatori alle Raccomandazioni Cliniche). Daniel Cury Ribeiro acknowledges support from the Sir Charles Hercus Health Research Fellowship -Health Research Council of New Zealand (18/111). Perminder S Sachdev acknowledges funding from the NHMRC Australia. Abdallah M Samy acknowledges support from a fellowship from the Egyptian Fulbright Mission Program. Milena M Santric-Milicevic acknowledges support from the Ministry of Education, Science and Technological Development of the Republic of Serbia (Contract No. 175087). Rodrigo Sarmiento-Suarez acknowledges institutional support from University of Applied and Environmental Sciences in Bogota, Colombia, and Carlos III Institute of Health in Madrid, Spain. Maria Ines Schmidt acknowledges grants from the Foundation for the Support of Research of the State of Rio Grande do Sul (IATS and PrInt) and the Brazilian Ministry of Health. Sheikh Mohammed Shariful Islam acknowledges a fellowship from the National Heart Foundation of Australia and Deakin University. Aziz Sheikh acknowledges support from Health Data Research UK. Kenji Shibuya acknowledges Japan Ministry of Education, Culture, Sports, Science and Technology. Joan B Soriano acknowledges support by Centro de Investigacion en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Rafael Tabares-Seisdedos acknowledges partial support from grant PI17/00719 from ISCIII-FEDER. Santosh Kumar Tadakamadla acknowledges support from the National Health and Medical Research Council Early Career Fellowship, Australia. Marcello Tonelli acknowledges the David Freeze Chair in Health Services Research at the University of Calgary, AB, Canada., "Peer Reviewed"
Published: 2020

27. Methylphenidate clinically oral doses improved brain and heart glutathione redox status and evoked renal and cardiac tissue injury in rats

Author: Félix Carvalho, Salomé Gonçalves-Monteiro, Margarida Duarte-Araújo, Vera Marisa Costa, Bastos Maria de Lourdes, João Paulo Capela, Sara Loureiro-Vieira, and José Alberto Duarte
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Administration, Oral, Striatum, Kidney, Nephrotoxicity, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Interstitial space, Internal medicine, mental disorders, medicine, Animals, Hippocampus (mythology), Rats, Wistar, Pharmacology, Cardiotoxicity, business.industry, Methylphenidate, Myocardium, Brain, Heart, General Medicine, Glutathione, Rats, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, chemistry, Central Nervous System Stimulants, business, Oxidation-Reduction, human activities, 030217 neurology & neurosurgery, medicine.drug
Abstract: Methylphenidate (MPH) is a first-line stimulant drug to treat attention deficit hyperactivity disorder (ADHD). Overdiagnosis of ADHD and MPH abuse lead to serious concerns about the possible long-term adverse consequences of MPH in healthy children and adolescents. We aimed to evaluate MPH effects in adolescent male Wistar rats (postnatal day 40) using an oral dose scheme (2 daily MPH doses 5 mg/kg in a 5% sucrose solution, 5 h apart, for 7 days) that mimics the therapeutic doses given to human adolescents. Twenty-four hours after the last MPH administration, rats were sacrificed and brain areas [cerebellum, prefrontal cortex (PFC), hippocampus, and striatum], peripheral organs (liver, heart, and kidneys), and blood were collected for biochemical and histological analysis. MPH treatment did not alter rats’ body temperature or weight, neither food or water intake throughout the experiment. The ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) significantly increased in the PFC and hippocampus of MPH-treated rats, meanwhile protein carbonylation remained unchanged in the brain. In the heart, the GSH/GSSG ratio and GSH levels were significantly increased, with decreased GSSG, while histology revealed significant damage, namely interstitial edema, vascular congestion, and presence of a fibrin-like material in the interstitial space. In the kidneys, MPH treatment resulted in extensive necrotic areas with cellular disorganization and cell infiltration, and immunohistochemistry analysis revealed a marked activation of nuclear factor-ĸB. This study showed that clinically relevant oral MPH doses improve the GSH redox status in the brain and heart, but evoke heart and kidney tissue damage to adolescent rats.
Published: 2018

28. The long-term neurotoxicity of doxorubicin in the brain of adult CD-1 mice

Author: Vera Marisa Costa, M. Ferreira, Margarida Duarte-Araújo, Eduarda Fernandes, A.O. Fernandes, Ana Reis-Mendes, Ricardo B. Ferreira, João Paulo Capela, F. Carvalho, A. Dias-Carvalho, and S.I. Sá
Subjects: business.industry, Neurotoxicity, medicine, Doxorubicin, General Medicine, Pharmacology, Toxicology, medicine.disease, business, Term (time), medicine.drug
Published: 2021

29. Chemical characterization and protective effect of the Bactris setosa Mart. fruit against oxidative/nitrosative stress

Author: Joana Schuelter Boeing, Daniela Ribeiro, Jesuí Vergílio Visentainer, Eduarda Fernandes, Renan Campos Chisté, Marisa Freitas, and Vera Marisa Costa
Subjects: Antioxidant, genetic structures, Nitrosation, medicine.medical_treatment, Cyanidin, Arecaceae, Protective Agents, medicine.disease_cause, 01 natural sciences, Antioxidants, Analytical Chemistry, chemistry.chemical_compound, 0404 agricultural biotechnology, Phenols, Botany, medicine, Humans, Food science, Carotenoid, Reactive nitrogen species, Cell Proliferation, chemistry.chemical_classification, Reactive oxygen species, biology, Plant Extracts, 010401 analytical chemistry, food and beverages, 04 agricultural and veterinary sciences, General Medicine, biology.organism_classification, Carotenoids, Reactive Nitrogen Species, 040401 food science, eye diseases, 0104 chemical sciences, Oxidative Stress, chemistry, Fruit, Seeds, Caco-2 Cells, Reactive Oxygen Species, Brazil, Oxidative stress, Food Science
Abstract: Bactris setosa Mart. is a Brazilian tree from the palm family (Arecaceae), whose fruits are scientifically underexploited. Here, we report, for the first time, the identification and quantification of phenolic compounds and carotenoids in the pulp, seed, and peel extracts of B. setosa fruits and their in vitro biological activity. The anthocyanins cyanidin deoxyhexose hexoside and cyanidin hexoside and other phenolic compounds were detected mainly in the peel but also in the pulp extracts. All-trans-lutein was the unique carotenoid identified and quantified, and only in the peel extract. All extracts were able to scavenge reactive oxygen and nitrogen species (ROS and RNS, respectively), to modulate human neutrophils' oxidative burst and to protect Caco-2 cells against oxidative damage, the peel extract being the most efficient. This study indicates that extracts from B. setosa fruits, especially the peel extract, are a source of bioactive compounds with promising antioxidant and anti-inflammatory properties.
Published: 2017

30. Toxicity of the amphetamine metabolites 4-hydroxyamphetamine and 4-hydroxynorephedrine in human dopaminergic differentiated SH-SY5Y cells

Author: João Paulo Capela, Luísa M. Ferreira, Fábio Claudiney da Costa Pereira, Paula S. Branco, M.D.L. Bastos, Félix Carvalho, Rita Feio-Azevedo, and Vera Marisa Costa
Subjects: 0301 basic medicine, p-Hydroxyamphetamine, SH-SY5Y, Cell Survival, Metabolite, Apoptosis, Pharmacology, Toxicology, p-Hydroxynorephedrine, Cell Line, Lethal Dose 50, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Carnitine, Lactate dehydrogenase, medicine, Humans, Cycloheximide, Amphetamine, Dose-Response Relationship, Drug, Dopaminergic Neurons, Dopaminergic, Neurotoxicity, Cell Differentiation, 4-Hydroxyamphetamine, General Medicine, medicine.disease, Acetylcysteine, 030104 developmental biology, chemistry, Biochemistry, Toxicity, Methylphenidate, Reactive Oxygen Species, 030217 neurology & neurosurgery, medicine.drug
Abstract: Amphetamine (AMPH) is a psychostimulant used worldwide by millions of patients in the clinical treatment of attention deficit hyperactivity disorder, narcolepsy or even obesity, and is also a drug of abuse. 4-Hydroxynorephedrine (4-OHNE) and 4-hydroxyamphetamine (4-OHAMPH) are two major metabolites known to persist in the brain longer than AMPH. The contribution of AMPH metabolites for its neurotoxicity is undetermined. We evaluated the toxicity of AMPH and its metabolites 4-OHNE and 4-OHAMPH, obtained by chemical synthesis, in human dopaminergic differentiated SH-SY5Y neurons. Cells were exposed to AMPH (concentration range 0-5mM) or 4-OHAMPH or 4-OHNE (concentration range 0-10mM) for 24 or 48h, and the viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) leakage assays. Results showed that for both AMPH and the metabolites a concentration-dependent toxicity was observed. The toxic concentration 50% (TC50) for AMPH and 4-OHNE following 24h exposure was circa 3.5mM and 8mM, respectively. For 4-OHAMPH the TC50 was not reached in the tested concentration range. N-acetyl cysteine, cycloheximide, l-carnitine, and methylphenidate were able to reduce cell death induced by AMPH TC50. Acridine orange/ethidium bromide staining showed evident signs of late apoptotic cells and necrotic cells following 24h exposure to AMPH 3.50mM. The 4-OHAMPH metabolite at 8.00mM originated few late apoptotic cells, whereas 4-OHNE at 8.00mM resulted in late apoptotic cells and necrotic cells, in a scenario similar to AMPH. In conclusion, the AMPH metabolite 4-OHNE is more toxic than 4-OHAMPH, nonetheless both are less toxic than the parent compound in vitro. The most toxic metabolite 4-OHNE has longer permanence in the brain, rendering likely its contribution for AMPH neurotoxicity.
Published: 2017

31. Correction to: In vitro mechanistic studies on α-amanitin and its putative antidotes

Author: Félix Carvalho, Vera Marisa Costa, Ricardo Pires das Neves, Daniela Ferreira Rodrigues, Maria de Lourdes Bastos, and Alexandra T. P. Carvalho
Subjects: business.industry, Health, Toxicology and Mutagenesis, Pharmacology toxicology, Medicine, General Medicine, Pharmacology, Toxicology, business, In vitro, Amanitin
Published: 2020

32. An effective antidotal combination of polymyxin B and methylprednisolone for α-amanitin intoxication

Author: Juliana Garcia, Maria de Lourdes Bastos, Daniela Ferreira Rodrigues, Antonio Bovolini, Félix Carvalho, Vera Marisa Costa, and José Alberto Duarte
Subjects: 0301 basic medicine, Male, endocrine system, animal structures, Health, Toxicology and Mutagenesis, Amanita, Antidotes, Anti-Inflammatory Agents, Mushroom Poisoning, 010501 environmental sciences, Pharmacology, Toxicology, medicine.disease_cause, 01 natural sciences, Methylprednisolone, Nephrotoxicity, 03 medical and health sciences, Mice, polycyclic compounds, medicine, Animals, Amanita phalloides, Mushroom poisoning, 0105 earth and related environmental sciences, Amanitin, Alpha-Amanitin, Polymyxin B, biology, Toxin, Chemistry, General Medicine, biology.organism_classification, medicine.disease, 030104 developmental biology, Treatment Outcome, Toxicity, Drug Therapy, Combination, medicine.drug
Abstract: Amanita phalloides is one of the most toxic mushrooms worldwide, and it is involved in the majority of human fatal cases of mushroom poisoning. α-Amanitin, the most deleterious toxin of A. phalloides to humans, inhibits RNA polymerase II (RNAPII), causing hepatic and renal failure. Previously, we have shown that polymyxin B (polB) reverts α-amanitin inhibition of RNAPII, although it was not able to guarantee the full survival of α-amanitin-intoxicated mice or prevent α-amanitin pro-inflammatory effects. α-Amanitin is also a substrate of the organic-anion-transporting polypeptide 1B3 (OATP1B3) and Na(+)-taurocholate cotransporter polypeptide (NTCP) transporters. Therefore, in the present work, we used a combination of polB [(2.5 mg/kg intraperitoneal (i.p.)] with the anti-inflammatory and NTCP inhibitor drug, methylprednisolone (MP) (10 mg/kg i.p.), as an attempt to fully revert α-amanitin-induced toxicity (0.33 mg/kg i.p.) in CD-1 mice. Results showed that the administration of the polB + MP combination, 4 h after α-amanitin, led to the full survival of the intoxicated animals, with a significant attenuation of α-amanitin-induced renal and hepatic necrosis. Also, the combination polB + MP led to a decrease of aminotransferase plasma levels, of the renal myeloperoxidase activity and of renal inflammatory cell infiltrate promoted by α-amanitin, although not preventing any of the hepatic pro-inflammatory effect of the toxin. The obtained results indicate that this combination may represent an important and valuable therapeutic approach to be used against α-amanitin intoxication.
Published: 2019

33. Aged rats are more vulnerable than adolescents to 'ecstasy'-induced toxicity

Author: Margarida Duarte-Araújo, Armanda Teixeira-Gomes, João Paulo Capela, Daniel José Barbosa, José Alberto Duarte, Vera Marisa Costa, Eduarda Fernandes, Inês R. Pita, M.D.L. Bastos, Fábio Claudiney da Costa Pereira, Félix Carvalho, Rita Feio-Azevedo, S. Gomes, and Fernanda Marques
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Aging, Serotonin, Fever, Health, Toxicology and Mutagenesis, Dopamine, N-Methyl-3,4-methylenedioxyamphetamine, Ecstasy, Hippocampus, Striatum, Toxicology, Serotonergic, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, mental disorders, Medicine, Animals, Rats, Wistar, business.industry, Neurotoxicity, Brain, MDMA, Heart, General Medicine, medicine.disease, 030104 developmental biology, Endocrinology, Liver, Neurotoxicity Syndromes, business, psychological phenomena and processes, 030217 neurology & neurosurgery, medicine.drug
Abstract: 3,4-Methylenedioxymethamphetamine (MDMA or “ecstasy”) is a widespread drug of abuse with known neurotoxic properties. The present study aimed to evaluate the differential toxic effects of MDMA in adolescent and aged Wistar rats, using doses pharmacologically comparable to humans. Adolescent (post-natal day 40) (3 × 5 mg/kg, 2 h apart) and aged (mean 20 months old) (2 × 5 mg/kg, 2 h apart) rats received MDMA intraperitoneally. Animals were killed 7 days later, and the frontal cortex, hippocampus, striatum and cerebellum brain areas were dissected, and heart, liver and kidneys were collected. MDMA caused hyperthermia in both treated groups, but aged rats had a more dramatic temperature elevation. MDMA promoted serotonergic neurotoxicity only in the hippocampus of aged, but not in the adolescents’ brain, and did not change the levels of dopamine or serotonin metabolite in the striatum of both groups. Differential responses according to age were also seen regarding brain p-Tau levels, a hallmark of a degenerative brain, since only aged animals had significant increases. MDMA evoked brain oxidative stress in the hippocampus and striatum of aged, and in the hippocampus, frontal cortex, and striatum brain areas of adolescents according to protein carbonylation, but only decreased GSH levels in the hippocampus of aged animals. The brain maturational stage seems crucial for MDMA-evoked serotonergic neurotoxicity. Aged animals were more susceptible to MDMA-induced tissue damage in the heart and kidneys, and both ages had an increase in liver fibrotic tissue content. In conclusion, age is a determinant factor for the toxic events promoted by “ecstasy”. This work demonstrated special susceptibility of aged hippocampus to MDMA neurotoxicity, as well as impressive damage to the heart and kidney tissue following “ecstasy”.
Published: 2018

34. A breakthrough on Amanita phalloides poisoning: an effective antidotal effect by polymyxin B

Author: Ricardo Jorge Dinis-Oliveira, Juliana Garcia, Marcelo Dutra Arbo, Félix Carvalho, Ricardo Silvestre, Maria de Lourdes Bastos, Paula Baptista, Alexandra T. P. Carvalho, Vera Marisa Costa, José Alberto Duarte, Teresa Baltazar, Daniel F. A. R. Dourado, and Universidade do Minho
Subjects: Male, endocrine system, Time Factors, animal structures, medicine.drug_class, Amanita, Health, Toxicology and Mutagenesis, Polymyxin, medicine.medical_treatment, Antidotes, Mushroom Poisoning, alpha-Amanitin, Molecular Dynamics Simulation, Biology, Kidney, Toxicology, medicine.disease_cause, Microbiology, Mice, chemistry.chemical_compound, In vivo, polycyclic compounds, medicine, Animals, Humans, Computer Simulation, Amanita phalloides, Renal Insufficiency, Antidote, Alpha-Amanitin, Polymyxin B, Science & Technology, Toxin, General Medicine, biology.organism_classification, 3. Good health, Molecular Docking Simulation, Survival Rate, medicine.anatomical_structure, Liver, chemistry, α-Amanitin, RNA polymerase II, Liver Failure, medicine.drug
Abstract: Amanita phalloides is responsible for more than 90 % of mushroom-related fatalities, and no effective antidote is available. a-Amanitin, the main toxin of A. phalloides, inhibits RNA polymerase II (RNAP II), causing hepatic and kidney failure. In silico studies included docking and molecular dynamics simulation coupled to molecular mechanics with generalized Born and surface area method energy decomposition on RNAP II. They were performed with a clinical drug that shares chemical similarities to a-amanitin, polymyxin B. The results show that polymyxin B potentially binds to RNAP II in the same interface of a-amanitin, preventing the toxin from binding to RNAP II. In vivo, the inhibition of the mRNA transcripts elicited by a-amanitin was efficiently reverted by polymyxin B in the kidneys. Moreover, polymyxin B significantly decreased the hepatic and renal a-amanitin-induced injury as seen by the histology and hepatic aminotransferases plasma data. In the survival assay, all animals exposed to a-amanitin died within 5 days, whereas 50 % survived up to 30 days when polymyxin B was administered 4, 8, and 12 h post-a-amanitin. Moreover, a single dose of polymyxin B administered concomitantly with a-amanitin was able to guarantee 100 % survival. Polymyxin B protects RNAP II from inactivation leading to an effective prevention of organ damage and increasing survival in a-amanitin-treated animals. The present use of clinically relevant concentrations of an already human-use-approved drug prompts the use of polymyxin B as an antidote for A. phalloides poisoning in humans., Juliana Garcia, Vera Marisa Costa, Ricardo Dinis-Oliveira and Ricardo Silvestre thank FCT-Foundation for Science and Technology-for their PhD grant (SFRH/BD/74979/2010), Post-doc grants (SFRH/BPD/63746/2009 and SFRH/BPD/110001/2015) and Investigator grants (IF/01147/2013) and (IF/00021/2014), respectively. This work was supported by the Fundacao para a Ciencia e Tecnologia (FCT) - project PTDC/DTPFTO/4973/2014 - and the European Union (FEDER funds through COMPETE) and National Funds (FCT, Fundacao para a Ciencia e Tecnologia) through project Pest-C/EQB/LA0006/2013.
Published: 2015

35. Inosine Strongly Enhances Proliferation of Human C32 Melanoma Cells through PLC-PKC-MEK1/2-ERK1/2 and PI3K Pathways

Author: Vera Marisa Costa, Paula Fresco, Ana Sofia Soares, and Carmen Diniz
Subjects: Skin Neoplasms, Tetrazolium Salts, Biology, Toxicology, Phosphatidylinositol 3-Kinases, Adenosine deaminase, Cell Line, Tumor, medicine, Humans, Inosine, Melanoma, PI3K/AKT/mTOR pathway, Cell Proliferation, Pharmacology, Mitogen-Activated Protein Kinase 3, Cell growth, General Medicine, Purinergic signalling, Adenosine A3 receptor, Adenosine receptor, Adenosine, Thiazoles, Bromodeoxyuridine, Biochemistry, Cancer research, biology.protein, Signal Transduction, medicine.drug
Abstract: Malignant melanoma is the most deadly type of skin cancer. The lack of effective pharmacological approaches for this tumour can be related to the incomplete understanding of the pathophysiological mechanisms involved in melanoma cell proliferation. Adenosine has growth-promoting and growth inhibitory effects on tumour cells. We aimed to investigate effects of adenosine and its metabolic product, inosine, on human C32 melanoma cells and the signalling pathways involved. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction and bromodeoxyuridine (BrdU) proliferation assays were used to evaluate adenosine, adenosine deaminase and inosine effects, in the absence or presence of adenosine receptor (AR), A3 AR and P2Y1 R antagonists and PLC, PKC, MEK1/2 and PI3K inhibitors. ERK1/2 levels were determined using an ELISA kit. Adenosine and inosine levels were quantified using an enzyme-coupled assay. Adenosine caused cell proliferation through AR activation. Adenosine deaminase increased inosine levels (nanomolar concentrations) on the extracellular space, in a time-dependent manner, inducing proliferation through A3 AR activation. Micromolar concentrations of inosine enhanced proliferation through A3 AR activation, causing an increase in ERK1/2 levels, and P2Y1 R activation via ENT-dependent mechanisms. We propose the simultaneous activation of PLC-PKC-MEK1/2-ERK1/2 and PI3K pathways as the main mechanism responsible for the proliferative effect elicited by inosine and its significant role in melanoma cancer progression.
Published: 2014

36. Combination of Cl-IB-MECA with paclitaxel is a highly effective cytotoxic therapy causing mTOR-dependent autophagy and mitotic catastrophe on human melanoma cells

Author: Vera Marisa Costa, Paula Fresco, Carmen Diniz, and Ana Sofia Soares
Subjects: Autophagosome, Cancer Research, Programmed cell death, Adenosine, Paclitaxel, Blotting, Western, Fluorescent Antibody Technique, Mitosis, Apoptosis, Pharmacology, Biology, chemistry.chemical_compound, Adenosine A3 Receptor Agonists, Autophagy, Tumor Cells, Cultured, Humans, Cytotoxicity, Melanoma, Mitotic catastrophe, PI3K/AKT/mTOR pathway, Cell Proliferation, TOR Serine-Threonine Kinases, Drug Synergism, General Medicine, Antineoplastic Agents, Phytogenic, Oncology, chemistry, Drug Therapy, Combination
Abstract: Metastatic melanoma is the deadliest form of skin cancer. It is highly resistant to conventional therapies, particularly to drugs that cause apoptosis as the main anticancer mechanism. Recently, induction of autophagic cell death is emerging as a novel therapeutic target for apoptotic-resistant cancers. We aimed to investigate the underlying mechanisms elicited by the cytotoxic combination of 2-chloro-N(6)-(3-iodobenzyl)-adenosine-5′-N-methyl-uronamide (Cl-IB-MECA, a selective A3 adenosine receptor agonist; 10 μM) and paclitaxel (10 ng/mL) on human C32 and A375 melanoma cell lines. Cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide reduction, neutral red uptake, and lactate dehydrogenase leakage assays, after 48-h incubation. Autophagosome and autolysosome formation was detected by fluorescence through monodansylcadaverine-staining and CellLight® Lysosomes-RFP-labelling, respectively. Cell nuclei were visualized by Hoechst staining, while levels of p62 were determined by an ELISA kit. Levels of mammalian target of rapamycin (mTOR) and the alterations of microtubule networks were evaluated by immunofluorescence. We demonstrated, for the first time, that the combination of Cl-IB-MECA with paclitaxel significantly increases cytotoxicity, with apoptosis and autophagy the major mechanisms involved in cell death. Induction of autophagy, using clinically relevant doses, was confirmed by visualization of autophagosome and autolysosome formation, and downregulation of mTOR and p62 levels. Caspase-dependent and caspase-independent mitotic catastrophe evidencing micro- and multinucleation was also observed in cells exposed to our combination. The combination of Cl-IB-MECA and paclitaxel causes significant cytotoxicity on two melanoma cell lines through multiple mechanisms of cell death. This multifactorial hit makes this therapy very promising as it will help to avoid melanoma multiresistance to chemotherapy and therefore potentially improve its treatment.
Published: 2014

37. The Heart As a Target for Xenobiotic Toxicity: The Cardiac Susceptibility to Oxidative Stress

Author: Félix Carvalho, Vera Marisa Costa, Maria de Lourdes Bastos, Fernando Remião, and José Alberto Duarte
Subjects: Antioxidant, medicine.medical_treatment, Antineoplastic Agents, Oxidative phosphorylation, Pharmacology, Biology, Toxicology, medicine.disease_cause, Xenobiotics, chemistry.chemical_compound, medicine, Animals, Humans, Receptor, Heart Failure, chemistry.chemical_classification, Reactive oxygen species, Myocardium, Heart, General Medicine, medicine.disease, Oxidative Stress, chemistry, Heart failure, Toxicity, Xenobiotic, Oxidative stress
Abstract: The heart is a target organ for oxidative stress-related injuries. Because of its very high energetic metabolic demand, the heart has the highest rate of production of reactive oxygen species, namely, hydrogen peroxide (H2O2), per gram of tissue. Additionally, the heart has lower levels of antioxidants and total activity of antioxidant enzymes when compared to other organs. Furthermore, drugs that have relevant antioxidant activity and that are used in the treatment of oxidative stress related cardiac diseases demonstrate better clinical cardiac outcomes than other drugs with similar receptor affinity but with no antioxidant activity. Several xenobiotics particularly target the heart and promote toxicity. Anticancer drugs, like anthracyclines, cyclophosphamide, mitoxantrone, and more recently tyrosine kinase targeting drugs, are well-known cardiac toxicants whose therapeutic application has been associated to a high prevalence of heart failure. High levels of catecholamines or drugs of abuse, namely, amphetamines, cocaine, and even the consumption of alcohol for long periods of time, are linked to cardiovascular abnormalities. Oxidative stress may be one common link for the cardiac toxicity elicited by these compounds. We aim to revise the mechanisms involved in cardiac lesions caused by the above-mentioned substances specially focusing in oxidative stress related pathways. Oxidative stress biomarkers can be useful in the early recognition of cardiotoxicity in patients treated with these drugs and aid to minimize the setting of cardiac irreversible events.
Published: 2013

38. Acetaminophen prevents oxidative burst and delays apoptosis in human neutrophils

Author: Marisa Freitas, Daniela Ribeiro, Félix Carvalho, Eduarda Fernandes, Graça Porto, Vera Marisa Costa, and Diana Couto
Subjects: Programmed cell death, Neutrophils, Apoptosis, Inflammation, In Vitro Techniques, Pharmacology, Toxicology, chemistry.chemical_compound, Centrifugation, Density Gradient, medicine, Humans, Annexin A5, Acetaminophen, Fluorescent Dyes, Respiratory Burst, Membrane Potential, Mitochondrial, chemistry.chemical_classification, Reactive oxygen species, digestive, oral, and skin physiology, Free Radical Scavengers, Hydrogen Peroxide, General Medicine, Glutathione, Analgesics, Non-Narcotic, Hypochlorous Acid, Respiratory burst, stomatognathic diseases, chemistry, Phorbol, Tetradecanoylphorbol Acetate, medicine.symptom, medicine.drug
Abstract: Acetaminophen is a frequently prescribed over-the-counter drug to reduce fever and pain in the event of inflammatory process. As neutrophils are relevant cells in inflammatory processes, the putative interaction of acetaminophen with these cells, if present, would be of paramount importance. The present study was undertaken to evaluate the effect of acetaminophen in human neutrophils' oxidative burst and lifespan in vitro. The obtained results demonstrate that acetaminophen efficiently modulates neutrophils' oxidative burst in phorbol myristate acetate-activated neutrophils, in a concentration-dependent manner, at in vivo relevant concentrations. It was clearly demonstrated that acetaminophen is a strong scavenger of HOCl and H2O2, which probably contributed to the effect observed in neutrophils. Acetaminophen also induced the depletion of glutathione in stimulated neutrophils, suggesting its transformation into a reactive intermediate. Obtained results further revealed that acetaminophen affects programmed cell death of human neutrophils, resulting in a delay of previously stimulated neutrophils-mediated apoptosis. Overall, our data suggested that acetaminophen has considerable potential to be included in anti-inflammatory therapeutic strategies, by preventing biological damage induced by an excessive production of reactive species generated in activated neutrophils and by extending the lifespan of neutrophils, favoring the elimination of pathogens, thus contributing to tissue healing and resolution of inflammation.
Published: 2013

39. The metabolic profile of mitoxantrone and its relation with mitoxantrone-induced cardiotoxicity

Author: Maria de Lourdes Bastos, Victor de Freitas, Fernando Remião, Vera Marisa Costa, Marcelo Dutra Arbo, Luciana Grazziotin Rossato, Laure Vilain, Carlos M. Palmeira, and Paula Guedes de Pinho
Subjects: Male, musculoskeletal diseases, S9 fraction, Time Factors, Heart Diseases, Health, Toxicology and Mutagenesis, Metabolite, Antineoplastic Agents, Pharmacology, Toxicology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cytochrome P-450 Enzyme System, immune system diseases, In vivo, medicine, Animals, Tissue Distribution, heterocyclic compounds, Enzyme Inhibitors, Rats, Wistar, skin and connective tissue diseases, Cytotoxicity, 030304 developmental biology, 0303 health sciences, Cardiotoxicity, Mitoxantrone, Bioactivation, Dose-Response Relationship, Drug, Cytochrome P-450 CYP2E1, Heart, LC/MS, General Medicine, Glutathione, Rats, 3. Good health, Metabolism, Liver, chemistry, 030220 oncology & carcinogenesis, Toxicity, medicine.drug
Abstract: Mitoxantrone (MTX) is an antitumor agent that causes cardiotoxicity in 18 % patients. The metabolic profile of MTX was assessed after incubation of 100 lM MTX with hepatic S9 fraction isolated from rats. The presence of MTX and its metabolites was also assessed in vivo through the analysis of liver and heart extracts of MTX-treated rats. The cytotoxic effects of MTX and MTX metabolites were evaluated in the H9c2 cells after 24-h incubation with MTX alone and MTX ? metabolites. The influence of CYP450- and CYP2E1-mediated metabolism for the cytotoxicity of MTX was assessed after 96-h incubation with MTX (100 nM and 1 lM) in the presence/ absence of CYP450 or CYP2E1 inhibitors. After 4-h incubation in supplemented S9 fraction, the MTX content was 35 % lower and 5 metabolites were identified: an acetoxy ester derivative (never described before), two glutathione conjugates, a monocarboxylic acid derivative, and the naphtoquinoxaline, the later commonly related to MTX pharmacological effects. The presence of MTX and naphtoquinoxaline metabolite was evidenced in vivo in liver and heart of MTX-treated rats. The cytotoxicity caused by MTX ? metabolites was higher than that observed in the H9c2 cells incubated with non-metabolized MTX group. The co-incubation of MTX with CYP450 and CYP2E1 inhibitors partially prevented the cytotoxicity observed in the MTX groups incubated with H9c2 cells, highlighting that the metabolism of MTX is relevant for its undesirable effects. The naphtoquinoxaline metabolite is described in heart and liver in vivo, highlighting that this metabolite accumulates in these tissues. It was demonstrated that MTX P450-mediated metabolism contributed to MTX toxicity. This work was supported by the Fundac¸a˜o para a Cieˆncia e Tecnologia (FCT)—project [EXPL/DTP-FTO/0290/2012]—QREN initiative with EU/FEDER financing through COMPETE—Operational Programme for Competitiveness Factors. LGR and VMC thank FCT for their Ph.D. grant (SFRH/BD/63473/2009) and Post-doc grant (SFRH/BPD/63746/2009), respectively. The authors are also grateful to Fundac¸a˜o para a Cieˆncia e a Tecnologia (FCT) for Grant No. PEst- C/EQB/LA0006/2011
Published: 2013

40. Naphthoquinoxaline metabolite of mitoxantrone is less cardiotoxic than the parent compound and it can be a more cardiosafe drug in anticancer therapy

Author: Félix Carvalho, Madalena Pinto, Rui A. Carvalho, Emília Sousa, Ana Sara Gomes, Fernando Remião, Vera Marisa Costa, Maria de Lourdes Bastos, and Ana Reis-Mendes
Subjects: musculoskeletal diseases, 0301 basic medicine, Oligomycin, Time Factors, Health, Toxicology and Mutagenesis, Metabolite, Antineoplastic Agents, Pharmacology, Toxicology, Cell Line, 03 medical and health sciences, chemistry.chemical_compound, Adenosine Triphosphate, Lactate dehydrogenase, Quinoxalines, medicine, Autophagy, Animals, Myocytes, Cardiac, Lactic Acid, Cytotoxicity, Membrane Potential, Mitochondrial, Mitoxantrone, Cardiotoxicity, ATP synthase, biology, Dose-Response Relationship, Drug, Adenine, General Medicine, Rats, 030104 developmental biology, chemistry, Toxicity, biology.protein, medicine.drug
Abstract: Mitoxantrone (MTX) is an antineoplastic agent used to treat several types of cancers and on multiple sclerosis, which shows a high incidence of cardiotoxicity. Still, the underlying mechanisms of MTX cardiotoxicity are poorly understood and the potential toxicity of its metabolites scarcely investigated. Therefore, this work aimed to synthesize the MTX-naphthoquinoxaline metabolite (NAPHT) and to compare its cytotoxicity to the parent compound in 7-day differentiated H9c2 cells using pharmacological relevant concentrations (0.01–5 µM). MTX was more toxic in equivalent concentrations in all cytotoxicity tests performed [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide reduction, neutral red uptake, and lactate dehydrogenase release assays] and times tested (24 and 48 h). Both MTX and NAPHT significantly decreased mitochondrial membrane potential in 7-day differentiated H9c2 cells after a 12-h incubation. However, energetic pathways were affected in a different manner after MTX or NAPHT incubation. ATP increased and lactate levels decreased after a 24-h incubation with MTX, whereas for the same incubation time and concentrations, NAPHT did not cause any significant effect. The increased activity of ATP synthase seems responsible for MTX-induced increases in ATP levels, as oligomycin (an inhibitor of ATP synthase) abrogated this effect on 5 µM MTX-incubated cells. 3-Methyladenine (an autophagy inhibitor) was the only molecule to give a partial protection against the cytotoxicity produced by MTX or NAPHT. To the best of our knowledge, this was the first broad study on NAPHT cardiotoxicity, and it revealed that the parent drug, MTX, caused a higher disruption in the energetic pathways in a cardiac model in vitro, whereas autophagy is involved in the toxicity of both compounds. In conclusion, NAPHT is claimed to largely contribute to MTX-anticancer properties; therefore, this metabolite should be regarded as a good option for a safer anticancer therapy since it is less cardiotoxic than MTX.
Published: 2016

41. Department of Error

Author: Maziar Moradi-Lakeh, Krishna K. Aryal, Mohamad-Hani Temsah, Ahmad Daryani, Claudio Alberto Davila, Achala Upendra Jayatilleke, David L. Smith, Chinwe Juliana Iwu, Kavumpurathu Raman Thankappan, Ibrahim Abdollahpour, Mehdi Fazlzadeh, Robert C. Reiner, Bineyam Taye, Dadi Marami, Ghulam Mustafa, Manasi Kumar, Mostafa Leili, Mehdi Sharif, Mohsen Naghavi, Maarten J. Postma, Chhabi Lal Ranabhat, Oluchi Okpala, Shivakumar K.M. Kondlahalli, Nihal Thomas, Man Mohan Mehndiratta, Ebrahim Babaee, Tsegaye Lolaso Lenjebo, Miliva Mozaffor, Carl Abelardo T. Antonio, Morteza Abdullatif Khafaie, Meysam Behzadifar, Carlos Miguel Rios González, Pallab K. Maulik, Ali H. Mokdad, Mehran Alijanzadeh, Florian Fischer, Lalit Dandona, Aso Mohammad Darwesh, Alemayehu Toma Mena, Jennifer Rickard, Benjamin K. Mayala, Seyed Mostafa Mir, Moslem Soofi, Bhaskaran Unnikrishnan, Boris Bikbov, Bereket Duko Adema, Jagdish Khubchandani, Sachin R Atre, Rafael Moreira Claro, Sandra B. Munro, Carlos Zambrana-Torrelio, Kassawmar Angaw Bogale, Soraya Siabani, Muluken Azage Yenesew, Birhan Tamene Alemnew, Anwar E. Ahmed, Morteza Shamsizadeh, Masresha Tessema Anegago, Muluken Bekele Sorrie, Vivekanand Jha, Gebrekiros Gebremichael Meles, Andre M. N. Renzaho, Muhammad Aziz Rahman, Hebat Allah Salah A. Yousof, Naohiro Yonemoto, Ahmad Ghashghaee, Kebede Embaye Gezae, Hadi Pourjafar, Junaid Khan, Farnam Mohebi, Marcel Ausloos, Manisha Dubey, Quynh Anh P. Nguyen, Assefa Desalew, Vera Marisa Costa, Mohammad Fareed, Ronny Westerman, Maciej Banach, Paul S. F. Yip, Kala M. Mehta, Mehdi Yaseri, Quique Bassat, Amir Almasi-Hashiani, Fatemeh Rajati, Irina Filip, Gelin Xu, Derrick A Bennett, Atalay Goshu Muluneh, Leeberk Raja Inbaraj, Edgar Denova-Gutiérrez, Fariba Ghassemi, Behzad Karami Matin, David C. Schwebel, Syed Ather Hussain, Milena Ilic, Xiu Ju Zhao, Jost B. Jonas, Dian Kusuma, Martin Amogre Ayanore, Mostafa Hosseini, Sanjay Zodpey, Birhanu Geta, Amaha Kahsay, Santosh Varughese, Cuong Tat Nguyen, Chalachew Genet Akal, Chabila C Mapoma, Aubrey J. Levine, Jacqueline Elizabeth Alcalde Rabanal, Hesham M. Al-Mekhlafi, Rufus A. Adedoyin, Gudlavalleti Vs Murthy, Amir Khater, Olufemi Ajumobi, Seth Christopher Yaw Appiah, Mehdi Ahmadi, Lorenzo Monasta, Mohammad Hossein Khosravi, Rizwan Suliankatchi Abdulkader, Richard C. Franklin, Dara K. Mohammad, Naznin Hossain, Dhirendra N Sinha, Shai Linn, Fisaha Haile Tesfay, Abdullah Al Mamun, Yoshan Moodley, Amjad Mohamadi-Bolbanabad, Hajer Elkout, Mohammad Zamani, Yousef Mohammad, Yousef Veisani, Iman El Sayed, Asmamaw Bizuneh Demis, Alex Yeshaneh, Sharath Burugina Nagaraja, Segun Emmanuel Ibitoye, Charles Shey Wiysonge, Pushpendra Kumar, Engida Yisma, Maysaa El Sayed Zaki, Kebede Deribe, Ali Akbar Fazaeli, Moritz U. G. Kraemer, Ayele Geleto Bali, Platon D. Lopukhov, Paula Moraga, Giovanni Damiani, Alebachew Fasil Ashagre, Hossein Farzam, Amir Kasaeian, Taye Abuhay Zewale, Ben Lacey, Mika Shigematsu, Bryan L. Sykes, Abdur Razzaque Sarker, Ali Kabir, Lal B. Rawal, Juan Sanabria, Ehsan Khodamoradi, Saeed Amini, Hasan Yusefzadeh, Josephine W. Ngunjiri, Aberash Abay Tassew, Sezer Kisa, Biruck Desalegn Yirsaw, Hosni Salem, Ayman Grada, Jean Jacques Noubiap, Mina Anjomshoa, Gebre Teklemariam Demoz, Sharareh Eskandarieh, Maryam Adabi, Nuworza Kugbey, Rahman Shiri, Melkamu Merid Mengesha, Zemenu Tadesse Tessema, Amir Radfar, Girmay Teklay Weldesamuel, Sahel Valadan Tahbaz, Nader Jahanmehr, Yuming Guo, Roghiyeh Faridnia, Mehdi Naderi, Ziad A. Memish, Adnan Kisa, Gbenga A. Kayode, Yafeng Wang, Ehsan Sadeghi, Behnam Heidari, Apurba Shil, Kamarul Imran Musa, Jagadish Rao Padubidri, Farshad Pourmalek, Saravanan Muthupandian, Navid Rabiee, Mario Poljak, Nima Hafezi-Nejad, Hagos Degefa Hidru, Jemal Abdu Mohammed, MohammadBagher Shamsi, Mohsen Asadi-Lari, Sameh Magdeldin, Berhe Etsay Tesfay, Khanh Bao Tran, James A Platts-Mills, Jan-Walter De Neve, Maria Jesus Rios-Blancas, Hedley Quintana, Félix Carvalho, Yun Jin Kim, Eric L. Ding, Noushin Mohammadifard, Saeed Safari, Addisu Melese, Rakesh Lodha, Reza Shirkoohi, Itamar S. Santos, Alireza Khatony, Mohammad Khazaei, Mekdes Tigistu Yilma, Taweewat Wiangkham, Hamed Kalani, Mayowa O. Owolabi, Mohammad Reza Sobhiyeh, Frank B. Osei, Narayan Bahadur Mahotra, Zewdie Aderaw Alemu, Konrad Pesudovs, Kewal Krishan, Samath D Dharmaratne, Ayalew Jejaw Zeleke, Osayomwanbo Osarenotor, Tina Beyranvand, Yahya Salimi, Winfried März, Sheikh Mohammed Shariful Islam, Azmeraw T. Amare, Julio Cesar Campuzano Rincon, Maha El Tantawi, Anusha Ganapati Bhat, Susanna Dunachie, Shymaa Enany, Anelisa Jaca, Desalegn Tadese Mengistu, Salvatore Rubino, Nelson J. Alvis-Zakzuk, Indang Trihandini, Bartosz Miazgowski, Huda Basaleem, Zahid A Butt, Vijay Kumar Chattu, Navid Manafi, Si Si, Joan B. Soriano, Victor Adekanmbi, Andrea Farioli, Masoud Moradi, Joseph Frostad, Collins Chansa, Enrico Rubagotti, Edward J Mills, Senbagam Duraisamy, Foad Abd-Allah, Moses K. Muriithi, Elias Merdassa Roro, Netsanet Fentahun, Kenji Shibuya, Amira Hamed Darwish, Ai-Min Wu, Tomohide Yamada, Lauren E. Schaeffer, Sonia Lewycka, Catalina Liliana Andrei, Ali Kazemi Karyani, Beyene Meressa Adhena, Shaimaa I. El-Jaafary, Francisco Rogerlandio Martins-Melo, Faris Lami, Aziz Eftekhari, Naser Mohammad Gholi Mezerji, André Karch, Suraj Bhattarai, Mona M. Khater, Paulina A. Lindstedt, Marcos Roberto Tovani-Palone, Kedir Hussein Abegaz, Padukudru Anand Mahesh, Alexandre C. Pereira, Ammas Siraj Mohammed, Mehdi Hosseinzadeh, Reta Tsegaye Gayesa, In-Hwan Oh, Dietrich Rothenbacher, Margaret Kosek, Yunquan Zhang, Ketema Bizuwork Gebremedhin, Rahul Gupta, Claudiu Herteliu, Nicole Davis Weaver, Dawit Zewdu Wondafrash, Oliver J. Brady, Samad Azari, Ebrahim M Yimer, Andrew T Olagunju, Ana Laura Manda, Ali Rostami, Aniruddha Deshpande, Ninuk Hariyani, Gulfaraz Khan, Narinder Pal Singh, Dabere Nigatu, Jae Il Shin, Preeti Dhillon, Duduzile Ndwandwe, Michelle L. Bell, Rakhi Dandona, Mojtaba Hoseini-Ghahfarokhi, Obinna Onwujekwe, Olatunji O. Adetokunboh, Tanuj Kanchan, Suleman Atique, Rovshan Khalilov, Ai Koyanagi, Ejaz Ahmad Khan, Jalal Arabloo, Ahmed Abdelalim, Van C. Lansingh, Ali Almasi, Catherine A. Welgan, Surendra Karki, Eirini Skiadaresi, Aleksandra Barac, Simon I. Hay, Hamid Yimam Hassen, Mohammad Ali Sahraian, Akram Pourshams, Mowafa Househ, Dilaram Acharya, Getnet Mengistu, Arya Haj-Mirzaian, Salman Khazaei, Bahram Armoon, Emerito Jose Aquino Faraon, Mu'awiyyah Babale Sufiyan, Harish Chander Gugnani, David Laith Rawaf, Ali S. Akanda, Till Bärnighausen, Veincent Christian Filipino Pepito, Ahmed Omar Bali, Norberto Perico, Sergio I. Prada, Mohammad Moradi-Joo, Helen Derara Diro, Gebremicheal Gebreslassie Kasahun, Andre Rodrigues Duraes, Ajay Patle, Simin Mouodi, Yuan-Pang Wang, Alireza Esteghamati, Paramjit Gill, Ahamarshan Jayaraman Nagarajan, Meghnath Dhimal, Hafiz Ansar Rasul Suleria, Saleh Salehi Zahabi, Nader Jafari Balalami, Lucas Earl, Haileab Fekadu Wolde, Doris D. V. Ortega-Altamirano, Beatriz Paulina Ayala Quintanilla, Franz Castro, Deborah Carvalho Malta, Desta Haftu Hayelom, Sebastian Vollmer, Getinet Ayano, Arianna Maever L. Amit, Bárbara Niegia Garcia de Goulart, John S. Ji, Raaj Kishore Biswas, Michael R.M. Abrigo, Arash Etemadi, Andrey Nikolaevich Briko, Nefsu Awoke, Anton Sokhan, Daniel Adane Endalew, Ibrahim Abdelmageed Ginawi, Jacek Jóźwiak, Mihajlo Jakovljevic, Degu Abate, Ali S. Shalash, Hamidreza Haririan, Lucas Guimarães Abreu, Davide Guido, Masoud Foroutan, Karzan Abdulmuhsin Mohammad, Niranjan Kissoon, Farkhonde Salehi, Ashish Awasthi, Hosein Shabaninejad, Trang Huyen Nguyen, Anthony Masaka, Getenet Dessie, Fakher Rahim, Aklilu Endalamaw, Kiana Ramezanzadeh, Farzad Manafi, Olayinka Stephen Ilesanmi, Vahid Alipour, Neeraj Bedi, Kimberly B. Johnson, Laurie B. Marczak, Mehran Shams-Beyranvand, Amira Shaheen, Zubair Kabir, Saleem Muhammad Rana, Marzieh Nojomi, Peter Njenga Keiyoro, Yared Asmare Aynalem, Tissa Wijeratne, Fiseha Wadilo Wada, Giuseppe Remuzzi, Carlo La Vecchia, Chuanhua Yu, Pascual R. Valdez, Senthilkumar Balakrishnan, Phetole Walter Mahasha, Liliana Preotescu, Tewodros Eshete Wonde, Keivan Ahmadi, Masood Ali Shaikh, Leticia Avila-Burgos, Ken Lee Chin, Dinh-Toi Chu, Francesco Saverio Violante, Yasir Waheed, Daniel Diaz, Rosario Cárdenas, Ibrahim A Khalil, Ernoiz Antriyandarti, Adrian Pana, Salman Rawaf, Nauman Khalid, Nejimu Biza Zepro, Turki Alanzi, Amir Jalali, Chukwudi A Nnaji, Kebadnew Mulatu Mihretie, Demelash Woldeyohannes Handiso, Nuruzzaman Khan, Takeshi Fukumoto, Christiane Dolecek, Melese Abate Reta, Vinay Nangia, Soumyadeep Bhaumik, Ravi Mehrotra, Seyed-Mohammad Fereshtehnejad, Brigette F. Blacker, Savita Lasrado, Seifadin Ahmed Shallo, Arash Ziapour, Krittika Bhattacharyya, Praveen Hoogar, Nicola Luigi Bragazzi, Mahdi Safdarian, Seyed Sina Naghibi Irvani, Chi Linh Hoang, Boikhutso Tlou, Manfred Accrombessi, Christopher J L Murray, Dragos Virgil Davitoiu, Hossein Poustchi, Farid Najafi, Sathish Thirunavukkarasu, Daniel Bekele Ketema, Dharmesh Kumar Lal, Vafa Rahimi-Movaghar, Christopher Troeger, Anbissa Muleta Senbeta, Subramanian Senthilkumaran, Paul H. Lee, Genet Melak Alamene, George C Patton, Andem Effiong, André Faro, Rushdia Ahmed, Colm McAlinden, Parvaneh Mirabi, Joshua Longbottom, Hagos Tasew Atalay, Alireza Rafiei, Somayeh Bohlouli, Temesgen Yihunie Akalu, Syed Mohamed Aljunid, Javad Nazari, Ismael R. Campos-Nonato, Eduarda Fernandes, Chandrashekhar T Sreeramareddy, Arvin Haj-Mirzaian, Sanghamitra Pati, Bakhtiar Piroozi, Rafael Alves Guimarães, Khaled Khatab, Evanson Z. Sambala, Mohsen Afarideh, Nelson Alvis-Guzman, Koku Sisay Tamirat, Mustafa Z. Younis, Hamed Zandian, Aparna Lal, Tamer H. Farag, Tahereh Pashaei, Benn Sartorius, Kidane Tadesse Gebremariam, Demelash Abewa Elemineh, Marwa Rashad Salem, Davide Rasella, Hedayat Abbastabar, Manu Raj Mathur, Peng Jia, Natalie Maria Cormier, Olatunde Aremu, Mohammad Reza Salahshoor, Kirsten E. Wiens, Ghobad Moradi, Srinivas Goli, Ruth W Kimokoti, Aliasghar Ahmad Kiadaliri, Khalid A Altirkawi, Ritesh G. Menezes, Molly K. Miller-Petrie, Alaa Badawi, Beriwan Abdulqadir Ali, Ensiyeh Jenabi, Getnet Azeze Gedefaw, Ahmed I. Hasaballah, Arash Tehrani-Banihashemi, Govinda Prasad Dhungana, Eleonora Dubljanin, Amir Hasanzadeh, Jasvinder A. Singh, Fereshteh Ansari, Dina Nur Anggraini Ningrum, Feleke Mekonnen Demeke, Agus Sudaryanto, Muhammad Ali, Yilma Chisha Dea Geramo, Leonardo Roever, Gebreamlak Gebremedhn Gebremeskel, Maheswar Satpathy, Asnakew Achaw Ayele, Seyyed Meysam Mousavi, Devasahayam J. Christopher, Malede Mequanent Sisay, Yibeltal Alemu Bekele, Tamirat Tesfaye Dasa, Gessessew Bugssa Hailu, Luca Ronfani, James Albright, Nathaniel J. Henry, Ionut Negoi, Dessalegn Ajema Berbada, Brijesh Sathian, Yousef Khader, Bal Govind Chauhan, Nikolay Ivanovich Briko, Hamideh Salimzadeh, Ali Bijani, Irfan Ullah, Shirin Djalalinia, Shanshan Li, Kebreab Paulos, Mohsen Bayati, Nasir Salam, Mohammad Ali Mansournia, Rajesh Sagar, Fatemeh Heydarpour, Siamak Sabour, Theo Vos, Tuomo J. Meretoja, Ireneous N. Soyiri, Mathew M. Baumann, Mehedi Hasan, Vishnu Renjith, Nuno Taveira, Getaneh Alemu Abebe, Pranab Chatterjee, Shafiu Mohammed, Dongyu Zhang, Abbas Mosapour, Muki Shey, Rajat Das Gupta, Muktar Beshir Ahmed, Satar Rezaei, Wondimeneh Shibabaw Shiferaw, Kenean Getaneh Tlaye, Eugenio Traini, Oladimeji Adebayo, Aisha Elsharkawy, David M. Pigott, Hadi Hassankhani, Anas M. Saad, Mohammad Rabiee, Sivan Yegnanarayana Iyer Saraswathy, Abdallah M. Samy, Ali Talha Khalil, Nelson G.M. Gomes, Afsaneh Arzani, Ayesha Humayun, Michael Tamene Haile, Huyen Phuc Do, Maryam Khayamzadeh, Rajeev Gupta, Davoud Adham, Farah Daoud, Jai K Das, Ana Isabel Ribeiro, Sameer Vali Gopalani, Joel M. Francis, Alyssa N. Sbarra, Brian J. Hall, Ravi Prakash Jha, David Teye Doku, Guoqing Hu, Erkin M. Mirrakhimov, Seyed Hossein Yahyazadeh Jabbari, S. Mohammad Sajadi, Shankar M Bakkannavar, Ali Yadollahpour, Masoud Behzadifar, and G Anil Kumar
Subjects: Burden of disease, 030219 obstetrics & reproductive medicine, business.industry, Low income and middle income countries, General Medicine, Specific mortality, 030204 cardiovascular system & hematology, Article, 3. Good health, 03 medical and health sciences, Geography, 0302 clinical medicine, Environmental health, Medicine, 030212 general & internal medicine, Geographical inequalities, business, Demography
Abstract: Reiner RC Jr, Hay SI. Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000–17: analysis for the Global Burden of Disease Study 2017. Lancet 2020; 395: 1779–801—In this Article, the author byline has been amended to Local Burden of Disease Diarrhoea Collaborators. This correction has been made to the online version as of June 4, 2020, and the printed version is correct. © 2020 Elsevier Ltd
Published: 2018

42. Cardiotoxicity of FAC (5-Fluorouracil + Adriamycin + Cyclophosphamide) Metabolotes in H9c2 Cardiac Differentiated Cells

Author: F. Carvalho, Vera Marisa Costa, Fernando Remião, E. Sousa, M.D.L. Bastos, and Ana Reis-Mendes
Subjects: Cardiotoxicity, Cyclophosphamide, Fluorouracil, business.industry, Cellular differentiation, medicine, Cancer research, General Medicine, Toxicology, business, medicine.drug
Published: 2018

43. Clorgyline and N-acetyl-L-cysteine provide partial protection against the toxicity of synthetic cathinones and methamphetamine on SH-SY5Y humans cells

Author: Félix Carvalho, João Paulo Capela, Soraia Bronze, M.D.L. Bastos, Vera Marisa Costa, Helena Gaspar, Janine Soares, and Susana Santos
Subjects: 0301 basic medicine, SH-SY5Y, Chemistry, General Medicine, Pharmacology, Methamphetamine, Toxicology, 03 medical and health sciences, 030104 developmental biology, Clorgyline, Toxicity, medicine, N-acetyl-L-cysteine, medicine.drug
Published: 2018

44. Evaluation of GSH adducts of adrenaline in biological samples

Author: Márcia Carvalho, Maria de Lourdes Bastos, Félix Carvalho, Fernando Remião, Francisco Lemos-Amado, Vera Marisa Costa, Renata Silva, Sílvia Boldt, and Helena Carmo
Subjects: Epinephrine, Clinical Biochemistry, Activated alumina, Conjugated system, Sensitivity and Specificity, Biochemistry, High-performance liquid chromatography, Analytical Chemistry, Adduct, Adrenaline, Coulometry, chemistry.chemical_compound, Catecholamines, Drug Discovery, Humans, Molecular Biology, Chromatography, High Pressure Liquid, Pharmacology, Chromatography, Chemistry, Reproducibility of Results, General Medicine, Glutathione, GSH adducts, Oxidative Stress, Oxidative stress, Toxicity, HPLC, Selectivity
Abstract: The sustained high release of catecholamines to circulation is a deleterious condition that may induce toxicity, which seems to be partially related to the products formed by oxidation of catecholamines that can be further conjugated with glutathione (GSH). The aim of the present study was to develop a method for the determination of GSH adducts of adrenaline in biological samples. Two position isomers of the glutathion-S-yl-adrenaline were synthesized and characterized by HPLC using diode array, coulometric and mass detectors. A method for the extraction of these adducts from human plasma was also developed, based on adsorption to activated alumina, which showed adequate recoveries and proved to be crucial in removing interferences from plasma. The selectivity, precision and linearity of the method were all within the accepted values for these parameters. Furthermore, the sensitivity of this method allows the detection of adduct amounts that are within the range of the expected concentrations for these adducts under certain pathophysiological conditions and/or drug treatments. In conclusion, the development of this method allows the direct analysis of GSH adducts of adrenaline in human plasma, providing a valuable tool for the study of the catecholamine oxidation process and its related toxicity.
Published: 2007

45. The putative pro-inflammatory effect and oxidative stress induced by polyacrylic acid-coated iron oxide nanoparticles in mice: a biodistribution and toxicological study

Author: Vera Marisa Costa, Eduarda Fernandes, José Rivas, Paulo P. Freitas, Diana Couto, Agostinho Almeida, Félix Carvalho, M. A. López-Quintela, M. C. Freitas, Renan Campos Chisté, and Faculdade de Farmácia
Subjects: chemistry.chemical_compound, Biodistribution, chemistry, Polyacrylic acid, medicine, Organic chemistry, General Medicine, Toxicology, medicine.disease_cause, Iron oxide nanoparticles, Oxidative stress, Nuclear chemistry
Published: 2015

46. Quantification of alpha-amanitin in biological samples by HPLC using simultaneous UV- diode array and electrochemical detection

Author: Maria de Lourdes Bastos, Félix Carvalho, Vera Marisa Costa, Paula Baptista, and Juliana Garcia
Subjects: Male, endocrine system, animal structures, Calibration curve, Clinical Biochemistry, Kidney, Biochemistry, High-performance liquid chromatography, Sensitivity and Specificity, Analytical Chemistry, Matrix (chemical analysis), chemistry.chemical_compound, Pharmacokinetics, In vivo, polycyclic compounds, Animals, Humans, Amanita phalloides, Perchloric acid, Rats, Wistar, Chromatography, High Pressure Liquid, Alpha-Amanitin, Chromatography, biology, Electrochemical, Reproducibility of Results, Cell Biology, General Medicine, Electrochemical Techniques, biology.organism_classification, Diode-array, Rats, High-performance liquid chromatographic, α-amanitin, chemistry, Liver, Linear Models, Female, Spectrophotometry, Ultraviolet, Citric acid
Abstract: α-Amanitin is a natural bicyclic octapeptide, from the family of amatoxins, present in the deadly mushroom species Amanita phalloides. The toxicological and clinical interests raised by this toxin, require highly sensitive, accurate and reproducible quantification methods for pharmacokinetic studies. In the present work, a high-performance liquid chromatographic (HPLC) method with in-line connected diode-array (DAD) and electrochemical (EC) detection was developed and validated to quantify α-amanitin in biological samples (namely liver and kidney). Sample pre-treatment consisted of a simple and unique deproteinization step with 5% perchloric acid followed by centrifuga tion at 16,000. ×g, 4. °C, for 20. min. The high recovery found for α-amanitin (≥96.8%) makes this procedure suitable for extracting α-amanitin from liver and kidney homogenates. The resulting supernatant was collected and injected into the HPLC. Mobile phase was composed by 20% methanol in 50. mM citric acid, and 0.46. mM octanessulfonic acid, adjusted to pH 5.5. The chromatographic runs took less than 22. min and no significant endogenous interferences were observed at the α-amanitin retention time. Calibration curves were linear with regression coefficients higher than 0.994. The overall inter- and intra-assay precision did not exceed 15.3%.The present method has low interferences with simple and fast processing steps, being a suitable procedure to support in vivo toxicokinetic studies involving α-amanitin. In fact, the validated method was successfully applied to quantify α-amanitin in biological samples following intraperitoneal α-amanitin administration to rats. Moreover, human plasma was also used as matrix and the purposed method was adequate for detection of α-amanitin in that matrix. The results clearly indicate that the proposed method is suitable to investigate the pharmacokinetic and tissue distribution of α-amanitin. Additionally, the method will be very useful in the development of novel and potent antidotes against amatoxins poisoning and to improve the knowledge of α-amanitin toxicity. This work received financial support from the European Union (FEDER funds through COMPETE) and National Funds (FCT, Fundação para a Ciência e Tecnologia) through project Pest- C/EQB/LA0006/2013. Juliana Garcia and Vera Marisa Costa thank FCT - Foundation for Science and Technology - for their PhD grant (SFRH/BD/74979/ 2010 ) and Post-doc grant (SFRH/BPD/63746/2009), respectively. info:eu-repo/semantics/publishedVersion
Published: 2015

47. Amanita phalloides poisoning: Mechanisms of toxicity and treatment

Author: Paula Baptista, Félix Carvalho, Juliana Garcia, Maria de Lourdes Bastos, Vera Marisa Costa, Alexandra T. P. Carvalho, and Paula Guedes de Pinho
Subjects: Amanita, Protein Conformation, medicine.medical_treatment, Poison control, Mushroom Poisoning, Pharmacology, Liver transplantation, Toxicology, Kidney, Peptides, Cyclic, Pharmacotherapy, medicine, Humans, Amanita phalloides, Mushroom poisoning, Antidote, biology, business.industry, General Medicine, Amatoxins, medicine.disease, biology.organism_classification, Toxicokinetics, Liver, RNA polymerase II, Therapy, Virotoxins, business, Food Science
Abstract: Amanita phalloides, also known as 'death cap', is one of the most poisonous mushrooms, being involved in the majority of human fatal cases of mushroom poisoning worldwide. This species contains three main groups of toxins: amatoxins, phallotoxins, and virotoxins. From these, amatoxins, especially α-amanitin, are the main responsible for the toxic effects in humans. It is recognized that α-amanitin inhibits RNA polymerase II, causing protein deficit and ultimately cell death, although other mechanisms are thought to be involved. The liver is the main target organ of toxicity, but other organs are also affected, especially the kidneys. Intoxication symptoms usually appear after a latent period and may include gastrointestinal disorders followed by jaundice, seizures, and coma, culminating in death. Therapy consists in supportive measures, gastric decontamination, drug therapy and, ultimately, liver transplantation if clinical condition worsens. The discovery of an effective antidote is still a major unsolved issue. The present paper examines the clinical toxicology of A. phalloides, providing the currently available information on the mechanisms of toxicityinvolved and on the current knowledge on the treatment prescribed against this type of mushrooms. Antidotal perspectives will be raised as to set the pace to new and improved therapy against these mushrooms. This work was supported by the Fundação para a Ciência e Tecnologia (FCT ) – project PTDC/DTPFTO/4973/2014 – and the European Union (FEDER funds through COMPETE) and National Funds (FCT, Fundação para a Ciência e Tecnologia) through project Pest-C/EQB/LA0006/2013. Juliana Garcia and Vera Marisa Costa thank FCT for their PhD grant (SFRH/BD/74979/2010) and Post-doc grants (SFRH/BPD/63746/2009 and SFRH/BPD/110001/2015), respectively. info:eu-repo/semantics/publishedVersion
Published: 2015

48. A mild cumulative dose of mitoxantrone leads to age-dependent cardiac injury in mice

Author: Félix Carvalho, Vera Marisa Costa, Maria de Lourdes Bastos, Vítor Seabra, José Alberto Duarte, and José Luís Dores-Sousa
Subjects: Mitoxantrone, medicine.medical_specialty, Cumulative dose, business.industry, medicine, Urology, Age dependent, General Medicine, Toxicology, business, medicine.drug
Published: 2015

49. Unveiling the cardiotoxicity of anticancer drugs: A comparative in vitro study between mitoxantrone and its naphthoquinoxaline metabolite

Author: A. Gomes, Madalena Pinto, Maria de Lourdes Bastos, Félix Carvalho, Rui A. Carvalho, Vera Marisa Costa, E. Sousa, Fernando Remião, and Ana Reis-Mendes
Subjects: Mitoxantrone, chemistry.chemical_compound, Cardiotoxicity, chemistry, business.industry, Metabolite, medicine, In vitro study, General Medicine, Pharmacology, Toxicology, business, medicine.drug
Published: 2015

50. Mitoxantrone elicits oxidative stress and proteomic changes in HL-1 cardiomyocytes at clinically relevant doses

Author: Célia M. Silveira, Félix Carvalho, Vera Marisa Costa, José Alberto Duarte, M.D.L. Bastos, João Paulo Capela, M.G. Almeida, Patricia Rodrigues, Fernando Remião, and R.P. Eleutério
Subjects: Mitoxantrone, business.industry, medicine, General Medicine, Pharmacology, Toxicology, business, medicine.disease_cause, Oxidative stress, medicine.drug
Published: 2015

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